- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05981768
Study to Evaluate Effect of Food on Bioavailability of Single 3 mg Tablet and Pharmacokinetics (PK) of Multiple 3 mg Doses in Healthy Adult Smokers
A Phase 1 Study to Investigate the Effect of Food on the Bioavailability of a Single Cytisinicline 3 mg Tablet and Evaluation of the Pharmacokinetics of Multiple 3 mg Doses (Three Times Daily) in Healthy Adult Smokers
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Daniel Cain
- Phone Number: 425.686.1546
- Email: dcain@achievelifesciences.com
Study Contact Backup
- Name: Michaelene Lewand, MA
- Phone Number: 425.686.1546
- Email: mlewand@achievelifesciences.com
Study Locations
-
-
-
Porto, Portugal, 4250-449
- BlueClinical Phase I
-
Contact:
- Marlene Fonseca, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Free written informed consent prior to any procedure required by the study.
- Willingness to accept and comply with all study procedures and restrictions.
- Male or female subject ≥ 18 years, at the date of signing the informed consent.
- Regular moderate combustible cigarette smokers (self-reported average of at least 10 cigarettes per day).
- Body mass index (BMI) of 18.0 to 30.0 kg/m^2, inclusive.
- Healthy subject, based on medical history, physical examination, vital signs, ECG and clinical laboratory tests.
- Negative test results for anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV-1Ab and anti-HIV-2Ab), Hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus antibodies (anti-HCVAb).
A female subject is eligible if she also meets one of the following criteria:
- is of non-childbearing potential (underwent a permanent sterilization method [eg, hysterectomy, bilateral salpingectomy or bilateral oophorectomy], is clinically diagnosed infertile, or is in a post-menopausal state); or
- is of childbearing potential and agrees to use an accepted contraceptive method from at least 4 weeks prior to admission and until at least 4 weeks after the last dose administration (Day 8).
Exclusion Criteria:
AT SCREENING
- Known hypersensitivity/allergic reaction to cytisinicline or any of the excipients.
- Known severe hypersensitivity reaction to any other drug.
- Any medical condition (eg, gastrointestinal, renal or hepatic, including peptic ulcer, inflammatory bowel disease or pancreatitis) or surgical condition (eg, cholecystectomy, gastrectomy) that may affect drug pharmacokinetics (absorption, distribution, metabolism or excretion) or subject safety.
- Stroke or acute myocardial infarction within the previous 3 months.
- History of hyperthyroidism.
- History of psychosis or of a psychotic event.
- Estimated renal creatinine clearance (CLCr) below the lower limit of the normal range (ie, 90-120 mL/min/1.73 m^2 for males and 80-110 mL/min/1.73 m^2 for females), based on creatinine clearance calculation by the Cockcroft-Gault formula and normalized to an average body surface area of 1.73 m^2.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the upper limit of the normal (ULN) range.
- Positive result in urine drugs-of-abuse or ethanol tests at Screening.
- Excessive caffeine consumption, defined as ≥ 800 mg per day.
- Veins unsuitable for intravenous puncture on either arm (eg, veins that are difficult to locate, access or puncture; veins with a tendency to rupture during or after puncture).
- Participation in any clinical trial within the previous 2 months.
- Use of any smoking cessation medications such as cytisinicline, bupropion, varenicline, nortriptyline, or any nicotine replacement therapy (NRT; eg, nicotine patch, nicotine chewing gum, or electronic cigarettes) in the previous 8 weeks.
- Participation in more than 2 clinical trials within the previous 12 months.
- Blood donation or significant blood loss (≥ 450 mL) due to any reason or had plasmapheresis within the previous 2 months.
- Female subjects who are lactating or pregnant by serum pregnancy test.
Any other condition that the investigator considers the subject to be unsuitable for the study.
AT ADMISSION
- Any recent disease or condition or treatment that, according to the investigator, would put the subject at undue risk due to study participation or occurred at a time frame in which may interfere with the pharmacokinetics of study drug.
Use of any medicinal products, prescription and non-prescription (including vitamins, food supplements, herbal supplements [including St John's Wort]), in the previous 2 weeks, unless in the investigator's opinion the medication does not interfere with the pharmacokinetics of study drug or compromise subject safety.
NOTE: The use of topical products without systemic absorption, acetaminophen (paracetamol) at doses of ≤ 2 grams/day, and hormonal contraceptives are acceptable.
- Use of any smoking cessation medications (eg, cytisinicline, bupropion, varenicline, nortriptyline, or any NRT eg, nicotine patch, nicotine chewing gum, or electronic cigarettes) since Screening.
- Positive result in drugs-of-abuse or ethanol tests.
- If female, positive pregnancy test in urine.
- Any other condition that the investigator considers to render the subject unsuitable for the study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part 1: Cytisinicline 3 mg Once Daily (QD), Fasting
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.
|
film-coated oral tablets containing 3 mg cytisinicline
Other Names:
|
Experimental: Part 1: Cytisinicline 3 mg QD, Fed
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.
|
film-coated oral tablets containing 3 mg cytisinicline
Other Names:
|
Experimental: Part 2: Cytisinicline 3 mg 3 Times Daily (TID)
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).
|
film-coated oral tablets containing 3 mg cytisinicline
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Observed Plasma Concentration (Cmax)
Time Frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
|
Time of Maximum Observed Plasma Concentration (Tmax)
Time Frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
|
Time Point Prior to the First Quantifiable Concentration (Tlag)
Time Frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
|
Time of Last Quantifiable Observed Concentration (Tlast)
Time Frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
|
Area Under Plasma Concentration-Time Curve (AUC) Over the Dosing Interval (AUC0-τ)
Time Frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
|
AUC From Time of Dosing (t=0h) to the Time of the Last Quantifiable Concentration (AUC0-t)
Time Frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
|
Total AUC Extrapolated to Infinity (AUC0-∞)
Time Frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
|
Percentage of AUC0-∞ Due to Extrapolation From the Time of the Last Quantifiable Concentration (Tlast) to Infinity (%AUCextrap)
Time Frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
|
Apparent Terminal Elimination Rate Constant (λz)
Time Frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
|
Apparent Terminal Elimination Half-Life (t1/2)
Time Frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
|
Apparent Clearance (CL/F)
Time Frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
|
Apparent Volume of Distribution (V/F)
Time Frame: Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
Day 1 (Period 1) and Day 3 (Period 2): pre-dose and up to 24 hours post-dose
|
|
Pre-dose Plasma Concentration (Ctrough) for Dose 1, Dose 2 and Dose 3
Time Frame: Days 5 to 8 (Period 3): pre-dose
|
Days 5 to 8 (Period 3): pre-dose
|
|
Cmax for Dose 1, Dose 2 and Dose 3
Time Frame: Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)
|
Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)
|
|
Tmax for Dose 1, Dose 2 and Dose 3
Time Frame: Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)
|
Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)
|
|
AUC0-τ for Dose 1, Dose 2 and Dose 3
Time Frame: Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)
|
τ=5 h for Dose 1 and Dose 2 and τ=24 h for Dose 3
|
Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)
|
Concentration Over the Dosing Interval (Cτ) for Dose 1, Dose 2 and Dose 3
Time Frame: Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)
|
τ=5 h for Dose 1 and Dose 2 and τ=24 h for Dose 3
|
Days 5-7 (Period 3): predose, Day 8 (Period 3): pre-dose and up to 5 hours post-dose (Doses 1 and 2), predose and up to 24 hours post-dose (Dose 3)
|
Apparent Terminal Elimination Half-Life Interval (t1/2) post Dose 3
Time Frame: Day 8 (Period 3): up to 24 hours post-dose 3
|
Day 8 (Period 3): up to 24 hours post-dose 3
|
|
Ratio of Cmax (R[Cmax])
Time Frame: Day 1 (Period 1) or Day 3 (Period 2), Day 8 (Period 3): Dose 1 (up to 5 hours post-dose)
|
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.
|
Day 1 (Period 1) or Day 3 (Period 2), Day 8 (Period 3): Dose 1 (up to 5 hours post-dose)
|
Ratio of AUC0-τ (R[AUC0-τ])
Time Frame: Day 1 (Period 1) or Day 3 (Period 2), Day 8 (Period 3): Dose 1 (up to 5 hours post-dose)
|
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.
|
Day 1 (Period 1) or Day 3 (Period 2), Day 8 (Period 3): Dose 1 (up to 5 hours post-dose)
|
R(AUC0-τ/AUC0-∞)
Time Frame: Day 1 (Period 1) or Day 3 (Period 2), Day 8 (Period 3): Dose 1 (up to 5 hours post-dose)
|
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.
|
Day 1 (Period 1) or Day 3 (Period 2), Day 8 (Period 3): Dose 1 (up to 5 hours post-dose)
|
Time to Steady State
Time Frame: Days 5 to 8 (Period 3): pre-dose
|
Time to steady state will be assessed by visual inspection of the Ctrough versus time plot.
|
Days 5 to 8 (Period 3): pre-dose
|
Number of Participants With Treatment Emergent Adverse Events (AEs)
Time Frame: From first dose of study drug through the End-of Study Visit (Day 28-31)
|
From first dose of study drug through the End-of Study Visit (Day 28-31)
|
|
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECG)
Time Frame: Baseline through Day 9
|
Baseline through Day 9
|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Time Frame: Baseline through Day 9
|
Baseline through Day 9
|
|
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Tests
Time Frame: Baseline through Day 9
|
Baseline through Day 9
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Marlene Fonseca, MD, Blue Clinical
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- ACH-CYT-11
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Smoking Cessation
-
University of Southern CaliforniaAmerican Cancer Society, Inc.CompletedSmoking | Smoking Cessation | Smoking, Cigarette | Smoking Behaviors | Cessation, SmokingUnited States
-
Nabi BiopharmaceuticalsNational Institute on Drug Abuse (NIDA)CompletedSmoking | Smoking Cessation | Tobacco CessationUnited States
-
Claremont Graduate UniversityNational Cancer Institute (NCI)CompletedSmoking | Smoking Cessation | Tobacco Use | Tobacco Smoking | Tobacco Use Cessation | Smoking, CigaretteUnited States
-
Heidelberg UniversityPfizerTerminatedSmoking | Smoking Cessation | Tobacco Use CessationGermany
-
Mayo ClinicNational Institute on Drug Abuse (NIDA)CompletedSmoking | Smoking Cessation | Tobacco Use | Tobacco Smoking | Tobacco Use Cessation | Smoking, Tobacco | Smoking, CigaretteUnited States
-
University of MiamiFlorida Department of HealthRecruitingSmoking Cessation | Tobacco Smoking | Tobacco Use CessationUnited States
-
University of VermontMayo Clinic; Alaska Native Tribal Health ConsortiumTerminatedSmoking | Smoking CessationUnited States
-
University of Wisconsin, MadisonCentiment LLCCompletedSmoking | Smoking CessationUnited States
-
Yale UniversityCompletedSmoking | Smoking CessationUnited States
-
Johns Hopkins UniversityMaryland Department of Health and Mental HygieneCompletedCOach2Quit TRIAL: Assessing a Prototype Personal Carbon Monoxide Monitor for Smoking Cessation (C2Q)Smoking | Smoking CessationUnited States
Clinical Trials on Cytisinicline
-
Achieve Life SciencesCompletedRenal ImpairmentSpain, Portugal
-
Achieve Life SciencesCompleted
-
Achieve Life SciencesCompletedSmoking CessationUnited States
-
Achieve Life SciencesCompletedSmoking CessationUnited States
-
Achieve Life SciencesCompletedVaping | E-Cig UseUnited States
-
Nabriva Therapeutics AGCompletedCommunity Acquired PneumoniaUnited States, Argentina, Brazil, Bulgaria, Chile, Georgia, Hungary, Korea, Republic of, Latvia, Mexico, Peru, Philippines, Poland, Romania, Russian Federation, Serbia, South Africa, Spain, Taiwan, Ukraine
-
Achieve Life SciencesCompleted