TerminatedNCT03303911Updated Oct 21, 2019Results posted

A Pharmacokinetic and Pharmacodynamic Evaluation of Cytisine in Healthy Smokers

A Phase 1/2 interventional study of Cytisine in Smoking Cessation, sponsored by Achieve Life Sciences. Terminated at 1 site in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-10-21.

Sponsored by Achieve Life Sciences · Phase 1/2, Interventional, and Treatment

Why this study was terminated

It has been difficult to recruit participants meeting study entry criteria that are \>65 years of age and not for any safety reasons.

Phase: Phase 1/2
Study type: Interventional
Enrollment: 26
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

The primary objectives of this study are:

To evaluate the pharmacokinetic (PK) parameters during repeat dosing of 1.5 mg or 3.0 mg cytisine when administered as the commercial 25-day schedule.
To evaluate the pharmacodynamic (PD) effects (e.g., reduction in smoking) with repeat dosing of 1.5 mg or 3.0 mg cytisine when administered as the commercial 25-day schedule.

Conditions studied

Smoking Cessation

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Smoking Cessation 350

In context

Smoking Cessation

350 studies on the registry are indexed under Smoking Cessation; 145 are open to participants now.

This study's enrollment of 26 is below the median of 150 across 326 interventional studies indexed under Smoking Cessation.

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Lead sponsor

Achieve Life Sciences is the lead sponsor of 31 studies on the registry; 1 is open to participants now.

Of its 12 completed or terminated interventional studies of FDA-regulated products, 8 (67%) have results posted.

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

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Regular moderate cigarette smokers (minimum 10 cigarettes per day) who want to stop smoking.
Urine cotinine >500 ng/mL.
Expired air carbon monoxide (CO) > 11 parts per million (no cigarette 1 hour before test).
Healthy males and females 18-65+ years of age.
1. If a female subject of child bearing potential, a negative pregnancy test at screening and admission and willing to use an effective method of contraception (unless of non-childbearing potential or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) from first dose until 3 months after last dose of cytisine.
2. If a female subject of non-child bearing potential, a negative pregnancy test at screening and admission. For the purposes of this study, this is defined as the subject being amenorrheic for at least 12 consecutive months or at least 4 months post-surgical sterilisation (including bilateral fallopian tube ligation or bilateral oophorectomy with or without hysterectomy). Menopausal status will be confirmed by demonstrating at screening that levels of follicle stimulating hormone (FSH) fall within the respective pathology reference range. In the event a subject's menopause status has been clearly established (for example, the subject indicates she has been amenorrheic for 10 years), but FSH levels are not consistent with a post-menopausal condition, determination of subject eligibility will be at Investigator's discretion following consultation with the Sponsor.
3. If a male subject, willing to use an effective method of contraception (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) from first dose until 3 months after last dose of cytisine.
Subject with no clinically significant abnormal serum biochemistry, haematology and urine examination values within 28 days before the first dose of cytisine.
Subject with negative urinary drugs of abuse screen, determined within 28 days before the first dose of cytisine (a positive alcohol result may be repeated at Investigator's discretion).
Subject with negative human immunodeficiency virus (HIV), hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results.
Subject with no clinically significant abnormalities in 12-lead ECG determined after minimum of 5 minutes in supine position within 28 days before the first dose of cytisine.
Subject with no clinically significant abnormalities in vital signs (systolic blood pressure between 90-150 mmHg (age 18-65) and 90-160 mmHg (age >65), diastolic blood pressure (DBP) between 50 and 90 mmHg, and pulse rate (PR) between 40 110 bpm, measured on the dominant arm after minimum of 5 minutes in supine position) determined within 28 days before first dose of cytisine.
Subject must be available to complete the study (including in-clinic stays and post study follow-up) and comply with study restrictions.
Subject must provide written informed consent to participate in the study.

Exclusion criteria

Exclusion Criteria:

Treatment with smoking cessation medications (bupropion, varenicline, any nicotine replacement therapy) within 8 weeks of first dose of cytisine.
Use of other forms of nicotine (e-cigarettes, smokeless tobacco) within 8 weeks of first dose of cytisine or are planning to use these products during study.
Known hypersensitivity/allergy reaction to varenicline, other cytisine-derivatives or any of the excipients in the Tabex formulation.
History of severe hypersensitivity reactions to any other drugs.
Current treatment with antihypertensive medicinal products, statins, tuberculostatics, cholinomimetics or anticholinesterase medicinal products.
History of any medical condition (e.g. gastrointestinal, renal or hepatic) or surgical condition (e.g. cholecystectomy, gastrectomy) that may affect drug pharmacokinetics (absorption, distribution, metabolism or excretion).
Female subjects who are breast feeding.
Difficulty in donating blood on either arm or known history.
History of alcoholism or drug abuse within last 2 years.
Use of non-prescription drugs, including vitamins, herbal and dietary supplements within 14 days (or 5 half-lives, whichever is longer) prior to the first dose of cytisine, unless in the opinion of the Principal Investigator the medication will not interfere with the study procedures or compromise subject safety.
Participated in any investigational drug clinical trial within the previous 3 months or a marketed drug trial within the previous 30 days prior to randomisation on Day 1.
Donation of 450 mL or more blood or had history of significant blood loss due to any reason or had plasmapheresis within 3 months before the first dose of cytisine.
Inability to communicate well with Principal Investigator or designees (i.e., language problem, poor mental development or impaired cerebral function).
Any other condition that the Principal Investigator considers making the subject unsuitable for this study.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 26 participants (actual)

Study arms

Experimental
Cytisine 1.5 mg
Multiple doses of 1.5 mg cytisine administered per 25-day schedule: * Days 1-3 (6 times daily) * Days 4-12 (5 times daily) * Days 13-16 (4 times daily) * Days 17-20 (3 times daily) * Days 21-24 (2 times daily) * Day 25 (Once daily)
Drug: Cytisine
Experimental
Cytisine 3.0 mg
Multiple doses of 3.0 mg cytisine administered per 25-day schedule: * Days 1-3 (6 times daily) * Days 4-12 (5 times daily) * Days 13-16 (4 times daily) * Days 17-20 (3 times daily) * Days 21-24 (2 times daily) * Day 25 (Once daily)
Drug: Cytisine

Interventions

DrugCytisine
film-coated tablets; depending on arm assignment, 1 or 2 tablets to be taken with 240 mL water for each dose
Also known as: Tabex

What researchers measure

Primary outcomes

Maximum Observed Plasma Concentration (Cmax)
Time frame: after the first dose and the last dose on Day 1; after the last dose on Days 2, 3, 12, 16, 20, 24; and after the morning dose on Day 25
Time of Occurrence of Cmax (Tmax)
Time frame: after the first dose and the last dose on Day 1; after the last dose on Days 2, 3, 12, 16, 20, 24; and after the morning dose on Day 25
Minimum Observed Plasma Concentration (Cmin)
Time frame: after the first dose on Days 4, 13, 17, 21 and 25
Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Sampling Time (AUC0-t)
Time frame: after the administration of the final dose of cytisine on Day 25
Total AUC From Time Zero to Infinity (AUC0-∞)
Time frame: after the administration of the final dose of cytisine on Day 25
Residual Area or Percentage of Extrapolated Part for the Calculation of AUC0-∞ (%AUC)
Time frame: after the administration of the final dose of cytisine on Day 25
Apparent Terminal Elimination Rate Constant (λz)
Time frame: after the administration of the final dose of cytisine on Day 25
Apparent Terminal Elimination Half-Life (t1/2)
Time frame: after the administration of the final dose of cytisine on Day 25
Number of Cigarettes Smoked Daily During Treatment and at Day 26
Time frame: Day 1 through Day 26
Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26
Time frame: Baseline, Day 1 through Day 26
Change From Baseline in Expired Air CO up to Day 26
Time frame: Baseline, Days 4, 13, 17, 21, 26
Number of Participants Who Ceased or Continued Smoking on Day 26
A status of "ceased smoking" is defined as not having smoked any cigarettes for the past 24 hours on Day 26 and having an expired CO level \<10 ppm on Day 26.
Time frame: Day 26
Change From Baseline Over Time in Urine Cotinine
Time frame: Baseline, Days 4, 13, 17, 21, 26
Change From Baseline Over Time in TCQ-SF Score: Emotionality
The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly disagree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Emotionality scores may range from 3 to 21, with lower scores indicating weaker emotional signs of tobacco craving.
Time frame: Baseline (Day -1), Days 4, 13, 17, 21, 26
Change From Baseline Over Time in TCQ-SF Score: Expectancy
The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly disagree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Expectancy scores may range from 3 to 21, with lower scores indicating less positive expectations about smoking.
Time frame: Baseline (Day -1), Days 4, 13, 17, 21, 26
Change From Baseline Over Time in TCQ-SF Score: Compulsivity
The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly agree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Compulsivity scores may range from 3 to 21, with lower scores indicating compulsion to smoke was a lesser component of tobacco craving.
Time frame: Baseline (Day -1), Days 4, 13, 17, 21, 26
Change From Baseline Over Time in TCQ-SF Score: Purposefulness
The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly disagree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Purposefulness scores may range from 3 to 21, with lower scores indicating stronger ability to not smoke.
Time frame: Baseline (Day -1), Days 4, 13, 17, 21, 26
Change From Baseline Over Time in TCQ-SF Score: Total Score
The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly disagree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Total scores may range from 12 to 84, with lower scores indicating lower tobacco craving.
Time frame: Baseline (Day -1), Days 4, 13, 17, 21, 26

Secondary outcomes

Cytisine Amount Excreted in Urine Over Time (Ae0-24h)
Time frame: Day 1 (6 times daily at 2-hour intervals); after the administration of the single dose of cytisine on Day 25
Percent of Drug Excreted in Urine (Ae%)
Time frame: Day 1 (6 times daily at 2-hour intervals); after the administration of the single dose of cytisine on Day 25
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuation of Study Drug Due to TEAEs
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with the treatment. A serious adverse event (SAE) is defined as an AE that results in any of the following: results in death; is life-threatening; requires hospitalisation or prolongs existing inpatient's hospitalisation; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; is an important medical event which requires medical intervention to prevent any of the above outcomes.TEAEs are defined as AEs not present prior to first administration of investigational product, or AEs present before first administration of investigational product that worsen after the participant receives the first dose of investigational product.
Time frame: From first dose of study drug through Day 26 plus 6-8 days
Number of Participants With Clinically Significant Values in Biochemistry, Hematology, and Urinalysis
Time frame: up to Day 26
Number of Participants With Clinically Significant Values in Vital Signs and Physical Examinations
Time frame: up to Day 26
Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Parameters
Time frame: up to Day 26
Number of Participants With Holter ECG Outlier Values
Based on the mean of the triplicate recordings at each time point. Increase (↑)/decrease (↓) calculated from Baseline (BL), defined as the mean of all recordings taken prior to dosing on Day 1 (i.e. -30 minutes and -15 minutes). A participant with multiple occurrences of an event is counted only once per event.
Time frame: on Day 1 and Day 25 at 30 and 15 minutes prior to the first dose and 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours post dose

Results

Posted Oct 21, 2019

Participant flow

Participant flow — Overall Study
Milestone	Cytisine 1.5 mg	Cytisine 3.0 mg
Started	13	13
Completed	13	13
Not completed	0	0

Outcome measures

PrimaryMaximum Observed Plasma Concentration (Cmax)

Time frame:: after the first dose and the last dose on Day 1; after the last dose on Days 2, 3, 12, 16, 20, 24; and after the morning dose on Day 25
Reported as:: Geometric mean · ng/mL

Maximum Observed Plasma Concentration (Cmax)
ng/mL	Cytisine 1.5 mg	Cytisine 3.0 mg
Day 1, first dose	21.1 ± 24.8	40.0 ± 26.8
Day 1, last dose	33.8 ± 20.0	81.4 ± 30.1
Day 2, last dose	32.9 ± 22.3	85.1 ± 20.9
Day 3, last dose	35.9 ± 21.7	88.1 ± 19.3
Day 12, last dose	29.9 ± 24.9	69.9 ± 31.5
Day 16, last dose	23.7 ± 31.4	50.5 ± 26.5
Day 20, last dose	23.0 ± 22.1	49.7 ± 30.9
Day 24, last dose	16.0 ± 28.3	42.0 ± 33.6
Day 25	12.6 ± 19.4	28.1 ± 27.4

PrimaryTime of Occurrence of Cmax (Tmax)

Time frame:: after the first dose and the last dose on Day 1; after the last dose on Days 2, 3, 12, 16, 20, 24; and after the morning dose on Day 25
Reported as:: Median · hours

Time of Occurrence of Cmax (Tmax)
hours	Cytisine 1.5 mg	Cytisine 3.0 mg
Day 1, first dose	0.500 (0.500 to 0.750)	0.750 (0.500 to 1.00)
Day 1, last dose	1.00 (0.00 to 2.50)	1.00 (0.00 to 2.50)
Day 2, last dose	1.00 (0.00 to 3.50)	1.00 (0.00 to 3.50)
Day 3, last dose	1.00 (0.500 to 3.00)	1.00 (0.00 to 2.03)
Day 12, last dose	1.00 (0.00 to 3.05)	1.02 (0.00 to 2.00)
Day 16, last dose	2.50 (0.00 to 4.02)	2.00 (1.00 to 6.50)
Day 20, last dose	1.50 (1.00 to 5.50)	1.00 (0.00 to 6.50)
Day 24, last dose	2.00 (1.00 to 4.00)	1.00 (1.00 to 3.00)
Day 25	2.50 (0.500 to 5.00)	2.25 (0.500 to 3.75)

PrimaryMinimum Observed Plasma Concentration (Cmin)

Time frame:: after the first dose on Days 4, 13, 17, 21 and 25
Reported as:: Geometric mean · ng/mL

Minimum Observed Plasma Concentration (Cmin)
ng/mL	Cytisine 1.5 mg	Cytisine 3.0 mg
Day 4, first dose	5.36 ± 47.7	13.2 ± 27.4
Day 13, first dose	5.16 ± 48.2	12.6 ± 33.0
Day 17, first dose	4.19 ± 64.7	8.50 ± 38.3
Day 21, first dose	3.13 ± 83.4	6.34 ± 39.0
Day 25	3.16 ± 188.9	3.74 ± 42.4

PrimaryArea Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Sampling Time (AUC0-t)

Time frame:: after the administration of the final dose of cytisine on Day 25
Reported as:: Geometric mean · h*ng/mL

Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Sampling Time (AUC0-t)
h*ng/mL	Cytisine 1.5 mg	Cytisine 3.0 mg
Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Sampling Time (AUC0-t)	67.0 ± 27.4	185 ± 32.3

PrimaryTotal AUC From Time Zero to Infinity (AUC0-∞)

Time frame:: after the administration of the final dose of cytisine on Day 25
Reported as:: Geometric mean · h*ng/mL

Total AUC From Time Zero to Infinity (AUC0-∞)
h*ng/mL	Cytisine 1.5 mg	Cytisine 3.0 mg
Total AUC From Time Zero to Infinity (AUC0-∞)	82.6 ± 30.4	213 ± 28.0

PrimaryResidual Area or Percentage of Extrapolated Part for the Calculation of AUC0-∞ (%AUC)

Time frame:: after the administration of the final dose of cytisine on Day 25
Reported as:: Geometric mean · percentage of extrapolated part

Residual Area or Percentage of Extrapolated Part for the Calculation of AUC0-∞ (%AUC)
percentage of extrapolated part	Cytisine 1.5 mg	Cytisine 3.0 mg
Residual Area or Percentage of Extrapolated Part for the Calculation of AUC0-∞ (%AUC)	18.0 ± 28.9	11.7 ± 40.1

PrimaryApparent Terminal Elimination Rate Constant (λz)

Time frame:: after the administration of the final dose of cytisine on Day 25
Reported as:: Geometric mean · 1/hour

Apparent Terminal Elimination Rate Constant (λz)
1/hour	Cytisine 1.5 mg	Cytisine 3.0 mg
Apparent Terminal Elimination Rate Constant (λz)	0.185 ± 26.4	0.152 ± 16.9

PrimaryApparent Terminal Elimination Half-Life (t1/2)

Time frame:: after the administration of the final dose of cytisine on Day 25
Reported as:: Mean · hours

Apparent Terminal Elimination Half-Life (t1/2)
hours	Cytisine 1.5 mg	Cytisine 3.0 mg
Apparent Terminal Elimination Half-Life (t1/2)	3.75 ± 24.7	4.57 ± 17.2

PrimaryNumber of Cigarettes Smoked Daily During Treatment and at Day 26

Time frame:: Day 1 through Day 26
Reported as:: Mean · cigarettes smoked in the past 24 hours

Number of Cigarettes Smoked Daily During Treatment and at Day 26
cigarettes smoked in the past 24 hours	Cytisine 1.5 mg	Cytisine 3.0 mg
Day -1	16.31 ± 3.401	18.08 ± 5.171
Day 1	7.31 ± 6.088	8.77 ± 6.882
Day 2	3.69 ± 1.437	4.08 ± 1.801
Day 3	4.00 ± 1.673	4.46 ± 1.854
Day 4	4.77 ± 2.682	6.15 ± 3.555
Day 5	4.08 ± 2.629	5.69 ± 3.568
Day 6	4.85 ± 3.826	7.00 ± 4.778
Day 7	4.19 ± 4.018	4.85 ± 4.180
Day 8	4.15 ± 3.760	5.38 ± 4.073
Day 9	4.77 ± 4.438	5.08 ± 4.555
Day 10	4.62 ± 4.234	4.54 ± 4.557
Day 11	3.81 ± 3.497	4.62 ± 4.292
Day 12	3.31 ± 3.545	3.69 ± 3.637
Day 13	4.15 ± 4.038	5.00 ± 4.163
Day 14	4.00 ± 3.786	3.69 ± 4.535
Day 15	4.23 ± 3.876	3.62 ± 4.331
Day 16	3.85 ± 3.648	3.08 ± 3.451
Day 17	4.00 ± 4.163	3.77 ± 4.781
Day 18	3.69 ± 3.903	3.92 ± 4.873
Day 19	3.69 ± 3.881	3.54 ± 4.789
Day 20	3.25 ± 3.671	2.58 ± 3.528
Day 21	4.54 ± 4.719	2.92 ± 4.462
Day 22	4.00 ± 4.163	3.00 ± 3.958
Day 23	4.38 ± 4.407	2.69 ± 4.151
Day 24	3.08 ± 2.985	2.38 ± 3.042
Day 25	1.17 ± 1.467	0.85 ± 1.214
Day 26	4.23 ± 4.206	3.00 ± 4.778

PrimaryChange From Baseline in Number of Cigarettes Smoked Daily up to Day 26

Time frame:: Baseline, Day 1 through Day 26
Reported as:: Mean · cigarettes smoked in the past 24 hours

Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26
cigarettes smoked in the past 24 hours	Cytisine 1.5 mg	Cytisine 3.0 mg
Day 1	-9.00 ± 5.745	-9.31 ± 7.169
Day 2	-12.62 ± 3.664	-14.00 ± 5.000
Day 3	-11.91 ± 3.885	-13.62 ± 5.723
Day 4	-11.54 ± 4.737	-11.92 ± 6.144
Day 5	-12.23 ± 4.475	-12.38 ± 5.665
Day 6	-11.46 ± 4.371	-11.08 ± 7.005
Day 7	-12.12 ± 4.718	-13.23 ± 5.388
Day 8	-12.15 ± 4.580	-12.69 ± 5.391
Day 9	-11.54 ± 5.333	-13.00 ± 5.845
Day 10	-11.69 ± 4.697	-13.54 ± 5.425
Day 11	-12.50 ± 4.173	-13.46 ± 4.789
Day 12	-13.00 ± 4.813	-14.38 ± 4.992
Day 13	-12.15 ± 4.543	-13.08 ± 6.873
Day 14	-12.31 ± 4.309	-14.38 ± 6.185
Day 15	-12.08 ± 4.212	-14.46 ± 5.592
Day 16	-12.46 ± 3.597	-15.00 ± 5.083
Day 17	-12.31 ± 4.768	-14.31 ± 5.721
Day 18	-12.62 ± 4.753	-14.15 ± 6.012
Day 19	-12.62 ± 4.556	-14.54 ± 5.577
Day 20	-13.17 ± 3.810	-15.83 ± 4.569
Day 21	-11.77 ± 5.262	-15.15 ± 5.535
Day 22	-12.31 ± 4.404	-15.08 ± 5.251
Day 23	-11.92 ± 4.873	-15.38 ± 5.091
Day 24	-13.23 ± 4.419	-15.69 ± 4.461
Day 25	-14.83 ± 3.407	-17.23 ± 4.850
Day 26	-12.08 ± 4.645	-15.08 ± 4.387

PrimaryChange From Baseline in Expired Air CO up to Day 26

Time frame:: Baseline, Days 4, 13, 17, 21, 26
Reported as:: Mean · ppm

Change From Baseline in Expired Air CO up to Day 26
ppm	Cytisine 1.5 mg	Cytisine 3.0 mg
Day 4	-13.2 ± 8.34	-13.8 ± 7.03
Day 13	-15.3 ± 8.02	-15.9 ± 6.84
Day 17	-16.0 ± 7.93	-16.2 ± 5.81
Day 21	-16.4 ± 7.79	-16.5 ± 6.08
Day 26	-17.2 ± 8.33	-17.9 ± 6.75

PrimaryNumber of Participants Who Ceased or Continued Smoking on Day 26

A status of "ceased smoking" is defined as not having smoked any cigarettes for the past 24 hours on Day 26 and having an expired CO level \<10 ppm on Day 26.

Time frame:: Day 26
Reported as:: Count of participants · Participants

Number of Participants Who Ceased or Continued Smoking on Day 26
Participants	Cytisine 1.5 mg	Cytisine 3.0 mg
Ceased Smoking	5	7
Continued Smoking	8	6

PrimaryChange From Baseline Over Time in Urine Cotinine

Time frame:: Baseline, Days 4, 13, 17, 21, 26
Reported as:: Mean · ng/mL

Change From Baseline Over Time in Urine Cotinine
ng/mL	Cytisine 1.5 mg	Cytisine 3.0 mg
Day 4	-1040.8 ± 579.78	-1339.2 ± 550.74
Day 13	-1010.0 ± 797.78	-1309.3 ± 761.77
Day 17	-1012.1 ± 710.39	-1405.2 ± 814.08
Day 21	-1095.1 ± 679.81	-1446.3 ± 828.68
Day 26	-1362.2 ± 545.84	-1640.2 ± 688.84

PrimaryChange From Baseline Over Time in TCQ-SF Score: Emotionality

The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly disagree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Emotionality scores may range from 3 to 21, with lower scores indicating weaker emotional signs of tobacco craving.

Time frame:: Baseline (Day -1), Days 4, 13, 17, 21, 26
Reported as:: Mean · score on a scale

Change From Baseline Over Time in TCQ-SF Score: Emotionality
score on a scale	Cytisine 1.5 mg	Cytisine 3.0 mg
Day 4	-5.2 ± 5.40	-6.0 ± 5.03
Day 13	-4.9 ± 5.96	-7.2 ± 4.88
Day 17	-5.8 ± 6.12	-7.3 ± 5.06
Day 21	-5.8 ± 6.38	-7.6 ± 5.09
Day 26	-5.7 ± 7.00	-8.2 ± 4.98

PrimaryChange From Baseline Over Time in TCQ-SF Score: Expectancy

The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly disagree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Expectancy scores may range from 3 to 21, with lower scores indicating less positive expectations about smoking.

Time frame:: Baseline (Day -1), Days 4, 13, 17, 21, 26
Reported as:: Mean · score on a scale

Change From Baseline Over Time in TCQ-SF Score: Expectancy
score on a scale	Cytisine 1.5 mg	Cytisine 3.0 mg
Day 4	-3.8 ± 5.89	-8.0 ± 6.00
Day 13	-3.5 ± 7.83	-8.4 ± 5.91
Day 17	-4.7 ± 6.96	-8.8 ± 5.82
Day 21	-5.2 ± 6.56	-9.2 ± 5.75
Day 26	-6.2 ± 6.40	-9.8 ± 6.15

PrimaryChange From Baseline Over Time in TCQ-SF Score: Compulsivity

The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly agree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Compulsivity scores may range from 3 to 21, with lower scores indicating compulsion to smoke was a lesser component of tobacco craving.

Time frame:: Baseline (Day -1), Days 4, 13, 17, 21, 26
Reported as:: Mean · score on a scale

Change From Baseline Over Time in TCQ-SF Score: Compulsivity
score on a scale	Cytisine 1.5 mg	Cytisine 3.0 mg
Day 4	-3.2 ± 3.18	-3.5 ± 4.74
Day 13	-3.7 ± 6.56	-4.9 ± 4.77
Day 17	-4.4 ± 6.32	-5.2 ± 4.44
Day 21	-4.4 ± 5.49	-5.3 ± 4.82
Day 26	-4.3 ± 5.94	-5.8 ± 4.59

PrimaryChange From Baseline Over Time in TCQ-SF Score: Purposefulness

The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly disagree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Purposefulness scores may range from 3 to 21, with lower scores indicating stronger ability to not smoke.

Time frame:: Baseline (Day -1), Days 4, 13, 17, 21, 26
Reported as:: Mean · score on a scale

Change From Baseline Over Time in TCQ-SF Score: Purposefulness
score on a scale	Cytisine 1.5 mg	Cytisine 3.0 mg
Day 4	-6.5 ± 2.93	-7.5 ± 4.99
Day 13	-6.6 ± 6.34	-9.1 ± 5.45
Day 17	-7.6 ± 6.33	-9.2 ± 6.09
Day 21	-7.8 ± 6.48	-10.3 ± 5.65
Day 26	-9.0 ± 5.15	-11.1 ± 5.54

PrimaryChange From Baseline Over Time in TCQ-SF Score: Total Score

The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly disagree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Total scores may range from 12 to 84, with lower scores indicating lower tobacco craving.

Time frame:: Baseline (Day -1), Days 4, 13, 17, 21, 26
Reported as:: Mean · score on a scale

Change From Baseline Over Time in TCQ-SF Score: Total Score
score on a scale	Cytisine 1.5 mg	Cytisine 3.0 mg
Day 4	-18.7 ± 12.88	-26.0 ± 16.06
Day 13	-18.7 ± 22.11	-29.6 ± 16.58
Day 17	-22.5 ± 22.17	-30.5 ± 16.51
Day 21	-23.2 ± 21.79	-32.5 ± 16.62
Day 26	-25.2 ± 20.55	-34.8 ± 16.85

SecondaryCytisine Amount Excreted in Urine Over Time (Ae0-24h)

Time frame:: Day 1 (6 times daily at 2-hour intervals); after the administration of the single dose of cytisine on Day 25
Reported as:: Geometric mean · mg

Cytisine Amount Excreted in Urine Over Time (Ae0-24h)
mg	Cytisine 1.5 mg	Cytisine 3.0 mg
Day 1	7.95 ± 14.3	16.5 ± 12.0
Day 25	1.54 ± 17.4	3.14 ± 12.6

SecondaryPercent of Drug Excreted in Urine (Ae%)

Time frame:: Day 1 (6 times daily at 2-hour intervals); after the administration of the single dose of cytisine on Day 25
Reported as:: Geometric mean · percentage of excreted drug

Percent of Drug Excreted in Urine (Ae%)
percentage of excreted drug	Cytisine 1.5 mg	Cytisine 3.0 mg
Day 1	88.3 ± 14.3	91.6 ± 12.0
Day 25	102 ± 17.4	105 ± 12.5

SecondaryNumber of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuation of Study Drug Due to TEAEs

An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with the treatment. A serious adverse event (SAE) is defined as an AE that results in any of the following: results in death; is life-threatening; requires hospitalisation or prolongs existing inpatient's hospitalisation; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; is an important medical event which requires medical intervention to prevent any of the above outcomes.TEAEs are defined as AEs not present prior to first administration of investigational product, or AEs present before first administration of investigational product that worsen after the participant receives the first dose of investigational product.

Time frame:: From first dose of study drug through Day 26 plus 6-8 days
Reported as:: Count of participants · Participants

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuation of Study Drug Due to TEAEs
Participants	Cytisine 1.5 mg	Cytisine 3.0 mg
TEAEs	9	9
Serious TEAEs	0	0
Discontinuation of Study Drug due to TEAE	0	0

SecondaryNumber of Participants With Clinically Significant Values in Biochemistry, Hematology, and Urinalysis

Time frame:: up to Day 26
Reported as:: Count of participants · Participants

Number of Participants With Clinically Significant Values in Biochemistry, Hematology, and Urinalysis
Participants	Cytisine 1.5 mg	Cytisine 3.0 mg
Biochemistry	0	0
Hematology	0	0
Urinalysis	0	0

SecondaryNumber of Participants With Clinically Significant Values in Vital Signs and Physical Examinations

Time frame:: up to Day 26
Reported as:: Count of participants · Participants

Number of Participants With Clinically Significant Values in Vital Signs and Physical Examinations
Participants	Cytisine 1.5 mg	Cytisine 3.0 mg
Vital Signs	0	0
Physical Examinations	0	0

SecondaryNumber of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Parameters

Time frame:: up to Day 26
Reported as:: Count of participants · Participants

Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Parameters
Participants	Cytisine 1.5 mg	Cytisine 3.0 mg
Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Parameters	0	0

SecondaryNumber of Participants With Holter ECG Outlier Values

Based on the mean of the triplicate recordings at each time point. Increase (↑)/decrease (↓) calculated from Baseline (BL), defined as the mean of all recordings taken prior to dosing on Day 1 (i.e. -30 minutes and -15 minutes). A participant with multiple occurrences of an event is counted only once per event.

Time frame:: on Day 1 and Day 25 at 30 and 15 minutes prior to the first dose and 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours post dose
Reported as:: Count of participants · Participants

Number of Participants With Holter ECG Outlier Values
Participants	Cytisine 1.5 mg	Cytisine 3.0 mg
Day 1: Heart Rate <50 bpm & ↓ ≥ 25%	0	0
Day 1: Heart Rate >100 bpm & ↑ ≥25%	1	0
Day 1: PR Interval >200 mSec & ↑ ≥25%	0	0
Day 1: QRS Duration >100 mSec & ↑ ≥25%	0	0
Day 1: QT Interval >500 mSec & BL ≤500 mSec	0	0
Day 1: QTcF Interval >500 mSec & BL ≤500 mSec	0	0
Day 1: QTcF Interval >480 mSec & BL ≤480 mSec	0	0
Day 1: QTcF Interval >450 mSec & BL ≤450 mSec	0	1
Day 25: Heart Rate <50 bpm & ↓ ≥ 25%	0	0
Day 25: Heart Rate >100 bpm & ↑ ≥25%	1	0
Day 25: PR Interval >200 mSec & ↑ ≥25%	0	0
Day 25: QRS Duration >100 mSec & ↑ ≥25%	0	1
Day 25: QT Interval >500 mSec & BL ≤500 mSec	0	0
Day 25: QTcF Interval >500 mSec & BL ≤500 mSec	0	0
Day 25: QTcF Interval >480 mSec & BL ≤480 mSec	0	0
Day 25: QTcF Interval >450 mSec & BL ≤450 mSec	0	0

Adverse events

Collected over From first dose of study drug through Day 26 plus 6-8 days. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Cytisine 1.5 mg	0/13 (0%)	0/13 (0%)	9/13 (69.2%)
Cytisine 3.0 mg	0/13 (0%)	0/13 (0%)	9/13 (69.2%)

Most frequent other events

Showing 10 of 19

Most frequent other events
Event	Cytisine 1.5 mg	Cytisine 3.0 mg
HeadacheNervous system disorders	4/13	6/13
NauseaGastrointestinal disorders	0/13	2/13
Abdominal pain upperGastrointestinal disorders	0/13	1/13
ConstipationGastrointestinal disorders	1/13	1/13
DyspepsiaGastrointestinal disorders	0/13	1/13
FlatulenceGastrointestinal disorders	0/13	1/13
Tooth lossGastrointestinal disorders	1/13	0/13
ToothacheGastrointestinal disorders	1/13	1/13
Chest discomfortGeneral disorders	0/13	1/13
Medical device site reactionGeneral disorders	1/13	1/13

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Cytisine 1.5 mg	Cytisine 3.0 mg	Total
<=18 years	0	0	0
Between 18 and 65 years	12	12	24
>=65 years	1	1	2

Age, Continuous
Age, Continuous(years)	Cytisine 1.5 mg	Cytisine 3.0 mg	Total
Mean	37.0 ± 12.87	40.9 ± 12.94	39.0 ± 12.80

Sex: Female, Male
Sex: Female, Male(Participants)	Cytisine 1.5 mg	Cytisine 3.0 mg	Total
Female	4	5	9
Male	9	8	17

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Cytisine 1.5 mg	Cytisine 3.0 mg	Total
White	13	12	25
Other, Not Specified	0	1	1

Expired Carbon Monoxide (CO) at Screening
Expired Carbon Monoxide (CO) at Screening(ppm)	Cytisine 1.5 mg	Cytisine 3.0 mg	Total
Mean	21.0 ± 8.02	20.7 ± 6.76	20.8 ± 7.27

Urine Cotinine at Screening
Urine Cotinine at Screening(ng/mL)	Cytisine 1.5 mg	Cytisine 3.0 mg	Total
Mean	1661.0 ± 502.57	1944.2 ± 611.61	1802.6 ± 567.13

Number of Cigarettes Smoked in the Past 24 hours on Day -1
Number of Cigarettes Smoked in the Past 24 hours on Day -1(cigarettes)	Cytisine 1.5 mg	Cytisine 3.0 mg	Total
Mean	16.31 ± 3.401	18.08 ± 5.171	17.19 ± 4.382

Tobacco Craving Questionnaire - Short Form (TCQ-SF) Emotionality Score at Day -1
Tobacco Craving Questionnaire - Short Form (TCQ-SF) Emotionality Score at Day -1(score on a scale)	Cytisine 1.5 mg	Cytisine 3.0 mg	Total
Mean	10.9 ± 5.25	11.7 ± 5.28	11.3 ± 5.18

5 further baseline measures are reported on the registry.

Study locations

1 site

Simbec Research Ltd
Cardiff, CF11 9AB, United Kingdom

References and documents

Study documents

Study protocol · Sep 21, 2017
Statistical analysis plan · Apr 23, 2018

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

Individual participant data

Plan to share: No

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reached

Ran from Oct 2017 to primary completion in Oct 2018, 11 months.

Results were first posted in Oct 2019, 1 year after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered: Sep 28, 2017
First posted: Oct 6, 2017
StartActual: Oct 6, 2017
Primary completionActual: Oct 5, 2018
CompletionActual: Oct 5, 2018
Results first posted: Oct 21, 2019
Last update: Oct 21, 2019

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Oct 21, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03303911
Lead sponsor: Achieve Life Sciences
Responsible party: Sponsor
First posted: Oct 6, 2017
Start date: Oct 6, 2017
Primary completion: Oct 5, 2018
Completion: Oct 5, 2018
Results posted: Oct 21, 2019
Last update: Oct 21, 2019

Study contacts

Annelize Koch, MD

principal investigator · Simbec Research Ltd (Simbec)

Oversight

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

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Oct 2019. You cannot join it, but the record below documents what was studied.

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Discussion

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