Smoking CessationPhase 1NCT02585024
Cytisine Pharmacokinetics and Dose Response (C-DRAKS 3 and C-DRAKS 4)
A Phase 1 study testing Cytisine in people with Smoking Cessation, run by University of Auckland, New Zealand at 1 site in New Zealand.
Trial summary
A number of pharmacotherapies are available for smoking cessation in New Zealand including nicotine replacement therapy, bupropion, an antidepressant medication and varenicline. Of these, varenicline is the most effective, but also the most expensive. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy 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
- 35 participants
- Where
- 1 siteNew Zealand
- Study dates
- Feb 2016to Mar 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- be at least 18 years of age,
- be able to provide written consent,
- have no significant medical or psychiatric disorder (see below under exclusion criteria)
- smoke at least 10 cigarettes a day
Who cannot join
- they are pregnant or breastfeeding,
- they are current users of NRT products,
- they are current users of non-NRT smoking cessation therapies (e.g. bupropion [Zyban®], clonidine, nortriptyline, or varenicline [Champix®]),
- they are enrolled in another smoking cessation programme (concurrent referral to a face-to-face provider from Quitline is acceptable) or other cessation study
- they have had a heart attack, stroke, or severe angina within the past three months,
- they have uncontrolled high blood pressure (> 150 mmHg systolic, > 100 mmHg diastolic),
Show all 11Show fewer
- they have phaeochromocytoma,
- they have been diagnosed with epilepsy
- they suffer from significant mental health problems
- they have severe renal impairment
- they are taking medications which are significantly affected by cessation of smoking (e.g. warfarin, olanzapine, clozapine, therophylline, etc.)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Cytisine as a Smoking Cessation Agent: Improving Adherence Through a Better Understanding of Pharmacokinetics and Dose Response
A number of pharmacotherapies are available for smoking cessation in New Zealand including nicotine replacement therapy, bupropion, an antidepressant medication and varenicline. Of these, varenicline is the most effective, but also the most expensive. Varenicline acts like nicotine and stimulates nicotine receptors in the brain, but to a lesser extent, and simultaneously block nicotine binding to its receptors and thus reduces the rewarding effects of cigarette smoking. Cytisine (Tabex® and Desmoxan®) is a plant alkaloid and also acts in a similar way to varenicline but is significantly cheaper. It has been used for more than 50 years in some parts of eastern and central Europe as an aid to quit smoking, but is not approved for use in many countries such as New Zealand, Australia, the UK or the US. Randomised, placebo-controlled trials have shown that cytisine is more effective than placebo and nicotine replacement therapy (NRT)for smoking cessation. However there is a paucity of pre-clinical data on cytisine. In particular, there are limited data on the pharmacokinetic and the dose response characteristics of cytisine. Furthermore, the current dosing regimen recommended by the manufacturer is complex and has no clear basis in empirical research.
Complexity of dosing has been shown to be a key factor in determining adherence. Therefore, a simpler regimen would likely maximise the effectiveness of treatment through improved adherence to the treatment regimen. The investigators therefore propose to undertake two studies to investigate the influence of dose, dosing frequency and dosing duration on the pharmacokinetics and tolerability of cytisine and cigarette craving in smokers.
Read the detailed description
see above
- Conditions
- Smoking Cessation
- Being tested
- Cytisine
- Keywords
- smoking, cytisine, Pharmacokinetics
- Medical subject headings
- Smoking Cessation, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CytisineDrug
Also called Cytisine, Desmoxan
| Study group | Role | What they receive |
|---|---|---|
| 1.5 mg cytisine | Experimental | 1.5 mg cytisine given as a single dose Receives: Drug: Cytisine |
| 3 mg cytisine | Experimental | 3 mg cytisine given as a single dose Receives: Drug: Cytisine |
| 4.5 mg cytisine | Experimental | 4.5 mg cytisine given as a single dose Receives: Drug: Cytisine |
| 1.5 mg cytisine six times a day | Experimental | 1.5 mg (1 capsule) is given six times a day (0, 2, 4, 6, 8 and 10 hours) for 5 days Receives: Drug: Cytisine |
| 3 mg cytisine three times a day | Experimental | 3 mg (2 capsules) are given three times a day (0, 4 and 8 hours) for 5 days Receives: Drug: Cytisine |
| 4.5 mg cytisine two times a day | Experimental | 4.5 mg (3 capsules) are given two times a day (0 and 6 hours) for 5 days Receives: Drug: Cytisine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Exposure (AUC)
Plasma cytisine concentrations will be measured in all groups for 24 hours. For Arms 4-6, we will continue to take blood samples to measure cytisine concentrations throughout the dosing period (Days 1-5). Days 3-5: one blood sample will be taken before the first dose for the day. On Day 5 an extra blood sample will be taken at 7.5 hours post the first dose for that day.
Measured: Arms 1-3: 24 hours; Arms 4-6: 24 hours, and up to Day 5
Secondary outcomes (5)
Nicotine and cotinine concentrations
Plasma nicotine and cotinine concentrations will be measured along with cytisine concentrations (from the same plasma samples)
Measured: Arms 1-3: 24 hours; Arms 4-6: 24 hours, and up to Day 5
Craving for cigarettes
The brief Questionnaire on Smoking Urges will be administered
Measured: Arms 1-3: 0, 1, 2, 4, 6, 8, 10 and 24 hours. Arms 4-6: 0, 2, 4 ,6, 8, 10, 24 hours; once on Days 3- 5
Blood pressure
Systolic and diastolic blood pressure (mm Hg) will be measured with a blood pressure monitor
Measured: Arms: 1-3: 0, 1, 2, 4, 6, 8, 10, 24 hours. Arms 4-6: 0, 2, 4, 6, 8, 10, 24 hours; once on Days 3- 5
Heart rate
Heart rate (beats per minute) will be simultaneously measured with blood pressure using a blood pressure monitor
Measured: Arms: 1-3: 0, 1, 2, 4, 6, 8, 10, 24 hours. Arms 4-6: 0, 2, 4, 6, 8, 10, 24 hours; once on Days 3- 5
Respiratory rate
Respiratory rate (breaths per minute) will be measured along with blood pressure and heart rate
Measured: Arms: 1-3: 0, 1, 2, 4, 6, 8, 10, 24 hours. Arms 4-6: 0, 2, 4, 6, 8, 10, 24 hours; once on Days 3- 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2015 (estimated)
- Study startFeb 2016
- Primary completionMar 2019
- Study completionMar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Auckland, New Zealand
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Natalie Walker, University of Auckland, New Zealand
- Investigators
- Soo Hee Jeong, Phd, Principal investigator, University of Auckland, New Zealand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02585024
- Sponsor's protocol ID
- AMRF reference 1 1 15 011
- Status last verified
- Mar 2019
- First submitted
- 21 Oct 2015
- Last updated
- 22 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Jeong SH, Sheridan J, Bullen C, Newcombe D, Walker N, Tingle M. Ascending single dose pharmacokinetics of cytisine in healthy adult smokers. Xenobiotica. 2019 Nov;49(11):1332-1337. doi: 10.1080/00498254.2018.1557760. Epub 2019 Jun 19.
PubMed 30526213
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cytisine as a Smoking Cessation Agent: Improving Adherence Through a Better Understanding of Pharmacokinetics and Dose Response
- ClinicalTrials.gov ID
- NCT02585024
- Acronym / sponsor ID
- AMRF reference 1 1 15 011
- Conditions
- Smoking Cessation
- Keywords
- smoking, cytisine, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 35 participants (actual)
- Lead sponsor
- University of Auckland, New ZealandUniversity, hospital or other
- Study start
- Feb 2016
- Primary completion
- Mar 2019 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 23 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A number of pharmacotherapies are available for smoking cessation in New Zealand including nicotine replacement therapy, bupropion, an antidepressant medication and varenicline. Of these, varenicline is the most effective, but also the most expensive. Varenicline acts like nicotine and stimulates nicotine receptors in the brain, but to a lesser extent, and simultaneously block nicotine binding to its receptors and thus reduces the rewarding effects of cigarette smoking. Cytisine (Tabex® and Desmoxan®) is a plant alkaloid and also acts in a similar way to varenicline but is significantly cheaper. It has been used for more than 50 years in some parts of eastern and central Europe as an aid to quit smoking, but is not approved for use in many countries such as New Zealand, Australia, the UK or the US. Randomised, placebo-controlled trials have shown that cytisine is more effective than placebo and nicotine replacement therapy (NRT)for smoking cessation. However there is a paucity of pre-clinical data on cytisine. In particular, there are limited data on the pharmacokinetic and the dose response characteristics of cytisine. Furthermore, the current dosing regimen recommended by the manufacturer is complex and has no clear basis in empirical research.
Complexity of dosing has been shown to be a key factor in determining adherence. Therefore, a simpler regimen would likely maximise the effectiveness of treatment through improved adherence to the treatment regimen. The investigators therefore propose to undertake two studies to investigate the influence of dose, dosing frequency and dosing duration on the pharmacokinetics and tolerability of cytisine and cigarette craving in smokers.
Detailed description
see above
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| 1.5 mg cytisine | Experimental | Drug: Cytisine1.5 mg cytisine given as a single dose |
| 3 mg cytisine | Experimental | Drug: Cytisine3 mg cytisine given as a single dose |
| 4.5 mg cytisine | Experimental | Drug: Cytisine4.5 mg cytisine given as a single dose |
| 1.5 mg cytisine six times a day | Experimental | Drug: Cytisine1.5 mg (1 capsule) is given six times a day (0, 2, 4, 6, 8 and 10 hours) for 5 days |
| 3 mg cytisine three times a day | Experimental | Drug: Cytisine3 mg (2 capsules) are given three times a day (0, 4 and 8 hours) for 5 days |
| 4.5 mg cytisine two times a day | Experimental | Drug: Cytisine4.5 mg (3 capsules) are given two times a day (0 and 6 hours) for 5 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- be at least 18 years of age,
- be able to provide written consent,
- have no significant medical or psychiatric disorder (see below under exclusion criteria)
- smoke at least 10 cigarettes a day
Key exclusion criteria (11 listed)
- they are pregnant or breastfeeding,
- they are current users of NRT products,
- they are current users of non-NRT smoking cessation therapies (e.g. bupropion [Zyban®], clonidine, nortriptyline, or varenicline [Champix®]),
- they are enrolled in another smoking cessation programme (concurrent referral to a face-to-face provider from Quitline is acceptable) or other cessation study
- they have had a heart attack, stroke, or severe angina within the past three months,
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: Cytisine, Desmoxan | Drug | 1.5 mg cytisine, 1.5 mg cytisine six times a day, 3 mg cytisine, 3 mg cytisine three times a day, 4.5 mg cytisine, 4.5 mg cytisine two times a day |
Primary outcome
Exposure (AUC)
Time frame: Arms 1-3: 24 hours; Arms 4-6: 24 hours, and up to Day 5
Plasma cytisine concentrations will be measured in all groups for 24 hours. For Arms 4-6, we will continue to take blood samples to measure cytisine concentrations throughout the dosing period (Days 1-5). Days 3-5: one blood sample will be taken before the first dose for the day. On Day 5 an extra blood sample will be taken at 7.5 hours post the first dose for that day.
5 secondary outcomes
Nicotine and cotinine concentrations
Time frame: Arms 1-3: 24 hours; Arms 4-6: 24 hours, and up to Day 5
Craving for cigarettes
Time frame: Arms 1-3: 0, 1, 2, 4, 6, 8, 10 and 24 hours. Arms 4-6: 0, 2, 4 ,6, 8, 10, 24 hours; once on Days 3- 5
Blood pressure
Time frame: Arms: 1-3: 0, 1, 2, 4, 6, 8, 10, 24 hours. Arms 4-6: 0, 2, 4, 6, 8, 10, 24 hours; once on Days 3- 5
Heart rate
Time frame: Arms: 1-3: 0, 1, 2, 4, 6, 8, 10, 24 hours. Arms 4-6: 0, 2, 4, 6, 8, 10, 24 hours; once on Days 3- 5
Respiratory rate
Time frame: Arms: 1-3: 0, 1, 2, 4, 6, 8, 10, 24 hours. Arms 4-6: 0, 2, 4, 6, 8, 10, 24 hours; once on Days 3- 5
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2019.
- Derived from this study: PubMed 30526213Jeong SH, Sheridan J, Bullen C, Newcombe D, Walker N, Tingle M. Ascending single dose pharmacokinetics of cytisine in healthy adult smokers. Xenobiotica. 2019 Nov;49(11):1332-1337. doi: 10.1080/00498254.2018.1557760. Epub 2019 Jun 19.
- 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.
Soo Hee Jeong, Phd principal investigator
University of Auckland, New Zealand
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 University of Auckland, New Zealand at 1 site in New Zealand.
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 4 inclusion and 11 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 22 Mar 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 New Zealand. 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?
The study was stopped early. Results are not available in the source record.
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?
Exposure (AUC) (time frame: Arms 1-3: 24 hours; Arms 4-6: 24 hours, and up to Day 5). 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 NCT02585024, which also lists 1 linked publication.
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 22 Mar 2019.