Trial of Cytisine in Adult Smokers

Phase 2

Completed

• Conditions: Smoking Cessation
• Interventions: Drug: Cytisine; Drug: Placebo Comparator; Behavioral: Behavioral support

• Registration Number: NCT03709823
• Lead Sponsor: Achieve Life Sciences

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-10-15
• Study First Submitted QC: 2018-10-15
• Study First Posted: 2018-10-17
• Study Start: 2018-11-13
• Primary Completion: 2019-04-23
• Study Completion: 2019-04-23
• Results First Submitted: 2020-04-16
• Status Verified: 2020-05
• Results First Submitted QC: 2020-05-14
• Last Update Submitted: 2020-05-14
• Results First Posted: 2020-05-18
• Last Update Posted: 2020-05-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 254

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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).
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).
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).

Trial Locations

Locations (8)

Coastal Carolina Research Center, Inc; 🇺🇸 Mount Pleasant, South Carolina, United States

Clinical Research Consortium; 🇺🇸 Tempe, Arizona, United States

Volunteer Research Group; 🇺🇸 Knoxville, Tennessee, United States

Los Angeles Clinical Trials; 🇺🇸 Burbank, California, United States

Central Kentucky Research Associates, LLC; 🇺🇸 Lexington, Kentucky, United States

Center for Pharmaceutical Research, LLC; 🇺🇸 Kansas City, Missouri, United States

Rochester Clinical Research, Inc; 🇺🇸 Rochester, New York, United States

FutureSearch Trails of Dallas, LP; 🇺🇸 Dallas, Texas, United States