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cytisine

Phase 2

Smoking Cessation | Small molecule | Psychiatry |Achieve Life Sciences, Inc.|Last Updated: Sep 17, 2020

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMC
Total Trials4
Total Enrollment365

FDA Designations

No designations recorded

Clinical trial landscape

cytisine · 4 trials · 1 indication

Phase 2 1Phase 1 3
NCT03709823Trial of Cytisine in Adult SmokersSmoking Cessation
COMPLETED254 Analytics
PHASE2COMPLETED
Trial of Cytisine in Adult Smokers
Smoking CessationUnlock trial analytics

Study Endpoints

Primary Endpoints

Primary Efficacy Analysis of Primary Outcome Measure: Percentage of Expected Cigarettes Smoked Per Participant During Study Treatment
Day 1 through Day 25

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).

Sensitivity Analysis of Primary Outcome Measure: Analysis for Percentage of Expected Cigarettes Smoked Versus Pooled Placebo Arms, Commercial Schedule
Day 1 through Day 25

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).

Sensitivity Analysis of Primary Outcome Measure: Analysis for Percentage of Expected Cigarettes Smoked Versus Pooled Placebo Arms, TID Schedule
Day 1 through Day 25

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).

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
Maximum Concentration (Cmax)
Pre-dose (within 60 minutes prior to dosing), up to 48 hours post-dose on Days 1-5
Area Under the Concentration Versus Time Curve (AUC) Extrapolated to Infinity (AUC0-∞)
Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5
Total Cytisine Excreted in Urine Over 48 Hours (Ae0-48h)
Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5
Percent of Total Cytisine Excreted in Urine Over 48 Hours (Ae0-48h%)
Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5
Plasma Cytisine Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax)
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)
Plasma Cytisine PK: Total Area Under the Curve From Time Zero to Infinity (AUC0-∞)
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)

Secondary Endpoints

Time to Cmax (Tmax)
Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5
Terminal Elimination Half-Life (T1/2)
Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5
AUC From Time of Dosing to Last Measurable Concentration (AUC0-t)
Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
1.5 mg Cytisine, Commercial ScheduleEXPERIMENTAL1.5 mg cytisine dose using the commercial 25-day titration schedule + behavioral support
3.0 mg Cytisine, Commercial ScheduleEXPERIMENTAL3.0 mg cytisine dose using the commercial 25-day titration schedule + behavioral support
Placebo, Commercial SchedulePLACEBO_COMPARATORPlacebo tablets using the commercial 25-day titration schedule + behavioral support
1.5 mg Cytisine, TID ScheduleEXPERIMENTAL1.5 mg cytisine dose for 25 days using a simplified 3 times daily (TID) schedule + behavioral support
3.0 mg Cytisine, TID ScheduleEXPERIMENTAL3.0 mg cytisine dose for 25 days using a simplified TID schedule + behavioral support
Placebo, TID SchedulePLACEBO_COMPARATORPlacebo tablets for 25 days using a simplified TID schedule + behavioral support
Cohort 1: Cytisine 6.0 mgEXPERIMENTALCytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
Cohort 1: PlaceboPLACEBO_COMPARATORPlacebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
Cohort 2: Cytisine 9.0 mgEXPERIMENTALCytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
Cohort 2: PlaceboPLACEBO_COMPARATORPlacebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
Cohort 3: Cytisine 12.0 mgEXPERIMENTALCytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
Cohort 3: PlaceboPLACEBO_COMPARATORPlacebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
Cohort 4: Cytisine 15.0 mgEXPERIMENTALCytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
Cohort 4: PlaceboPLACEBO_COMPARATORPlacebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
Cohort 5: Cytisine 18.0 mgEXPERIMENTALCytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
Cohort 5: PlaceboPLACEBO_COMPARATORPlacebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
Cohort 6: Cytisine 21.0 mgEXPERIMENTALCytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
Cohort 6: PlaceboPLACEBO_COMPARATORPlacebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
Cohort 7: Cytisine 24.0 mgEXPERIMENTALCytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
Cohort 7: PlaceboPLACEBO_COMPARATORPlacebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
Cohort 8: Cytisine 27.0 mgEXPERIMENTALCytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
Cohort 8: PlaceboPLACEBO_COMPARATORPlacebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
Cohort 9: Cytisine 30.0 mgEXPERIMENTALCytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
Cohort 9: PlaceboPLACEBO_COMPARATORPlacebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.
Schedule A: Fed Then FastedEXPERIMENTALSchedule A (6 participants): * Period 1: cytisine (2 x 1.5 mg tablets) will be administered 30 minutes after the start of a high fat breakfast (fed state) * Period 2: cytisine (2 x 1.5 mg tablets) will be administered after an overnight fast of at least 10 hours (fasting state)
Schedule B: Fasted Then FedEXPERIMENTALSchedule B (6 participants): * Period 1: cytisine (2 x 1.5 mg tablets) will be administered after an overnight fast of at least 10 hours (fasting state) * Period 2: cytisine (2 x 1.5 mg tablets) will be administered 30 minutes after the start of a high fat breakfast (fed state)

Interventions

NameTypeDescription
CytisineDRUGfilm coated tablet containing 1.5 mg cytisine in a single tablet
Placebo ComparatorDRUG1.5 mg cellulose powder to match final weight of the cytisine tablet
Behavioral supportBEHAVIORAL12 behavioral support sessions by a qualified staff member plus supportive literature and online resources
placeboDRUGmatching placebo oral tablet
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites8

Inclusion Criteria: 1. Male or female subjects, age ≥ 18 years. 2. Current daily cigarette smokers (averaging ≥ 10 cigarettes per day upon completing a 7-day screening diary) and who intend to quit smoking. 3. Expired air carbon monoxide (CO) ≥ 10 parts per million (ppm). 4. Failed at least one pre...

Countries:United StatesPortugalUnited Kingdom
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Frequently asked questions about cytisine

What is cytisine used for?

Cytisine is an investigational small molecule being developed for smoking cessation. It is currently in Phase 2 clinical development and has not been approved by the FDA. The drug is being studied in adult smokers to evaluate its effectiveness as a smoking cessation aid.

What does cytisine target?

Cytisine is a small molecule that acts as a nicotinic acetylcholine receptor partial agonist. It binds to the same receptors in the brain that nicotine targets, which may help reduce cravings and withdrawal symptoms associated with smoking cessation.

Who makes cytisine?

Cytisine is being developed by Achieve Life Sciences, Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol ACHV. The company is conducting clinical trials to evaluate the drug's safety and efficacy for smoking cessation.

What phase is cytisine in?

Cytisine is currently in Phase 2 clinical development for smoking cessation. It has completed four clinical trials, including Phase 1 and Phase 2 studies, but it remains investigational and has not received FDA approval. The drug is still being evaluated in clinical studies.

What clinical trials is cytisine in?

Cytisine has completed four clinical trials, including NCT03268343, NCT03509948, NCT03709823, and NCT03848208. These studies evaluated the drug's bioavailability, safety, and efficacy in adult smokers across the United Kingdom, United States, and Portugal.

Is cytisine the same as other smoking cessation drugs?

Cytisine is a distinct investigational compound being developed by Achieve Life Sciences. It is not the same as FDA-approved smoking cessation drugs like varenicline or bupropion. Cytisine is a plant-derived alkaloid that acts as a nicotinic receptor partial agonist, similar in mechanism to varenicline.