Smoking CessationPhase 1NCT03509948

A Study in Healthy Smokers to Investigate the Effect of Food on the Bioavailability of Cytisine in a New Formulation

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

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This will be an open-label, randomised, 2-treatment period, single-dose crossover study to determine the comparative bioavailability and renal elimination following single-dose administration of 3.0 mg cytisine in healthy smokers under fed and fasted conditions. Read more about this study

Who is it for?: Ages 18 to 55 years
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: 13 participants
Where: 1 siteUnited Kingdom
Study dates: 27 Apr 2018to 12 Jun 2018
Phase: Phase 1
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 to 55 years
All sexes
No healthy volunteers
Adult

Who may be able to join

To be Confirmed at Screening
Subject is current cigarette smoker.
Healthy males and females between 18 and 55 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.
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.

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Subject with a body mass index (BMI) of 23-28 kg/m^2. BMI = body weight in kg / [height in m^2].
Subject with no clinically significant abnormal serum biochemistry or haematology 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 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 90-140 mmHg, diastolic blood pressure (DBP) between 50 and 90 mmHg, and pulse rate (PR) between 40-100 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 post study follow-up) and comply with study restrictions.
Subject must provide written informed consent to participate in the study.
To be Re-Confirmed Prior to Dosing
Subject continues to meet all screening inclusion criteria (before the cytisine dose).
Subject has a negative urinary drugs of abuse screen (including alcohol).
Female subject has a negative urine pregnancy test.

Who cannot join

To be Confirmed at Screening
Known hypersensitivity/allergy reaction to varenicline, other cytisine-derivatives or any of the excipients in the Tabex formulation (cellulose, talc, magnesium).
History of severe hypersensitivity reactions to any other drugs.
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).
Female subjects who are breast feeding.
Difficulty in donating blood on either arm or known history.

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History of alcoholism or drug abuse within last 2 years.
Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 14 days (or 5 half-lives, whichever is longer) prior to the cytisine dose, unless in the opinion of the 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 randomization on Day 1 of Period 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 cytisine dose.
Any inability or difficulty in fasting.
Inability to communicate well with Investigators (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.
To be Re-Confirmed Prior to Dosing:
Development of any exclusion criteria since screening.
Use of prescription or 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.
Participation in a clinical study since the screening visit.
Donation of 450 mL or more blood since the screening visit.

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: A Phase 1 Open Label, Randomized, Two-Way Crossover Study in Healthy Smokers to Investigate the Effect of Food on the Bioavailability of Cytisine in a New Formulation

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
cytisine 1.5 mg film-coated tablets

Study groups in NCT03509948
Study group	Role	What they receive
Schedule A: Fed Then Fasted	Experimental	Schedule A (6 participants): * Period 1: cytisine (2 x 1.5 mg tablets) will be administered 30 minutes after the start of a high fat breakfast (fed state) * Period 2: cytisine (2 x 1.5 mg tablets) will be administered after an overnight fast of at least 10 hours (fasting state) Receives: Drug: cytisine
Schedule B: Fasted Then Fed	Experimental	Schedule B (6 participants): * Period 1: cytisine (2 x 1.5 mg tablets) will be administered after an overnight fast of at least 10 hours (fasting state) * Period 2: cytisine (2 x 1.5 mg tablets) will be administered 30 minutes after the start of a high fat breakfast (fed state) Receives: Drug: cytisine

What is being measured

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

Maximum Concentration (Cmax)
Measured: Pre-dose (within 60 minutes prior to dosing), up to 48 hours post-dose on Days 1-5
Area Under the Concentration Versus Time Curve (AUC) Extrapolated to Infinity (AUC0-∞)
Measured: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5
Total Cytisine Excreted in Urine Over 48 Hours (Ae0-48h)
Measured: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5
Percent of Total Cytisine Excreted in Urine Over 48 Hours (Ae0-48h%)
Measured: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5

Secondary outcomes (5)

Time to Cmax (Tmax)
Measured: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5
Terminal Elimination Half-Life (T1/2)
Measured: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5
AUC From Time of Dosing to Last Measurable Concentration (AUC0-t)
Measured: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Withdrawal of Study Drug
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant 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 death; is life-threatening; requires hospitalization or prolongs existing inpatient hospitalization; 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. Relationship of the TEAE to study drug was evaluated as: definite, probably, possible, unlikely, or not related.
Measured: Baseline (Day 0) through Day 5 plus 6-8 days
Number of Participants With Clinically Significant Biochemistry, Hematology, Urinalysis, and/or 12-lead Electrocardiogram (ECG) Values
Measured: Screening through Day 5

Timeline

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

27 Apr 201812 Jun 2018

First posted27 Apr 2018
Study start27 Apr 2018
Primary completion10 Jun 2018
Study completion12 Jun 2018

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
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03509948
Sponsor's protocol ID: ACH-CYT-07
Status last verified: Sep 2019
First submitted: 17 Apr 2018
Last updated: 24 Sep 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

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Study at a glance

From the registry record, last updated by the sponsor on 24 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1 Open Label, Randomized, Two-Way Crossover Study in Healthy Smokers to Investigate the Effect of Food on the Bioavailability of Cytisine in a New Formulation
ClinicalTrials.gov ID: NCT03509948
Acronym / sponsor ID: ACH-CYT-07
Conditions: Smoking Cessation
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 13 participants (actual)
Lead sponsor: Achieve Life SciencesIndustry (pharma, biotech, devices)
Study start: 27 Apr 2018 (actual)
Primary completion: 10 Jun 2018 (actual)
Study completion: 12 Jun 2018 (actual)
First posted: 27 Apr 2018 (actual)
Results: Posted 12 Sep 2019

Clinical summary

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

Study design

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

Arm	Type	Receives
Schedule A: Fed Then Fasted	Experimental	Drug: cytisineSchedule A (6 participants): * Period 1: cytisine (2 x 1.5 mg tablets) will be administered 30 minutes after the start of a high fat breakfast (fed state) * Period 2: cytisine (2 x 1.5 mg tablets) will be administered after an overnight fast of at least 10 hours (fasting state)
Schedule B: Fasted Then Fed	Experimental	Drug: cytisineSchedule B (6 participants): * Period 1: cytisine (2 x 1.5 mg tablets) will be administered after an overnight fast of at least 10 hours (fasting state) * Period 2: cytisine (2 x 1.5 mg tablets) will be administered 30 minutes after the start of a high fat breakfast (fed state)

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (18 listed)

To be Confirmed at Screening
Subject is current cigarette smoker.
Healthy males and females between 18 and 55 years of age.
Subject with a body mass index (BMI) of 23-28 kg/m^2. BMI = body weight in kg / [height in m^2].
Subject with no clinically significant abnormal serum biochemistry or haematology values within 28 days before the first dose of cytisine.

Key exclusion criteria (18 listed)

To be Confirmed at Screening
Known hypersensitivity/allergy reaction to varenicline, other cytisine-derivatives or any of the excipients in the Tabex formulation (cellulose, talc, magnesium).
History of severe hypersensitivity reactions to any other drugs.
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).
Female subjects who are breast feeding.

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: Tabexcytisine 1.5 mg film-coated tablets	Drug	Schedule A: Fed Then Fasted, Schedule B: Fasted Then Fed

Primary outcome

Maximum Concentration (Cmax)
Time frame: Pre-dose (within 60 minutes prior to dosing), up to 48 hours post-dose on Days 1-5
Area Under the Concentration Versus Time Curve (AUC) Extrapolated to Infinity (AUC0-∞)
Time frame: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5
Total Cytisine Excreted in Urine Over 48 Hours (Ae0-48h)
Time frame: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5
Percent of Total Cytisine Excreted in Urine Over 48 Hours (Ae0-48h%)
Time frame: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5

5 secondary outcomes

Time to Cmax (Tmax)
Time frame: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5
Terminal Elimination Half-Life (T1/2)
Time frame: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5
AUC From Time of Dosing to Last Measurable Concentration (AUC0-t)
Time frame: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Withdrawal of Study Drug
Time frame: Baseline (Day 0) through Day 5 plus 6-8 days
Number of Participants With Clinically Significant Biochemistry, Hematology, Urinalysis, and/or 12-lead Electrocardiogram (ECG) Values
Time frame: Screening through Day 5

Results and safety

Results posted to the registry on 12 Sep 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
3 mg Cytisine, Schedule A: Fed Then Fasted	6	6
3 mg Cytisine, Schedule B: Fasted Then Fed	7	6

Primary outcome: Maximum Concentration (Cmax)

Time frame: Pre-dose (within 60 minutes prior to dosing), up to 48 hours post-dose on Days 1-5. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	3 mg Cytisine: Fed n = 12	3 mg Cytisine: Fasted n = 12
Value	26.2 (37.2)	32.9 (23.7)

3 mg Cytisine: Fed vs 3 mg Cytisine: Fasted: Geometric Least Squares Mean: 79.57 (90% CI 66.40 to 95.35)

Population analysed: Pharmacokinetic (PK) Set: All randomized participants who received both doses of cytisine and had sufficient, protocol-compliant plasma concentration-time profiles.

Primary outcome: Area Under the Concentration Versus Time Curve (AUC) Extrapolated to Infinity (AUC0-∞)

Time frame: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5. Geometric mean (Geometric Coefficient of Variation). Unit: h*ng/mL

Measure	3 mg Cytisine: Fed n = 12	3 mg Cytisine: Fasted n = 12
Value	165 (17.5)	179 (13.7)

3 mg Cytisine: Fed vs 3 mg Cytisine: Fasted: Geometric Least Squares Mean: 92.08 (90% CI 88.37 to 95.95)

Population analysed: PK Set: All randomized participants who received both doses of cytisine and had sufficient, protocol-compliant plasma concentration-time profiles.

Primary outcome: Total Cytisine Excreted in Urine Over 48 Hours (Ae0-48h)

Time frame: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5. Geometric mean (Geometric Coefficient of Variation). Unit: mg

Measure	3 mg Cytisine: Fed n = 12	3 mg Cytisine: Fasted n = 12
Value	2.40 (21.3)	2.64 (15.4)

3 mg Cytisine: Fed vs 3 mg Cytisine: Fasted: Geometric Least Squares Mean: 90.89 (90% CI 84.99 to 97.20)

Population analysed: Urine Excretion Set: All participants who received both doses of cytisine and had sufficient, protocol-compliant plasma concentration-time profiles.

Primary outcome: Percent of Total Cytisine Excreted in Urine Over 48 Hours (Ae0-48h%)

Time frame: Pre-dose (within 60 minutes prior to dosing) up to 48 hours post dose on Days 1-5. Mean (Standard Deviation). Unit: percent of cytisine excreted in urine

Measure	3 mg Cytisine: Fed n = 12	3 mg Cytisine: Fasted n = 12
Value	82.60 (17.627)	89.22 (13.777)

Population analysed: Urine Excretion Set: All participants who received both doses of cytisine and had sufficient, protocol-compliant plasma concentration-time profiles.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline (Day 0) through Day 5 plus 6-8 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
3 mg Cytisine: Fed	0 of 12 (0%)	2 of 12 (16.7%)	0 of 12
3 mg Cytisine: Fasted	0 of 13 (0%)	0 of 13 (0%)	0 of 13

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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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.

Ezanul Abd Wahab, 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 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 18 inclusion and 18 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: finished, as of the sponsor's last update on 24 Sep 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 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.

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 12 Sep 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 Concentration (Cmax) (time frame: Pre-dose (within 60 minutes prior to dosing), up to 48 hours post-dose on Days 1-5). The study lists 4 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 NCT03509948.

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 24 Sep 2019.