Smoking CessationPhase 1/2NCT03303911

A Pharmacokinetic and Pharmacodynamic Evaluation of Cytisine in Healthy Smokers

A Phase 1/2 study testing Cytisine in people with Smoking Cessation, run by Achieve Life Sciences at 1 site in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

The primary objectives of this study are: To evaluate the pharmacokinetic (PK) parameters during repeat dosing of 1.5 mg or 3.0 mg cytisine when administered as the commercial 25-day schedule. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Smoking Cessation
What is being tested?: Cytisine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 26 participants
Where: 1 siteUnited Kingdom
Study dates: 6 Oct 2017to 5 Oct 2018
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 14Show fewer

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.
Subject with no clinically significant abnormal serum biochemistry, haematology and urine examination values within 28 days before the first dose of cytisine.
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).
Subject with negative human immunodeficiency virus (HIV), hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results.
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.
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.
Subject must be available to complete the study (including in-clinic stays and post study follow-up) and comply with study restrictions.
Subject must provide written informed consent to participate in the study.

Who cannot join

Treatment with smoking cessation medications (bupropion, varenicline, any nicotine replacement therapy) within 8 weeks of first dose of cytisine.
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.
Known hypersensitivity/allergy reaction to varenicline, other cytisine-derivatives or any of the excipients in the Tabex formulation.
History of severe hypersensitivity reactions to any other drugs.
Current treatment with antihypertensive medicinal products, statins, tuberculostatics, cholinomimetics or anticholinesterase medicinal products.
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).

Show all 14Show fewer

Female subjects who are breast feeding.
Difficulty in donating blood on either arm or known history.
History of alcoholism or drug abuse within last 2 years.
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.
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.
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.
Inability to communicate well with Principal Investigator or designees (i.e., language problem, poor mental development or impaired cerebral function).
Any other condition that the Principal Investigator considers making the subject unsuitable for this study.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Simbec Research Ltd
Cardiff, CF11 9AB

Other trials in United Kingdom

About this study

Official title: Repeat-Dose Pharmacokinetic and Pharmacodynamic Evaluation of Cytisine in Healthy Smokers

The primary objectives of this study are:

To evaluate the pharmacokinetic (PK) parameters during repeat dosing of 1.5 mg or 3.0 mg cytisine when administered as the commercial 25-day schedule.
To evaluate the pharmacodynamic (PD) effects (e.g., reduction in smoking) with repeat dosing of 1.5 mg or 3.0 mg cytisine when administered as the commercial 25-day schedule.

Conditions: Smoking Cessation
Being tested: Cytisine
Medical subject headings: Smoking Cessation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CytisineDrug
Also called Tabex
film-coated tablets; depending on arm assignment, 1 or 2 tablets to be taken with 240 mL water for each dose

Study groups in NCT03303911
Study group	Role	What they receive
Cytisine 1.5 mg	Experimental	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) Receives: Drug: Cytisine
Cytisine 3.0 mg	Experimental	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) Receives: Drug: Cytisine

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Observed Plasma Concentration (Cmax)
Measured: 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
Time of Occurrence of Cmax (Tmax)
Measured: 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
Minimum Observed Plasma Concentration (Cmin)
Measured: after the first dose on Days 4, 13, 17, 21 and 25
Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Sampling Time (AUC0-t)
Measured: after the administration of the final dose of cytisine on Day 25
Total AUC From Time Zero to Infinity (AUC0-∞)
Measured: after the administration of the final dose of cytisine on Day 25
Residual Area or Percentage of Extrapolated Part for the Calculation of AUC0-∞ (%AUC)
Measured: after the administration of the final dose of cytisine on Day 25
Apparent Terminal Elimination Rate Constant (λz)
Measured: after the administration of the final dose of cytisine on Day 25
Apparent Terminal Elimination Half-Life (t1/2)
Measured: after the administration of the final dose of cytisine on Day 25
Number of Cigarettes Smoked Daily During Treatment and at Day 26
Measured: Day 1 through Day 26
Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26
Measured: Baseline, Day 1 through Day 26
Change From Baseline in Expired Air CO up to Day 26
Measured: Baseline, Days 4, 13, 17, 21, 26
Number of Participants Who Ceased or Continued Smoking on Day 26
A status of "ceased smoking" is defined as not having smoked any cigarettes for the past 24 hours on Day 26 and having an expired CO level <10 ppm on Day 26.
Measured: Day 26
Change From Baseline Over Time in Urine Cotinine
Measured: Baseline, Days 4, 13, 17, 21, 26
Change From Baseline Over Time in TCQ-SF Score: Emotionality
The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly disagree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Emotionality scores may range from 3 to 21, with lower scores indicating weaker emotional signs of tobacco craving.
Measured: Baseline (Day -1), Days 4, 13, 17, 21, 26
Change From Baseline Over Time in TCQ-SF Score: Expectancy
The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly disagree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Expectancy scores may range from 3 to 21, with lower scores indicating less positive expectations about smoking.
Measured: Baseline (Day -1), Days 4, 13, 17, 21, 26
Change From Baseline Over Time in TCQ-SF Score: Compulsivity
The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly agree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Compulsivity scores may range from 3 to 21, with lower scores indicating compulsion to smoke was a lesser component of tobacco craving.
Measured: Baseline (Day -1), Days 4, 13, 17, 21, 26
Change From Baseline Over Time in TCQ-SF Score: Purposefulness
The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly disagree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Purposefulness scores may range from 3 to 21, with lower scores indicating stronger ability to not smoke.
Measured: Baseline (Day -1), Days 4, 13, 17, 21, 26
Change From Baseline Over Time in TCQ-SF Score: Total Score
The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly disagree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Total scores may range from 12 to 84, with lower scores indicating lower tobacco craving.
Measured: Baseline (Day -1), Days 4, 13, 17, 21, 26

Secondary outcomes (7)

Cytisine Amount Excreted in Urine Over Time (Ae0-24h)
Measured: Day 1 (6 times daily at 2-hour intervals); after the administration of the single dose of cytisine on Day 25
Percent of Drug Excreted in Urine (Ae%)
Measured: Day 1 (6 times daily at 2-hour intervals); after the administration of the single dose of cytisine on Day 25
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuation of Study Drug Due to TEAEs
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with the treatment. A serious adverse event (SAE) is defined as an AE that results in any of the following: results in death; is life-threatening; requires hospitalisation or prolongs existing inpatient's hospitalisation; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; is an important medical event which requires medical intervention to prevent any of the above outcomes.TEAEs are defined as AEs not present prior to first administration of investigational product, or AEs present before first administration of investigational product that worsen after the participant receives the first dose of investigational product.
Measured: From first dose of study drug through Day 26 plus 6-8 days
Number of Participants With Clinically Significant Values in Biochemistry, Hematology, and Urinalysis
Measured: up to Day 26
Number of Participants With Clinically Significant Values in Vital Signs and Physical Examinations
Measured: up to Day 26
Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Parameters
Measured: up to Day 26
Number of Participants With Holter ECG Outlier Values
Based on the mean of the triplicate recordings at each time point. Increase (↑)/decrease (↓) calculated from Baseline (BL), defined as the mean of all recordings taken prior to dosing on Day 1 (i.e. -30 minutes and -15 minutes). A participant with multiple occurrences of an event is counted only once per event.
Measured: on Day 1 and Day 25 at 30 and 15 minutes prior to the first dose and 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours post dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Oct 20175 Oct 2018

First posted6 Oct 2017
Study start6 Oct 2017
Primary completion5 Oct 2018
Study completion5 Oct 2018

Why it stopped: It has been difficult to recruit participants meeting study entry criteria that are \>65 years of age and not for any safety reasons.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Smoking CessationStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03303911
Sponsor's protocol ID: ACH-CYT-02
Status last verified: Oct 2019
First submitted: 28 Sep 2017
Last updated: 21 Oct 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Scalable TELeheaLth Cancer CARe: The STELLAR Program to Treat Cancer Risk Behaviors
Obesity, Smoking Cessation
Not yet recruiting
Smoking Cessation Program for Lao People With HIV
Smoking Cessation, HIV
RecruitingPhase 3
Studying NMDA and Sigma-1 in Smoking Cessation Treatment (SUMMIT)
Smoking Cessation
Not yet recruiting
Impacto 2.0: Mobile Smoking Cessation Across Texas
Cigarette Smoking, Smoking Cessation
Not yet recruitingObservational study
PROMETHEE: A Shared Interregional Tele-Tobacco Cessation Platform Embedded Within the IMPULSION Lung Cancer Screening Program
Smoking Cessation, Lung Cancer Screening

All Smoking Cessation trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Repeat-Dose Pharmacokinetic and Pharmacodynamic Evaluation of Cytisine in Healthy Smokers
ClinicalTrials.gov ID: NCT03303911
Acronym / sponsor ID: ACH-CYT-02
Conditions: Smoking Cessation
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: It has been difficult to recruit participants meeting study entry criteria that are \>65 years of age and not for any safety reasons.
Enrolment: 26 participants (actual)
Lead sponsor: Achieve Life SciencesIndustry (pharma, biotech, devices)
Study start: 6 Oct 2017 (actual)
Primary completion: 5 Oct 2018 (actual)
Study completion: 5 Oct 2018 (actual)
First posted: 6 Oct 2017 (actual)
Results: Posted 21 Oct 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The primary objectives of this study are:

To evaluate the pharmacokinetic (PK) parameters during repeat dosing of 1.5 mg or 3.0 mg cytisine when administered as the commercial 25-day schedule.
To evaluate the pharmacodynamic (PD) effects (e.g., reduction in smoking) with repeat dosing of 1.5 mg or 3.0 mg cytisine when administered as the commercial 25-day schedule.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Cytisine 1.5 mg	Experimental	Drug: CytisineMultiple 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)
Cytisine 3.0 mg	Experimental	Drug: CytisineMultiple 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)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

Regular moderate cigarette smokers (minimum 10 cigarettes per day) who want to stop smoking.
Urine cotinine >500 ng/mL.
Expired air carbon monoxide (CO) > 11 parts per million (no cigarette 1 hour before test).
Healthy males and females 18-65+ years of age.
Subject with no clinically significant abnormal serum biochemistry, haematology and urine examination values within 28 days before the first dose of cytisine.

Key exclusion criteria (14 listed)

Treatment with smoking cessation medications (bupropion, varenicline, any nicotine replacement therapy) within 8 weeks of first dose of cytisine.
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.
Known hypersensitivity/allergy reaction to varenicline, other cytisine-derivatives or any of the excipients in the Tabex formulation.
History of severe hypersensitivity reactions to any other drugs.
Current treatment with antihypertensive medicinal products, statins, tuberculostatics, cholinomimetics or anticholinesterase medicinal products.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CytisineAlso: Tabexfilm-coated tablets; depending on arm assignment, 1 or 2 tablets to be taken with 240 mL water for each dose	Drug	Cytisine 1.5 mg, Cytisine 3.0 mg

Primary outcome

Maximum Observed Plasma Concentration (Cmax)
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
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
Minimum Observed Plasma Concentration (Cmin)
Time frame: after the first dose on Days 4, 13, 17, 21 and 25
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
Total AUC From Time Zero to Infinity (AUC0-∞)
Time frame: after the administration of the final dose of cytisine on Day 25
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
Apparent Terminal Elimination Rate Constant (λz)
Time frame: after the administration of the final dose of cytisine on Day 25
Apparent Terminal Elimination Half-Life (t1/2)
Time frame: after the administration of the final dose of cytisine on Day 25
Number of Cigarettes Smoked Daily During Treatment and at Day 26
Time frame: Day 1 through Day 26
Change From Baseline in Number of Cigarettes Smoked Daily up to Day 26
Time frame: Baseline, Day 1 through Day 26
Change From Baseline in Expired Air CO up to Day 26
Time frame: Baseline, Days 4, 13, 17, 21, 26
Number of Participants Who Ceased or Continued Smoking on Day 26
Time frame: Day 26
A status of "ceased smoking" is defined as not having smoked any cigarettes for the past 24 hours on Day 26 and having an expired CO level <10 ppm on Day 26.
Change From Baseline Over Time in Urine Cotinine
Time frame: Baseline, Days 4, 13, 17, 21, 26
Change From Baseline Over Time in TCQ-SF Score: Emotionality
Time frame: Baseline (Day -1), Days 4, 13, 17, 21, 26
The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly disagree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Emotionality scores may range from 3 to 21, with lower scores indicating weaker emotional signs of tobacco craving.
Change From Baseline Over Time in TCQ-SF Score: Expectancy
Time frame: Baseline (Day -1), Days 4, 13, 17, 21, 26
The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly disagree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Expectancy scores may range from 3 to 21, with lower scores indicating less positive expectations about smoking.
Change From Baseline Over Time in TCQ-SF Score: Compulsivity
Time frame: Baseline (Day -1), Days 4, 13, 17, 21, 26
The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly agree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Compulsivity scores may range from 3 to 21, with lower scores indicating compulsion to smoke was a lesser component of tobacco craving.
Change From Baseline Over Time in TCQ-SF Score: Purposefulness
Time frame: Baseline (Day -1), Days 4, 13, 17, 21, 26
The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly disagree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Purposefulness scores may range from 3 to 21, with lower scores indicating stronger ability to not smoke.
Change From Baseline Over Time in TCQ-SF Score: Total Score
Time frame: Baseline (Day -1), Days 4, 13, 17, 21, 26
The TCQ-SF is a 12-item questionnaire that assesses 4 components of tobacco craving: emotionality (3 items), expectancy (3 items), compulsivity (3 items) and purposefulness (3 items). Responses to each item are scored from 1 (strongly disagree) through 7 (strongly disagree). Component scores are defined as the sum of the scores within each component. The total score is defined as the sum of the 4 component scores. Total scores may range from 12 to 84, with lower scores indicating lower tobacco craving.

7 secondary outcomes

Cytisine Amount Excreted in Urine Over Time (Ae0-24h)
Time frame: Day 1 (6 times daily at 2-hour intervals); after the administration of the single dose of cytisine on Day 25
Percent of Drug Excreted in Urine (Ae%)
Time frame: Day 1 (6 times daily at 2-hour intervals); after the administration of the single dose of cytisine on Day 25
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuation of Study Drug Due to TEAEs
Time frame: From first dose of study drug through Day 26 plus 6-8 days
Number of Participants With Clinically Significant Values in Biochemistry, Hematology, and Urinalysis
Time frame: up to Day 26
Number of Participants With Clinically Significant Values in Vital Signs and Physical Examinations
Time frame: up to Day 26
Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Parameters
Time frame: up to Day 26
Number of Participants With Holter ECG Outlier Values
Time frame: on Day 1 and Day 25 at 30 and 15 minutes prior to the first dose and 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours and 24 hours post dose

Results and safety

Results posted to the registry on 21 Oct 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cytisine 1.5 mg	13	13
Cytisine 3.0 mg	13	13

Primary outcome: Maximum Observed Plasma Concentration (Cmax)

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. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Cytisine 1.5 mg n = 13	Cytisine 3.0 mg n = 13
Day 1, first dose	21.1 (24.8)	40.0 (26.8)
Day 1, last dose	33.8 (20.0)	81.4 (30.1)
Day 2, last dose	32.9 (22.3)	85.1 (20.9)
Day 3, last dose	35.9 (21.7)	88.1 (19.3)
Day 12, last dose	29.9 (24.9)	69.9 (31.5)
Day 16, last dose	23.7 (31.4)	50.5 (26.5)
Day 20, last dose	23.0 (22.1)	49.7 (30.9)
Day 24, last dose	16.0 (28.3)	42.0 (33.6)

Population analysed: Pharmacokinetic (PK) Set: All randomized participants who completed all cytisine dosing on Days 1-3, completed \>90% cytisine dosing on Days 4-25 and complied with protocol-specified criteria. Participants with an assessment at given timepoint.

Primary outcome: 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. Median (Full Range). Unit: hours

Measure	Cytisine 1.5 mg n = 13	Cytisine 3.0 mg n = 13
Day 1, first dose	0.500 (0.500 to 0.750)	0.750 (0.500 to 1.00)
Day 1, last dose	1.00 (0.00 to 2.50)	1.00 (0.00 to 2.50)
Day 2, last dose	1.00 (0.00 to 3.50)	1.00 (0.00 to 3.50)
Day 3, last dose	1.00 (0.500 to 3.00)	1.00 (0.00 to 2.03)
Day 12, last dose	1.00 (0.00 to 3.05)	1.02 (0.00 to 2.00)
Day 16, last dose	2.50 (0.00 to 4.02)	2.00 (1.00 to 6.50)
Day 20, last dose	1.50 (1.00 to 5.50)	1.00 (0.00 to 6.50)
Day 24, last dose	2.00 (1.00 to 4.00)	1.00 (1.00 to 3.00)

Population analysed: PK Set: All randomized participants who completed all cytisine dosing on Days 1-3, completed \>90% cytisine dosing on Days 4-25 and complied with protocol-specified criteria. Participants with an assessment at given time point.

Primary outcome: Minimum Observed Plasma Concentration (Cmin)

Time frame: after the first dose on Days 4, 13, 17, 21 and 25. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Cytisine 1.5 mg n = 13	Cytisine 3.0 mg n = 13
Day 4, first dose	5.36 (47.7)	13.2 (27.4)
Day 13, first dose	5.16 (48.2)	12.6 (33.0)
Day 17, first dose	4.19 (64.7)	8.50 (38.3)
Day 21, first dose	3.13 (83.4)	6.34 (39.0)
Day 25	3.16 (188.9)	3.74 (42.4)

Primary outcome: 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. Geometric mean (Geometric Coefficient of Variation). Unit: h*ng/mL

Measure	Cytisine 1.5 mg n = 12	Cytisine 3.0 mg n = 13
Value	67.0 (27.4)	185 (32.3)

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose of study drug through Day 26 plus 6-8 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cytisine 1.5 mg	0 of 13 (0%)	9 of 13 (69.2%)	0 of 13
Cytisine 3.0 mg	0 of 13 (0%)	9 of 13 (69.2%)	0 of 13

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Smoking Cessation

Recruiting
Scalable TELeheaLth Cancer CARe: The STELLAR Program to Treat Cancer Risk Behaviors
Obesity, Smoking Cessation
Not yet recruiting
Smoking Cessation Program for Lao People With HIV
Smoking Cessation, HIV
RecruitingPhase 3
Studying NMDA and Sigma-1 in Smoking Cessation Treatment (SUMMIT)
Smoking Cessation
Not yet recruiting
Impacto 2.0: Mobile Smoking Cessation Across Texas
Cigarette Smoking, Smoking Cessation
Not yet recruitingObservational study
PROMETHEE: A Shared Interregional Tele-Tobacco Cessation Platform Embedded Within the IMPULSION Lung Cancer Screening Program
Smoking Cessation, Lung Cancer Screening

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Annelize Koch, MD principal investigator

Simbec Research Ltd (Simbec)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cytisine in people with Smoking Cessation, run by Achieve Life Sciences at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Observed Plasma Concentration (Cmax) (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). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03303911.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2019; AzTrials last refreshed its copy on 8 Nov 2026.