Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Cytisinicline · 8 trials · 5 indications
Assess whether subjects randomized to Arm B (3 mg cytisinicline TID for 12 weeks plus behavioral support) have a higher probability of nicotine vaping cessation from Week 9 to Week 12 post-randomization as compared to subjects randomized to Arm A (placebo TID for 12 weeks plus behavioral support). Successful vaping cessation is defined as weekly vaping abstinence during the last 4 weeks of the 12-week treatment period (Week 9 through Week 12) using quantitative cotinine levels at \<10 ng/mL for biochemical verification and subject's self-report of no vaping using a daily electronic diary
Smoking abstinence as verified by weekly expired carbon monoxide (CO) measurements ≤ 10 parts per million (ppm).
Smoking abstinence as verified by weekly expired CO measurements ≤ 10 ppm.
Vaping abstinence verified weekly using quantitative saliva cotinine levels at \< 10 ng/mL for biochemical verification and participants' self-report of no vaping.
τ=5 h for Dose 1 and Dose 2 and τ=24 h for Dose 3
τ=5 h for Dose 1 and Dose 2 and τ=24 h for Dose 3
Accumulation of cytisinicline following TID administration will be assessed by estimating R(Cmax), where R is the ratio of the pharmacokinetic parameter following administration of Dose 1 on Day 8 vs. single-dose administration under fasting conditions during Period 1 or 2.
Accumulation of cytisinicline following TID administration will be assessed by estimating R(AUC0-τ), where R is the ratio of the pharmacokinetic parameter following administration of Dose 1 on Day 8 vs. single-dose administration under fasting conditions during Period 1 or 2.
Time invariance will be assessed as R(AUC0-τ/AUC0-∞), where AUC0-τ is estimated on Day 8 Dose 1 and AUC0-∞ is estimated for the single-dose under fasting conditions during Period 1 or 2.
Time to steady state will be assessed by visual inspection of the Ctrough versus time plot.
| Arm | Type | Description |
|---|---|---|
| Arm A | PLACEBO_COMPARATOR | 12 weeks of placebo + behavioral support; 400 subjects |
| Arm B | ACTIVE_COMPARATOR | 12 weeks cytisinicline + behavioral support; 400 subjects |
| Cytisinicline 3 mg TID | EXPERIMENTAL | Cytisinicline 3 mg TID for 52 weeks. |
| Placebo + Behavioral Support | PLACEBO_COMPARATOR | One placebo tablet orally (PO) three times daily (TID) for 12 weeks plus behavioral support |
| 6-Week Cytisinicline + 6-Week Placebo + Behavioral Support | EXPERIMENTAL | One cytisinicline tablet PO TID for 6 weeks followed by one placebo tablet PO TID for 6 weeks plus behavioral support |
| 12-Week Cytisinicline + Behavioral Support | EXPERIMENTAL | One cytisinicline tablet PO TID for 12 weeks plus behavioral support |
| Cytisinicline + Placebo + Behavioral Support | EXPERIMENTAL | one cytisinicline tablet PO TID plus behavioral support for 6 weeks followed by one placebo tablet PO TID plus behavioral support for 6 weeks |
| Cytisinicline + Behavioral Support | EXPERIMENTAL | one cytisinicline tablet PO TID plus behavioral support for 12 weeks |
| Part 1: Cytisinicline 3 mg Once Daily (QD), Fasting | EXPERIMENTAL | 3 mg cytisinicline tablet administered in the morning, between 7:00 and 9:00 AM, in fasting conditions on Day 1 (Period 1) or Day 3 (Period 2). Participants will fast overnight for at least 10 hours before cytisinicline administration and will continue to fast for 4 hours after dosing. |
| Part 1: Cytisinicline 3 mg QD, Fed | EXPERIMENTAL | 3 mg cytisinicline tablet administered in the morning, between 7:00 and 9:00 AM, in fed conditions on Day 1 (Period 1) or Day 3 (Period 2). After an overnight fasting of at least 10 hours, participants will consume a standard high-fat-high-calorie meal within 30 minutes. Cytisinicline will be administered with 240 mL of water within 5 minutes after completion of the meal. |
| Part 2: Cytisinicline 3 mg 3 Times Daily (TID) | EXPERIMENTAL | 3 mg cytisinicline tablet administered TID each day on Day 5 to 8 (Period 3) as follows: Dose 1 will be administered in the morning between 7:00 and 9:00 AM,; Dose 2 at 5 hours (±10 minutes) after Dose 1; Dose 3 at 5 hours (±10 minutes) after Dose 2. Cytisinicline will be administered on an empty stomach (cytisinicline given at least 2 hours before food or 1 hour after food). |
| Group 1: Normal Renal Function | EXPERIMENTAL | Participants with normal renal function receive a 3 mg single dose of cytisinicline. |
| Group 2: Mild Renal Impairment | EXPERIMENTAL | Participants with mild renal impairment receive a 3 mg single dose of cytisinicline. |
| Group 3: Moderate Renal Impairment | EXPERIMENTAL | Participants with moderate renal impairment receive a 3 mg single dose of cytisinicline. |
| Group 4: Severe Renal Impairment | EXPERIMENTAL | Participants with severe renal impairment receive a 3 mg single dose of cytisinicline. |
| Group 5: ESRD Participants Undergoing Dialysis | EXPERIMENTAL | Participants with ESRD undergoing dialysis receive a 3 mg single dose of cytisinicline on 2 occasions: after and prior to a dialysis session. |
| Sequence 1 | EXPERIMENTAL | Participants will receive the assigned study drug after an overnight fast on Day 1 during each of 4 periods in the following order: * Cytisinicline, 6 mg (therapeutic dose) (2 cytisinicline tablets+6 placebo tablets) * Cytisinicline, 24 mg (supratherapeutic dose) (8 cytisinicline tablets) * Placebo (negative control) (8 placebo tablets) * Moxifloxacin 400 mg PO (positive control) (1 tablet) There will be a minimum 5 day washout between dosing periods. |
| Sequence 2 | EXPERIMENTAL | Participants will receive the assigned study drug after an overnight fast on Day 1 during each of 4 periods in the following order: * Cytisinicline, 24 mg (supratherapeutic dose) (8 cytisinicline tablets) * Moxifloxacin 400 mg PO (positive control) (1 tablet) * Cytisinicline, 6 mg (therapeutic dose) (2 cytisinicline tablets+6 placebo tablets) * Placebo (negative control) (8 placebo tablets) There will be a minimum 5 day washout between dosing periods. |
| Sequence 3 | EXPERIMENTAL | Participants will receive the assigned study drug after an overnight fast on Day 1 during each of 4 periods in the following order: * Placebo (negative control) (8 placebo tablets) * Cytisinicline, 6 mg (therapeutic dose) (2 cytisinicline tablets+6 placebo tablets) * Moxifloxacin 400 mg PO (positive control) (1 tablet) * Cytisinicline, 24 mg (supratherapeutic dose) (8 cytisinicline tablets) There will be a minimum 5 day washout between dosing periods. |
| Sequence 4 | EXPERIMENTAL | Participants will receive the assigned study drug after an overnight fast on Day 1 during each of 4 periods in the following order: * Moxifloxacin 400 mg PO (positive control) (1 tablet) * Placebo (negative control) (8 placebo tablets) * Cytisinicline, 24 mg (supratherapeutic dose) (8 cytisinicline tablets) * Cytisinicline, 6 mg (therapeutic dose) (2 cytisinicline tablets+6 placebo tablets) There will be a minimum 5 day washout between dosing periods. |
| Sequence 5 | EXPERIMENTAL | Participants will receive the assigned study drug after an overnight fast on Day 1 during each of 4 periods in the following order: * Cytisinicline, 24 mg (supratherapeutic dose) (8 cytisinicline tablets) * Placebo (negative control) (8 placebo tablets) * Cytisinicline, 6 mg (therapeutic dose) (2 cytisinicline tablets+6 placebo tablets) * Moxifloxacin 400 mg PO (positive control) (1 tablet) There will be a minimum 5 day washout between dosing periods. |
| Sequence 6 | EXPERIMENTAL | Participants will receive the assigned study drug after an overnight fast on Day 1 during each of 4 periods in the following order: * Placebo (negative control) (8 placebo tablets) * Moxifloxacin 400 mg PO (positive control) (1 tablet) * Cytisinicline, 24 mg (supratherapeutic dose) (8 cytisinicline tablets) * Cytisinicline, 6 mg (therapeutic dose) (2 cytisinicline tablets+6 placebo tablets) There will be a minimum 5 day washout between dosing periods. |
| Sequence 7 | EXPERIMENTAL | Participants will receive the assigned study drug after an overnight fast on Day 1 during each of 4 periods in the following order: * Cytisinicline, 6 mg (therapeutic dose) (2 cytisinicline tablets+6 placebo tablets) * Cytisinicline, 24 mg (supratherapeutic dose) (8 cytisinicline tablets) * Moxifloxacin 400 mg PO (positive control) (1 tablet) * Placebo (negative control) (8 placebo tablets) There will be a minimum 5 day washout between dosing periods. |
| Sequence 8 | EXPERIMENTAL | Participants will receive the assigned study drug after an overnight fast on Day 1 during each of 4 periods in the following order: * Moxifloxacin 400 mg PO (positive control) (1 tablet) * Cytisinicline, 6 mg (therapeutic dose) (2 cytisinicline tablets+6 placebo tablets) * Placebo (negative control) (8 placebo tablets) * Cytisinicline, 24 mg (supratherapeutic dose) (8 cytisinicline tablets) There will be a minimum 5 day washout between dosing periods. |
| Name | Type | Description |
|---|---|---|
| Cytisinicline | DRUG | Tablet, 3 times a day (TID), 12 weeks |
| Placebo | DRUG | Tablet, 3 times a day (TID), 12 weeks |
| Behavioral Support | BEHAVIORAL | 16 behavioral support sessions, starting prior to randomization and through Week 12, 3 additional sessions during the follow-up period. |
| Moxifloxacin | DRUG | 400 mg tablets |
Inclusion Criteria: * Male or female subjects, age ≥18 years. * Test positive for cotinine using a point-of-care Oral Fluid Screening Device (OFD) with positive detection at ≥30 ng/mL cotinine. * Current daily nicotine-containing electronic cigarette usage as recorded in a screening diary for at le...
Cytisinicline is an investigational small molecule being developed for smoking cessation and vaping cessation. It is also being studied in patients with renal impairment. The drug is in Phase 3 clinical development and has received Breakthrough Therapy designation from the FDA.
Cytisinicline is being developed by Achieve Life Sciences, Inc., a biopharmaceutical company traded on the Nasdaq under the ticker symbol ACHV. The company is conducting Phase 3 clinical trials for smoking cessation with this investigational drug.
Cytisinicline is in Phase 3 clinical development for smoking cessation. It is an investigational drug and has not been approved by the FDA. The drug has received Breakthrough Therapy designation, which is granted to expedite development and review of promising therapies.
Cytisinicline has completed two Phase 3 trials for smoking cessation: NCT04576949 with 810 participants and NCT05206370 with 792 participants, both in the United States. It also completed Phase 1 trials NCT05566288 and NCT05981768 in Portugal, studying cardiac effects and food effects on bioavailability.
Cytisinicline is a small molecule that acts as a partial agonist at nicotinic acetylcholine receptors. By binding to these receptors, it is thought to reduce nicotine cravings and withdrawal symptoms, helping smokers and vapers quit their habit. This mechanism is similar to other smoking cessation aids.
Cytisinicline is a form of cytisine, a naturally occurring alkaloid found in the seeds of the Laburnum tree. It has been used for smoking cessation in Eastern Europe for decades. Achieve Life Sciences is developing this purified form as a potential FDA-approved therapy.