Clinical trial NCT02585024: Cytisine Pharmacokinetics and Dose Response (C-DRAKS 3 and C-DRAKS 4)
Official title: Cytisine as a Smoking Cessation Agent: Improving Adherence Through a Better Understanding of Pharmacokinetics and Dose Response
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Smoking Cessation
Keywords: smoking
cytisine
Pharmacokinetics
Lead sponsor: University of Auckland, New Zealand
Sponsor class: OTHER
First posted: 2015-10-23
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Detailed description: see above

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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),
* 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.)

Primary outcomes:
measure: Exposure (AUC)
timeFrame: Arms 1-3: 24 hours; Arms 4-6: 24 hours, and up to Day 5
Secondary outcomes:
measure: Nicotine and cotinine concentrations
timeFrame: Arms 1-3: 24 hours; Arms 4-6: 24 hours, and up to Day 5
measure: Craving for cigarettes
timeFrame: 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
measure: Blood pressure
timeFrame: 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
measure: Heart rate
timeFrame: 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
measure: Respiratory rate
timeFrame: 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
Other outcomes:
Locations:
city: Auckland
country: New Zealand
facility: Soo Hee Jeong
Study officials:
affiliation: University of Auckland, New Zealand
name: Soo Hee Jeong, Phd
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.