Trial of Cytisine in Adult Smokers | NCT03709823

NCT03709823

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
1.5 mg Cytisine, Commercial Schedule	Experimental	1.5 mg cytisine dose using the commercial 25-day titration schedule + behavioral support	Drug: Cytisine Behavioral: Behavioral support
3.0 mg Cytisine, Commercial Schedule	Experimental	3.0 mg cytisine dose using the commercial 25-day titration schedule + behavioral support	Drug: Cytisine Behavioral: Behavioral support
Placebo, Commercial Schedule	Placebo Comparator	Placebo tablets using the commercial 25-day titration schedule + behavioral support	Drug: Placebo Comparator Behavioral: Behavioral support
1.5 mg Cytisine, TID Schedule	Experimental	1.5 mg cytisine dose for 25 days using a simplified 3 times daily (TID) schedule + behavioral support	Drug: Cytisine Behavioral: Behavioral support
3.0 mg Cytisine, TID Schedule	Experimental	3.0 mg cytisine dose for 25 days using a simplified TID schedule + behavioral support

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Cytisine	Drug	film coated tablet containing 1.5 mg cytisine in a single tablet	1.5 mg Cytisine, Commercial Schedule 1.5 mg Cytisine, TID Schedule 3.0 mg Cytisine, Commercial Schedule

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Primary Efficacy Analysis of Primary Outcome Measure: Percentage of Expected Cigarettes Smoked Per Participant During Study Treatment	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).	Day 1 through Day 25
Sensitivity Analysis of Primary Outcome Measure: Analysis for Percentage of Expected Cigarettes Smoked Versus Pooled Placebo Arms, Commercial Schedule	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).	Day 1 through Day 25
Sensitivity Analysis of Primary Outcome Measure: Analysis for Percentage of Expected Cigarettes Smoked Versus Pooled Placebo Arms, TID Schedule	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 Module

Eligibility Criteria

Inclusion Criteria:

Male or female subjects, age ≥ 18 years.
Current daily cigarette smokers (averaging ≥ 10 cigarettes per day upon completing a 7-day screening diary) and who intend to quit smoking.
Expired air carbon monoxide (CO) ≥ 10 parts per million (ppm).
Failed at least one previous attempt to stop smoking with or without therapeutic support.
Willing to initiate study treatment on the day after randomization and set a quit date that is 5-7 days after starting treatment.
Willing to actively participate in the study's smoking cessation behavioral support provided throughout the study.
Able to fully understand all study requirements, willing to participate, comply with dosing schedule, and sign the Informed Consent Form.

Exclusion Criteria:

Known hypersensitivity to cytisine or any of the excipients.
Positive urinary drugs of abuse screen, determined within 28 days before the first dose of cytisine.
Clinically significant abnormal serum chemistry or hematology values within 28 days of randomization (i.e. requiring treatment).
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).
Body mass index (BMI) classification for being underweight (< 18.5 kg/m^2) or having ≥ Class 2 obesity (≥ 35 kg/m^2).
Recent history (within 3 months) of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident or hospitalization for congestive heart failure.
Current uncontrolled hypertension (blood pressure ≥ 160/100 mmHg).
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).
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).
Women who are pregnant or breast-feeding.
Male or Female subjects of child bearing potential who do not agree to use acceptable methods of birth control during the study treatment period.
Participation in a clinical study with an investigational drug within 4 weeks of randomization.
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.
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.
Any other reason that the investigator views the subject should not participate or would be unable to fulfill the requirements for the study.

Name	Affiliation	Role
Mitchell Nides, PhD	Los Angeles Clinical Trials	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Research Consortium		Tempe	Arizona	85283	United States
Los Angeles Clinical Trials

Arm/Group Information

ID	Title	Description
FG000	1.5 mg Cytisine, Commercial Schedule	1.5 mg cytisine dose using the commercial 25-day titration schedule + behavioral support
FG001	3.0 mg Cytisine, Commercial Schedule	3.0 mg cytisine dose using the commercial 25-day titration schedule + behavioral support
FG002	Placebo, Commercial Schedule	Placebo tablets using the commercial 25-day titration schedule + behavioral support
FG003	1.5 mg Cytisine, TID Schedule	1.5 mg cytisine dose for 25 days using a simplified 3 times daily (TID) schedule + behavioral support
FG004	3.0 mg Cytisine, TID Schedule	3.0 mg cytisine dose for 25 days using a simplified TID schedule + behavioral support
FG005	Placebo, TID Schedule	Placebo tablets for 25 days using a simplified TID schedule + behavioral support

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	1.5 mg Cytisine, Commercial Schedule	1.5 mg cytisine dose using the commercial 25-day titration schedule + behavioral support
BG001	3.0 mg Cytisine, Commercial Schedule	3.0 mg cytisine dose using the commercial 25-day titration schedule + behavioral support

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Primary Efficacy Analysis of Primary Outcome Measure: Percentage of Expected Cigarettes Smoked Per Participant During Study Treatment

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).

Posted

Least Squares Mean

Standard Error

percentage of cigarettes smoked

Day 1 through Day 25

ID	Title

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	1.5 mg Cytisine, Commercial Schedule	1.5 mg cytisine dose using the commercial 25-day titration schedule + behavioral support

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 15, 2019	Apr 16, 2020	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	May 29, 2019	Apr 16, 2020	SAP_001.pdf

ID	Term
D015438	Health Behavior
D001519	Behavior

ID	Term
C004712	cytisine
D001521	Behavior Therapy

ID	Term
D011613	Psychotherapy
D004191	Behavioral Disciplines and Activities

OG000	1.5 mg Cytisine, Commercial Schedule	1.5 mg cytisine dose using the commercial 25-day titration schedule + behavioral support
OG001	3.0 mg Cytisine, Commercial Schedule	3.0 mg cytisine dose using the commercial 25-day titration schedule + behavioral support
OG002	Placebo, Commercial Schedule	Placebo tablets using the commercial 25-day titration schedule + behavioral support
OG003	1.5 mg Cytisine, TID Schedule	1.5 mg cytisine dose for 25 days using a simplified TID schedule + behavioral support
OG004	3.0 mg Cytisine, TID Schedule	3.0 mg cytisine dose for 25 days using a simplified TID schedule + behavioral support
OG005	Placebo, TID Schedule	Placebo tablets for 25 days using a simplified TID schedule + behavioral support