Smoking cessation
Conditions
Interventions
Trade Name: Tabex® (Cytisine)
Product Name: Tabex® (Cytisine)
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Cytisine
CAS
Sponsors
Achieve Life Sciences Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be Confirmed at Screening 1. Regular moderate cigarette smokers (minimum 10 cigarettes per day) who want to stop smoking. 2. Fagerstrom Nicotine Dependence Rating of 6 or greater. 3. Urine cotinine >500 ng/mL. 4. Expired air carbon monoxide (CO) > 10 parts per million. 5. Healthy males and females 18-65+ years of age. a. If a female subject of child bearing potential, a negative pregnancy test at screening and admission and willing to use an effective method of contraception (unless of non-childbearing potential or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) from first dose until 3 months after last dose of cytisine. b. If a female subject of non-child bearing potential, a negative pregnancy test at screening and admission. For the purposes of this study, this is defined as the subject being amenorrheic for at least 12 consecutive months or at least 4 months post-surgical sterilisation (including bilateral fallopian tube ligation or bilateral oophorectomy with or without hysterectomy). Menopausal status will be confirmed by demonstrating at screening that levels of follicle stimulating hormone (FSH) fall within the respective pathology reference range. In the event a subject's menopause status has been clearly established (for example, the subject indicates she has been amenorrheic for 10 years), but FSH levels are not consistent with a post-menopausal condition, determination of subject eligibility will be at Investigator's discretion following consultation with the Sponsor. c. If a male subject, willing to use an effective method of contraception (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) from first dose until 3 months after last dose of cytisine. 6. Subject with no clinically significant abnormal serum biochemistry, haematology and urine examination values within 28 days before the first dose of cytisine. Subjects on stable medications (e.g. statins, thyroxine, etc) to maintain/control laboratory values are eligible if they meet the above criteria. 7. Subject with negative urinary drugs of abuse screen, determined within 28 days before the first dose of cytisine (a positive alcohol result may be repeated at Investigator's discretion). 8. Subject with negative human immunodeficiency virus (HIV), hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results. 9. Subject with no clinically significant abnormalities in 12-lead ECG determined after minimum of 5 minutes in supine position within 28 days before the first dose of cytisine. 10. Subject with no clinically significant abnormalities in vital signs (systolic blood pressure between 90-150 mmHg, diastolic blood pressure (DBP) between 50 and 90 mmHg, and pulse rate (PR) between 40-110 bpm, measured on the dominant arm after minimum of 5 minutes in supine position) determined within 28 days before first dose of cytisine. Subjects taking stable doses of antihypertensives are eligible if their hypertension is well controlled and the above criteria are met. 11. Subject must be available to complete the study (including in-clinic stays and post study follow-up) and co
Exclusion criteria
Exclusion criteria: To be Confirmed at Screening 1. Treatment with smoking cessation medications (bupropion, varenicline, any nicotine replacement therapy [NRT]) within 8 weeks of first dose of cytisine. 2. Known hypersensitivity/allergy reaction to varenicline, other cytisine-derivatives or any of the excipients in the Tabex formulation (lactose, cellulose, talc, magnesium). 3. History of severe hypersensitivity reactions to any other drugs. 4. History of any medical condition (e.g. gastrointestinal, renal or hepatic) or surgical condition (e.g. cholecystectomy, gastrectomy) that may affect drug pharmacokinetics (absorption, distribution, metabolism or excretion). 5. Difficulty in donating blood on either arm or known history. 6. History of alcoholism or drug abuse within last 2 years. 7. Use of non-prescription drugs, including vitamins, herbal and dietary supplements within 14 days (or 5 half-lives, whichever is longer) prior to the first dose of cytisine, unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise subject safety. 8. Participated in any investigational drug clinical trial within the previous 3 months or a marketed drug trial within the previous 30 days prior to randomization on Day 1 of Period 1. 9. Donation of 450 mL or more blood or had history of significant blood loss due to any reason or had plasmapheresis within 3 months before the first dose of cytisine. 10. Inability to communicate well with Investigators (i.e., language problem, poor mental development or impaired cerebral function). 11. Any other condition that the Principal Investigator considers making the subject unsuitable for this study. To be Re-Confirmed Prior to Start of Dosing (Day -1): 1. Development of any exclusion criteria since screening. 2. Use of non-prescription drugs, including vitamins, herbal and dietary supplements since screening, unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise subject safety. 3. Participation in a clinical study since the screening visit. 4. Donation of 450 mL or more blood since the screening visit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This study will be looking at Cytisine (Tabex®) to know how the body absorb and gets rid of the drug as well as for benefits (e.g reduction in smoking) when administered at either 1.5 mg or 3 mg doses for 25 days using the commercial administrative schedule for this marketed product in subjects who smoke and want to stop smoking.; Secondary Objective: • To compare the PK parameters and tolerability for repeat dosing of 1.5 mg and 3.0 mg cytisine during the 25-day schedule in healthy smokers at 18-65 and >65 (elderly) years of age. • To assess the renal elimination of cytisine via measurement of urinary concentrations of cytisine during treatment on Day 1 and Day 25. • To evaluate for effects on QT/QTc interval prolongation and cardiac safety during treatment on Day 1 and Day 25 in healthy smokers at 18-65 and >65 (elderly) years of age. ; Primary end point(s): PK parameters (predominately Cmax and Cmin values) will be evaluated during Days 1-3, and after the last dose administered on Days 12, 16, 20, and 24, prior to the next dose level change on the next day. PD parameters (predominantly reduction in smoking by expired air monoxide (CO), urine cotinine results and number of cigarettes smoked daily) will be evaluated during study treatment and at the post follow-up visit, compared to baseline. ; Timepoint(s) of evaluation of this end point: Cmax levels will be determined by collecting blood samples after the first daily doses on Days 1-3, and after the last evening dose on Days 3, 12, 16, 20 and 24. Cmin levels will be determined prior to each dose level change with pre-dose morning blood samples on Days 4, 13, 17, 21 and 25. Cmax, Tmax, t1/2 and AUC calculations will be assessed by collecting additional blood samples after the final dose on Day 25. | — |
Countries
United Kingdom
Contacts
Public ContactAnthony Clarke
Achieve Life Sciences Inc
Outcome results
None listed