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A Study in Healthy Volunteers to Investigate the Effect of Food on the Bioavailability of Cytisine

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: NCT03268343
Recruitment Status : Completed
First Posted : August 31, 2017
Results First Posted : February 7, 2019
Last Update Posted : February 26, 2019
Sponsor:
Information provided by (Responsible Party):
Achieve Life Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Smoking Cessation
Intervention Drug: Cytisine
Enrollment 24
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 3 mg Cytisine, Schedule A: Fed Then Fasted 3 mg Cytisine, Schedule B: Fasted Then Fed
Hide Arm/Group Description
  • Period 1: Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state).
  • Period 2: Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state).
  • Period 1: Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state).
  • Period 2: Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state).
Period Title: Overall Study
Started 12 12
Completed 12 12
Not Completed 0 0
Arm/Group Title 3 mg Cytisine
Hide Arm/Group Description

3 mg Cytisine, Schedule A: Fed Then Fasted

  • Period 1: Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state).

  • Period 2: Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state).

    3 mg Cytisine, Schedule B: Fasted Then Fed

  • Period 1: Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state).
  • Period 2: Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state).
Overall Number of Baseline Participants 24
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants
35.1  (10.25)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Female
13
  54.2%
Male
11
  45.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 24 participants
Caucasian
23
  95.8%
Other, Not Specified
1
   4.2%
1.Primary Outcome
Title Plasma Cytisine Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax)
Hide Description [Not Specified]
Time Frame Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Set: All participants who received doses under both fed and fasted conditions and did not have an occurrence of vomiting which rendered the concentration profile unreliable. (Two participants were excluded for vomiting before twice the median Tmax had been reached following 3 mg cytisine administered in a fed state.)
Arm/Group Title 3 mg Cytisine, Fed 3 mg Cytisine, Fasted
Hide Arm/Group Description:
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state).
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state).
Overall Number of Participants Analyzed 22 22
Mean (Standard Deviation)
Unit of Measure: ng/mL
22.9  (5.44) 30.8  (7.91)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 3 mg Cytisine, Fed, 3 mg Cytisine, Fasted
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric LS Mean Ratio (%)
Estimated Value 74.71
Confidence Interval (2-Sided) 90%
66.39 to 84.08
Estimation Comments fed / fasted; results obtained using an ANOVA with fixed effects of treatment, period, sequence and participant (sequence).
2.Primary Outcome
Title Plasma Cytisine PK: Total Area Under the Curve From Time Zero to Infinity (AUC0-∞)
Hide Description [Not Specified]
Time Frame Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Set: All participants who received doses under both fed and fasted conditions and did not have an occurrence of vomiting which rendered the concentration profile unreliable. (Two participants were excluded for vomiting before twice the median Tmax had been reached following 3 mg cytisine administered in a fed state.)
Arm/Group Title 3 mg Cytisine, Fed 3 mg Cytisine, Fasted
Hide Arm/Group Description:
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state).
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state).
Overall Number of Participants Analyzed 22 22
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
170  (30.3) 176  (33.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 3 mg Cytisine, Fed, 3 mg Cytisine, Fasted
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric LS Mean Ratio (%)
Estimated Value 97.04
Confidence Interval (2-Sided) 90%
94.20 to 99.98
Estimation Comments fed / fasted; results obtained using an ANOVA with fixed effects of treatment, period, sequence and participant (sequence).
3.Secondary Outcome
Title Plasma Cytisine PK: Time of Occurrence of Cmax (Tmax)
Hide Description [Not Specified]
Time Frame Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Set: All participants who received doses under both fed and fasted conditions and did not have an occurrence of vomiting which rendered the concentration profile unreliable. (Two participants were excluded for vomiting before twice the median Tmax had been reached following 3 mg cytisine administered in a fed state.)
Arm/Group Title 3 mg Cytisine, Fed 3 mg Cytisine, Fasted
Hide Arm/Group Description:
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state).
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state).
Overall Number of Participants Analyzed 22 22
Median (Full Range)
Unit of Measure: hours
2.75
(0.500 to 6.12)
0.75
(0.333 to 3.00)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 3 mg Cytisine, Fed, 3 mg Cytisine, Fasted
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Wilcoxon Signed-Rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 1.38
Confidence Interval (2-Sided) 95%
0.50 to 2.25
Estimation Comments Hodges-Lehmann method
4.Secondary Outcome
Title Plasma Cytisine PK: AUC From Time Zero to the Last Sampling Time (AUC0-t)
Hide Description [Not Specified]
Time Frame Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Set: All participants who received doses under both fed and fasted conditions and did not have an occurrence of vomiting which rendered the concentration profile unreliable. (Two participants were excluded for vomiting before twice the median Tmax had been reached following 3 mg cytisine administered in a fed state.)
Arm/Group Title 3 mg Cytisine, Fed 3 mg Cytisine, Fasted
Hide Arm/Group Description:
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state).
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state).
Overall Number of Participants Analyzed 22 22
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
163  (29.4) 169  (33.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 3 mg Cytisine, Fed, 3 mg Cytisine, Fasted
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric LS Mean Ratio (%)
Estimated Value 96.52
Confidence Interval (2-Sided) 90%
93.30 to 99.85
Estimation Comments fed / fasted; results obtained using an ANOVA with fixed effects of treatment, period, sequence and participant (sequence).
5.Secondary Outcome
Title Plasma Cytisine PK: Residual Area, or Percentage of Extrapolated Part for the Calculation of AUC0-∞ (AUC%)
Hide Description [Not Specified]
Time Frame Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Set: All participants who received doses under both fed and fasted conditions and did not have an occurrence of vomiting which rendered the concentration profile unreliable. (Two participants were excluded for vomiting before twice the median Tmax had been reached following 3 mg cytisine administered in a fed state.)
Arm/Group Title 3 mg Cytisine, Fed 3 mg Cytisine, Fasted
Hide Arm/Group Description:
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state).
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state).
Overall Number of Participants Analyzed 22 22
Mean (Standard Deviation)
Unit of Measure: percentage of extrapolated part
4.37  (1.40) 3.85  (1.46)
6.Secondary Outcome
Title Plasma Cytisine PK: Apparent Terminal Elimination Rate Constant (Lambda z)
Hide Description [Not Specified]
Time Frame Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Set: All participants who received doses under both fed and fasted conditions and did not have an occurrence of vomiting which rendered the concentration profile unreliable. (Two participants were excluded for vomiting before twice the median Tmax had been reached following 3 mg cytisine administered in a fed state.)
Arm/Group Title 3 mg Cytisine, Fed 3 mg Cytisine, Fasted
Hide Arm/Group Description:
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state).
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state).
Overall Number of Participants Analyzed 22 22
Mean (Standard Deviation)
Unit of Measure: 1/hour
0.154  (0.0391) 0.156  (0.0314)
7.Secondary Outcome
Title Plasma Cytisine PK: Apparent Terminal Elimination Half-Life (t1/2)
Hide Description [Not Specified]
Time Frame Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Set: All participants who received doses under both fed and fasted conditions and did not have an occurrence of vomiting which rendered the concentration profile unreliable. (Two participants were excluded for vomiting before twice the median Tmax had been reached following 3 mg cytisine administered in a fed state.)
Arm/Group Title 3 mg Cytisine, Fed 3 mg Cytisine, Fasted
Hide Arm/Group Description:
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state).
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state).
Overall Number of Participants Analyzed 22 22
Mean (Standard Deviation)
Unit of Measure: hours
4.77  (1.16) 4.59  (0.832)
8.Secondary Outcome
Title Urine Cytisine PK: Amount Excreted in Urine Over Time (Ae)
Hide Description [Not Specified]
Time Frame Pre-dose (within 30 minutes prior to first dose); 0-2 hours, 2-4 hours, 4-8 hours, 8-12 hours and 12-24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Set: All participants who received doses under both fed and fasted conditions and did not have an occurrence of vomiting which rendered the concentration profile unreliable. (Two participants were excluded for vomiting before twice the median Tmax had been reached following 3 mg cytisine administered in a fed state.)
Arm/Group Title 3 mg Cytisine, Fed 3 mg Cytisine, Fasted
Hide Arm/Group Description:
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state).
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state).
Overall Number of Participants Analyzed 22 22
Mean (Standard Deviation)
Unit of Measure: mg
2.59  (0.407) 2.47  (0.357)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 3 mg Cytisine, Fed, 3 mg Cytisine, Fasted
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric LS Mean Ratio (%)
Estimated Value 104.75
Confidence Interval (2-Sided) 95%
98.97 to 110.87
Estimation Comments fed / fasted; results obtained using an ANOVA with fixed effects of treatment, period, sequence and participant (sequence).
9.Secondary Outcome
Title Urine Cytisine PK: Percentage of Drug Excreted in Urine (Ae%)
Hide Description To assess the renal elimination of cytisine via measurement of urinary concentrations of cytisine.
Time Frame Pre-dose (within 30 minutes prior to first dose); 0-2 hours, 2-4 hours, 4-8 hours, 8-12 hours and 12-24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Set: All participants who received doses under both fed and fasted conditions and did not have an occurrence of vomiting which rendered the concentration profile unreliable. (Two participants were excluded for vomiting before twice the median Tmax had been reached following 3 mg cytisine administered in a fed state.)
Arm/Group Title 3 mg Cytisine, Fed 3 mg Cytisine, Fasted
Hide Arm/Group Description:
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state).
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state).
Overall Number of Participants Analyzed 22 22
Mean (Standard Deviation)
Unit of Measure: percentage of drug excreted
86.5  (13.6) 82.4  (11.9)
10.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuation of Study Drug Due to AEs, by Severity and Relationship
Hide Description An adverse event (AE) is defined as any untoward medical occurrence which does not necessarily have a causal relationship with the treatment. TEAEs are defined as AEs not present prior to first administration of investigational product, or AEs present before first administration of study drug that worsen after the subject receives the first dose of study drug. A serious adverse event (SAE) is defined as an AE that: results in death; is life-threatening; requires hospitalization or prolongs existing inpatient's hospitalization; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; is an important medical event which requires medical intervention to prevent any of the above outcomes. Event severity was categorized as mild, moderate, or severe. Relationship of event to study drug was categorized as definite, probably, possible, unlikely, not related, or not applicable (N/A).
Time Frame Day -1 to Day 7 plus 6-8 days (post-study follow-up)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set: all participants who received at least one dose of cytisine.
Arm/Group Title 3 mg Cytisine, Fed 3 mg Cytisine, Fasted
Hide Arm/Group Description:
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state).
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state).
Overall Number of Participants Analyzed 24 24
Measure Type: Number
Unit of Measure: participants
≥ 1 TEAE 6 7
≥ 1 Serious TEAE 0 0
≥ 1 TEAE Leading to Withdrawal of Study Drug 0 0
≥ 1 Mild TEAE 6 7
≥ 1 Moderate TEAE 0 0
≥ 1 Severe TEAE 0 0
≥ 1 TEAE Definitely Related to Study Drug 0 0
≥ 1 TEAE Probably Related to Study Drug 1 1
≥ 1 TEAE Possibly Related to Study Drug 3 5
≥ 1 TEAE Unlikely Related to Study Drug 1 1
≥ 1 TEAE Not Related to Study Drug 0 0
≥ 1 TEAE Relationship to Study Drug = N/A 1 0
Time Frame Day -1 to Day 7 plus 6-8 days (post-study follow-up)
Adverse Event Reporting Description For each reporting group, a participant was counted only once per system organ class and preferred term. Consequently, if the same preferred term was observed for a participant in both fed and fasted states, the participant was counted only once in the "3 mg Cytisine, Overall" reporting group for that preferred term.
 
Arm/Group Title 3 mg Cytisine, Fed 3 mg Cytisine, Fasted 3 mg Cytisine, Overall
Hide Arm/Group Description Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state). Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state).

Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state).

Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state).
All-Cause Mortality
3 mg Cytisine, Fed 3 mg Cytisine, Fasted 3 mg Cytisine, Overall
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/24 (0.00%)   0/24 (0.00%)   0/24 (0.00%) 
Hide Serious Adverse Events
3 mg Cytisine, Fed 3 mg Cytisine, Fasted 3 mg Cytisine, Overall
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/24 (0.00%)   0/24 (0.00%)   0/24 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
3 mg Cytisine, Fed 3 mg Cytisine, Fasted 3 mg Cytisine, Overall
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/24 (25.00%)   7/24 (29.17%)   10/24 (41.67%) 
Gastrointestinal disorders       
Abdominal pain lower † 1  0/24 (0.00%)  1/24 (4.17%)  1/24 (4.17%) 
Nausea † 1  1/24 (4.17%)  1/24 (4.17%)  2/24 (8.33%) 
Vomiting † 1  2/24 (8.33%)  1/24 (4.17%)  3/24 (12.50%) 
General disorders       
Feeling hot † 1  0/24 (0.00%)  1/24 (4.17%)  1/24 (4.17%) 
Infections and infestations       
Rhinitis † 1  1/24 (4.17%)  0/24 (0.00%)  1/24 (4.17%) 
Nervous system disorders       
Dizziness † 1  2/24 (8.33%)  3/24 (12.50%)  4/24 (16.67%) 
Headache † 1  2/24 (8.33%)  2/24 (8.33%)  3/24 (12.50%) 
Hypoaesthesia † 1  1/24 (4.17%)  0/24 (0.00%)  1/24 (4.17%) 
Somnolence † 1  0/24 (0.00%)  1/24 (4.17%)  1/24 (4.17%) 
Skin and subcutaneous tissue disorders       
Cold sweat † 1  1/24 (4.17%)  0/24 (0.00%)  1/24 (4.17%) 
Erythema † 1  0/24 (0.00%)  1/24 (4.17%)  1/24 (4.17%) 
Surgical and medical procedures       
Tooth repair † 1  0/24 (0.00%)  1/24 (4.17%)  1/24 (4.17%) 
1
Term from vocabulary, MedDRA 20.0
†
Indicates events were collected by systematic assessment
[Not Specified]
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, Senior Director 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: NCT03268343    
Other Study ID Numbers: ACH-CYT-01
2017-001562-19 ( EudraCT Number )
First Submitted: August 25, 2017
First Posted: August 31, 2017
Results First Submitted: August 27, 2018
Results First Posted: February 7, 2019
Last Update Posted: February 26, 2019