Smoking Cessation
Conditions
Brief summary
The objectives of this study are: 1. To assess the tolerability and safety of cytisine as a single oral dose. 2. To define the Cmax levels associated to the occurrence of dose-limiting adverse events.
Interventions
DRUGcytisine
cytisine film-coated oral tablet
DRUGplacebo
matching placebo oral tablet
Sponsors
Achieve Life Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Subjects must meet ALL of the following criteria to be eligible for inclusion into the study: 1. Free written informed consent prior to any procedure required by the study. 2. Male or female subjects, age ≥18 years, at the time of signing the informed consent. 3. Current daily cigarette smokers (averaging at least 10 cigarettes per day in the past 30 days). 4. Expired air carbon monoxide (CO) ≥10 ppm. 5. Able to swallow multiple tablets at one time. 6. Able to fully understand, comply with all study requirements.
Exclusion criteria
Subjects meeting ANY of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | From first dose of study drug through Day 6 | An adverse event (AE) is defined as any untoward medical occurrence that does not necessarily have to have a causal relationship with the treatment. A serious AE is any untoward medical occurrence or effect, that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; or is an important medical event which requires medical intervention to prevent one of the above. Treatment emergent events are those that occurred after the first dose of study drug. |
| Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | Day 1: Pre-dose (within 30 minutes prior to dosing), 15, 30, 40, 50 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours (+/-2 minutes) post-dose | — |
| Pharmacokinetics: Time to Occurrence of Cmax (Tmax) | Day 1: Pre-dose (within 30 minutes prior to dosing), 15, 30, 40, 50 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours (+/-2 minutes) post-dose | — |
Countries
Portugal
Participant flow
Recruitment details
Participants were enrolled in a single center in Portugal.
Pre-assignment details
Participants were randomly assigned to receive a single oral dose of cytisine or placebo in a 3:1 ratio (6 cytisine:2 placebo) for each dose cohort. Seventy-four (74) participants were randomized; 2 were withdrawn from the study by physician decision before dosing (1 due to high blood pressure and 1 due to noncompliance with protocol restrictions).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo to match Cytisine 6-30 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 18 |
| Cytisine 6 mg Cytisine 6 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 6 |
| Cytisine 9 mg Cytisine 9 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 6 |
| Cytisine 12 mg Cytisine 12 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 6 |
| Cytisine 15 mg Cytisine 15 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 6 |
| Cytisine 18 mg Cytisine 18 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 6 |
| Cytisine 21 mg Cytisine 21 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 6 |
| Cytisine 24 mg Cytisine 24 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 6 |
| Cytisine 27 mg Cytisine 27 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 6 |
| Cytisine 30 mg Cytisine 30 mg administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours. | 6 |
| Total | 72 |
Baseline characteristics
| Characteristic | Placebo | Cytisine 6 mg | Cytisine 9 mg | Cytisine 12 mg | Cytisine 15 mg | Cytisine 18 mg | Cytisine 21 mg | Cytisine 24 mg | Cytisine 27 mg | Cytisine 30 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 31.3 years STANDARD_DEVIATION 7.5 | 44.5 years STANDARD_DEVIATION 12.1 | 35.7 years STANDARD_DEVIATION 8.2 | 35.3 years STANDARD_DEVIATION 11.1 | 34.7 years STANDARD_DEVIATION 7.5 | 37.8 years STANDARD_DEVIATION 12.9 | 30.3 years STANDARD_DEVIATION 8.1 | 30.0 years STANDARD_DEVIATION 5.5 | 30.3 years STANDARD_DEVIATION 4.6 | 29.7 years STANDARD_DEVIATION 8.9 | 33.5 years STANDARD_DEVIATION 9.2 |
| Race/Ethnicity, Customized Multiple Races | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 18 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 71 Participants |
| Sex: Female, Male Female | 10 Participants | 4 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 28 Participants |
| Sex: Female, Male Male | 8 Participants | 2 Participants | 4 Participants | 4 Participants | 3 Participants | 4 Participants | 4 Participants | 4 Participants | 5 Participants | 6 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 5 / 18 | 2 / 6 | 1 / 6 | 4 / 6 | 3 / 6 | 2 / 6 | 1 / 6 | 2 / 6 | 2 / 6 | 4 / 6 |
| serious Total, serious adverse events | 0 / 18 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation
An adverse event (AE) is defined as any untoward medical occurrence that does not necessarily have to have a causal relationship with the treatment. A serious AE is any untoward medical occurrence or effect, that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; or is an important medical event which requires medical intervention to prevent one of the above. Treatment emergent events are those that occurred after the first dose of study drug.
Time frame: From first dose of study drug through Day 6
Population: Safety Set: all participants who received study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Any TEAE | 5 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | TEAE Leading to Study Discontinuation | 0 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Serious TEAE | 0 participants |
| Cytisine 6 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | TEAE Leading to Study Discontinuation | 0 participants |
| Cytisine 6 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Any TEAE | 2 participants |
| Cytisine 6 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Serious TEAE | 0 participants |
| Cytisine 9 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Any TEAE | 1 participants |
| Cytisine 9 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | TEAE Leading to Study Discontinuation | 0 participants |
| Cytisine 9 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Serious TEAE | 0 participants |
| Cytisine 12 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Any TEAE | 4 participants |
| Cytisine 12 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Serious TEAE | 0 participants |
| Cytisine 12 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | TEAE Leading to Study Discontinuation | 0 participants |
| Cytisine 15 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Serious TEAE | 0 participants |
| Cytisine 15 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | TEAE Leading to Study Discontinuation | 0 participants |
| Cytisine 15 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Any TEAE | 3 participants |
| Cytisine 18 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Any TEAE | 2 participants |
| Cytisine 18 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Serious TEAE | 0 participants |
| Cytisine 18 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | TEAE Leading to Study Discontinuation | 0 participants |
| Cytisine 21 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Any TEAE | 1 participants |
| Cytisine 21 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | TEAE Leading to Study Discontinuation | 0 participants |
| Cytisine 21 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Serious TEAE | 0 participants |
| Cytisine 24 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | TEAE Leading to Study Discontinuation | 0 participants |
| Cytisine 24 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Serious TEAE | 0 participants |
| Cytisine 24 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Any TEAE | 2 participants |
| Cytisine 27 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Any TEAE | 2 participants |
| Cytisine 27 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Serious TEAE | 0 participants |
| Cytisine 27 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | TEAE Leading to Study Discontinuation | 0 participants |
| Cytisine 30 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Serious TEAE | 0 participants |
| Cytisine 30 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | TEAE Leading to Study Discontinuation | 0 participants |
| Cytisine 30 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Study Discontinuation | Any TEAE | 4 participants |
Primary
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax)
Time frame: Day 1: Pre-dose (within 30 minutes prior to dosing), 15, 30, 40, 50 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours (+/-2 minutes) post-dose
Population: Pharmacokinetic Analysis Set: all participants who received a dose of cytisine and had evaluable pharmacokinetic data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | 71.05 ng/mL |
| Cytisine 6 mg | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | 93.62 ng/mL |
| Cytisine 9 mg | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | 94.27 ng/mL |
| Cytisine 12 mg | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | 126.45 ng/mL |
| Cytisine 15 mg | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | 134.94 ng/mL |
| Cytisine 18 mg | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | 150.08 ng/mL |
| Cytisine 21 mg | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | 171.44 ng/mL |
| Cytisine 24 mg | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | 151.05 ng/mL |
| Cytisine 27 mg | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) | 166.65 ng/mL |
Primary
Pharmacokinetics: Time to Occurrence of Cmax (Tmax)
Time frame: Day 1: Pre-dose (within 30 minutes prior to dosing), 15, 30, 40, 50 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, and 3 hours (+/-2 minutes) post-dose
Population: Pharmacokinetic Analysis Set: all participants who received a dose of cytisine and had evaluable pharmacokinetic data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Pharmacokinetics: Time to Occurrence of Cmax (Tmax) | 0.83 hours |
| Cytisine 6 mg | Pharmacokinetics: Time to Occurrence of Cmax (Tmax) | 1.38 hours |
| Cytisine 9 mg | Pharmacokinetics: Time to Occurrence of Cmax (Tmax) | 1.88 hours |
| Cytisine 12 mg | Pharmacokinetics: Time to Occurrence of Cmax (Tmax) | 1.88 hours |
| Cytisine 15 mg | Pharmacokinetics: Time to Occurrence of Cmax (Tmax) | 2.00 hours |
| Cytisine 18 mg | Pharmacokinetics: Time to Occurrence of Cmax (Tmax) | 1.89 hours |
| Cytisine 21 mg | Pharmacokinetics: Time to Occurrence of Cmax (Tmax) | 2.50 hours |
| Cytisine 24 mg | Pharmacokinetics: Time to Occurrence of Cmax (Tmax) | 2.75 hours |
| Cytisine 27 mg | Pharmacokinetics: Time to Occurrence of Cmax (Tmax) | 2.50 hours |