Cytisine Pharmacokinetics and Dose Response (C-DRAKS 3 and C-DRAKS 4)

NCT ID: NCT02585024

Last Updated: 2019-03-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2019-03-31

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

Conditions

Smoking Cessation

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

1.5 mg cytisine

1.5 mg cytisine given as a single dose

Group Type: EXPERIMENTAL

Cytisine

Intervention Type: DRUG

3 mg cytisine

3 mg cytisine given as a single dose

Group Type: EXPERIMENTAL

Cytisine

Intervention Type: DRUG

4.5 mg cytisine

4.5 mg cytisine given as a single dose

Group Type: EXPERIMENTAL

Cytisine

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

Cytisine

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

Cytisine

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

Cytisine

Intervention Type: DRUG

Interventions

Cytisine

Intervention Type: DRUG

Other Intervention Names

Cytisine, Desmoxan

Eligibility Criteria

Inclusion Criteria

• be at least 18 years of age,
• be able to provide written consent,

Exclusion Criteria

• smoke at least 10 cigarettes a day

• 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.)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Auckland, New Zealand

OTHER

Sponsor Role: lead

Responsible Party

Natalie Walker

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Soo Hee Jeong, Phd

Role: PRINCIPAL_INVESTIGATOR

University of Auckland, New Zealand

Locations

Soo Hee Jeong

Auckland, , New Zealand

Countries

New Zealand

References

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.

Reference Type: DERIVED

PMID: 30526213 (View on PubMed)

Other Identifiers

AMRF reference 1 1 15 011

Identifier Type: -

Identifier Source: org_study_id