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CompletedNCT06366087SABERUpdated Jan 27, 2026Results posted

Sublingual Atropine Bioequivalence by Route of Administration (SABER)

A Phase 1 interventional study of Atropine Sulfate Ophthalmic Solution USP, 1% and Atropine Sulfate Injection, USP 8 mg/20 mL (0.4 mg/mL) in Atropine Bioequivalence, sponsored by Biomedical Advanced Research and Development Authority. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-01-27.

Sponsored by Biomedical Advanced Research and Development Authority · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
46
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

A randomized, two-period, two-sequence, crossover study to assess the bioequivalence, bioavailability, and pharmacokinetics (PK) of a single dose of atropine administered sublingually (SL) or intramuscularly (IM) in healthy adult volunteers.

Read the detailed description

This is a randomized, two-period, two-sequence, crossover study to assess the bioequivalence, bioavailability, and pharmacokinetics (PK) of a single dose of atropine administered SL or IM in healthy adult volunteers. A total of 46 healthy male and non-pregnant female volunteers will be randomized, with the goal of obtaining at least 36 evaluable participants in the per protocol population. Additional participants may be randomized if participants are withdrawn prior to receiving one or both doses of study drug. Eligible participants will be randomized at a 1:1 ratio to receive one of two treatment dosing sequences (A [Visit 1 SL, Visit 2 IM] or B [Visit 1 IM, Visit 2 SL]).

Volunteers will be screened for study participation from Days -14 to -3. Eligible participants will be enrolled and randomized to receive one of two dosing sequences (Sequence A or Sequence B) until the target enrollment for the study is met. Once randomized, each participant will receive 2 doses of atropine separated by a wash out period of 6 ±1 days. During Visit 1 (Day 1) and Visit 2 (Day 8), participants will be administered SL or IM atropine, according to their randomly assigned dosing sequence. At each dosing visit, blood samples for PK will be collected at time 0 (pre-dose) and at 13 time points post-dose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes and 2, 2.5, 4, 6, and 8 hours after dosing. Participants will be discharged from the clinic after the 8-hour blood sample collection. Participants will be followed for approximately 6 days after their last dose.

02

Conditions studied

  • Atropine Bioequivalence

Keywords

  • Pharmaceutical Solutions
  • Adjuvants, Anesthesia
  • Anti-Arrhythmia Agents
  • Bronchodilator Agents
  • Autonomic Agents
  • Peripheral Nervous System Agents
  • Physiological Effects of Drugs
  • Anti-Asthmatic Agents
  • Respiratory System Agents
  • Mydriatics
  • Parasympatholytics
  • Muscarinic Antagonists
  • Cholinergic Antagonists
  • Cholinergic Agents
  • Neurotransmitter Agents
  • Molecular Mechanisms of Pharmacological Action
  • Atropine
  • Ophthalmic Solutions
03

Who can participate

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

Inclusion criteria

  1. Healthy male and non-pregnant female volunteers between the ages of 18 and 65 years, inclusive, at time of consent.
  2. Willing and able to provide written informed consent.

  3. Females who are of childbearing potential and are sexually active with a male partner must have used an adequate method of birth control for at least 2 months prior to Screening and must agree to continue using an adequate method of birth control from Screening through Follow-up (Day 15).

    1. A female of childbearing potential is defined as a post onset of menarche and premenopausal female capable of becoming pregnant. This does not include females who meet any of the following conditions: menopausal >2 years, tubal ligation >1 year, bilateral salpingo-oophorectomy, or hysterectomy.
    2. Adequate contraception is defined as a contraceptive method with a failure rate of less than 1% per year when used consistently and correctly and when applicable, in accordance with the product label. Examples include oral contraceptives, injectable progestogen, implants of etonogestrel or levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device or intrauterine system, or male partner sterilization at least 6 months prior to the participant's Screening Visit.
  4. In the judgment of the investigator, the participant is in good health, based on review of medical history and the results of Screening evaluation (including vital signs, physical examination, 12-lead electrocardiogram [ECG], and Screening laboratory assessments, performed no more than 14 days prior to randomization into the study).
  5. Able to comply with the dosing instructions and available to complete the study Schedule of Assessments.

Exclusion criteria

Exclusion Criteria:

  1. Females who have a positive pregnancy test or who are breastfeeding.
  2. Participants with thyroid disease as evidenced by a thyroid-stimulating hormone (TSH) \<0.9 × lower limit of normal (LLN) or > 1.2 × upper limit of normal (ULN) at Screening (This Screening test will not be repeated prior to subsequent dosing).
  3. Participants with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or serum creatinine >1.5 × ULN at Screening. (These Screening tests will not be repeated prior to subsequent dosing.)
  4. Have known human immunodeficiency virus (HIV), or acute or chronic hepatitis B or hepatitis C infection based on medical history; or test positive for any of these at Screening. Participants who have been effectively treated for hepatitis C, as evidenced by a negative hepatitis C RNA confirmation test and who no longer require antiviral therapy, are eligible for participation. (These Screening tests will not be repeated prior to subsequent dosing.)
  5. Participants who took any prescription medications (with the exception of oral contraceptives or hormone replacement therapy) within 30 days of Screening. Prior to each dose, the investigator will review prohibited medication use and determine whether the participant should be terminated from further dosing.
  6. Participants who took any over-the-counter medication/vitamins/herbal supplements in the last 72 hours prior to Screening. Prior to each dose, the investigator will review prohibited medication use and determine whether the participant should be terminated from further dosing.
  7. Participants who are current smokers or are currently using any oral nicotine/oral tobacco product (e.g. snuff, chew, lozenges, nicotine gum, pouches) or electronic cigarette or vaping device (e.g., e-cigarette, mod, vape pen, JUUL, e-cigar, e-hookah, e-pipe, vape pods) or have used any of these products within 6 months prior to Screening.
  8. Participants with glaucoma and/or history of ocular surgery (including LasikTM), ocular trauma, or congenital ocular disorder.
  9. Participants with any history of heart disease, including but not limited to hypertension, coronary artery disease, arrhythmia (treated or untreated), congestive heart failure, pacemaker, history of vasovagal syncope, any supraventricular tachycardia, peripheral vascular disease, or claudication.
  10. Participants with clinically significant arrhythmias or abnormal conduction; abnormal conduction is defined as a prolonged PR or QRS, or a QTc ≥450 msec for males or ≥470 msec for females.
  11. Participants with a history of partial organic pyloric stenosis, chronic constipation, gastroparesis, or other gastrointestinal motility issues.
  12. Participants with a history of xerostomia due to an underlying disease or previous radiation therapy to the head and neck.
  13. Males with history of symptomatic prostatic hypertrophy; males or females with a history of urinary hesitancy or retention.
  14. Participants with a blood pressure >140/90 mm Hg taken after the participant has been seated and resting for at least five minutes.
  15. Participants with a history or current diagnosis of myasthenia gravis.
  16. Participants who have donated blood within 8 weeks of Screening or intend to donate blood during the study period.
  17. Participants with a history of drug or alcohol abuse in the last two years or evidence of a positive urine drug test at Screening. (This Screening test will not be repeated prior to subsequent dosing.)
  18. Participants with a known sensitivity or prior adverse reaction to atropine.
  19. Participants who have consumed alcohol within 24 hours prior to each Pre-dose Visit. (This will be assessed only at Visit 1 [Pre-dose] and Visit 2 [Pre-dose].)
  20. Participants with any other condition that, in the opinion of the investigator, would pose a health risk to the participant if enrolled, would interfere with SL or IM administration of study drug, or would otherwise interfere with interpretation of study results.
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
46 participants (actual)

Study arms

  • Experimental
    Sublingual

    1 mg (100 µL of a 1% w/v solution), administered SL by pipette with at least a 30 second dwell time without swallowing.

    Drug: Atropine Sulfate Ophthalmic Solution USP, 1%

  • Active comparator
    Intramuscular

    Multidose vial presentation, 1 mg (2.5 ml) administered by IM injection into the mid-anterolateral thigh.

    Drug: Atropine Sulfate Injection, USP 8 mg/20 mL (0.4 mg/mL)

Interventions

  • DrugAtropine Sulfate Ophthalmic Solution USP, 1%

    Atropine Sulfate Ophthalmic Solution, USP 1% manufactured by Bausch \& Lomb Americas Inc., is a sterile topical anti-muscarinic indicated for mydriasis, cycloplegia, and penalization of the healthy eye to treat amblyopia. Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains the active ingredient atropine sulfate 10 mg, equivalent to 8.3 mg of atropine. Inactive ingredients are boric acid, hydroxypropyl methylcellulose, and water for injection, USP; hydrochloric acid and/or sodium hydroxide may be added to adjust pH (3.5 to 6.0). Atropine Sulfate Ophthalmic Solution, USP 1% will be supplied in 0.4 mL single-dose vials and will be administered as a single dose to a single participant. 100 μL of Atropine Sulfate Ophthalmic Solution, USP 1% will be given sublingually by pipette to deliver 1.0 mg of atropine sulfate. Before administration, participants will be told to swallow. Once given, participants will be told to try not to swallow for 30 seconds and then swallow normally.

  • DrugAtropine Sulfate Injection, USP 8 mg/20 mL (0.4 mg/mL)

    Atropine sulfate injection, USP is a muscarinic antagonist used for temporary blockade of severe/life-threatening muscarinic effects and to treat symptomatic bradycardia. Atropine Sulfate Injection, USP, 8 mg/20 mL (0.4 mg/mL) manufactured by Fresenius Kabi is a sterile, nonpyrogenic, isotonic, clear solution of atropine sulfate in water for injection with sodium chloride sufficient to render the solution isotonic. Each mL contains atropine sulfate, 0.4 mg; benzyl alcohol, 9 mg; and sodium chloride 9 mg; it may also contain sulfuric acid for pH adjustment, pH 3.5 (3.0 to 3.8). Atropine Sulfate Injection, USP will be supplied in 8 mg/20 mL multidose vials (0.4 mg/mL). Each vial will be used to administer multiple doses to multiple participants. 2.5 mL will be injected into the mid-anterolateral thigh to deliver 1.0 mg of atropine sulfate. Vials will be dated/timed and will not be given after 24 hours of first entry.

05

What researchers measure

Primary outcomes

  1. The Bioequivalence of Atropine Sulfate Administered SL Versus Administered IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Infinity (AUCinf).

    Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and route using noncompartmental analysis (NCA) methods. AUCinf is summarized by route of administration as the geometric mean and coefficient of variation of the geometric mean for all evaluable participants and expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model. Bioequivalence will be considered met if the 90% CI of the ratio for AUCinf lies within 80.00 to 125.00%.

    Time frame: Pre-dose through 8 hours post-dose at Days 1 and 8

  2. The Bioequivalence of Atropine Sulfate Administered SL Versus Administered IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time of Last Quantifiable Data Point (AUCt).

    Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and route using noncompartmental analysis (NCA) methods. AUCt is summarized by route of administration as the geometric mean and coefficient of variation of the geometric mean for all evaluable participants and expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model. Bioequivalence will be considered met if the 90% CI of the ratio for AUCt lies within 80.00 to 125.00%.

    Time frame: Pre-dose through 8 hours post-dose at Days 1 and 8

Secondary outcomes

  1. AUC45 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 45 Minutes (AUC45)

    Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. AUC45 is summarized by route of administration as the geometric mean and coefficient of variation for the geometric mean for all evaluable participants expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model

    Time frame: 0 hour (pre-dose), 5, 10, 15, 20, 30, and 45 minutes post-dose on Days 1 and 8

  2. AUC60 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 60 Minutes (AUC60)

    Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. AUC60 is summarized by route of administration as the geometric mean and coefficient of variation for the geometric mean for all evaluable participants expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.

    Time frame: 0 hour (pre-dose), 5, 10, 15, 20, 30, 45, and 60 minutes post-dose at Days 1 and 8

  3. AUC90 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 90 (AUC90)

    Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. AUC90 is summarized by route of administration as the geometric mean and coefficient of variation for the geometric mean for all evaluable participants expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.

    Time frame: 0 (pre-dose), 5, 10, 15, 20, 30, 45, 60, and 90 minutes post-dose at Days 1 and 8

  4. AUC120 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 120 Minutes (AUC120)

    Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. AUC120 is summarized by route of administration as the geometric mean and coefficient of variation for the geometric mean for all evaluable participants expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.

    Time frame: 0 (pre-dose), 5, 10, 15, 20, 30, 45, 60, 90, and 120 minutes post-dose at Days 1 and 8

  5. AUC150 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 150 Minutes (AUC150)

    Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. AUC150 is summarized by route of administration as the geometric mean and coefficient of variation for the geometric mean for all evaluable participants expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.

    Time frame: 0 (pre-dose), 5, 10, 15, 20, 30, 45, 60, 90, 120, and 150 minutes post-dose at Days 1 and 8

  6. AUC240 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 240 Minutes (AUC240)

    Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. AUC240 is summarized by route of administration as the geometric mean and coefficient of variation for the geometric mean for all evaluable participants expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.

    Time frame: 0 (pre-dose), 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, and 240 minutes post-dose at Days 1 and 8

  7. The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Maximum Measured Plasma Concentration (Cmax)

    Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. Cmax is summarized by route of administration as the geometric mean and coefficient of variation of the geometric mean for all evaluable participants and expressed as ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.

    Time frame: Pre-dose through 8 hours post-dose at Days 1 and 8

  8. The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Time to Cmax (Tmax)

    Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. tmax is summarized by route of administration as the mean and standard deviation for all evaluable participants and expressed as minutes.

    Time frame: Pre-dose through 8 hours post-dose at Days 1 and 8

  9. The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Apparent Terminal Elimination Half-life (t1/2)

    Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. t1/2 is summarized by route of administration as the mean and standard deviation for all evaluable participants and expressed as minutes.

    Time frame: Pre-dose through 8 hours post-dose at Days 1 and 8

  10. The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Terminal Elimination Rate Constant (λz)

    Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. λz is summarized by route of administration as the mean and standard deviation for all evaluable participants and expressed as 1/min.

    Time frame: Pre-dose through 8 hours post-dose at Days 1 and 8

  11. The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Volume of Distribution (Vd/F)

    Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. Vd/F is summarized by route of administration as the mean and standard deviation for all evaluable participants and expressed as mL.

    Time frame: Pre-dose through 8 hours post-dose at Days 1 and 8

  12. The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Total Body Clearance (CL/F)

    Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. CL/F is summarized by route of administration as the mean and standard deviation for all evaluable participants and expressed as mL/min.

    Time frame: Pre-dose through 8 hours post-dose at Days 1 and 8

  13. The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Absorption Rate Constant (Ka)

    Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. Ka is summarized by route of administration as the mean and standard deviation for all evaluable participants and expressed 1/min.

    Time frame: Pre-dose through 8 hours post-dose at Days 1 and 8

06

Results

Posted Apr 4, 2025

Participant flow

Participants were recruited at a single US site between April 2024 and May 2024. Potential participants signed informed consent before undergoing any screening procedures to confirm eligibility.

Participant flow — Overall Study
MilestoneSequence A: Atropine Sulfate Sublingual - Atropine Sulfate IntramuscularSequence B: Atropine Sulfate Intramuscular - Atropine Sulfate Sublingual
Started2323
Completed2322
Not completed01
Withdrew: Withdrawal by subject01

Outcome measures

PrimaryThe Bioequivalence of Atropine Sulfate Administered SL Versus Administered IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Infinity (AUCinf).

Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and route using noncompartmental analysis (NCA) methods. AUCinf is summarized by route of administration as the geometric mean and coefficient of variation of the geometric mean for all evaluable participants and expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model. Bioequivalence will be considered met if the 90% CI of the ratio for AUCinf lies within 80.00 to 125.00%.

Time frame:
Pre-dose through 8 hours post-dose at Days 1 and 8
Reported as:
Geometric mean · min*ng/mL
The Bioequivalence of Atropine Sulfate Administered SL Versus Administered IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Infinity (AUCinf).
min*ng/mLSublingualIntramuscular
The Bioequivalence of Atropine Sulfate Administered SL Versus Administered IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Infinity (AUCinf).562.456 ± 23.0814.860 ± 19.0
Statistical analysis
  • Sublingual vs Intramuscular · Mixed Models Analysis · Ratio of geometric least-square means: 0.70 · 90% CI 0.670 to 0.724Bioequivalence will be considered met if the 90% CI of the ratio for AUCinf lies within 80.00 to 125.00%.
PrimaryThe Bioequivalence of Atropine Sulfate Administered SL Versus Administered IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time of Last Quantifiable Data Point (AUCt).

Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and route using noncompartmental analysis (NCA) methods. AUCt is summarized by route of administration as the geometric mean and coefficient of variation of the geometric mean for all evaluable participants and expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model. Bioequivalence will be considered met if the 90% CI of the ratio for AUCt lies within 80.00 to 125.00%.

Time frame:
Pre-dose through 8 hours post-dose at Days 1 and 8
Reported as:
Geometric mean · min*ng/mL
The Bioequivalence of Atropine Sulfate Administered SL Versus Administered IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time of Last Quantifiable Data Point (AUCt).
min*ng/mLSublingualIntramuscular
The Bioequivalence of Atropine Sulfate Administered SL Versus Administered IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time of Last Quantifiable Data Point (AUCt).456.944 ± 22.7683.672 ± 20.5
Statistical analysis
  • Sublingual vs Intramuscular · Mixed Models Analysis · Ratio of geometric least-square means: 0.67 · 90% CI 0.640 to 0.697Bioequivalence will be considered met if the 90% CI of the ratio for AUCt lies within 80.00 to 125.00%.
SecondaryAUC45 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 45 Minutes (AUC45)

Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. AUC45 is summarized by route of administration as the geometric mean and coefficient of variation for the geometric mean for all evaluable participants expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model

Time frame:
0 hour (pre-dose), 5, 10, 15, 20, 30, and 45 minutes post-dose on Days 1 and 8
Reported as:
Geometric mean · min*ng/mL
AUC45 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 45 Minutes (AUC45)
min*ng/mLSublingualIntramuscular
AUC45 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 45 Minutes (AUC45)11.559 ± 98.9106.046 ± 34.9
Statistical analysis
  • Sublingual vs Intramuscular · Mixed Models Analysis · Ratio of geometric least-square means: 0.11 · 90% CI 0.088 to 0.136
SecondaryAUC60 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 60 Minutes (AUC60)

Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. AUC60 is summarized by route of administration as the geometric mean and coefficient of variation for the geometric mean for all evaluable participants expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.

Time frame:
0 hour (pre-dose), 5, 10, 15, 20, 30, 45, and 60 minutes post-dose at Days 1 and 8
Reported as:
Geometric mean · min*ng/mL
AUC60 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 60 Minutes (AUC60)
min*ng/mLSublingualIntramuscular
AUC60 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 60 Minutes (AUC60)21.903 ± 103.1145.215 ± 31.8
Statistical analysis
  • Sublingual vs Intramuscular · Mixed Models Analysis · Ratio of geometric least-square means: 0.15 · 90% CI 0.120 to 0.189
SecondaryAUC90 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 90 (AUC90)

Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. AUC90 is summarized by route of administration as the geometric mean and coefficient of variation for the geometric mean for all evaluable participants expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.

Time frame:
0 (pre-dose), 5, 10, 15, 20, 30, 45, 60, and 90 minutes post-dose at Days 1 and 8
Reported as:
Geometric mean · min*ng/mL
AUC90 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 90 (AUC90)
min*ng/mLSublingualIntramuscular
AUC90 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 90 (AUC90)56.521 ± 74.2217.844 ± 27.8
Statistical analysis
  • Sublingual vs Intramuscular · Mixed Models Analysis · Ratio of geometric least-square means: 0.26 · 90% CI 0.217 to 0.309
SecondaryAUC120 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 120 Minutes (AUC120)

Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. AUC120 is summarized by route of administration as the geometric mean and coefficient of variation for the geometric mean for all evaluable participants expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.

Time frame:
0 (pre-dose), 5, 10, 15, 20, 30, 45, 60, 90, and 120 minutes post-dose at Days 1 and 8
Reported as:
Geometric mean · min*ng/mL
AUC120 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 120 Minutes (AUC120)
min*ng/mLSublingualIntramuscular
AUC120 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 120 Minutes (AUC120)103.146 ± 52.9283.847 ± 25.8
Statistical analysis
  • Sublingual vs Intramuscular · Mixed Models Analysis · Ratio of geometric least-square means: 0.36 · 90% CI 0.318 to 0.416
SecondaryAUC150 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 150 Minutes (AUC150)

Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. AUC150 is summarized by route of administration as the geometric mean and coefficient of variation for the geometric mean for all evaluable participants expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.

Time frame:
0 (pre-dose), 5, 10, 15, 20, 30, 45, 60, 90, 120, and 150 minutes post-dose at Days 1 and 8
Reported as:
Geometric mean · min*ng/mL
AUC150 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 150 Minutes (AUC150)
min*ng/mLSublingualIntramuscular
AUC150 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 150 Minutes (AUC150)151.441 ± 41.5343.066 ± 24.6
Statistical analysis
  • Sublingual vs Intramuscular · Mixed Models Analysis · Ratio of geometric least-square means: 0.44 · 90% CI 0.396 to 0.492
SecondaryAUC240 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 240 Minutes (AUC240)

Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. AUC240 is summarized by route of administration as the geometric mean and coefficient of variation for the geometric mean for all evaluable participants expressed as min\*ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.

Time frame:
0 (pre-dose), 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, and 240 minutes post-dose at Days 1 and 8
Reported as:
Geometric mean · min*ng/mL
AUC240 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 240 Minutes (AUC240)
min*ng/mLSublingualIntramuscular
AUC240 - The Relative Bioavailability (Plasma Concentrations) of Atropine Sulfate Administered SL Versus IM as Measured by Area Under the Analyte Concentration Versus Time Curve to Time 240 Minutes (AUC240)275.948 ± 27.5484.704 ± 22.7
Statistical analysis
  • Sublingual · Mixed Models Analysis · Ratio of geometric least-square means: 0.57 · 90% CI 0.532 to 0.608
SecondaryThe Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Maximum Measured Plasma Concentration (Cmax)

Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. Cmax is summarized by route of administration as the geometric mean and coefficient of variation of the geometric mean for all evaluable participants and expressed as ng/mL. Geometric ratios of least-square means and associated 90% confidence intervals are reported from a linear mixed model.

Time frame:
Pre-dose through 8 hours post-dose at Days 1 and 8
Reported as:
Geometric mean · ng/mL
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Maximum Measured Plasma Concentration (Cmax)
ng/mLSublingualIntramuscular
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Maximum Measured Plasma Concentration (Cmax)1.805 ± 26.63.176 ± 35.0
Statistical analysis
  • Sublingual vs Intramuscular · Mixed Models Analysis · Ratio of geometric least-square means: 0.57 · 90% CI 0.524 to 0.620
SecondaryThe Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Time to Cmax (Tmax)

Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. tmax is summarized by route of administration as the mean and standard deviation for all evaluable participants and expressed as minutes.

Time frame:
Pre-dose through 8 hours post-dose at Days 1 and 8
Reported as:
Mean · min
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Time to Cmax (Tmax)
minSublingualIntramuscular
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Time to Cmax (Tmax)118.0 ± 49.1934.3 ± 22.20
SecondaryThe Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Apparent Terminal Elimination Half-life (t1/2)

Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. t1/2 is summarized by route of administration as the mean and standard deviation for all evaluable participants and expressed as minutes.

Time frame:
Pre-dose through 8 hours post-dose at Days 1 and 8
Reported as:
Mean · min
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Apparent Terminal Elimination Half-life (t1/2)
minSublingualIntramuscular
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Apparent Terminal Elimination Half-life (t1/2)171.089 ± 31.7096175.682 ± 35.6344
SecondaryThe Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Terminal Elimination Rate Constant (λz)

Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. λz is summarized by route of administration as the mean and standard deviation for all evaluable participants and expressed as 1/min.

Time frame:
Pre-dose through 8 hours post-dose at Days 1 and 8
Reported as:
Mean · 1/min
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Terminal Elimination Rate Constant (λz)
1/minSublingualIntramuscular
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Terminal Elimination Rate Constant (λz)0.0042 ± 0.000770.0041 ± 0.00082
SecondaryThe Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Volume of Distribution (Vd/F)

Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. Vd/F is summarized by route of administration as the mean and standard deviation for all evaluable participants and expressed as mL.

Time frame:
Pre-dose through 8 hours post-dose at Days 1 and 8
Reported as:
Mean · mL
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Volume of Distribution (Vd/F)
mLSublingualIntramuscular
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Volume of Distribution (Vd/F)447.17 ± 119.864316.62 ± 88.157
SecondaryThe Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Total Body Clearance (CL/F)

Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. CL/F is summarized by route of administration as the mean and standard deviation for all evaluable participants and expressed as mL/min.

Time frame:
Pre-dose through 8 hours post-dose at Days 1 and 8
Reported as:
Mean · mL/min
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Total Body Clearance (CL/F)
mL/minSublingualIntramuscular
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Total Body Clearance (CL/F)1823.440 ± 420.50161248.156 ± 226.2500
SecondaryThe Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Absorption Rate Constant (Ka)

Blood samples to measure atropine plasma concentrations were collected during each dosing visit at the following time points: time 0 (predose), and postdose at 5, 10, 15, 20, 30, 45, 60, and 90 minutes, and 2, 2.5, 4, 6, and 8 hours. PK parameters were estimated for each subject and period using noncompartmental analysis (NCA) methods. Ka is summarized by route of administration as the mean and standard deviation for all evaluable participants and expressed 1/min.

Time frame:
Pre-dose through 8 hours post-dose at Days 1 and 8
Reported as:
Mean · 1/min
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Absorption Rate Constant (Ka)
1/minSublingualIntramuscular
The Relative Bioavailability of Atropine Sulfate Administered SL Versus IM as Measured by Absorption Rate Constant (Ka)0.022 ± 0.01470.117 ± 0.2034

Adverse events

Collected over Treatment-emergent adverse events were reported from the time the participant received the first dose of atropine at Day 1 until completion of the follow-up period at Day 15... Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Sublingual0/45 (0%)0/45 (0%)14/45 (31.1%)
Intramuscular0/46 (0%)0/46 (0%)22/46 (47.8%)
Most frequent other events
Most frequent other events
EventSublingualIntramuscular
Dry mouthGastrointestinal disorders12/4522/46
Dry eyeEye disorders1/450/46
DiarrhoeaGastrointestinal disorders1/450/46
HeadacheNervous system disorders1/451/46
PresyncopeNervous system disorders1/450/46
PalpitationsCardiac disorders0/451/46

Baseline characteristics

Age, Continuous
Age, Continuous(years)Sequence A: Atropine Sulfate Sublingual - Atropine Sulfate IntramuscularSequence B: Atropine Sulfate Intramuscular - Atropine Sulfate SublingualTotal
Mean42.4 ± 11.6441.4 ± 14.6541.9 ± 13.09
Sex: Female, Male
Sex: Female, Male(Participants)Sequence A: Atropine Sulfate Sublingual - Atropine Sulfate IntramuscularSequence B: Atropine Sulfate Intramuscular - Atropine Sulfate SublingualTotal
Female91423
Male14923
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Sequence A: Atropine Sulfate Sublingual - Atropine Sulfate IntramuscularSequence B: Atropine Sulfate Intramuscular - Atropine Sulfate SublingualTotal
Hispanic or Latino325
Not Hispanic or Latino202141
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Sequence A: Atropine Sulfate Sublingual - Atropine Sulfate IntramuscularSequence B: Atropine Sulfate Intramuscular - Atropine Sulfate SublingualTotal
American Indian or Alaska Native112
Asian011
Native Hawaiian or Other Pacific Islander101
Black or African American10717
White101121
More than one race134
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Sequence A: Atropine Sulfate Sublingual - Atropine Sulfate IntramuscularSequence B: Atropine Sulfate Intramuscular - Atropine Sulfate SublingualTotal
United States232346
07

Study locations

1 site
  • Johnson County Clin-Trials (JCCT)
    Lenexa, Kansas 66219, United States
08

References and documents

Study documents

  • Study protocol · Feb 13, 2024
  • Statistical analysis plan · Apr 25, 2024
  • Informed consent form · Mar 22, 2024

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

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT06366087
Lead sponsor
Biomedical Advanced Research and Development Authority
Collaborators
Rho Federal Systems Division, Inc., Allucent Government Services (US), LLC
Responsible party
Sponsor
First posted
Apr 15, 2024
Start date
Apr 15, 2024
Primary completion
May 15, 2024
Completion
May 22, 2024
Results posted
Apr 4, 2025
Last update
Jan 27, 2026

Study contacts

Derek Eisnor, MD
study chair · Biomedical Advanced Research and Development Authority
Michael Schwartz, MD
study chair · Biomedical Advanced Research and Development Authority

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
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