Trial of Cytisine in Adult Smokers

NCT03709823 | Completed Phase 2 Results FDA Drug

• 1 other identifier: ACH-CYT-09
• Study Type: interventional
• Target: 254
• Locations: 1 country
• Sites: 8

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.

Conditions

Smoking Cessation

Outcome Measures

Primary Outcomes (3)

• 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).

  Day 1 through Day 25

Study Arms (6)

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

Drug: Cytisine; Behavioral: Behavioral support

Placebo, TID Schedule

PLACEBO COMPARATOR

Placebo tablets for 25 days using a simplified TID schedule + behavioral support

Drug: Placebo Comparator; Behavioral: Behavioral support

Interventions

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; 3.0 mg Cytisine, TID Schedule

Placebo Comparator DRUG

1.5 mg cellulose powder to match final weight of the cytisine tablet

Placebo, Commercial Schedule; Placebo, TID Schedule

Behavioral support BEHAVIORAL

12 behavioral support sessions by a qualified staff member plus supportive literature and online resources

1.5 mg Cytisine, Commercial Schedule; 1.5 mg Cytisine, TID Schedule; 3.0 mg Cytisine, Commercial Schedule; 3.0 mg Cytisine, TID Schedule; Placebo, Commercial Schedule; Placebo, TID Schedule

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Achieve Life Sciences: lead

Study Sites (8)

Clinical Research Consortium

Tempe, Arizona, 85283, United States

Location

Los Angeles Clinical Trials

Burbank, California, 91505, United States

Location

Central Kentucky Research Associates, LLC

Lexington, Kentucky, 40509, United States

Location

Center for Pharmaceutical Research, LLC

Kansas City, Missouri, 64114, United States

Location

Rochester Clinical Research, Inc

Rochester, New York, 14609, United States

Location

Coastal Carolina Research Center, Inc

Mt. Pleasant, South Carolina, 29464, United States

Location

Volunteer Research Group

Knoxville, Tennessee, 37920, United States

Location

FutureSearch Trails of Dallas, LP

Dallas, Texas, 57231, United States

Location

MeSH Terms

Conditions

Smoking Cessation

Interventions

cytisine; Behavior Therapy

Condition Hierarchy (Ancestors)

Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Psychotherapy; Behavioral Disciplines and Activities

Results Point of Contact

• Title: Daniel Cain, Vice President, Clinical Research
• Organization: Achieve Life Sciences

dcain@achievelifesciences.com

425.686.1546

Study Officials

• Mitchell Nides, PhD

  Los Angeles Clinical Trials

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2018
• First Posted: October 17, 2018
• Study Start: November 13, 2018
• Primary Completion: April 23, 2019
• Study Completion: April 23, 2019
• Last Updated: May 18, 2020
• Results First Posted: May 18, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)