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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02585024




Registration number
NCT02585024
Ethics application status
Date submitted
21/10/2015
Date registered
23/10/2015
Date last updated
22/03/2019

Titles & IDs
Public title
Cytisine Pharmacokinetics and Dose Response (C-DRAKS 3 and C-DRAKS 4)
Scientific title
Cytisine as a Smoking Cessation Agent: Improving Adherence Through a Better Understanding of Pharmacokinetics and Dose Response
Secondary ID [1] 0 0
AMRF reference 1 1 15 011
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Smoking Cessation 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: 1.5 mg cytisine - 1.5 mg cytisine given as a single dose

Experimental: 3 mg cytisine - 3 mg cytisine given as a single dose

Experimental: 4.5 mg cytisine - 4.5 mg cytisine given as a single dose

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

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

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
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Exposure (AUC)
Timepoint [1] 0 0
Arms 1-3: 24 hours; Arms 4-6: 24 hours, and up to Day 5
Secondary outcome [1] 0 0
Nicotine and cotinine concentrations
Timepoint [1] 0 0
Arms 1-3: 24 hours; Arms 4-6: 24 hours, and up to Day 5
Secondary outcome [2] 0 0
Craving for cigarettes
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Blood pressure
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Heart rate
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
Respiratory rate
Timepoint [5] 0 0
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

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.)

Study design
Purpose of the study
Other
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2019
Sample size
Target
Accrual to date
Final
35
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Other
Name
University of Auckland, New Zealand
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02585024
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
Soo Hee Jeong, Phd
Address 0 0
University of Auckland, New Zealand
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02585024