Trial of Cytisine in Adult Smokers

• Sponsor: Achieve Life Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03709823
• Collaborator: (none)
• Enrollment: 254
• Locations: 8
• Arms: 6
• Actual Duration (Months): 5.3
• Patients Per Site: 31.8
• Patients Per Site Per Month: 6

Study Details

Study Description

Brief Summary

This placebo-controlled Phase 2b trial is being conducted at sites within the United States (US) to evaluate the effectiveness cytisine dosage (1.5 mg, 3.0 mg) and administration schedule (commercial titration versus simplified 3 times daily [TID] schedule) within a 25-day treatment period.

Condition or Disease	Intervention/Treatment	Phase
Smoking Cessation	Drug: Cytisine; Drug: Placebo Comparator; Behavioral: Behavioral support	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 254 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-blind, Randomized, Placebo-controlled Phase 2b Trial of Cytisine in Adult Smokers
• Actual Study Start Date: Nov 13, 2018
• Actual Primary Completion Date: Apr 23, 2019
• Actual Study Completion Date: Apr 23, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1.5 mg Cytisine, Commercial Schedule 1.5 mg cytisine dose using the commercial 25-day titration schedule + behavioral support	Drug: Cytisine; film coated tablet containing 1.5 mg cytisine in a single tablet; Behavioral: Behavioral support; 12 behavioral support sessions by a qualified staff member plus supportive literature and online resources
Experimental: 3.0 mg Cytisine, Commercial Schedule 3.0 mg cytisine dose using the commercial 25-day titration schedule + behavioral support	Drug: Cytisine; film coated tablet containing 1.5 mg cytisine in a single tablet; Behavioral: Behavioral support; 12 behavioral support sessions by a qualified staff member plus supportive literature and online resources
Placebo Comparator: Placebo, Commercial Schedule Placebo tablets using the commercial 25-day titration schedule + behavioral support	Drug: Placebo Comparator; 1.5 mg cellulose powder to match final weight of the cytisine tablet; Behavioral: Behavioral support; 12 behavioral support sessions by a qualified staff member plus supportive literature and online resources
Experimental: 1.5 mg Cytisine, TID Schedule 1.5 mg cytisine dose for 25 days using a simplified 3 times daily (TID) schedule + behavioral support	Drug: Cytisine; film coated tablet containing 1.5 mg cytisine in a single tablet; Behavioral: Behavioral support; 12 behavioral support sessions by a qualified staff member plus supportive literature and online resources
Experimental: 3.0 mg Cytisine, TID Schedule 3.0 mg cytisine dose for 25 days using a simplified TID schedule + behavioral support	Drug: Cytisine; film coated tablet containing 1.5 mg cytisine in a single tablet; Behavioral: Behavioral support; 12 behavioral support sessions by a qualified staff member plus supportive literature and online resources
Placebo Comparator: Placebo, TID Schedule Placebo tablets for 25 days using a simplified TID schedule + behavioral support	Drug: Placebo Comparator; 1.5 mg cellulose powder to match final weight of the cytisine tablet; Behavioral: Behavioral support; 12 behavioral support sessions by a qualified staff member plus supportive literature and online resources

Outcome Measures

Primary Outcome Measures

1. Primary Efficacy Analysis of Primary Outcome Measure: Percentage of Expected Cigarettes Smoked Per Participant During Study Treatment [Day 1 through Day 25]

   The daily cigarette counts (number of cigarettes smoked in the past 24 hours) were self-reported by participants in the diary. Percentage of expected cigarettes smoked was computed for each participant at the end of treatment (cigarette score), based on daily cigarette counts during treatment vs the screening period. The percentage of expected cigarettes smoked was computed as Y = (100 x N) / (T x R) where N represents total number of cigarettes smoked each day over the treatment period from Day 1 to Day 25; T represents number of post-randomization days where number of cigarettes smoked is recorded; and R represents the average number of cigarettes smoked daily over the 7-day screening period as baseline. T*R represents the total number of cigarettes that would have been smoked without intervention over the number of recorded days. Separate statistical analyses were performed for the two cytisine administration schedules (commercial and TID).

2. Sensitivity Analysis of Primary Outcome Measure: Analysis for Percentage of Expected Cigarettes Smoked Versus Pooled Placebo Arms, Commercial Schedule [Day 1 through Day 25]

   The daily cigarette counts (number of cigarettes smoked in the past 24 hours) were self-reported by participants in the diary. Percentage of expected cigarettes smoked was computed for each participant at the end of treatment (cigarette score), based on daily cigarette counts during treatment vs the screening period. (See Outcome Measure 1 description for details.) The sensitivity analysis of the primary outcome measure was only performed if results of "Statistical Analysis 5" for Outcome Measure 1 demonstrated the placebo treatment arms (commercial and TID) were not significantly different, and so could be pooled. Separate statistical analyses were performed for the two cytisine administration schedules (commercial and TID).

3. Sensitivity Analysis of Primary Outcome Measure: Analysis for Percentage of Expected Cigarettes Smoked Versus Pooled Placebo Arms, TID Schedule [Day 1 through Day 25]

   The daily cigarette counts (number of cigarettes smoked in the past 24 hours) were self-reported by participants in the diary. Percentage of expected cigarettes smoked was computed for each participant at the end of treatment (cigarette score), based on daily cigarette counts during treatment vs the screening period. (See Outcome Measure 1 description for details.) The sensitivity analysis of the primary outcome measure was only performed if results of "Statistical Analysis 5" for Outcome Measure 1 demonstrated the placebo treatment arms (commercial and TID) were not significantly different, and so could be pooled. Separate statistical analyses were performed for the two cytisine administration schedules (commercial and TID).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female subjects, age ≥ 18 years.

2. Current daily cigarette smokers (averaging ≥ 10 cigarettes per day upon completing a 7-day screening diary) and who intend to quit smoking.

3. Expired air carbon monoxide (CO) ≥ 10 parts per million (ppm).

4. Failed at least one previous attempt to stop smoking with or without therapeutic support.

5. Willing to initiate study treatment on the day after randomization and set a quit date that is 5-7 days after starting treatment.

6. Willing to actively participate in the study's smoking cessation behavioral support provided throughout the study.

7. Able to fully understand all study requirements, willing to participate, comply with dosing schedule, and sign the Informed Consent Form.

Exclusion Criteria:

1. Known hypersensitivity to cytisine or any of the excipients.

2. Positive urinary drugs of abuse screen, determined within 28 days before the first dose of cytisine.

3. Clinically significant abnormal serum chemistry or hematology values within 28 days of randomization (i.e. requiring treatment).

4. Clinically significant abnormalities in 12-lead electrocardiogram (ECG) determined after minimum of 5 minutes in supine position within 28 days of randomization (i.e. requiring treatment or further assessment).

5. Body mass index (BMI) classification for being underweight (< 18.5 kg/m^{2) or having ≥ Class 2 obesity (≥ 35 kg/m}2).

6. Recent history (within 3 months) of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident or hospitalization for congestive heart failure.

7. Current uncontrolled hypertension (blood pressure ≥ 160/100 mmHg).

8. Documented diagnosis of schizophrenia or bipolar psychiatric illness; currently psychotic; having suicidal ideation (Suicide Behaviors Questionnaire-Revised [SBQ-R] score ≥ 7); or current symptoms of moderate to severe depression (Hospital Anxiety and Depression Scale [HADS] score ≥ 11).

9. Renal impairment defined as a creatinine clearance (CrCl) < 60 mL/min (estimated with the Cockroft-Gault equation) or hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.0 times the upper limit of normal (ULN).

10. Women who are pregnant or breast-feeding.

11. Male or Female subjects of child bearing potential who do not agree to use acceptable methods of birth control during the study treatment period.

12. Participation in a clinical study with an investigational drug within 4 weeks of randomization.

13. Treatment with other smoking cessation medications (bupropion, varenicline, nortriptyline, or any nicotine replacement therapy [NRT]) within 4 weeks of randomization or planned use of these other smoking cessation medications during the study.

14. Use within 2 weeks of randomization or planned use during the study of non-cigarette nicotine products (e-cigarettes, pipe tobacco, cigars, snuff, chewing tobacco, hookah) or marijuana vaping or smoking.

15. Any other reason that the investigator views the subject should not participate or would be unable to fulfill the requirements for the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Consortium	Tempe	Arizona	United States	85283
2	Los Angeles Clinical Trials	Burbank	California	United States	91505
3	Central Kentucky Research Associates, LLC	Lexington	Kentucky	United States	40509
4	Center for Pharmaceutical Research, LLC	Kansas City	Missouri	United States	64114
5	Rochester Clinical Research, Inc	Rochester	New York	United States	14609
6	Coastal Carolina Research Center, Inc	Mount Pleasant	South Carolina	United States	29464
7	Volunteer Research Group	Knoxville	Tennessee	United States	37920
8	FutureSearch Trails of Dallas, LP	Dallas	Texas	United States	57231

Sponsors and Collaborators

• Achieve Life Sciences

Investigators

• Principal Investigator: Mitchell Nides, PhD, Los Angeles Clinical Trials

Study Documents (Full-Text)

• Study Protocol - Apr 15, 2019
• Statistical Analysis Plan - May 29, 2019

More Information

Publications

None provided.

• Responsible Party: Achieve Life Sciences
• ClinicalTrials.gov Identifier: NCT03709823
• Other Study ID Numbers: ACH-CYT-09
• First Posted: Oct 17, 2018
• Last Update Posted: May 18, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Study Results

Participant Flow

Arm/Group Title	1.5 mg Cytisine, Commercial Schedule	3.0 mg Cytisine, Commercial Schedule	Placebo, Commercial Schedule	1.5 mg Cytisine, TID Schedule	3.0 mg Cytisine, TID Schedule	Placebo, TID Schedule
Arm/Group Description	1.5 mg cytisine dose using the commercial 25-day titration schedule + behavioral support	3.0 mg cytisine dose using the commercial 25-day titration schedule + behavioral support	Placebo tablets using the commercial 25-day titration schedule + behavioral support	1.5 mg cytisine dose for 25 days using a simplified 3 times daily (TID) schedule + behavioral support	3.0 mg cytisine dose for 25 days using a simplified TID schedule + behavioral support	Placebo tablets for 25 days using a simplified TID schedule + behavioral support
Period Title: Overall Study
STARTED	51	50	25	52	50	26
COMPLETED	48	45	22	50	49	26
NOT COMPLETED	3	5	3	2	1	0

Baseline Characteristics

Arm/Group Title	1.5 mg Cytisine, Commercial Schedule	3.0 mg Cytisine, Commercial Schedule	Placebo, Commercial Schedule	1.5 mg Cytisine, TID Schedule	3.0 mg Cytisine, TID Schedule	Placebo, TID Schedule	Total
Arm/Group Description	1.5 mg cytisine dose using the commercial 25-day titration schedule + behavioral support	3.0 mg cytisine dose using the commercial 25-day titration schedule + behavioral support	Placebo tablets using the commercial 25-day titration schedule + behavioral support	1.5 mg cytisine dose for 25 days using a simplified TID schedule + behavioral support	3.0 mg cytisine dose for 25 days using a simplified TID schedule + behavioral support	Placebo tablets for 25 days using a simplified TID schedule + behavioral support	Total of all reporting groups
Overall Participants	51	50	25	52	50	26	254
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.8 (11.46)	50.0 (13.20)	51.0 (15.16)	47.0 (13.67)	46.3 (12.88)	47.0 (12.64)	48.4 (13.04)
Sex: Female, Male (Count of Participants)
Female	28 54.9%	20 40%	14 56%	29 55.8%	25 50%	17 65.4%	133 52.4%
Male	23 45.1%	30 60%	11 44%	23 44.2%	25 50%	9 34.6%	121 47.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 2%	0 0%	1 1.9%	0 0%	0 0%	2 0.8%
Asian	0 0%	0 0%	0 0%	1 1.9%	1 2%	1 3.8%	3 1.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	7 13.7%	9 18%	3 12%	13 25%	7 14%	7 26.9%	46 18.1%
White	43 84.3%	40 80%	21 84%	37 71.2%	41 82%	18 69.2%	200 78.7%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 2%	0 0%	1 4%	0 0%	1 2%	0 0%	3 1.2%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	5 9.8%	1 2%	2 8%	6 11.5%	1 2%	0 0%	15 5.9%
Not Hispanic or Latino	45 88.2%	49 98%	23 92%	46 88.5%	49 98%	26 100%	238 93.7%
Native American	1 2%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.4%
Average Number of Cigarettes Smoked per Day Over 7 Consecutive Days (cigarettes per day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cigarettes per day]	17.6 (5.30)	18.0 (5.51)	16.7 (4.28)	18.0 (6.69)	18.0 (6.12)	18.0 (5.96)	17.8 (5.75)

Outcome Measures

1. Primary Outcome

Title	Primary Efficacy Analysis of Primary Outcome Measure: Percentage of Expected Cigarettes Smoked Per Participant During Study Treatment
Description	The daily cigarette counts (number of cigarettes smoked in the past 24 hours) were self-reported by participants in the diary. Percentage of expected cigarettes smoked was computed for each participant at the end of treatment (cigarette score), based on daily cigarette counts during treatment vs the screening period. The percentage of expected cigarettes smoked was computed as Y = (100 x N) / (T x R) where N represents total number of cigarettes smoked each day over the treatment period from Day 1 to Day 25; T represents number of post-randomization days where number of cigarettes smoked is recorded; and R represents the average number of cigarettes smoked daily over the 7-day screening period as baseline. T*R represents the total number of cigarettes that would have been smoked without intervention over the number of recorded days. Separate statistical analyses were performed for the two cytisine administration schedules (commercial and TID).
Time Frame	Day 1 through Day 25

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1.5 mg Cytisine, Commercial Schedule	3.0 mg Cytisine, Commercial Schedule	Placebo, Commercial Schedule	1.5 mg Cytisine, TID Schedule	3.0 mg Cytisine, TID Schedule	Placebo, TID Schedule
Arm/Group Description	1.5 mg cytisine dose using the commercial 25-day titration schedule + behavioral support	3.0 mg cytisine dose using the commercial 25-day titration schedule + behavioral support	Placebo tablets using the commercial 25-day titration schedule + behavioral support	1.5 mg cytisine dose for 25 days using a simplified TID schedule + behavioral support	3.0 mg cytisine dose for 25 days using a simplified TID schedule + behavioral support	Placebo tablets for 25 days using a simplified TID schedule + behavioral support
Measure Participants	51	50	25	52	50	26
Least Squares Mean (Standard Error) [percentage of cigarettes smoked]	26.62 (3.085)	25.04 (3.123)	47.10 (4.417)	29.40 (3.046)	32.50 (3.105)	35.30 (4.392)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1.5 mg Cytisine, Commercial Schedule, Placebo, Commercial Schedule
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	Based on analysis of variance models with percent of expected cigarettes smoked as the dependent variable, treatment and body mass index class as main fixed effects, with covariate of baseline cigarettes.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference vs. Placebo
	Estimated Value	-20.48
	Confidence Interval	(2-Sided) 95%; -31.141 to -9.821
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	3.0 mg Cytisine, Commercial Schedule, Placebo, Commercial Schedule
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Based on analysis of variance models with percent of expected cigarettes smoked as the dependent variable, treatment and body mass index class as main fixed effects, with covariate of baseline cigarettes.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference vs. Placebo
	Estimated Value	-22.07
	Confidence Interval	(2-Sided) 95%; -32.791 to -11.342
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	1.5 mg Cytisine, TID Schedule, Placebo, TID Schedule
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2708
	Comments	Based on analysis of variance models with percent of expected cigarettes smoked as the dependent variable, treatment and body mass index class as main fixed effects, with covariate of baseline cigarettes.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference vs. Placebo
	Estimated Value	-5.90
	Confidence Interval	(2-Sided) 95%; -16.463 to 4.660
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	3.0 mg Cytisine, TID Schedule, Placebo, TID Schedule
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6018
	Comments	Based on analysis of variance models with percent of expected cigarettes smoked as the dependent variable, treatment and body mass index class as main fixed effects, with covariate of baseline cigarettes.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference vs. Placebo
	Estimated Value	-2.81
	Confidence Interval	(2-Sided) 95%; -13.438 to 7.820
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Commercial Schedule, Placebo, TID Schedule
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1025
	Comments	Based on analysis of variance models with percent of expected cigarettes smoked as the dependent variable, treatment and body mass index class as main fixed effects, with covariate of baseline cigarettes.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference vs. Commercial Sched.
	Estimated Value	-12.17
	Confidence Interval	(2-Sided) 95%; -26.869 to 2.535
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Sensitivity Analysis of Primary Outcome Measure: Analysis for Percentage of Expected Cigarettes Smoked Versus Pooled Placebo Arms, Commercial Schedule
Description	The daily cigarette counts (number of cigarettes smoked in the past 24 hours) were self-reported by participants in the diary. Percentage of expected cigarettes smoked was computed for each participant at the end of treatment (cigarette score), based on daily cigarette counts during treatment vs the screening period. (See Outcome Measure 1 description for details.) The sensitivity analysis of the primary outcome measure was only performed if results of "Statistical Analysis 5" for Outcome Measure 1 demonstrated the placebo treatment arms (commercial and TID) were not significantly different, and so could be pooled. Separate statistical analyses were performed for the two cytisine administration schedules (commercial and TID).
Time Frame	Day 1 through Day 25

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1.5 mg Cytisine, Commercial Schedule	3.0 mg Cytisine, Commercial Schedule	Pooled Placebo
Arm/Group Description	1.5 mg cytisine dose using the commercial 25-day titration schedule + behavioral support	3.0 mg cytisine dose using the commercial 25-day titration schedule + behavioral support	Placebo tablets using the commercial 25-day titration schedule + behavioral support pooled with Placebo tablets for 25 days using a simplified TID schedule + behavioral support
Measure Participants	51	50	51
Least Squares Mean (Standard Error) [percentage of expected cigarettes smoked]	26.68 (3.065)	25.08 (3.100)	41.29 (3.099)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1.5 mg Cytisine, Commercial Schedule, Placebo, Commercial Schedule
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments	Based on analysis of variance models with percent of expected cigarettes smoked as the dependent variable, treatment and body mass index class as main fixed effects, with covariate of baseline cigarettes.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference vs. Placebo
	Estimated Value	-14.61
	Confidence Interval	(2-Sided) 95%; -23.216 to -6.009
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	3.0 mg Cytisine, Commercial Schedule, Placebo, Commercial Schedule
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments	Based on analysis of variance models with percent of expected cigarettes smoked as the dependent variable, treatment and body mass index class as main fixed effects, with covariate of baseline cigarettes.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference vs. Placebo
	Estimated Value	-16.20
	Confidence Interval	(2-Sided) 95%; -24.862 to -7.548
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Sensitivity Analysis of Primary Outcome Measure: Analysis for Percentage of Expected Cigarettes Smoked Versus Pooled Placebo Arms, TID Schedule
Description	The daily cigarette counts (number of cigarettes smoked in the past 24 hours) were self-reported by participants in the diary. Percentage of expected cigarettes smoked was computed for each participant at the end of treatment (cigarette score), based on daily cigarette counts during treatment vs the screening period. (See Outcome Measure 1 description for details.) The sensitivity analysis of the primary outcome measure was only performed if results of "Statistical Analysis 5" for Outcome Measure 1 demonstrated the placebo treatment arms (commercial and TID) were not significantly different, and so could be pooled. Separate statistical analyses were performed for the two cytisine administration schedules (commercial and TID).
Time Frame	Day 1 through Day 25

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1.5 mg Cytisine, TID Schedule	3.0 mg Cytisine, TID Schedule	Pooled Placebo
Arm/Group Description	1.5 mg cytisine dose for 25 days using a simplified TID schedule + behavioral support	3.0 mg cytisine dose for 25 days using a simplified TID schedule + behavioral support	Placebo tablets using the commercial 25-day titration schedule + behavioral support pooled with Placebo tablets for 25 days using a simplified TID schedule + behavioral support
Measure Participants	52	50	51
Least Squares Mean (Standard Error) [percentage of expected cigarettes smoked]	29.29 (3.291)	32.41 (3.355)	41.71 (3.358)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1.5 mg Cytisine, Commercial Schedule, Placebo, Commercial Schedule
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0091
	Comments	Based on analysis of variance models with percent of expected cigarettes smoked as the dependent variable, treatment and body mass index class as main fixed effects, with covariate of baseline cigarettes.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference vs. Placebo
	Estimated Value	-12.41
	Confidence Interval	(2-Sided) 95%; -21.695 to -3.135
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	3.0 mg Cytisine, Commercial Schedule, Placebo, Commercial Schedule
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0518
	Comments	Based on analysis of variance models with percent of expected cigarettes smoked as the dependent variable, treatment and body mass index class as main fixed effects, with covariate of baseline cigarettes.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference vs. Placebo
	Estimated Value	-9.30
	Confidence Interval	(2-Sided) 95%; -18.667 to 0.075
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From 1st dose of study drug through Week 8 (± 3 days) post-randomization
Arm/Group Title	1.5 mg Cytisine, Commercial Schedule		3.0 mg Cytisine, Commercial Schedule		Placebo, Commercial Schedule		1.5 mg Cytisine, TID Schedule		3.0 mg Cytisine, TID Schedule		Placebo, TID Schedule
Arm/Group Description	1.5 mg cytisine dose using the commercial 25-day titration schedule + behavioral support		3.0 mg cytisine dose using the commercial 25-day titration schedule + behavioral support		Placebo tablets using the commercial 25-day titration schedule + behavioral support		1.5 mg cytisine dose for 25 days using a simplified TID schedule + behavioral support		3.0 mg cytisine dose for 25 days using a simplified TID schedule + behavioral support		Placebo tablets for 25 days using a simplified TID schedule + behavioral support
All Cause Mortality
	1.5 mg Cytisine, Commercial Schedule		3.0 mg Cytisine, Commercial Schedule		Placebo, Commercial Schedule		1.5 mg Cytisine, TID Schedule		3.0 mg Cytisine, TID Schedule		Placebo, TID Schedule
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/50 (0%)		0/25 (0%)		0/52 (0%)		0/50 (0%)		0/26 (0%)
Serious Adverse Events
	1.5 mg Cytisine, Commercial Schedule		3.0 mg Cytisine, Commercial Schedule		Placebo, Commercial Schedule		1.5 mg Cytisine, TID Schedule		3.0 mg Cytisine, TID Schedule		Placebo, TID Schedule
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/50 (0%)		0/25 (0%)		0/52 (0%)		0/50 (0%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	1.5 mg Cytisine, Commercial Schedule		3.0 mg Cytisine, Commercial Schedule		Placebo, Commercial Schedule		1.5 mg Cytisine, TID Schedule		3.0 mg Cytisine, TID Schedule		Placebo, TID Schedule
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/51 (31.4%)		16/50 (32%)		5/25 (20%)		15/52 (28.8%)		14/50 (28%)		8/26 (30.8%)
Gastrointestinal disorders
Constipation	0/51 (0%)		0/50 (0%)		0/25 (0%)		1/52 (1.9%)		3/50 (6%)		1/26 (3.8%)
Nausea	5/51 (9.8%)		3/50 (6%)		1/25 (4%)		1/52 (1.9%)		3/50 (6%)		4/26 (15.4%)
General disorders
Fatigue	1/51 (2%)		2/50 (4%)		1/25 (4%)		3/52 (5.8%)		1/50 (2%)		1/26 (3.8%)
Infections and infestations
Gastroenteritis	1/51 (2%)		0/50 (0%)		0/25 (0%)		2/52 (3.8%)		1/50 (2%)		2/26 (7.7%)
Upper respiratory tract infection	3/51 (5.9%)		2/50 (4%)		3/25 (12%)		5/52 (9.6%)		3/50 (6%)		4/26 (15.4%)
Nervous system disorders
Headache	1/51 (2%)		1/50 (2%)		0/25 (0%)		6/52 (11.5%)		2/50 (4%)		2/26 (7.7%)
Psychiatric disorders
Abnormal dreams	4/51 (7.8%)		7/50 (14%)		1/25 (4%)		4/52 (7.7%)		3/50 (6%)		0/26 (0%)
Anxiety	1/51 (2%)		1/50 (2%)		0/25 (0%)		0/52 (0%)		1/50 (2%)		3/26 (11.5%)
Insomnia	3/51 (5.9%)		4/50 (8%)		1/25 (4%)		4/52 (7.7%)		3/50 (6%)		0/26 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/51 (0%)		0/50 (0%)		0/25 (0%)		0/52 (0%)		0/50 (0%)		2/26 (7.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Principal Investigators are bound by requirements outlined in their individual clinical trial agreements with regard to publication of trial results.