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CompletedNCT05664672Updated Dec 9, 2024Results posted

Study to Evaluate Changes in Smokers Using on!® Nicotine Pouches

An interventional study of OTDN Product 1 and OTDN Product 2 in Tobacco Use, sponsored by Altria Client Services LLC. Completed at 3 sites in United States. Open to participants aged 21 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-12-09.

Sponsored by Altria Client Services LLC · Not applicable, Interventional, and Other

From the registry’s dates

  • Registered 1 year 7 months after the study started (first participant enrolled May 2021, registered Dec 2022).
Phase
Not applicable
Study type
Interventional
Enrollment
149
Allocation
Randomized
Ages
21 Years to 65 Years
Sex
All
01

Study summary

The purpose of this study is to generate evidence regarding the extent of reduction in exposure to selected HPHCs in adult smokers switching to on!® NPs. The study intends to determine changes in exposure to selected HPHCs by measuring biomarkers in adult smokers who completely switch from smoking to use of on!® NP compared to those who continue smoking cigarettes or stop using all tobacco products.

Read the detailed description

This is an open-label, randomized, 5 parallel-group clinical study evaluating changes in exposure to selected harmful and potentially harmful constituents (HPHCs) and product use behavior in adult smokers who are randomly assigned to 1 of the 5 groups; continue smoking, partially or completely switch to oral tobacco-derived nicotine products, or stop using any tobacco products for 7 days.

02

Conditions studied

  • Tobacco Use

Keywords

  • Tobacco
  • Smoking
03

In context

Lead sponsor

Altria Client Services LLC is the lead sponsor of 9 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
21 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  1. Voluntary consent to participate in this study documented on the signed ICF
  2. Smoking history (self-reported at screening) of an average of at least 10 but no more than 30 factory-manufactured combustible cigarettes (either menthol or non-menthol) daily for at least 12 months prior to screening. Brief periods (ie, up to 7 consecutive days) of non-smoking during the 3 months prior to screening (eg, due to illness or participation in a study where smoking was prohibited) will be permitted
  3. Positive urine cotinine (≥ 500 ng/mL) at screening

  4. Female subjects who are heterosexually active and of childbearing potential (eg, neither surgically sterile at least 6 months prior to check-in nor postmenopausal with amenorrhea for at least 12 months prior to check-in with follicle-stimulating hormone [FSH] levels consistent with postmenopausal status) must have been using one of the following forms of contraception for the time period indicated and agree to continue using it through completion of the study:

    • Hormonal (eg, oral, vaginal ring, transdermal patch, implant, injection) consistently for at least 3 months prior to check-in, double barrier (ie, condom with spermicide or diaphragm with spermicide) consistently for at least 4 weeks prior to check-in, an intrauterine device for at least 4 months prior to check-in
    • Exclusive partner who has been vasectomized for at least 6 months (inclusive) prior to check-in

    Female subjects of childbearing potential who are not currently engaging in heterosexual intercourse must agree to use one of the above methods of birth control through completion of study, in the event that they have heterosexual intercourse during the course of the study.

  5. Female subjects who are of nonchildbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to check-in:

    Hysteroscopic sterilization (including Essure® or similar nonsurgical sterilization procedures); bilateral tubal ligation or bilateral salpingectomy; hysterectomy; bilateral oophorectomy

    Or be postmenopausal with amenorrhea for at least 12 months prior to check-in and have FSH levels consistent with postmenopausal status

  6. Willing to comply with the requirements of the study
  7. Willing to use all 3 on!® NP after the Product Trial at check-in
  8. Willing and able to abstain from cigarettes from Day 1 through the end of the study (EOS)
  9. Healthy adult males and females, 21 to 65 years of age, inclusive at screening, with subjects aged 46 to 65 years being fully vaccinated for COVID-19 (SARS-CoV-2) at least 14 days before the screening visit.

Exclusion criteria

Exclusion Criteria:

  1. Use of any type of tobacco- or nicotine-containing products other than manufactured cigarettes (eg, e-vapor products, roll-your-own cigarettes, bidis, snuff, nicotine inhaler, pipe, cigar, chewing tobacco, nicotine patch, nicotine spray, nicotine lozenge, or nicotine gum) in the 7 days prior to check-in
  2. Self-reported puffers (ie, adult smokers who draw smoke from the cigarette into the mouth and throat but do not inhale)
  3. Planning to quit smoking in the next 30 days (from screening visit)
  4. History or presence of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, urologic, existing respiratory diseases, immunologic, psychiatric, lymphatic, or cardiovascular disease, or any other condition that, in the opinion of the investigator, would jeopardize the safety of the subject or impact the validity of the study results
  5. Clinically significant abnormal findings on the vital signs, physical examination, medical history, electrocardiogram (ECG), or clinical laboratory results, in the opinion of the investigator
  6. Positive test for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus at screening
  7. History or presence of any type of malignant tumors
  8. Current evidence or any history of congestive heart failure
  9. Diabetes mellitus (fasting glucose ≥126 mg/L [7 mmol/L]) that is not controlled by diet/exercise alone, in the opinion of the investigator
  10. An acute illness (eg, upper respiratory infection, viral infection) requiring treatment with prescribed medicines within 2 weeks prior to check-in
  11. Dentition that prevents subjects from using on!® NP products
  12. Allergic to or cannot tolerate mint flavoring agents or phenylalanine
  13. Any planned surgery from the time of screening through EOS
  14. History of drug or alcohol abuse within 24 months prior to check-in
  15. Fever (ie, body temperature >100.5°F) at screening or check-in. One recheck may be performed at the investigator's discretion
  16. Body mass index greater than 40.0 kg/m2 or less than 18.0 kg/m2 at screening
  17. Systolic blood pressure >150 mmHg and/or diastolic blood pressure > 90 mmHg at screening or check-in, measured after being seated for at least 5 minutes. One recheck may be performed at the investigator's discretion
  18. Estimated creatinine clearance (by Cockcroft-Gault equation) \< 80 mL/minute at screening
  19. Serum alanine aminotransferase ≥1.5 times the upper limit of normal and/or aspartate aminotransferase ≥1.5 times the upper limit of normal at screening
  20. Positive screen for alcohol (breath) or any of the following drugs of abuse (urine), regardless of the reason of use: amphetamines, methamphetamines, opiates, cannabinoids, or cocaine at screening or check-in
  21. Female subjects who are pregnant (positive serum pregnancy test at screening or urine pregnancy test at check-in), lactating, or intend to become pregnant from screening through EOS
  22. Use of prescription or over-the-counter bronchodilator medication (eg, inhaled or oral ß-agonists) within 12 months prior to check-in
  23. Use of medications or foods known or are suspected to interact with cytochrome P450 2A6 (including, but not limited to, amiodarone, amlodipine, amobarbital, buprenorphine, clofibrate, clotrimazole, desipramine, disulfiram, entacapone, fenofibrate, isoniazid, grapefruit, ketoconazole, letrozole, methimazole, methoxsalen, metyrapone, miconazole, modafinil, orphenadrine, pentobarbital, phenobarbital, pilocarpine, primidone, propoxyphene, quinidine, rifampicin, rifampin, secobarbital, selegiline, sulconazole, tioconazole, tranylcypromine) within 14 days or 5 half-lives of the drug, whichever is longer, prior to check-in or during the study
  24. Use of antibiotic treatment within 2 weeks prior to check-in
  25. Plasma donation within 7 days prior to check-in
  26. Donation of blood or blood products (with the exception of plasma as noted above), had significant blood loss, or received whole blood or a blood product transfusion within 56 days prior to check-in
  27. Participation in a previous clinical study for an investigational drug, device, biologic, or a tobacco product within 30 days prior to check-in
  28. Participation in 2 or more Altria Client Services (ALCS) studies within the past 12-month period prior to check-in
  29. Subject or a first-degree relative (ie, parent, sibling, child, spouse/partner) is a current or former employee of the tobacco industry or a named party or class representative in litigation with any tobacco company
  30. Subject or a first-degree relative (ie, parent, sibling, child, spouse/partner) is a current employee of the study site
  31. Positive result for coronavirus disease (COVID)-19 (SARS-CoV-2) test at screening or check-in
  32. One or more "yes" answers to any of the questions on the COVID-19 (SARS-CoV-2) screening questionnaire (provided by the study site) at screening or check-in.
  33. Have been diagnosed with major depressive disorder or have a history of suicide attempt.
05

Study design

Phase
Not applicable
Primary purpose
Other
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
149 participants (actual)

Study arms

  • No intervention
    Group 1 (CC)

    Subjects will be asked to continue smoking their UBCs ad libitum for 7 days.

  • Experimental
    Group 2 (NP2)

    Subjects will exclusively use 2 mg NP, using at least 3 pouches per day for 7 days.

    Other: OTDN Product 1

  • Experimental
    Group 3 (NP4)

    Subjects will exclusively use 4 mg NP, using at least 3 pouches per day for 7 days.

    Other: OTDN Product 2

  • Experimental
    Group 4 (NP8)

    Subjects will exclusively use 8 mg NP, using at least 3 pouches per day for 7 days.

    Other: OTDN Product 3

  • Experimental
    Group 5 (NT)

    Subjects will completely stop all tobacco product usage for 7 days.

    Other: No Tobacco

Interventions

  • OtherOTDN Product 1

    Mint on!® 2 mg nicotine pouches

  • OtherOTDN Product 2

    Mint on!® 4 mg nicotine pouches

  • OtherOTDN Product 3

    Mint on!® 8 mg nicotine pouches

  • OtherNo Tobacco

    subjects completely stop all tobacco product usage for 7 days

06

What researchers measure

Primary outcomes

  1. NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urinary creatinine-adjusted total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

Secondary outcomes

  1. NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urinary creatinine-adjusted Nicotine Equivalents (NE) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during the 24 hours was converted to 24-hour urine volume using the assumed density of 1 gram (g) equals 1 milliliter (mL). The amount of biomarker was calculated as follows: NE concentration (μg/mL) = (nicotine \[ng/mL\]/162.23 \[mg/mmol\] + nicotine-gluc \[ng/mL\]/338.36 \[mg/mmol\] + cotinine \[ng/mL\]/176.22 \[mg/mmol\] + cotinine-gluc \[ng/mL\]/352.34 \[mg/mmol\] + trans-3'-hydroxycotinine \[ng/mL\]/192.22 \[mg/mmol\] + trans-3'-hydroxycotinine-gluc \[ng/mL\]/368.34 \[mg/mmol\]) × 162.23 (mg/mmol) × 1 μg/1000 ng Adjusted Nicotine equivalents (mg NE/g creatinine) = NE concentration (μg/mL) × 100 / Creatinine concentration (mg/dL) Absolute change from baseline = Post Randomization Value - Baseline Value

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

  2. 2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urinary creatinine-adjusted 2-aminonaphthalene (2-AN) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

  3. 4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urinary creatinine-adjusted 4-aminobiphenyl (4-ABP) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

  4. HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urinary creatinine-adjusted 2-hydroxyethylmercapturic acid (HEMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

  5. CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urinary creatinine-adjusted cyanoethylmercapturic acid (CEMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

  6. SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urinary creatinine-adjusted S-phenylmercapturic acid (SPMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

  7. HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urinary creatinine-adjusted 3-hydroxy-1-methylpropylmercapturic acid (HMPMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

  8. 3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urinary creatinine-adjusted 3-hydroxypropylmercapturic acid (3-HPMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

  9. 2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urinary creatinine-adjusted 2-hydroxypropylmercapturic acid (2-HPMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

  10. AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urinary creatinine-adjusted N-acetyl-S-(2-carbamoylethyl) cysteine (AAMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

  11. GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urinary creatinine-adjusted N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-1-cysteine (GAMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

  12. 2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urinary creatinine-adjusted 2-hydroxybutenylmercapturic acid (2-MHBMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

  13. 2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urinary creatinine-adjusted 2-OH-Fluorene (2-OH-Flu) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

  14. 2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urinary creatinine-adjusted 2-Naphthol (2-OH-Nap) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

  15. 1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urinary creatinine-adjusted 1-OH-Phenanthrene (1-OH-Phe) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

  16. 3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urinary creatinine-adjusted 3-hydroxybenzo\[a\]pyrene (3-OH-B\[a\]P) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

  17. Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urine mutagenicity (Rev/24h) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. 250 mL urine sample will be concentrated to 1 mL and used for urine mutagenicity testing. Measurement results are reported as revertants/μL. Urine mutagenicity count in the 24-hour urine was calculated as: Urine mutagenicity (revertants/250 mL) = Urine mutagenicity (revertants/μL) x 1000V, where V is the volume after concentration in mL Urine mutagenicity (revertants/24 hour) = Urine mutagenicity (revertants/250 mL) x \[24h urine volume(mL) ÷ V\], where V is the volume in mL of urine sample used for the mutagenicity test

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

  18. 1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of 24-hour urinary creatinine-adjusted 1-hydroxypyrene (1-OH-Pyr) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

    Time frame: Samples collected over 24 hours on Day -1 (baseline) and Day 7

  19. Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

    Summary of blood carboxyhemoglobin (%) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. The absolute change from baseline of urine biomarker amount excreted in 24 hours and blood biomarker concentration will be calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value where Baseline = Day -1

    Time frame: Samples collected at approximately 21:30 on Day -1 (baseline) and Day 7

  20. Summary of Cigarettes Smoked Per Day (CPD)

    The number of cigarettes smoked per day (CPD) from 07:00 to 23:00 on Day 1 to Day 7 was collected to assess produce use behavior. Subjects in NP2, NP4, NP8 and NT groups were not allowed to use cigarettes starting at Day 1.

    Time frame: Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study

  21. Summary of Total Number of Nicotine Pouches Used Per Day (NPPD)

    The number of nicotine pouches used per day (NPPD) from 07:00 to 23:00 on Day 1 to Day 7 was collected to assess produce use behavior. Only subjects in NP2, NP4 and NP8 groups used nicotine pouches during the study.

    Time frame: Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study

  22. Summary of Average Number of Nicotine Pouches Per Use

    The average number of nicotine pouches per use occasion (NPPU) from 07:00 to 23:00 on Day 1 to Day 7 was collected to assess produce use behavior. Only subjects in NP2, NP4 and NP8 groups used nicotine pouches during the study.

    Time frame: Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study

  23. Summary of Average Duration of Each Nicotine Pouch Use

    The average duration (in minutes) of each nicotine pouch use from 07:00 to 23:00 on Day 1 to Day 7 was collected to assess produce use behavior. Only subjects in NP2, NP4 and NP8 groups used nicotine pouches during the study.

    Time frame: Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study

07

Results

Posted Dec 9, 2024

Participant flow

Participant flow — Overall Study
MilestoneNot AssignedGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Started32928303029
Completed02825302522
Not completed313057
Withdrew: Adverse event000001
Withdrew: Withdrawal by subject013056
Withdrew: Failure to meet randomization criteria200000
Withdrew: Met eligibility criteria but not needed100000

Outcome measures

PrimaryNNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urinary creatinine-adjusted total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · ng/g
NNAL Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
ng/gGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)363 ± 239274 ± 203312 ± 201293 ± 213392 ± 308
Day 7330 ± 22467.8 ± 70.073.2 ± 42.764.7 ± 51.071.3 ± 62.2
Change from Baseline to Day 7-32.8 ± 67.6-206 ± 146-239 ± 172-228 ± 171-321 ± 290
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 24.2 · 95% CI 15.9 to 37.0Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 25.3 · 95% CI 17.1 to 37.3Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 22.4 · 95% CI 14.9 to 33.7Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 16.5 · 95% CI 10.8 to 25.3Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.1148 · Ratio of geometric ls means (test/ref): 147 · 95% CI 93.7 to 230Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 0.0440 · Ratio of geometric ls means (test/ref): 153 · 95% CI 101 to 233Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.2422 · Ratio of geometric ls means (test/ref): 136 · 95% CI 87.8 to 210Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
SecondaryNE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urinary creatinine-adjusted Nicotine Equivalents (NE) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during the 24 hours was converted to 24-hour urine volume using the assumed density of 1 gram (g) equals 1 milliliter (mL). The amount of biomarker was calculated as follows: NE concentration (μg/mL) = (nicotine \[ng/mL\]/162.23 \[mg/mmol\] + nicotine-gluc \[ng/mL\]/338.36 \[mg/mmol\] + cotinine \[ng/mL\]/176.22 \[mg/mmol\] + cotinine-gluc \[ng/mL\]/352.34 \[mg/mmol\] + trans-3'-hydroxycotinine \[ng/mL\]/192.22 \[mg/mmol\] + trans-3'-hydroxycotinine-gluc \[ng/mL\]/368.34 \[mg/mmol\]) × 162.23 (mg/mmol) × 1 μg/1000 ng Adjusted Nicotine equivalents (mg NE/g creatinine) = NE concentration (μg/mL) × 100 / Creatinine concentration (mg/dL) Absolute change from baseline = Post Randomization Value - Baseline Value

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · mg/g
NE Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
mg/gGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)11.6 ± 6.558.73 ± 4.4210.3 ± 4.8310.5 ± 5.9912.2 ± 7.34
Day 710.4 ± 5.105.79 ± 5.018.80 ± 6.6611.8 ± 8.450.978 ± 2.35
Change from Baseline to Day 7-1.20 ± 3.81-2.94 ± 3.80-1.50 ± 5.811.34 ± 6.77-11.2 ± 6.89
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = 0.0994 · Ratio of geometric ls means (test/ref): 49.9 · 95% CI 22.7 to 110Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = 0.4162 · Ratio of geometric ls means (test/ref): 65.8 · 95% CI 32.0 to 135Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = 1.0000 · Ratio of geometric ls means (test/ref): 101 · 95% CI 47.5 to 215Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 2.23 · 95% CI 1.01 to 4.94Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 2230 · 95% CI 965 to 5160Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 2940 · 95% CI 1350 to 6400Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 4530 · 95% CI 2020 to 10200Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
Secondary2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urinary creatinine-adjusted 2-aminonaphthalene (2-AN) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · ng/g
2-AN Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
ng/gGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)21.7 ± 11.517.0 ± 9.9321.6 ± 12.019.8 ± 11.220.6 ± 11.7
Day 720.2 ± 11.31.07 ± 0.7281.82 ± 1.361.45 ± 1.351.29 ± 1.01
Change from Baseline to Day 7-1.58 ± 5.10-16.0 ± 9.77-19.8 ± 11.8-18.3 ± 10.9-19.3 ± 11.7
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 5.69 · 95% CI 3.29 to 9.87Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 8.08 · 95% CI 4.88 to 13.4Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 6.58 · 95% CI 3.88 to 11.2Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 6.03 · 95% CI 3.46 to 10.5Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.9972 · Ratio of geometric ls means (test/ref): 94.4 · 95% CI 52.7 to 169Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 0.4655 · Ratio of geometric ls means (test/ref): 134 · 95% CI 77.9 to 230Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.9851 · Ratio of geometric ls means (test/ref): 109 · 95% CI 62.1 to 192Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
Secondary4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urinary creatinine-adjusted 4-aminobiphenyl (4-ABP) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · ng/g
4-ABP Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
ng/gGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)13.8 ± 6.7410.2 ± 5.0413.3 ± 6.2912.8 ± 6.2212.8 ± 6.81
Day 713.2 ± 7.441.42 ± 0.4501.97 ± 0.7491.72 ± 0.9851.92 ± 1.04
Change from Baseline to Day 7-0.589 ± 4.53-8.75 ± 4.94-11.3 ± 6.04-11.1 ± 5.81-10.9 ± 6.58
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 13.7 · 95% CI 9.72 to 19.2Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 16.6 · 95% CI 12.1 to 22.6Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 13.4 · 95% CI 9.68 to 18.6Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 15.7 · 95% CI 11.2 to 22.2Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.7167 · Ratio of geometric ls means (test/ref): 86.8 · 95% CI 60.6 to 124Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 0.9864 · Ratio of geometric ls means (test/ref): 105 · 95% CI 75.3 to 147Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.5911 · Ratio of geometric ls means (test/ref): 85.1 · 95% CI 60.1 to 120Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
SecondaryHEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urinary creatinine-adjusted 2-hydroxyethylmercapturic acid (HEMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · μg/g
HEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
μg/gGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)5.19 ± 5.342.98 ± 1.695.64 ± 5.295.65 ± 6.113.90 ± 3.42
Day 74.63 ± 4.470.959 ± 0.6601.18 ± 0.7581.55 ± 1.111.30 ± 0.762
Change from Baseline to Day 7-0.559 ± 1.80-2.03 ± 1.40-4.46 ± 4.63-4.09 ± 5.50-2.60 ± 3.22
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 29.6 · 95% CI 21.8 to 40.0Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 28.3 · 95% CI 21.5 to 37.4Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 33.1 · 95% CI 24.8 to 44.2Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 37.5 · 95% CI 27.7 to 50.9Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.1950 · Ratio of geometric ls means (test/ref): 78.8 · 95% CI 57.3 to 108Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 0.0699 · Ratio of geometric ls means (test/ref): 75.5 · 95% CI 56.1 to 102Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.7041 · Ratio of geometric ls means (test/ref): 88.3 · 95% CI 64.7 to 120Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
SecondaryCEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urinary creatinine-adjusted cyanoethylmercapturic acid (CEMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · μg/g
CEMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
μg/gGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)163 ± 74.1133 ± 65.0154 ± 83.4170 ± 72.9160 ± 94.8
Day 7150 ± 72.117.4 ± 10.318.9 ± 10.723.0 ± 13.116.0 ± 11.6
Change from Baseline to Day 7-12.4 ± 28.9-116 ± 56.6-135 ± 75.8-147 ± 67.5-144 ± 85.4
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 13.3 · 95% CI 9.57 to 18.4Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 13.3 · 95% CI 9.84 to 17.9Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 13.6 · 95% CI 9.93 to 18.6Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 9.28 · 95% CI 6.67 to 12.9Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.0404 · Ratio of geometric ls means (test/ref): 143 · 95% CI 101 to 202Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 0.0243 · Ratio of geometric ls means (test/ref): 143 · 95% CI 104 to 198Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.0215 · Ratio of geometric ls means (test/ref): 146 · 95% CI 105 to 205Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
SecondarySPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urinary creatinine-adjusted S-phenylmercapturic acid (SPMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · μg/g
SPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
μg/gGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)4.41 ± 3.293.03 ± 2.243.90 ± 2.413.79 ± 2.703.54 ± 3.18
Day 74.14 ± 3.240.149 ± 0.1080.183 ± 0.1060.186 ± 0.1400.171 ± 0.107
Change from Baseline to Day 7-0.265 ± 0.810-2.88 ± 2.17-3.72 ± 2.38-3.61 ± 2.67-3.37 ± 3.09
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 5.37 · 95% CI 3.69 to 7.80Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 5.65 · 95% CI 4.01 to 7.96Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 5.61 · 95% CI 3.92 to 8.03Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 6.09 · 95% CI 4.17 to 8.89Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.8335 · Ratio of geometric ls means (test/ref): 88.1 · 95% CI 59.4 to 131Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 0.9622 · Ratio of geometric ls means (test/ref): 92.9 · 95% CI 64.2 to 134Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.9531 · Ratio of geometric ls means (test/ref): 92.1 · 95% CI 62.8 to 135Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
SecondaryHMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urinary creatinine-adjusted 3-hydroxy-1-methylpropylmercapturic acid (HMPMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · μg/g
HMPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
μg/gGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)371 ± 161303 ± 121325 ± 167338 ± 143353 ± 198
Day 7345 ± 15953.4 ± 10.457.1 ± 25.048.6 ± 10.355.2 ± 12.4
Change from Baseline to Day 7-25.6 ± 75.6-250 ± 120-268 ± 163-290 ± 142-298 ± 197
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 18.0 · 95% CI 14.4 to 22.3Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 18.0 · 95% CI 14.8 to 22.1Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 15.8 · 95% CI 12.8 to 19.4Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 18.2 · 95% CI 14.6 to 22.7Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.9993 · Ratio of geometric ls means (test/ref): 98.4 · 95% CI 78.2 to 124Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 0.9998 · Ratio of geometric ls means (test/ref): 98.9 · 95% CI 79.7 to 123Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.3019 · Ratio of geometric ls means (test/ref): 86.4 · 95% CI 69.1 to 108Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
Secondary3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urinary creatinine-adjusted 3-hydroxypropylmercapturic acid (3-HPMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · μg/g
3-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
μg/gGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)1250 ± 605969 ± 4141160 ± 5501170 ± 5161200 ± 844
Day 71170 ± 614195 ± 98.9259 ± 118215 ± 98.7281 ± 205
Change from Baseline to Day 7-82.7 ± 299-774 ± 410-897 ± 557-957 ± 494-923 ± 836
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 18.3 · 95% CI 13.2 to 25.3Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 23.7 · 95% CI 17.6 to 31.9Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 19.3 · 95% CI 14.2 to 26.4Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 24.0 · 95% CI 17.3 to 33.3Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.1530 · Ratio of geometric ls means (test/ref): 76.1 · 95% CI 54.0 to 107Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 0.9999 · Ratio of geometric ls means (test/ref): 98.6 · 95% CI 71.7 to 136Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.3025 · Ratio of geometric ls means (test/ref): 80.5 · 95% CI 57.8 to 112Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
Secondary2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urinary creatinine-adjusted 2-hydroxypropylmercapturic acid (2-HPMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · μg/g
2-HPMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
μg/gGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)52.7 ± 28.739.2 ± 19.447.3 ± 28.445.4 ± 23.841.4 ± 23.6
Day 750.9 ± 31.89.44 ± 3.8711.9 ± 3.9712.5 ± 7.4311.9 ± 3.97
Change from Baseline to Day 7-1.81 ± 13.8-29.8 ± 20.4-35.4 ± 26.9-33.0 ± 26.0-29.6 ± 22.4
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 22.7 · 95% CI 17.0 to 30.4Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 28.1 · 95% CI 21.6 to 36.6Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 27.5 · 95% CI 20.8 to 36.2Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 28.7 · 95% CI 21.4 to 38.4Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.1843 · Ratio of geometric ls means (test/ref): 79.4 · 95% CI 58.6 to 108Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 0.9994 · Ratio of geometric ls means (test/ref): 98.1 · 95% CI 73.9 to 130Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.9891 · Ratio of geometric ls means (test/ref): 95.9 · 95% CI 71.4 to 129Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
SecondaryAAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urinary creatinine-adjusted N-acetyl-S-(2-carbamoylethyl) cysteine (AAMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · μg/g
AAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
μg/gGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)92.6 ± 30.582.6 ± 36.195.6 ± 29.794.0 ± 36.494.3 ± 46.0
Day 787.7 ± 31.829.4 ± 6.9639.1 ± 12.736.7 ± 13.435.9 ± 10.4
Change from Baseline to Day 7-4.90 ± 19.0-53.1 ± 33.0-56.5 ± 27.0-57.3 ± 32.1-58.3 ± 43.1
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 37.3 · 95% CI 30.4 to 45.7Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 44.0 · 95% CI 36.5 to 53.1Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 41.8 · 95% CI 34.4 to 50.9Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 42.9 · 95% CI 34.9 to 52.7Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.3027 · Ratio of geometric ls means (test/ref): 86.9 · 95% CI 70.0 to 108Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 0.9926 · Ratio of geometric ls means (test/ref): 103 · 95% CI 83.9 to 125Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.9938 · Ratio of geometric ls means (test/ref): 97.5 · 95% CI 79.1 to 120Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
SecondaryGAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urinary creatinine-adjusted N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-1-cysteine (GAMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · μg/g
GAMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
μg/gGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)14.4 ± 6.1513.1 ± 5.2714.3 ± 4.2914.7 ± 5.2314.1 ± 5.89
Day 714.1 ± 6.485.93 ± 1.947.58 ± 1.887.30 ± 2.247.26 ± 2.26
Change from Baseline to Day 7-0.256 ± 3.59-7.20 ± 3.99-6.77 ± 3.51-7.35 ± 4.11-6.79 ± 4.94
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 46.3 · 95% CI 39.5 to 54.4Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 55.6 · 95% CI 48.0 to 64.4Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 52.7 · 95% CI 45.2 to 61.5Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 54.9 · 95% CI 46.7 to 64.5Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.0504 · Ratio of geometric ls means (test/ref): 84.4 · 95% CI 71.2 to 100Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 0.9988 · Ratio of geometric ls means (test/ref): 101 · 95% CI 86.4 to 119Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.9238 · Ratio of geometric ls means (test/ref): 96.0 · 95% CI 81.4 to 113Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
Secondary2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urinary creatinine-adjusted 2-hydroxybutenylmercapturic acid (2-MHBMA) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · μg/g
2-MHBMA Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
μg/gGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)1.93 ± 1.531.24 ± 1.121.60 ± 1.661.47 ± 1.371.26 ± 1.15
Day 71.74 ± 1.330.0359 ± 0.03380.0487 ± 0.04660.0460 ± 0.04130.0729 ± 0.0800
Change from Baseline to Day 7-0.194 ± 0.517-1.20 ± 1.11-1.56 ± 1.63-1.43 ± 1.36-1.19 ± 1.11
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 3.71 · 95% CI 1.88 to 7.31Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 4.25 · 95% CI 2.28 to 7.93Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 4.24 · 95% CI 2.20 to 8.14Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 6.40 · 95% CI 3.22 to 12.7Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.1840 · Ratio of geometric ls means (test/ref): 57.9 · 95% CI 28.3 to 119Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 0.3552 · Ratio of geometric ls means (test/ref): 66.4 · 95% CI 34.0 to 130Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.3810 · Ratio of geometric ls means (test/ref): 66.2 · 95% CI 33.0 to 133Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
Secondary2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urinary creatinine-adjusted 2-OH-Fluorene (2-OH-Flu) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · μg/g
2-OH-Flu Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
μg/gGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)2.24 ± 1.111.71 ± 0.8902.01 ± 1.082.14 ± 1.092.08 ± 1.11
Day 72.08 ± 1.170.280 ± 0.1440.356 ± 0.1410.361 ± 0.2250.345 ± 0.203
Change from Baseline to Day 7-0.159 ± 0.401-1.43 ± 0.777-1.65 ± 0.995-1.78 ± 0.916-1.73 ± 0.931
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 16.8 · 95% CI 13.0 to 21.8Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 20.5 · 95% CI 16.2 to 25.9Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 18.2 · 95% CI 14.3 to 23.4Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 17.8 · 95% CI 13.7 to 23.1Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.9589 · Ratio of geometric ls means (test/ref): 94.5 · 95% CI 72.0 to 124Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 0.4442 · Ratio of geometric ls means (test/ref): 115 · 95% CI 89.3 to 148Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.9975 · Ratio of geometric ls means (test/ref): 103 · 95% CI 78.8 to 133Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
Secondary2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urinary creatinine-adjusted 2-Naphthol (2-OH-Nap) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · μg/g
2-OH-Nap Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
μg/gGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)11.1 ± 5.0811.5 ± 8.4612.6 ± 5.5613.8 ± 7.0111.8 ± 7.60
Day 710.6 ± 5.065.16 ± 6.385.26 ± 3.894.80 ± 4.386.00 ± 5.56
Change from Baseline to Day 7-0.550 ± 2.55-6.38 ± 3.86-7.31 ± 5.20-9.00 ± 5.09-5.81 ± 5.91
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 36.5 · 95% CI 23.9 to 55.6Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 39.9 · 95% CI 27.1 to 59.0Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 30.2 · 95% CI 20.1 to 45.5Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = 0.0002 · Ratio of geometric ls means (test/ref): 48.9 · 95% CI 31.9 to 75.0Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.2938 · Ratio of geometric ls means (test/ref): 74.5 · 95% CI 47.6 to 117Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 0.5552 · Ratio of geometric ls means (test/ref): 81.6 · 95% CI 53.7 to 124Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.0254 · Ratio of geometric ls means (test/ref): 61.7 · 95% CI 39.9 to 95.5Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
Secondary1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urinary creatinine-adjusted 1-OH-Phenanthrene (1-OH-Phe) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · μg/g
1-OH-Phe Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
μg/gGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)0.218 ± 0.1070.162 ± 0.08160.172 ± 0.09380.171 ± 0.09020.191 ± 0.0895
Day 70.203 ± 0.1080.0804 ± 0.03970.0804 ± 0.03970.0674 ± 0.03800.0833 ± 0.0431
Change from Baseline to Day 7-0.0142 ± 0.0517-0.0818 ± 0.0592-0.0918 ± 0.0738-0.103 ± 0.0685-0.107 ± 0.0818
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 52.1 · 95% CI 40.4 to 67.1Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 49.3 · 95% CI 39.0 to 62.2Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 40.8 · 95% CI 32.0 to 52.1Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 45.9 · 95% CI 35.7 to 59.2Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.5817 · Ratio of geometric ls means (test/ref): 113 · 95% CI 86.8 to 148Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 0.8852 · Ratio of geometric ls means (test/ref): 107 · 95% CI 83.7 to 138Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.6070 · Ratio of geometric ls means (test/ref): 88.9 · 95% CI 68.7 to 115Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
Secondary3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urinary creatinine-adjusted 3-hydroxybenzo\[a\]pyrene (3-OH-B\[a\]P) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · pg/g
3-OH-B[a]P Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
pg/gGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)216 ± 155139 ± 111223 ± 158172 ± 139166 ± 101
Day 7246 ± 21530.8 ± 50.982.5 ± 10557.7 ± 77.684.8 ± 174
Change from Baseline to Day 730.0 ± 192-108 ± 109-141 ± 186-115 ± 160-80.8 ± 195
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 13.2 · 95% CI 5.44 to 32.0Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 23.8 · 95% CI 10.7 to 53.3Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = 0.0003 · Ratio of geometric ls means (test/ref): 24.7 · 95% CI 10.6 to 57.4Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = 0.0002 · Ratio of geometric ls means (test/ref): 22.3 · 95% CI 9.21 to 54.1Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.4280 · Ratio of geometric ls means (test/ref): 59.1 · 95% CI 23.3 to 150Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 0.9990 · Ratio of geometric ls means (test/ref): 107 · 95% CI 44.8 to 255Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.9958 · Ratio of geometric ls means (test/ref): 110 · 95% CI 44.9 to 272Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
SecondaryUrine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urine mutagenicity (Rev/24h) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. 250 mL urine sample will be concentrated to 1 mL and used for urine mutagenicity testing. Measurement results are reported as revertants/μL. Urine mutagenicity count in the 24-hour urine was calculated as: Urine mutagenicity (revertants/250 mL) = Urine mutagenicity (revertants/μL) x 1000V, where V is the volume after concentration in mL Urine mutagenicity (revertants/24 hour) = Urine mutagenicity (revertants/250 mL) x \[24h urine volume(mL) ÷ V\], where V is the volume in mL of urine sample used for the mutagenicity test

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · Revertants / 24 hours
Urine Mutagenicity Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
Revertants / 24 hoursGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)13300 ± 140008770 ± 94809170 ± 111007580 ± 821012000 ± 12700
Day 710800 ± 130001710 ± 31502400 ± 35501920 ± 24403390 ± 5250
Change from Baseline to Day 7-2460 ± 8160-6980 ± 9170-6770 ± 11800-5650 ± 7460-8640 ± 9980
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means: -50.8 · 95% CI -77.7 to -23.9Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means: -45.0 · 95% CI -69.6 to -20.3Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = 0.0003 · Ratio of geometric ls means: -42.3 · 95% CI -68.2 to -16.5Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = 0.0004 · Ratio of geometric ls means: -44.8 · 95% CI -72.6 to -17.0Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.9551 · Ratio of geometric ls means: -6.05 · 95% CI -35.2 to 23.1Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 1.0000 · Ratio of geometric ls means: -0.198 · 95% CI -27.3 to 26.9Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.9981 · Ratio of geometric ls means: 2.48 · 95% CI -25.6 to 30.6Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale.
Secondary1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of 24-hour urinary creatinine-adjusted 1-hydroxypyrene (1-OH-Pyr) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. Total urine weight (g) collected during 24 hours was converted to 24-hour urine volume using assumed density of 1 g = 1 mL Amount of biomarker was calculated as: Urine Biomarker (unit2/24 hours) = Urine biomarker concentration \[unit1/mL\] × 24h urine volume \[mL\] ÷ 1000, where: unit2 = ng if unit1 = pg; unit2 = μg if unit1 = ng Adjusted Urine biomarker (unit2/g creatinine) = Urine biomarker concentration (unit1/mL) × 100 / Creatinine concentration (mg/dL), where unit2 = ng if unit1 = pg, and unit2 = μg if unit 1 = ng The absolute change from baseline of urine biomarker amount excreted in 24 hours was calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value

Time frame:
Samples collected over 24 hours on Day -1 (baseline) and Day 7
Reported as:
Mean · μg/g
1-OH-Pyr Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
μg/gGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)0.208 ± 0.1470.148 ± 0.1020.145 ± 0.09120.174 ± 0.1140.174 ± 0.115
Day 70.198 ± 0.1460.0489 ± 0.04850.0485 ± 0.03690.0506 ± 0.03720.0509 ± 0.0325
Change from Baseline to Day 7-0.00991 ± 0.102-0.0989 ± 0.0704-0.0969 ± 0.0817-0.123 ± 0.0822-0.123 ± 0.0935
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 31.7 · 95% CI 18.7 to 53.9Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 28.5 · 95% CI 17.6 to 46.2Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 24.3 · 95% CI 14.7 to 40.2Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means (test/ref): 28.1 · 95% CI 16.6 to 47.7Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.9511 · Ratio of geometric ls means (test/ref): 113 · 95% CI 64.7 to 197Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 1.0000 · Ratio of geometric ls means (test/ref): 101 · 95% CI 60.4 to 170Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.9003 · Ratio of geometric ls means (test/ref): 86.5 · 95% CI 50.6 to 148Geometric LSM calculated by transforming the natural-log LS means back to the linear scale. Ratio of geometric LSM expressed as percentage. In statistical model, group \& gender included as fixed effects; baseline value included as covariate.
SecondaryCarboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days

Summary of blood carboxyhemoglobin (%) in subjects using nicotine pouches (NP) for 7 days versus subjects who continue to smoke cigarettes for 7 days and subjects who stopped using any tobacco products for 7 days. The absolute change from baseline of urine biomarker amount excreted in 24 hours and blood biomarker concentration will be calculated as follows: Absolute change from baseline = Post Randomization Value - Baseline Value where Baseline = Day -1

Time frame:
Samples collected at approximately 21:30 on Day -1 (baseline) and Day 7
Reported as:
Mean · percent saturation
Carboxyhemoglobin (COHb) Exposure in Subjects Using Nicotine Pouches for 7 Days Versus Subjects Who Continue to Smoke Cigarettes for 7 Days
percent saturationGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
Day -1 (Baseline)11.8 ± 4.2010.3 ± 3.5911.3 ± 3.2011.1 ± 5.2511.0 ± 3.84
Day 711.3 ± 4.294.99 ± 1.674.60 ± 1.144.60 ± 0.9184.22 ± 1.02
Change from Baseline to Day 7-0.585 ± 4.00-5.35 ± 4.01-6.65 ± 3.28-6.49 ± 5.12-6.77 ± 3.50
Statistical analysis
  • Group 1 (CC) vs Group 2 (NP2) · ANCOVA · p = <.0001 · Ratio of geometric ls means: 46.4 · 95% CI 37.1 to 58.0Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale.
  • Group 1 (CC) vs Group 3 (NP4) · ANCOVA · p = <.0001 · Ratio of geometric ls means: 43.1 · 95% CI 35.1 to 52.9Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale.
  • Group 1 (CC) vs Group 4 (NP8) · ANCOVA · p = <.0001 · Ratio of geometric ls means: 44.1 · 95% CI 35.5 to 54.6Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale.
  • Group 1 (CC) vs Group 5 (NT) · ANCOVA · p = <.0001 · Ratio of geometric ls means: 39.1 · 95% CI 31.0 to 49.4Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale.
  • Group 2 (NP2) vs Group 5 (NT) · ANCOVA · p = 0.2351 · Ratio of geometric ls means: 119 · 95% CI 93.2 to 151Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale.
  • Group 3 (NP4) vs Group 5 (NT) · ANCOVA · p = 0.6570 · Ratio of geometric ls means: 110 · 95% CI 87.7 to 138Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale.
  • Group 4 (NP8) vs Group 5 (NT) · ANCOVA · p = 0.5112 · Ratio of geometric ls means: 113 · 95% CI 89.1 to 142Geometric least squares means were calculated by transforming the natural-log LS means back to the linear scale. Est. para. is ratio of geometric LS means for natural-log (expressed as a percentage), natural-log transformed back to the linear scale.
SecondarySummary of Cigarettes Smoked Per Day (CPD)

The number of cigarettes smoked per day (CPD) from 07:00 to 23:00 on Day 1 to Day 7 was collected to assess produce use behavior. Subjects in NP2, NP4, NP8 and NT groups were not allowed to use cigarettes starting at Day 1.

Time frame:
Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study
Reported as:
Mean · cigarettes per day
Summary of Cigarettes Smoked Per Day (CPD)
cigarettes per dayGroup 1 (CC)
Day 116.1 ± 5.91
Day 215.8 ± 6.11
Day 315.6 ± 6.26
Day 414.8 ± 7.25
Day 515.8 ± 6.79
Day 615.8 ± 7.56
Day 715.9 ± 7.18
SecondarySummary of Total Number of Nicotine Pouches Used Per Day (NPPD)

The number of nicotine pouches used per day (NPPD) from 07:00 to 23:00 on Day 1 to Day 7 was collected to assess produce use behavior. Only subjects in NP2, NP4 and NP8 groups used nicotine pouches during the study.

Time frame:
Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study
Reported as:
Mean · nicotine pouches per day
Summary of Total Number of Nicotine Pouches Used Per Day (NPPD)
nicotine pouches per dayGroup 2 (NP2)Group 3 (NP4)Group 4 (NP8)
Day 19.78 ± 6.009.77 ± 5.647.27 ± 4.96
Day 29.22 ± 6.1610.2 ± 5.476.93 ± 4.06
Day 310.5 ± 7.129.87 ± 5.537.34 ± 4.56
Day 49.48 ± 6.4610.2 ± 6.257.15 ± 4.00
Day 510.1 ± 6.8210.4 ± 5.707.36 ± 4.24
Day 610.7 ± 6.3410.1 ± 5.717.12 ± 3.88
Day 710.8 ± 7.7711.2 ± 6.917.60 ± 4.24
SecondarySummary of Average Number of Nicotine Pouches Per Use

The average number of nicotine pouches per use occasion (NPPU) from 07:00 to 23:00 on Day 1 to Day 7 was collected to assess produce use behavior. Only subjects in NP2, NP4 and NP8 groups used nicotine pouches during the study.

Time frame:
Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study
Reported as:
Mean · nicotine pouches per use
Summary of Average Number of Nicotine Pouches Per Use
nicotine pouches per useGroup 2 (NP2)Group 3 (NP4)Group 4 (NP8)
Day 11.19 ± 0.3091.22 ± 0.2851.09 ± 0.204
Day 21.22 ± 0.4341.28 ± 0.4041.15 ± 0.378
Day 31.26 ± 0.4681.33 ± 0.5751.21 ± 0.444
Day 41.25 ± 0.4361.32 ± 0.3891.18 ± 0.308
Day 51.26 ± 0.4201.33 ± 0.4191.13 ± 0.255
Day 61.35 ± 0.4611.35 ± 0.4811.13 ± 0.256
Day 71.37 ± 0.5131.38 ± 0.4731.13 ± 0.227
SecondarySummary of Average Duration of Each Nicotine Pouch Use

The average duration (in minutes) of each nicotine pouch use from 07:00 to 23:00 on Day 1 to Day 7 was collected to assess produce use behavior. Only subjects in NP2, NP4 and NP8 groups used nicotine pouches during the study.

Time frame:
Data was collected from 07:00 to 23:00 each day starting from Day 1 to Day 7/end of study
Reported as:
Mean · minutes
Summary of Average Duration of Each Nicotine Pouch Use
minutesGroup 2 (NP2)Group 3 (NP4)Group 4 (NP8)
Day 123.5 ± 13.322.4 ± 10.319.1 ± 11.4
Day 225.1 ± 11.825.1 ± 13.221.6 ± 13.6
Day 327.6 ± 13.425.5 ± 14.523.3 ± 13.5
Day 427.6 ± 15.125.4 ± 11.026.2 ± 18.5
Day 527.4 ± 14.227.3 ± 13.226.8 ± 18.8
Day 630.1 ± 13.826.0 ± 13.128.9 ± 20.2
Day 725.5 ± 13.024.5 ± 12.427.3 ± 19.7

Adverse events

Collected over Adverse events were monitored from the time the subject first signs the ICF (within 28 days prior to randomization) to final discharge from the study (up to 8 days after randomization).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Not Assigned0/2 (0%)0/2 (0%)0/2 (0%)
Group 1 (CC)0/29 (0%)0/29 (0%)5/29 (17.2%)
Group 2 (NP2)0/28 (0%)0/28 (0%)15/28 (53.6%)
Group 3 (NP4)0/30 (0%)0/30 (0%)9/30 (30%)
Group 4 (NP8)0/30 (0%)0/30 (0%)15/30 (50%)
Group 5 (NT)0/29 (0%)0/29 (0%)12/29 (41.4%)
Most frequent other events
Showing 10 of 45
Most frequent other events
EventNot AssignedGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)
HeadacheNervous system disorders0/24/296/285/304/304/29
NauseaGastrointestinal disorders0/20/290/280/304/301/29
ConstipationGastrointestinal disorders0/20/292/280/300/301/29
Nasal congestionRespiratory, thoracic and mediastinal disorders0/20/292/280/300/300/29
AnxietyPsychiatric disorders0/20/290/280/300/302/29
InsomniaPsychiatric disorders0/20/290/280/300/302/29
StomatitisGastrointestinal disorders0/20/290/282/301/300/29
DyspepsiaGastrointestinal disorders0/20/291/280/300/301/29
ToothacheGastrointestinal disorders0/20/291/280/300/301/29
Gingival discomfortGastrointestinal disorders0/20/291/280/300/300/29

Baseline characteristics

The Baseline Analysis Population includes all subjects randomized to a study group (Group 1, 2, 3, 4 or 5), and any subject who was enrolled in the study but failed to meet randomization criteria and was discontinued by the PI. Subjects who met eligibility requirements but were not needed for the study are not included in the Baseline Analysis Population.

Age, Continuous
Age, Continuous(years)Not AssignedGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)Total
Mean36.0 ± 12.7334.2 ± 7.5133.6 ± 6.7335.9 ± 8.4931.7 ± 6.5335.5 ± 7.2934.2 ± 7.40
Sex: Female, Male
Sex: Female, Male(Participants)Not AssignedGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)Total
Female1131213131264
Male1161617171784
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Not AssignedGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)Total
Hispanic or Latino0110013
Not Hispanic or Latino22827303028145
Unknown or Not Reported0000000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Not AssignedGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)Total
American Indian or Alaska Native0000022
Asian0000000
Native Hawaiian or Other Pacific Islander0000000
Black or African American08713161054
White2212017141791
More than one race0010001
Unknown or Not Reported0000000
Height (cm)
Height (cm)(cm)Not AssignedGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)Total
Mean170.00 ± 11.314171.41 ± 10.442174.16 ± 9.357173.42 ± 8.530172.35 ± 10.216172.32 ± 9.781172.73 ± 9.600
Body Weight (kg)
Body Weight (kg)(kg)Not AssignedGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)Total
Mean89.55 ± 14.21388.67 ± 19.96892.61 ± 21.94991.28 ± 20.29185.82 ± 19.02788.74 ± 19.28489.39 ± 19.971
Body Mass Index (kg/m^2)
Body Mass Index (kg/m^2)(kg/m^2)Not AssignedGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)Total
Mean30.87 ± 0.81330.05 ± 5.52830.42 ± 6.24230.35 ± 6.33628.94 ± 6.07729.80 ± 5.68729.90 ± 5.925
Cigarettes per Day
Cigarettes per Day(Cigarettes per day)Not AssignedGroup 1 (CC)Group 2 (NP2)Group 3 (NP4)Group 4 (NP8)Group 5 (NT)Total
Mean16.50 ± 4.95016.03 ± 5.51916.14 ± 5.84816.23 ± 5.42516.57 ± 6.37216.69 ± 5.43916.34 ± 5.660

2 further baseline measures are reported on the registry.

08

Study locations

3 sites
  • CKRA
    Lexington, Kentucky 40509, United States
  • QPS
    Springfield, Missouri 65802, United States
  • NOCCR
    Knoxville, Tennessee 37920, United States
09

References and documents

Study documents

  • Study protocol · Jun 30, 2021
  • Study protocol · Apr 28, 2021
  • Study protocol · Mar 9, 2021
  • Statistical analysis plan · Jul 30, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 9, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT05664672
Lead sponsor
Altria Client Services LLC
Collaborators
Covance
Responsible party
Sponsor
First posted
Dec 27, 2022
Start date
May 11, 2021
Primary completion
Aug 31, 2021
Completion
Aug 31, 2021
Results posted
Dec 9, 2024
Last update
Dec 9, 2024

Study contacts

William J Howitt, MD
principal investigator · QPS Holdings LLC
William Smith, MD
principal investigator · NOCCR
Mark Adams, MD
principal investigator · CKRA

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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