Trial of Cytisine in Adult Smokers

• ClinicalTrials.gov Identifier: NCT03709823
• Recruitment Status: Completed
• First Posted: October 17, 2018
• Results First Posted: May 18, 2020
• Last Update Posted: May 18, 2020
• Sponsor: Achieve Life Sciences
• Information provided by (Responsible Party): Achieve Life Sciences

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 (Clinical Trial)
• 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: November 13, 2018
• Actual Primary Completion Date: April 23, 2019
• Actual Study Completion Date: April 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

United States, Arizona

Clinical Research Consortium

Tempe, Arizona, United States, 85283

United States, California

Los Angeles Clinical Trials

Burbank, California, United States, 91505

United States, Kentucky

Central Kentucky Research Associates, LLC

Lexington, Kentucky, United States, 40509

United States, Missouri

Center for Pharmaceutical Research, LLC

Kansas City, Missouri, United States, 64114

United States, New York

Rochester Clinical Research, Inc

Rochester, New York, United States, 14609

United States, South Carolina

Coastal Carolina Research Center, Inc

Mount Pleasant, South Carolina, United States, 29464

United States, Tennessee

Volunteer Research Group

Knoxville, Tennessee, United States, 37920

United States, Texas

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)

Documents provided by Achieve Life Sciences:

Study Protocol  [PDF] April 15, 2019

Statistical Analysis Plan  [PDF] May 29, 2019

More Information

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

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No