A Pharmacokinetic and Pharmacodynamic Evaluation of Cytisine in Healthy Smokers

Repeat-Dose Pharmacokinetic and Pharmacodynamic Evaluation of Cytisine in Healthy Smokers

Status

Terminated

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03303911

Enrollment

Registered

2017-10-06

Start date

2017-10-06

Completion date

2018-10-05

Last updated

2019-10-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Smoking Cessation

Brief 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.

Interventions

DRUGCytisine

film-coated tablets; depending on arm assignment, 1 or 2 tablets to be taken with 240 mL water for each dose

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Regular moderate cigarette smokers (minimum 10 cigarettes per day) who want to stop smoking. 2. Urine cotinine \>500 ng/mL. 3. Expired air carbon monoxide (CO) \> 11 parts per million (no cigarette 1 hour before test). 4. 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. 5. Subject with no clinically significant abnormal serum biochemistry, haematology and urine examination values within 28 days before the first dose of cytisine. 6. 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). 7. Subject with negative human immunodeficiency virus (HIV), hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results. 8. 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. 9. 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. 10. Subject must be available to complete the study (including in-clinic stays and post study follow-up) and comply with study restrictions. 11. Subject must provide written informed consent to participate in the study.

Exclusion criteria

1. Treatment with smoking cessation medications (bupropion, varenicline, any nicotine replacement therapy) within 8 weeks of first dose of cytisine. 2. 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. 3. Known hypersensitivity/allergy reaction to varenicline, other cytisine-derivatives or any of the excipients in the Tabex formulation. 4. History of severe hypersensitivity reactions to any other drugs. 5. Current treatment with antihypertensive medicinal products, statins, tuberculostatics, cholinomimetics or anticholinesterase medicinal products. 6. 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). 7. Female subjects who are breast feeding. 8. Difficulty in donating blood on either arm or known history. 9. History of alcoholism or drug abuse within last 2 years. 10. 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. 11. 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. 12. 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. 13. Inability to communicate well with Principal Investigator or designees (i.e., language problem, poor mental development or impaired cerebral function). 14. Any other condition that the Principal Investigator considers making the subject unsuitable for this study.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline Over Time in TCQ-SF Score: Total Score	Baseline (Day -1), Days 4, 13, 17, 21, 26	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.
Change From Baseline in Expired Air CO up to Day 26	Baseline, Days 4, 13, 17, 21, 26	—
Number of Participants Who Ceased or Continued Smoking on Day 26	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.
Change From Baseline Over Time in Urine Cotinine	Baseline, Days 4, 13, 17, 21, 26	—
Change From Baseline Over Time in TCQ-SF Score: Emotionality	Baseline (Day -1), Days 4, 13, 17, 21, 26	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.
Change From Baseline Over Time in TCQ-SF Score: Expectancy	Baseline (Day -1), Days 4, 13, 17, 21, 26	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.
Change From Baseline Over Time in TCQ-SF Score: Compulsivity	Baseline (Day -1), Days 4, 13, 17, 21, 26	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.
Change From Baseline Over Time in TCQ-SF Score: Purposefulness	Baseline (Day -1), Days 4, 13, 17, 21, 26	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.
Maximum Observed Plasma Concentration (Cmax)	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)	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)	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)	after the administration of the final dose of cytisine on Day 25	—
Total AUC From Time Zero to Infinity (AUC0-∞)	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)	after the administration of the final dose of cytisine on Day 25	—
Apparent Terminal Elimination Rate Constant (λz)	after the administration of the final dose of cytisine on Day 25	—
Apparent Terminal Elimination Half-Life (t1/2)	after the administration of the final dose of cytisine on Day 25	—
Number of Cigarettes Smoked Daily During Treatment and at Day 26	Day 1 through Day 26	—
Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Baseline, Day 1 through Day 26	—

Secondary

Measure	Time frame	Description
Cytisine Amount Excreted in Urine Over Time (Ae0-24h)	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%)	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	From first dose of study drug through Day 26 plus 6-8 days	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.
Number of Participants With Clinically Significant Values in Vital Signs and Physical Examinations	up to Day 26	—
Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Parameters	up to Day 26	—
Number of Participants With Holter ECG Outlier Values	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	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.
Number of Participants With Clinically Significant Values in Biochemistry, Hematology, and Urinalysis	up to Day 26	—

Countries

United Kingdom

Participant flow

Participants by arm

Arm	Count
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)	13
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)	13
Total	26

Baseline characteristics

Characteristic	Cytisine 1.5 mg	Cytisine 3.0 mg	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	1 Participants	1 Participants	2 Participants
Age, Categorical Between 18 and 65 years	12 Participants	12 Participants	24 Participants
Age, Continuous	37.0 years STANDARD_DEVIATION 12.87	40.9 years STANDARD_DEVIATION 12.94	39.0 years STANDARD_DEVIATION 12.8
Expired Carbon Monoxide (CO) at Screening	21.0 ppm STANDARD_DEVIATION 8.02	20.7 ppm STANDARD_DEVIATION 6.76	20.8 ppm STANDARD_DEVIATION 7.27
Fagerström Test for Nicotine Dependence Total Score at Day -1	4.7 score on a scale STANDARD_DEVIATION 1.6	5.3 score on a scale STANDARD_DEVIATION 1.38	5.0 score on a scale STANDARD_DEVIATION 1.5
Number of Cigarettes Smoked in the Past 24 hours on Day -1	16.31 cigarettes STANDARD_DEVIATION 3.401	18.08 cigarettes STANDARD_DEVIATION 5.171	17.19 cigarettes STANDARD_DEVIATION 4.382
Race/Ethnicity, Customized Other, Not Specified	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized White	13 Participants	12 Participants	25 Participants
Sex: Female, Male Female	4 Participants	5 Participants	9 Participants
Sex: Female, Male Male	9 Participants	8 Participants	17 Participants
TCQ-SF Compulsivity Score at Day -1	9.5 score on a scale STANDARD_DEVIATION 4.61	9.5 score on a scale STANDARD_DEVIATION 4.33	9.5 score on a scale STANDARD_DEVIATION 4.38
TCQ-SF Expectancy Score at Day -1	11.4 score on a scale STANDARD_DEVIATION 5.19	14.0 score on a scale STANDARD_DEVIATION 6.47	12.7 score on a scale STANDARD_DEVIATION 5.9
TCQ-SF Purposefulness Score at Day -1	14.9 score on a scale STANDARD_DEVIATION 3.57	15.6 score on a scale STANDARD_DEVIATION 5.27	15.3 score on a scale STANDARD_DEVIATION 4.42
TCQ-SF Total Score at Day -1	46.7 score on a scale STANDARD_DEVIATION 12.96	50.8 score on a scale STANDARD_DEVIATION 16.89	48.7 score on a scale STANDARD_DEVIATION 14.9
Tobacco Craving Questionnaire - Short Form (TCQ-SF) Emotionality Score at Day -1	10.9 score on a scale STANDARD_DEVIATION 5.25	11.7 score on a scale STANDARD_DEVIATION 5.28	11.3 score on a scale STANDARD_DEVIATION 5.18
Urine Cotinine at Screening	1661.0 ng/mL STANDARD_DEVIATION 502.57	1944.2 ng/mL STANDARD_DEVIATION 611.61	1802.6 ng/mL STANDARD_DEVIATION 567.13

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 13	0 / 13
other Total, other adverse events	9 / 13	9 / 13
serious Total, serious adverse events	0 / 13	0 / 13

Outcome results

Primary

Apparent Terminal Elimination Half-Life (t1/2)

Time frame: after the administration of the final dose of cytisine on Day 25

Population: PK Set: All randomized participants who completed all cytisine dosing on Days 1-3, completed \>90% cytisine dosing on Days 4-25 and complied with protocol-specified criteria. Participants with an assessment.

Arm	Measure	Value (MEAN)	Dispersion
Cytisine 1.5 mg	Apparent Terminal Elimination Half-Life (t1/2)	3.75 hours	Standard Deviation 24.7
Cytisine 3.0 mg	Apparent Terminal Elimination Half-Life (t1/2)	4.57 hours	Standard Deviation 17.2

Primary

Apparent Terminal Elimination Rate Constant (λz)

Time frame: after the administration of the final dose of cytisine on Day 25

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cytisine 1.5 mg	Apparent Terminal Elimination Rate Constant (λz)	0.185 1/hour	Geometric Coefficient of Variation 26.4
Cytisine 3.0 mg	Apparent Terminal Elimination Rate Constant (λz)	0.152 1/hour	Geometric Coefficient of Variation 16.9

Primary

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cytisine 1.5 mg	Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Sampling Time (AUC0-t)	67.0 h*ng/mL	Geometric Coefficient of Variation 27.4
Cytisine 3.0 mg	Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Sampling Time (AUC0-t)	185 h*ng/mL	Geometric Coefficient of Variation 32.3

Primary

Change From Baseline in Expired Air CO up to Day 26

Time frame: Baseline, Days 4, 13, 17, 21, 26

Population: PD Set: All participants in the PK set who had an available baseline result and at least 1 on-treatment result with regards to urine cotinine, expired air CO or daily cigarette consumption and did not incur a major protocol deviation in a way that may have invalidated or biased the PD results.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cytisine 1.5 mg	Change From Baseline in Expired Air CO up to Day 26	Day 13	-15.3 ppm	Standard Deviation 8.02
Cytisine 1.5 mg	Change From Baseline in Expired Air CO up to Day 26	Day 21	-16.4 ppm	Standard Deviation 7.79
Cytisine 1.5 mg	Change From Baseline in Expired Air CO up to Day 26	Day 17	-16.0 ppm	Standard Deviation 7.93
Cytisine 1.5 mg	Change From Baseline in Expired Air CO up to Day 26	Day 26	-17.2 ppm	Standard Deviation 8.33
Cytisine 1.5 mg	Change From Baseline in Expired Air CO up to Day 26	Day 4	-13.2 ppm	Standard Deviation 8.34
Cytisine 3.0 mg	Change From Baseline in Expired Air CO up to Day 26	Day 26	-17.9 ppm	Standard Deviation 6.75
Cytisine 3.0 mg	Change From Baseline in Expired Air CO up to Day 26	Day 4	-13.8 ppm	Standard Deviation 7.03
Cytisine 3.0 mg	Change From Baseline in Expired Air CO up to Day 26	Day 13	-15.9 ppm	Standard Deviation 6.84
Cytisine 3.0 mg	Change From Baseline in Expired Air CO up to Day 26	Day 17	-16.2 ppm	Standard Deviation 5.81
Cytisine 3.0 mg	Change From Baseline in Expired Air CO up to Day 26	Day 21	-16.5 ppm	Standard Deviation 6.08

Primary

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

Time frame: Baseline, Day 1 through Day 26

Population: PD Set: All participants in the PK set who had an available baseline result and at least 1 on-treatment result with regards to urine cotinine, expired air CO or daily cigarette consumption and did not incur a major protocol deviation. Participants with a valid assessment at given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 7	-12.12 cigarettes smoked in the past 24 hours	Standard Deviation 4.718
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 2	-12.62 cigarettes smoked in the past 24 hours	Standard Deviation 3.664
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 3	-11.91 cigarettes smoked in the past 24 hours	Standard Deviation 3.885
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 4	-11.54 cigarettes smoked in the past 24 hours	Standard Deviation 4.737
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 5	-12.23 cigarettes smoked in the past 24 hours	Standard Deviation 4.475
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 6	-11.46 cigarettes smoked in the past 24 hours	Standard Deviation 4.371
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 1	-9.00 cigarettes smoked in the past 24 hours	Standard Deviation 5.745
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 8	-12.15 cigarettes smoked in the past 24 hours	Standard Deviation 4.58
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 9	-11.54 cigarettes smoked in the past 24 hours	Standard Deviation 5.333
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 10	-11.69 cigarettes smoked in the past 24 hours	Standard Deviation 4.697
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 11	-12.50 cigarettes smoked in the past 24 hours	Standard Deviation 4.173
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 12	-13.00 cigarettes smoked in the past 24 hours	Standard Deviation 4.813
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 13	-12.15 cigarettes smoked in the past 24 hours	Standard Deviation 4.543
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 14	-12.31 cigarettes smoked in the past 24 hours	Standard Deviation 4.309
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 15	-12.08 cigarettes smoked in the past 24 hours	Standard Deviation 4.212
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 16	-12.46 cigarettes smoked in the past 24 hours	Standard Deviation 3.597
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 17	-12.31 cigarettes smoked in the past 24 hours	Standard Deviation 4.768
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 18	-12.62 cigarettes smoked in the past 24 hours	Standard Deviation 4.753
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 19	-12.62 cigarettes smoked in the past 24 hours	Standard Deviation 4.556
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 20	-13.17 cigarettes smoked in the past 24 hours	Standard Deviation 3.81
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 21	-11.77 cigarettes smoked in the past 24 hours	Standard Deviation 5.262
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 22	-12.31 cigarettes smoked in the past 24 hours	Standard Deviation 4.404
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 23	-11.92 cigarettes smoked in the past 24 hours	Standard Deviation 4.873
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 24	-13.23 cigarettes smoked in the past 24 hours	Standard Deviation 4.419
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 25	-14.83 cigarettes smoked in the past 24 hours	Standard Deviation 3.407
Cytisine 1.5 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 26	-12.08 cigarettes smoked in the past 24 hours	Standard Deviation 4.645
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 20	-15.83 cigarettes smoked in the past 24 hours	Standard Deviation 4.569
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 1	-9.31 cigarettes smoked in the past 24 hours	Standard Deviation 7.169
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 14	-14.38 cigarettes smoked in the past 24 hours	Standard Deviation 6.185
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 2	-14.00 cigarettes smoked in the past 24 hours	Standard Deviation 5
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 25	-17.23 cigarettes smoked in the past 24 hours	Standard Deviation 4.85
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 3	-13.62 cigarettes smoked in the past 24 hours	Standard Deviation 5.723
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 15	-14.46 cigarettes smoked in the past 24 hours	Standard Deviation 5.592
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 4	-11.92 cigarettes smoked in the past 24 hours	Standard Deviation 6.144
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 21	-15.15 cigarettes smoked in the past 24 hours	Standard Deviation 5.535
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 5	-12.38 cigarettes smoked in the past 24 hours	Standard Deviation 5.665
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 16	-15.00 cigarettes smoked in the past 24 hours	Standard Deviation 5.083
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 6	-11.08 cigarettes smoked in the past 24 hours	Standard Deviation 7.005
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 24	-15.69 cigarettes smoked in the past 24 hours	Standard Deviation 4.461
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 7	-13.23 cigarettes smoked in the past 24 hours	Standard Deviation 5.388
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 17	-14.31 cigarettes smoked in the past 24 hours	Standard Deviation 5.721
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 8	-12.69 cigarettes smoked in the past 24 hours	Standard Deviation 5.391
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 22	-15.08 cigarettes smoked in the past 24 hours	Standard Deviation 5.251
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 9	-13.00 cigarettes smoked in the past 24 hours	Standard Deviation 5.845
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 18	-14.15 cigarettes smoked in the past 24 hours	Standard Deviation 6.012
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 10	-13.54 cigarettes smoked in the past 24 hours	Standard Deviation 5.425
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 26	-15.08 cigarettes smoked in the past 24 hours	Standard Deviation 4.387
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 11	-13.46 cigarettes smoked in the past 24 hours	Standard Deviation 4.789
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 19	-14.54 cigarettes smoked in the past 24 hours	Standard Deviation 5.577
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 12	-14.38 cigarettes smoked in the past 24 hours	Standard Deviation 4.992
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 23	-15.38 cigarettes smoked in the past 24 hours	Standard Deviation 5.091
Cytisine 3.0 mg	Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26	Day 13	-13.08 cigarettes smoked in the past 24 hours	Standard Deviation 6.873

Primary

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.