Trial Outcomes & Findings for A Study in Healthy Smokers to Investigate the Effect of Food on the Bioavailability of Cytisine in a New Formulation (NCT NCT03509948)
NCT ID: NCT03509948
Last Updated: 2019-09-24
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
13 participants
Primary outcome timeframe
Pre-dose (within 60 minutes prior to dosing), up to 48 hours post-dose on Days 1-5
Results posted on
2019-09-24
Participant Flow
Participant milestones
| Measure |
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 Study
STARTED
|
6
|
7
|
|
Overall Study
COMPLETED
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
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 Study
Protocol Violation
|
0
|
1
|
Baseline Characteristics
A Study in Healthy Smokers to Investigate the Effect of Food on the Bioavailability of Cytisine in a New Formulation
Baseline characteristics by cohort
| Measure |
All Study Participants
n=13 Participants
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).
|
|---|---|
|
Age, Continuous
|
33.3 years
STANDARD_DEVIATION 11.87 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
13 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose (within 60 minutes prior to dosing), up to 48 hours post-dose on Days 1-5Population: Pharmacokinetic (PK) Set: All randomized participants who received both doses of cytisine and had sufficient, protocol-compliant plasma concentration-time profiles.
Outcome measures
| Measure |
3 mg Cytisine: Fed
n=12 Participants
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state)
|
3 mg Cytisine: Fasted
n=12 Participants
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state)
|
|---|---|---|
|
Maximum Concentration (Cmax)
|
26.2 ng/mL
Geometric Coefficient of Variation 37.2
|
32.9 ng/mL
Geometric Coefficient of Variation 23.7
|
PRIMARY outcome
Timeframe: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5Population: PK Set: All randomized participants who received both doses of cytisine and had sufficient, protocol-compliant plasma concentration-time profiles.
Outcome measures
| Measure |
3 mg Cytisine: Fed
n=12 Participants
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state)
|
3 mg Cytisine: Fasted
n=12 Participants
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state)
|
|---|---|---|
|
Area Under the Concentration Versus Time Curve (AUC) Extrapolated to Infinity (AUC0-∞)
|
165 h*ng/mL
Geometric Coefficient of Variation 17.5
|
179 h*ng/mL
Geometric Coefficient of Variation 13.7
|
PRIMARY outcome
Timeframe: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5Population: Urine Excretion Set: All participants who received both doses of cytisine and had sufficient, protocol-compliant plasma concentration-time profiles.
Outcome measures
| Measure |
3 mg Cytisine: Fed
n=12 Participants
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state)
|
3 mg Cytisine: Fasted
n=12 Participants
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state)
|
|---|---|---|
|
Total Cytisine Excreted in Urine Over 48 Hours (Ae0-48h)
|
2.40 mg
Geometric Coefficient of Variation 21.3
|
2.64 mg
Geometric Coefficient of Variation 15.4
|
PRIMARY outcome
Timeframe: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5Population: Urine Excretion Set: All participants who received both doses of cytisine and had sufficient, protocol-compliant plasma concentration-time profiles.
Outcome measures
| Measure |
3 mg Cytisine: Fed
n=12 Participants
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state)
|
3 mg Cytisine: Fasted
n=12 Participants
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state)
|
|---|---|---|
|
Percent of Total Cytisine Excreted in Urine Over 48 Hours (Ae0-48h%)
|
82.60 percent of cytisine excreted in urine
Standard Deviation 17.627
|
89.22 percent of cytisine excreted in urine
Standard Deviation 13.777
|
SECONDARY outcome
Timeframe: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5Population: PK Set: All randomized participants who received both doses of cytisine and had sufficient, protocol-compliant plasma concentration-time profiles.
Outcome measures
| Measure |
3 mg Cytisine: Fed
n=12 Participants
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state)
|
3 mg Cytisine: Fasted
n=12 Participants
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state)
|
|---|---|---|
|
Time to Cmax (Tmax)
|
1.50 hours
Interval 0.5 to 6.0
|
0.750 hours
Interval 0.333 to 1.5
|
SECONDARY outcome
Timeframe: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5Population: PK Set: All randomized participants who received both doses of cytisine and had sufficient, protocol-compliant plasma concentration-time profiles.
Outcome measures
| Measure |
3 mg Cytisine: Fed
n=12 Participants
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state)
|
3 mg Cytisine: Fasted
n=12 Participants
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state)
|
|---|---|---|
|
Terminal Elimination Half-Life (T1/2)
|
4.59 hours
Standard Deviation 0.566
|
4.73 hours
Standard Deviation 0.437
|
SECONDARY outcome
Timeframe: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5Population: PK Set: All randomized participants who received both doses of cytisine and had sufficient, protocol-compliant plasma concentration-time profiles.
Outcome measures
| Measure |
3 mg Cytisine: Fed
n=12 Participants
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state)
|
3 mg Cytisine: Fasted
n=12 Participants
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state)
|
|---|---|---|
|
AUC From Time of Dosing to Last Measurable Concentration (AUC0-t)
|
158 h*ng/mL
Geometric Coefficient of Variation 17.2
|
173 h*ng/mL
Geometric Coefficient of Variation 13.2
|
SECONDARY outcome
Timeframe: Baseline (Day 0) through Day 5 plus 6-8 daysPopulation: Safety Set: All randomized participants who received at least 1 dose of cytisine.
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with the treatment. A serious adverse event (SAE) is defined as an AE that: results in death; is life-threatening; requires hospitalization or prolongs existing inpatient 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. TEAEs are defined as AEs not present prior to first administration of investigational product, or AEs present before first administration of investigational product that worsen after the participant receives the first dose of investigational product. Relationship of the TEAE to study drug was evaluated as: definite, probably, possible, unlikely, or not related.
Outcome measures
| Measure |
3 mg Cytisine: Fed
n=12 Participants
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state)
|
3 mg Cytisine: Fasted
n=13 Participants
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state)
|
|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Withdrawal of Study Drug
TEAE
|
2 Participants
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Withdrawal of Study Drug
Serious TEAE
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Withdrawal of Study Drug
TEAE Leading to withdrawal of study drug
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Withdrawal of Study Drug
Mild TEAE
|
2 Participants
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Withdrawal of Study Drug
Moderate TEAE
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Withdrawal of Study Drug
Severe TEAE
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Withdrawal of Study Drug
TEAE Relationship: Unlikely
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Withdrawal of Study Drug
TEAE Relationship: Not Related
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Screening through Day 5Population: Safety Set: All randomized participants who received at least 1 dose of cytisine.
Outcome measures
| Measure |
3 mg Cytisine: Fed
n=12 Participants
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state)
|
3 mg Cytisine: Fasted
n=13 Participants
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state)
|
|---|---|---|
|
Number of Participants With Clinically Significant Biochemistry, Hematology, Urinalysis, and/or 12-lead Electrocardiogram (ECG) Values
Hematology
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Biochemistry, Hematology, Urinalysis, and/or 12-lead Electrocardiogram (ECG) Values
Biochemistry
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Biochemistry, Hematology, Urinalysis, and/or 12-lead Electrocardiogram (ECG) Values
Urinalysis
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Biochemistry, Hematology, Urinalysis, and/or 12-lead Electrocardiogram (ECG) Values
ECG
|
0 Participants
|
0 Participants
|
Adverse Events
3 mg Cytisine: Fed
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
3 mg Cytisine: Fasted
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
3 mg Cytisine: Fed
n=12 participants at risk
Cytisine (2 x 1.5 mg tablets) administered 30 minutes after the start of a high fat breakfast (fed state)
|
3 mg Cytisine: Fasted
n=13 participants at risk
Cytisine (2 x 1.5 mg tablets) administered after an overnight fast of at least 10 hours (fasting state)
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
8.3%
1/12 • Baseline (Day 0) through Day 5 plus 6-8 days
TEAEs are presented
|
0.00%
0/13 • Baseline (Day 0) through Day 5 plus 6-8 days
TEAEs are presented
|
|
Nervous system disorders
Headache
|
8.3%
1/12 • Baseline (Day 0) through Day 5 plus 6-8 days
TEAEs are presented
|
0.00%
0/13 • Baseline (Day 0) through Day 5 plus 6-8 days
TEAEs are presented
|
Additional Information
Daniel Cain, Vice President, Clinical Research
Achieve Life Sciences
Phone: 425.686.1546
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Principal Investigators are bound by requirements outlined in their individual clinical trial agreements with regard to publication of trial results.
- Publication restrictions are in place
Restriction type: OTHER