A Single Dose-escalation Study of Cytisine in Adult Smokers

NCT ID: NCT03848208

Last Updated: 2020-09-17

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

74 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-28

Study Completion Date

2019-09-12

Brief Summary

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The objectives of this study are:

1. To assess the tolerability and safety of cytisine as a single oral dose.
2. To define the Cmax levels associated to the occurrence of dose-limiting adverse events.

Detailed Description

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Conditions

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Smoking Cessation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Cohort 1: Cytisine 6.0 mg

Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Group Type EXPERIMENTAL

cytisine

Intervention Type DRUG

cytisine film-coated oral tablet

Cohort 1: Placebo

Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

matching placebo oral tablet

Cohort 2: Cytisine 9.0 mg

Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Group Type EXPERIMENTAL

cytisine

Intervention Type DRUG

cytisine film-coated oral tablet

Cohort 2: Placebo

Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

matching placebo oral tablet

Cohort 3: Cytisine 12.0 mg

Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Group Type EXPERIMENTAL

cytisine

Intervention Type DRUG

cytisine film-coated oral tablet

Cohort 3: Placebo

Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

matching placebo oral tablet

Cohort 4: Cytisine 15.0 mg

Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Group Type EXPERIMENTAL

cytisine

Intervention Type DRUG

cytisine film-coated oral tablet

Cohort 4: Placebo

Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

matching placebo oral tablet

Cohort 5: Cytisine 18.0 mg

Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Group Type EXPERIMENTAL

cytisine

Intervention Type DRUG

cytisine film-coated oral tablet

Cohort 5: Placebo

Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

matching placebo oral tablet

Cohort 6: Cytisine 21.0 mg

Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Group Type EXPERIMENTAL

cytisine

Intervention Type DRUG

cytisine film-coated oral tablet

Cohort 6: Placebo

Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

matching placebo oral tablet

Cohort 7: Cytisine 24.0 mg

Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Group Type EXPERIMENTAL

cytisine

Intervention Type DRUG

cytisine film-coated oral tablet

Cohort 7: Placebo

Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

matching placebo oral tablet

Cohort 8: Cytisine 27.0 mg

Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Group Type EXPERIMENTAL

cytisine

Intervention Type DRUG

cytisine film-coated oral tablet

Cohort 8: Placebo

Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

matching placebo oral tablet

Cohort 9: Cytisine 30.0 mg

Cytisine will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Group Type EXPERIMENTAL

cytisine

Intervention Type DRUG

cytisine film-coated oral tablet

Cohort 9: Placebo

Placebo will be administered in the morning, orally, with 240 mL of water, after fasting overnight for at least 10 hours.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

matching placebo oral tablet

Interventions

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cytisine

cytisine film-coated oral tablet

Intervention Type DRUG

placebo

matching placebo oral tablet

Intervention Type DRUG

Other Intervention Names

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Tabex cytisinicline

Eligibility Criteria

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Inclusion Criteria

Subjects must meet ALL of the following criteria to be eligible for inclusion into the study:

1. Free written informed consent prior to any procedure required by the study.
2. Male or female subjects, age ≥18 years, at the time of signing the informed consent.
3. Current daily cigarette smokers (averaging at least 10 cigarettes per day in the past 30 days).
4. Expired air carbon monoxide (CO) ≥10 ppm.
5. Able to swallow multiple tablets at one time.
6. Able to fully understand, comply with all study requirements.

Exclusion Criteria

1. Known hypersensitivity to cytisine or any of the excipients.
2. Known severe hypersensitivity to any other drug.
3. Positive urinary drugs of abuse screen, determined within 28 days before cytisine/placebo dosing.
4. Positive ethanol breath test.
5. Clinically significant abnormal serum chemistry, hematology, coagulation or urinalysis values within 28 days of randomization (i.e. requiring treatment or monitoring).
6. Clinically significant abnormalities in 12-lead echocardiogram (ECG) determined after minimum of 5 minutes in supine position within 28 days of randomization (i.e. requiring treatment or further assessment).
7. Body Mass Index (BMI) classification for being underweight (\<18.5 kg/m2) or having ≥Class 2 obesity (≥35 kg/m2).
8. History of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident, cardiac arrhythmia, or hospitalization for congestive heart failure.
9. Blood pressure ≥160/100 mmHg, measured on the dominant arm, after at least 3 minutes in supine position.
10. Creatinine clearance (CrCl) \<80 mL/min (estimated with the Cockroft-Gault equation).
11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.0 x the upper limit of normal (ULN).
12. Any inability to comply with study restrictions (See Section 9)
13. Any inability or difficulty in fasting.
14. Difficulty in donating blood on either arm.
15. If woman of childbearing potential, positive result in serum beta-human chorionic gonadotropin (hCG) pregnancy test.
16. Women who are breast-feeding.
17. Subjects who do not agree to use acceptable methods of birth control during the study (See Section 9.4).
18. Participation in a clinical study with an investigational drug within the previous 2 months.
19. Participation in more than 2 clinical trials within the previous 12 months.
20. Any other reason that the investigator views the subject should not participate or would be unable to fulfill the requirements for the study.

21. Any recent disease or condition or treatment that, according to the Investigator, would put the subject at undue risk due to study participation.
22. Positive urinary drugs of abuse screen.
23. Positive ethanol breath test.
24. If female of childbearing potential, positive result in urine beta-hCG pregnancy test.
25. Any other reason that the investigator views the subject should not participate or would be unable to fulfill the requirements for the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Achieve Life Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marlene Fonseca, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital da Prelada

Locations

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BlueClinical

Porto, , Portugal

Site Status

Countries

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Portugal

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2018-003344-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ACH-CYT-08

Identifier Type: -

Identifier Source: org_study_id

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