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Trial of Cytisine in Adult Smokers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
Information provided by (Responsible Party):
Achieve Life Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Smoking Cessation
Interventions Drug: Cytisine
Drug: Placebo Comparator
Behavioral: Behavioral support
Enrollment 254
Recruitment Details  
Pre-assignment Details  
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
Hide 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
Reason Not Completed
Adverse Event             0             0             1             0             0             0
Lost to Follow-up             2             2             2             1             1             0
Withdrawal by Subject             1             3             0             0             0             0
Other, Not Specified             0             0             0             1             0             0
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
Hide 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 Number of Baseline Participants 51 50 25 52 50 26 254
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 51 participants 50 participants 25 participants 52 participants 50 participants 26 participants 254 participants
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  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 50 participants 25 participants 52 participants 50 participants 26 participants 254 participants
Female
28
  54.9%
20
  40.0%
14
  56.0%
29
  55.8%
25
  50.0%
17
  65.4%
133
  52.4%
Male
23
  45.1%
30
  60.0%
11
  44.0%
23
  44.2%
25
  50.0%
9
  34.6%
121
  47.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 50 participants 25 participants 52 participants 50 participants 26 participants 254 participants
American Indian or Alaska Native
0
   0.0%
1
   2.0%
0
   0.0%
1
   1.9%
0
   0.0%
0
   0.0%
2
   0.8%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.9%
1
   2.0%
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
   0.0%
0
   0.0%
0
   0.0%
Black or African American
7
  13.7%
9
  18.0%
3
  12.0%
13
  25.0%
7
  14.0%
7
  26.9%
46
  18.1%
White
43
  84.3%
40
  80.0%
21
  84.0%
37
  71.2%
41
  82.0%
18
  69.2%
200
  78.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   2.0%
0
   0.0%
1
   4.0%
0
   0.0%
1
   2.0%
0
   0.0%
3
   1.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 50 participants 25 participants 52 participants 50 participants 26 participants 254 participants
Hispanic or Latino
5
   9.8%
1
   2.0%
2
   8.0%
6
  11.5%
1
   2.0%
0
   0.0%
15
   5.9%
Not Hispanic or Latino
45
  88.2%
49
  98.0%
23
  92.0%
46
  88.5%
49
  98.0%
26
 100.0%
238
  93.7%
Native American
1
   2.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.4%
Average Number of Cigarettes Smoked per Day Over 7 Consecutive Days   [1] 
Mean (Standard Deviation)
Unit of measure:  Cigarettes per day
Number Analyzed 51 participants 50 participants 25 participants 52 participants 50 participants 26 participants 254 participants
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)
[1]
Measure Description: As reported in the participant's 7-day diary, which was completed between screening visits 1 and 2.
1.Primary Outcome
Title Primary Efficacy Analysis of Primary Outcome Measure: Percentage of Expected Cigarettes Smoked Per Participant During Study Treatment
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 51 50 25 52 50 26
Least Squares Mean (Standard Error)
Unit of Measure: 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)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1.5 mg Cytisine, Commercial Schedule, Placebo, Commercial Schedule
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference vs. Placebo
Estimated Value -20.48
Confidence Interval (2-Sided) 95%
-31.141 to -9.821
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 3.0 mg Cytisine, Commercial Schedule, Placebo, Commercial Schedule
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference vs. Placebo
Estimated Value -22.07
Confidence Interval (2-Sided) 95%
-32.791 to -11.342
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 1.5 mg Cytisine, TID Schedule, Placebo, TID Schedule
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference vs. Placebo
Estimated Value -5.90
Confidence Interval (2-Sided) 95%
-16.463 to 4.660
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 3.0 mg Cytisine, TID Schedule, Placebo, TID Schedule
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference vs. Placebo
Estimated Value -2.81
Confidence Interval (2-Sided) 95%
-13.438 to 7.820
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Commercial Schedule, Placebo, TID Schedule
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
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
Estimation Comments [Not Specified]
2.Primary Outcome
Title Sensitivity Analysis of Primary Outcome Measure: Analysis for Percentage of Expected Cigarettes Smoked Versus Pooled Placebo Arms, Commercial Schedule
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1.5 mg Cytisine, Commercial Schedule 3.0 mg Cytisine, Commercial Schedule Pooled Placebo
Hide 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
Overall Number of Participants Analyzed 51 50 51
Least Squares Mean (Standard Error)
Unit of Measure: percentage of expected cigarettes smoked
26.68  (3.065) 25.08  (3.100) 41.29  (3.099)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1.5 mg Cytisine, Commercial Schedule, Pooled Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference vs. Placebo
Estimated Value -14.61
Confidence Interval (2-Sided) 95%
-23.216 to -6.009
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 3.0 mg Cytisine, Commercial Schedule, Pooled Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference vs. Placebo
Estimated Value -16.20
Confidence Interval (2-Sided) 95%
-24.862 to -7.548
Estimation Comments [Not Specified]
3.Primary Outcome
Title Sensitivity Analysis of Primary Outcome Measure: Analysis for Percentage of Expected Cigarettes Smoked Versus Pooled Placebo Arms, TID Schedule
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1.5 mg Cytisine, TID Schedule 3.0 mg Cytisine, TID Schedule Pooled Placebo
Hide 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
Overall Number of Participants Analyzed 52 50 51
Least Squares Mean (Standard Error)
Unit of Measure: percentage of expected cigarettes smoked
29.29  (3.291) 32.41  (3.355) 41.71  (3.358)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1.5 mg Cytisine, TID Schedule, Pooled Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference vs. Placebo
Estimated Value -12.41
Confidence Interval (2-Sided) 95%
-21.695 to -3.135
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 3.0 mg Cytisine, TID Schedule, Pooled Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference vs. Placebo
Estimated Value -9.30
Confidence Interval (2-Sided) 95%
-18.667 to 0.075
Estimation Comments [Not Specified]
Time Frame From 1st dose of study drug through Week 8 (± 3 days) post-randomization
Adverse Event Reporting 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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/51 (0.00%)   0/50 (0.00%)   0/25 (0.00%)   0/52 (0.00%)   0/50 (0.00%)   0/26 (0.00%) 
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/51 (0.00%)   0/50 (0.00%)   0/25 (0.00%)   0/52 (0.00%)   0/50 (0.00%)   0/26 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   16/51 (31.37%)   16/50 (32.00%)   5/25 (20.00%)   15/52 (28.85%)   14/50 (28.00%)   8/26 (30.77%) 
Gastrointestinal disorders             
Constipation  1  0/51 (0.00%)  0/50 (0.00%)  0/25 (0.00%)  1/52 (1.92%)  3/50 (6.00%)  1/26 (3.85%) 
Nausea  1  5/51 (9.80%)  3/50 (6.00%)  1/25 (4.00%)  1/52 (1.92%)  3/50 (6.00%)  4/26 (15.38%) 
General disorders             
Fatigue  1  1/51 (1.96%)  2/50 (4.00%)  1/25 (4.00%)  3/52 (5.77%)  1/50 (2.00%)  1/26 (3.85%) 
Infections and infestations             
Gastroenteritis  1  1/51 (1.96%)  0/50 (0.00%)  0/25 (0.00%)  2/52 (3.85%)  1/50 (2.00%)  2/26 (7.69%) 
Upper respiratory tract infection  1  3/51 (5.88%)  2/50 (4.00%)  3/25 (12.00%)  5/52 (9.62%)  3/50 (6.00%)  4/26 (15.38%) 
Nervous system disorders             
Headache  1  1/51 (1.96%)  1/50 (2.00%)  0/25 (0.00%)  6/52 (11.54%)  2/50 (4.00%)  2/26 (7.69%) 
Psychiatric disorders             
Abnormal dreams  1  4/51 (7.84%)  7/50 (14.00%)  1/25 (4.00%)  4/52 (7.69%)  3/50 (6.00%)  0/26 (0.00%) 
Anxiety  1  1/51 (1.96%)  1/50 (2.00%)  0/25 (0.00%)  0/52 (0.00%)  1/50 (2.00%)  3/26 (11.54%) 
Insomnia  1  3/51 (5.88%)  4/50 (8.00%)  1/25 (4.00%)  4/52 (7.69%)  3/50 (6.00%)  0/26 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Cough  1  0/51 (0.00%)  0/50 (0.00%)  0/25 (0.00%)  0/52 (0.00%)  0/50 (0.00%)  2/26 (7.69%) 
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Principal Investigators are bound by requirements outlined in their individual clinical trial agreements with regard to publication of trial results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Daniel Cain, Vice President, Clinical Research
Organization: Achieve Life Sciences
Phone: 425.686.1546
EMail: dcain@achievelifesciences.com
Layout table for additonal information
Responsible Party: Achieve Life Sciences
ClinicalTrials.gov Identifier: NCT03709823    
Other Study ID Numbers: ACH-CYT-09
First Submitted: October 15, 2018
First Posted: October 17, 2018
Results First Submitted: April 16, 2020
Results First Posted: May 18, 2020
Last Update Posted: May 18, 2020