Smoking CessationPhase 1NCT03268343
A Study in Healthy Volunteers to Investigate the Effect of Food on the Bioavailability of Cytisine
A Phase 1 study testing Cytisine in people with Smoking Cessation, run by Achieve Life Sciences at 1 site in United Kingdom.
Trial summary
This will be an open-label, randomised, 2-period, single-dose crossover study to determine the comparative bioavailability of cytisine following single-dose administration in healthy male and female subjects under fed and fasted conditions. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- 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
- 24 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 8 Aug 2017to 1 Sep 2017
- 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
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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 investigational medicinal product (IMP).
- 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 IMP.
- Subject with a body mass index (BMI) of 18-32 kg/m^2. BMI = body weight in kg / [height in m]^2.
- Subject with no clinically significant abnormal serum biochemistry, haematology and urine examination values within 28 days before the first dose of IMP.
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- Subject with negative urinary drugs of abuse screen, determined within 28 days before the first dose of IMP (a positive alcohol or cotinine 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 IMP.
- 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 IMP.
- 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.
Who cannot join
- Known hypersensitivity/allergy reaction to varenicline, other cytisine-derivatives or any of the excipients in the Tabex formulation (lactose, 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).
- Difficulty in donating blood on either arm or known history.
- History of alcoholism or drug abuse within last 2 years.
- Regular nicotine intake (e.g., smoking, nicotine patch, nicotine chewing gum or electronic cigarettes) within previous 3 months and inability to refrain from nicotine intake from Screening until end of study.
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- 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 first dose of IMP, 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 first dose of IMP.
- Any special food restrictions that may hinder ability to consume the high fat breakfast provided during the study; such as lactose intolerance, vegan, low-fat, low sodium, etc.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1 Open Label, Randomized, Two-Way Crossover Study in Healthy Volunteers to Investigate the Effect of Food on the Bioavailability of Cytisine
This will be an open-label, randomised, 2-period, single-dose crossover study to determine the comparative bioavailability of cytisine following single-dose administration in healthy male and female subjects under fed and fasted conditions.
The study will be comprised of a pre-study screen, followed by 2 treatment periods (1 and 2) and a post-study follow-up.
- 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 group | Role | What they receive |
|---|---|---|
| Schedule A: Fed Then Fasted | Experimental | Schedule A (12 subjects):
* 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 (12 subjects):
* 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.
Plasma Cytisine Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax)
Measured: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Plasma Cytisine PK: Total Area Under the Curve From Time Zero to Infinity (AUC0-∞)
Measured: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Secondary outcomes (8)
Plasma Cytisine PK: Time of Occurrence of Cmax (Tmax)
Measured: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Plasma Cytisine PK: AUC From Time Zero to the Last Sampling Time (AUC0-t)
Measured: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Plasma Cytisine PK: Residual Area, or Percentage of Extrapolated Part for the Calculation of AUC0-∞ (AUC%)
Measured: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Plasma Cytisine PK: Apparent Terminal Elimination Rate Constant (Lambda z)
Measured: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Plasma Cytisine PK: Apparent Terminal Elimination Half-Life (t1/2)
Measured: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Urine Cytisine PK: Amount Excreted in Urine Over Time (Ae)
Measured: Pre-dose (within 30 minutes prior to first dose); 0-2 hours, 2-4 hours, 4-8 hours, 8-12 hours and 12-24 hours post-dose
Urine Cytisine PK: Percentage of Drug Excreted in Urine (Ae%)
To assess the renal elimination of cytisine via measurement of urinary concentrations of cytisine.
Measured: Pre-dose (within 30 minutes prior to first dose); 0-2 hours, 2-4 hours, 4-8 hours, 8-12 hours and 12-24 hours post-dose
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuation of Study Drug Due to AEs, by Severity and Relationship
An adverse event (AE) is defined as any untoward medical occurrence which does not necessarily have a causal relationship with the treatment. TEAEs are defined as AEs not present prior to first administration of investigational product, or AEs present before first administration of study drug that worsen after the subject receives the first dose of study drug. A serious adverse event (SAE) is defined as an AE that: results in death; is life-threatening; requires hospitalization or prolongs existing inpatient's 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. Event severity was categorized as mild, moderate, or severe. Relationship of event to study drug was categorized as definite, probably, possible, unlikely, not related, or not applicable (N/A).
Measured: Day -1 to Day 7 plus 6-8 days (post-study follow-up)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2017
- Study start8 Aug 2017
- Primary completion26 Aug 2017
- Study completion1 Sep 2017
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
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Achieve Life Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Annelize Koch, MD, Principal investigator, Simbec Research Ltd (Simbec)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03268343
- Sponsor's protocol ID
- ACH-CYT-01
- Other IDs
- 2017-001562-19, 2017
- Status last verified
- Feb 2019
- First submitted
- 25 Aug 2017
- Last updated
- 26 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 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 Volunteers to Investigate the Effect of Food on the Bioavailability of Cytisine
- ClinicalTrials.gov ID
- NCT03268343
- Acronym / sponsor ID
- ACH-CYT-01
- Conditions
- Smoking Cessation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Achieve Life SciencesIndustry (pharma, biotech, devices)
- Study start
- 8 Aug 2017 (actual)
- Primary completion
- 26 Aug 2017 (actual)
- Study completion
- 1 Sep 2017 (actual)
- First posted
- 31 Aug 2017 (actual)
- Results
- Posted 7 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This will be an open-label, randomised, 2-period, single-dose crossover study to determine the comparative bioavailability of cytisine following single-dose administration in healthy male and female subjects under fed and fasted conditions.
The study will be comprised of a pre-study screen, followed by 2 treatment periods (1 and 2) and a post-study follow-up.
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 (12 subjects): * 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 (12 subjects): * 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
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Healthy males and females between 18 and 55 years of age.
- Subject with a body mass index (BMI) of 18-32 kg/m^2. BMI = body weight in kg / [height in m]^2.
- Subject with no clinically significant abnormal serum biochemistry, haematology and urine examination values within 28 days before the first dose of IMP.
- Subject with negative urinary drugs of abuse screen, determined within 28 days before the first dose of IMP (a positive alcohol or cotinine 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.
Key exclusion criteria (13 listed)
- Known hypersensitivity/allergy reaction to varenicline, other cytisine-derivatives or any of the excipients in the Tabex formulation (lactose, 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).
- Difficulty in donating blood on either arm or known history.
- History of alcoholism or drug abuse within last 2 years.
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
Plasma Cytisine Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax)
Time frame: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Plasma Cytisine PK: Total Area Under the Curve From Time Zero to Infinity (AUC0-∞)
Time frame: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
8 secondary outcomes
Plasma Cytisine PK: Time of Occurrence of Cmax (Tmax)
Time frame: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Plasma Cytisine PK: AUC From Time Zero to the Last Sampling Time (AUC0-t)
Time frame: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Plasma Cytisine PK: Residual Area, or Percentage of Extrapolated Part for the Calculation of AUC0-∞ (AUC%)
Time frame: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Plasma Cytisine PK: Apparent Terminal Elimination Rate Constant (Lambda z)
Time frame: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Plasma Cytisine PK: Apparent Terminal Elimination Half-Life (t1/2)
Time frame: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)
Urine Cytisine PK: Amount Excreted in Urine Over Time (Ae)
Time frame: Pre-dose (within 30 minutes prior to first dose); 0-2 hours, 2-4 hours, 4-8 hours, 8-12 hours and 12-24 hours post-dose
Urine Cytisine PK: Percentage of Drug Excreted in Urine (Ae%)
Time frame: Pre-dose (within 30 minutes prior to first dose); 0-2 hours, 2-4 hours, 4-8 hours, 8-12 hours and 12-24 hours post-dose
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuation of Study Drug Due to AEs, by Severity and Relationship
Time frame: Day -1 to Day 7 plus 6-8 days (post-study follow-up)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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.
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 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 12 inclusion and 13 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 26 Feb 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 7 Feb 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?
Plasma Cytisine Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) (time frame: Pre-dose (within 60 minutes of dosing); 15 minutes, 20 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours and 24 hours post-dose (+/- 1 minute)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Feb 2019.