Cytisine Pharmacokinetics and Dose Response (C-DRAKS 3 and C-DRAKS 4)
Study Details
Study Description
Brief 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. 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
see above
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1.5 mg cytisine 1.5 mg cytisine given as a single dose |
Drug: Cytisine
Other Names:
|
| Experimental: 3 mg cytisine 3 mg cytisine given as a single dose |
Drug: Cytisine
Other Names:
|
| Experimental: 4.5 mg cytisine 4.5 mg cytisine given as a single dose |
Drug: Cytisine
Other Names:
|
| Experimental: 1.5 mg cytisine six times a day 1.5 mg (1 capsule) is given six times a day (0, 2, 4, 6, 8 and 10 hours) for 5 days |
Drug: Cytisine
Other Names:
|
| Experimental: 3 mg cytisine three times a day 3 mg (2 capsules) are given three times a day (0, 4 and 8 hours) for 5 days |
Drug: Cytisine
Other Names:
|
| Experimental: 4.5 mg cytisine two times a day 4.5 mg (3 capsules) are given two times a day (0 and 6 hours) for 5 days |
Drug: Cytisine
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Exposure (AUC) [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.
Secondary Outcome Measures
- Nicotine and cotinine concentrations [Arms 1-3: 24 hours; Arms 4-6: 24 hours, and up to Day 5]
Plasma nicotine and cotinine concentrations will be measured along with cytisine concentrations (from the same plasma samples)
- Craving for cigarettes [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]
The brief Questionnaire on Smoking Urges will be administered
- Blood pressure [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]
Systolic and diastolic blood pressure (mm Hg) will be measured with a blood pressure monitor
- Heart rate [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 (beats per minute) will be simultaneously measured with blood pressure using a blood pressure monitor
- Respiratory rate [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 (breaths per minute) will be measured along with blood pressure and heart rate
Eligibility Criteria
Criteria
Inclusion Criteria:
-
be at least 18 years of age,
-
be able to provide written consent,
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have no significant medical or psychiatric disorder (see below under exclusion criteria)
-
smoke at least 10 cigarettes a day
Exclusion Criteria:
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they are pregnant or breastfeeding,
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they are current users of NRT products,
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they are current users of non-NRT smoking cessation therapies (e.g. bupropion [Zyban®], clonidine, nortriptyline, or varenicline [Champix®]),
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they are enrolled in another smoking cessation programme (concurrent referral to a face-to-face provider from Quitline is acceptable) or other cessation study
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they have had a heart attack, stroke, or severe angina within the past three months,
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they have uncontrolled high blood pressure (> 150 mmHg systolic, > 100 mmHg diastolic),
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they have phaeochromocytoma,
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they have been diagnosed with epilepsy
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they suffer from significant mental health problems
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they have severe renal impairment
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they are taking medications which are significantly affected by cessation of smoking (e.g. warfarin, olanzapine, clozapine, therophylline, etc.)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Soo Hee Jeong | Auckland | New Zealand | 1072 |
Sponsors and Collaborators
- University of Auckland, New Zealand
Investigators
- Principal Investigator: Soo Hee Jeong, Phd, University of Auckland, New Zealand
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AMRF reference 1 1 15 011