Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 4 of 9 for:    CYTISINE

A Pharmacokinetic and Pharmacodynamic Evaluation of Cytisine in Healthy Smokers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03303911
Recruitment Status : Terminated (It has been difficult to recruit participants meeting study entry criteria that are >65 years of age and not for any safety reasons.)
First Posted : October 6, 2017
Last Update Posted : May 31, 2019
Sponsor:
Information provided by (Responsible Party):
Achieve Life Sciences

Brief Summary:
This is an open-label, randomised, multi-dose study to evaluate the pharmacokinetic (PK) profile and pharmacodynamic (PD) effect of cytisine when administered at doses of 1.5 mg and 3.0 mg following the commercialised 25-day schedule.

Condition or disease Intervention/treatment Phase
Smoking Cessation Drug: Cytisine Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Repeat-Dose Pharmacokinetic and Pharmacodynamic Evaluation of Cytisine in Healthy Smokers
Actual Study Start Date : October 6, 2017
Actual Primary Completion Date : October 5, 2018
Actual Study Completion Date : October 5, 2018

Arm Intervention/treatment
Experimental: Cytisine 1.5 mg

Multiple doses of 1.5 mg cytisine administered per 25-day schedule:

  • Days 1-3 (6 times daily)
  • Days 4-12 (5 times daily)
  • Days 13-16 (4 times daily)
  • Days 17-20 (3 times daily)
  • Days 21-24 (2 times daily)
  • Day 25 (Once daily)
Drug: Cytisine
film-coated tablets; depending on arm assignment, 1 or 2 tablets to be taken with 240 mL water for each dose
Other Name: Tabex

Experimental: Cytisine 3.0 mg

Multiple doses of 3.0 mg cytisine administered per 25-day schedule:

  • Days 1-3 (6 times daily)
  • Days 4-12 (5 times daily)
  • Days 13-16 (4 times daily)
  • Days 17-20 (3 times daily)
  • Days 21-24 (2 times daily)
  • Day 25 (Once daily)
Drug: Cytisine
film-coated tablets; depending on arm assignment, 1 or 2 tablets to be taken with 240 mL water for each dose
Other Name: Tabex




Primary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: after the first dose and the last dose on Day 1; after the first dose on Day 21; after the last dose on Days 2, 3, 12, 16, 20, 24; and after the morning dose on Day 25 ]
  2. Time of Occurrence of Cmax (Tmax) [ Time Frame: after the first dose and the last dose on Day 1, after the last dose on Days 2, 3, 12, 16, 20, 24 and after the morning dose on Day 25 ]
  3. Minimum Observed Plasma Concentration (Cmin) [ Time Frame: after the first dose on Days 4, 13, 17, 21 and 25 ]
  4. Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Sampling Time (AUC0-t) [ Time Frame: after the administration of the final dose of cytisine on Day 25 ]
  5. Total AUC From Time Zero to Infinity (AUC0-∞) [ Time Frame: after the administration of the final dose of cytisine on Day 25 ]
  6. Residual Area or Percentage of Extrapolated Part for the Calculation of AUC0-∞ (%AUC) [ Time Frame: after the administration of the final dose of cytisine on Day 25 ]
  7. Apparent Terminal Elimination Rate Constant (λz) [ Time Frame: after the administration of the final dose of cytisine on Day 25 ]
  8. Apparent Terminal Elimination Half-Life (t1/2) [ Time Frame: after the administration of the final dose of cytisine on Day 25 ]
  9. Number of Cigarettes Smoked Daily During Treatment and at Day 26 [ Time Frame: Day 1 through Day 26 ]
  10. Change from Baseline in Number of Cigarettes Smoked Daily up to Day 26 [ Time Frame: Day 1 through Day 26 ]
  11. Change from Baseline in Expired Air Carbon Monoxide (CO) up to Day 26 [ Time Frame: Baseline, Days 4, 13, 17, 21, 26 ]
  12. Number of Participants Who Ceased or Continued Smoking on Day 26 [ Time Frame: Day 26 ]
  13. Change From Baseline Over Time in Urine Cotinine [ Time Frame: Baseline, Days 4, 13, 17, 21, 26 ]
  14. Change From Baseline Over Time in Tobacco Craving Questionnaire - Short Form (TCQ-SF) Score: Emotionality [ Time Frame: Baseline (Day -1), Days 4, 13, 17, 21, 26 ]
  15. Change From Baseline Over Time in TCQ-SF Score: Expectancy [ Time Frame: Baseline (Day -1), Days 4, 13, 17, 21, 26 ]
  16. Change From Baseline Over Time in TCQ-SF Score: Compulsivity [ Time Frame: Baseline (Day -1), Days 4, 13, 17, 21, 26 ]
  17. Change From Baseline Over Time in TCQ-SF Score: Purposefulness [ Time Frame: Baseline (Day -1), Days 4, 13, 17, 21, 26 ]
  18. Change From Baseline Over Time in TCQ-SF Score: Total Score [ Time Frame: Baseline (Day -1), Days 4, 13, 17, 21, 26 ]

Secondary Outcome Measures :
  1. Cytisine Amount Excreted in Urine Over Time (Ae0-24h) [ Time Frame: after the administration of the final dose of cytisine on Day 25 ]
  2. Percent of Drug Excreted in Urine (Ae%) [ Time Frame: Day 1 and Day 25: pre-dose and 0-24 hours post-dose ]
  3. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs [ Time Frame: From first dose of study drug through Day 26 plus 6-8 days ]
  4. Number of Participants With Clinically Significant Values in Baseline in Biochemistry, Hematology, and Urinalysis [ Time Frame: up to Day 26 ]
  5. Number of Participants With Clinically Significant Values in Vital Signs and Physical Examinations [ Time Frame: up to Day 26 ]
  6. Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Parameters [ Time Frame: up to Day 26 ]
  7. Number of Participants With Holter ECG Outlier Values [ Time Frame: up to Day 26 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Regular moderate cigarette smokers (minimum 10 cigarettes per day) who want to stop smoking.
  2. Urine cotinine >500 ng/mL.
  3. Expired air carbon monoxide (CO) > 11 parts per million (no cigarette 1 hour before test).
  4. Healthy males and females 18-65+ years of age.

    1. 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.
    2. 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.
    3. 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.
  5. Subject with no clinically significant abnormal serum biochemistry, haematology and urine examination values within 28 days before the first dose of cytisine.
  6. 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).
  7. Subject with negative human immunodeficiency virus (HIV), hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results.
  8. 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.
  9. Subject with no clinically significant abnormalities in vital signs (systolic blood pressure between 90-150 mmHg (age 18-65) and 90-160 mmHg (age >65), 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.
  10. Subject must be available to complete the study (including in-clinic stays and post study follow-up) and comply with study restrictions.
  11. Subject must provide written informed consent to participate in the study.

Exclusion Criteria:

  1. Treatment with smoking cessation medications (bupropion, varenicline, any nicotine replacement therapy) within 8 weeks of first dose of cytisine.
  2. Use of other forms of nicotine (e-cigarettes, smokeless tobacco) within 8 weeks of first dose of cytisine or are planning to use these products during study.
  3. Known hypersensitivity/allergy reaction to varenicline, other cytisine-derivatives or any of the excipients in the Tabex formulation.
  4. History of severe hypersensitivity reactions to any other drugs.
  5. Current treatment with antihypertensive medicinal products, statins, tuberculostatics, cholinomimetics or anticholinesterase medicinal products.
  6. 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).
  7. Female subjects who are breast feeding.
  8. Difficulty in donating blood on either arm or known history.
  9. History of alcoholism or drug abuse within last 2 years.
  10. 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 Principal Investigator the medication will not interfere with the study procedures or compromise subject safety.
  11. Participated in any investigational drug clinical trial within the previous 3 months or a marketed drug trial within the previous 30 days prior to randomisation on Day 1.
  12. 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.
  13. Inability to communicate well with Principal Investigator or designees (i.e., language problem, poor mental development or impaired cerebral function).
  14. Any other condition that the Principal Investigator considers making the subject unsuitable for this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03303911


Locations
Layout table for location information
United Kingdom
Simbec Research Ltd
Cardiff, United Kingdom, CF11 9AB
Sponsors and Collaborators
Achieve Life Sciences
Investigators
Layout table for investigator information
Principal Investigator: Annelize Koch, MD Simbec Research Ltd (Simbec)

Layout table for additonal information
Responsible Party: Achieve Life Sciences
ClinicalTrials.gov Identifier: NCT03303911     History of Changes
Other Study ID Numbers: ACH-CYT-02
First Posted: October 6, 2017    Key Record Dates
Last Update Posted: May 31, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No