Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000002785
Ethics application status
Approved
Date submitted
11/12/2012
Date registered
2/01/2013
Date last updated
6/02/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Cytisine as a smoking cessation aid: measuring blood levels, craving, withdrawal and mood over a course of treatment
Scientific title
Cytisine as a smoking cessation aid: measuring blood levels, craving, withdrawal and mood over a course of treatment
Secondary ID [1] 281646 0
NIL
Universal Trial Number (UTN)
Trial acronym
C-DRAKS 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Smoking 287931 0
Condition category
Condition code
Other 288311 288311 0 0
Conditions of unknown or disputed aetiology (such as chronic fatigue syndrome/myalgic encephalomyelitis)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants are provided with a 25 day supply of cytisine tablets. Each tablet contains 1.5mg of cytisine:
Dosing schedule by the oral route:
Days 1-3: 1 tablet every 2 hours through the waking day (up to six tablets per day)
Days 4-12: 1 tablet every 2.5 hours (up to 5 per day); designated Quit date is day 5
Days 13-16: 1 tablet every 3 hours (up to 4 per day)
Days 17-20: 1 tablet every 4-5 hours (3 per day)
Days 21-25: 1 tablet every 6 hours (2 per day)

Participants are observed over the 25 days of cytisine intervention
Intervention code [1] 286183 0
Not applicable
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 288483 0
Cytisine plasma levels measured by blood samples
Timepoint [1] 288483 0
just before the first dose, then 2, 4, 6, 8, 10, 24 hours and then in the morning on days 2, 3, 4, 5, 6, 13, 14, 17, 18, 21, 22, 25 (plus again after 2, 4, and 6 hours), and day 26.
Secondary outcome [1] 300289 0
Cotinine levels in saliva using Nicalert sticks.
Timepoint [1] 300289 0
days 1,2,3,4,5,6,13,14,17,18,21,22,25
Secondary outcome [2] 300368 0
vital signs - electronic blood pressure and pulse monitor
Timepoint [2] 300368 0
just before the first dose, then 2, 4, 6, 8, 10, 24 hours and then in the morning on days 2, 3, 4, 5, 6, 13, 14, 17, 18, 21, 22, 25 (plus again after 2, 4, and 6 hours), and day 26.
Secondary outcome [3] 300369 0
craving for cigarettes (Brief Questionnaire on Smoking Urges1)
Timepoint [3] 300369 0
days 1,2,3,4,5,6,13,14,17,18,21,22,25, 26
Secondary outcome [4] 300370 0
withdrawal (Mood and Physical Symptoms Score (MPSS), and the modified Cigarette Evaluation Questionnaire),
Timepoint [4] 300370 0
days 1,2,3,4,5,6,13,14,17,18,21,22,25, 26
Secondary outcome [5] 300371 0
mood (Profile of Mood States (POMS))
Timepoint [5] 300371 0
days 1,2,3,4,5,6,13,14,17,18,21,22,25, 26
Secondary outcome [6] 300372 0
metabolites in urine
Timepoint [6] 300372 0
urine samples on days 1,2,3,4,5,6,13,14,17,18,21,22,25, 26

Eligibility
Key inclusion criteria
Smokers
They will be eligible for inclusion in the trial if:
- they are at least 18 years of age,
- they are able to provide written consent,
- willing to attempt to quit smoking
- are currently a regular smoker.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
-pregnant or breastfeeding,
-current users of NRT products,
-current users of non-NRT smoking cessation therapies (e.g. buproprion [registered tradename Zyban], clonidine, nortriptyline, or varenicline [registered tradename Champix]),
-enrolled in another smoking cessation programme
-have had a heart attack, stroke, or severe angina within the previous two weeks,
-have uncontrolled high blood pressure (> 150 mmHg systolic, > 100 mmHg diastolic),
-have phaeochromocytoma,
-suffer from schizophrenia.
-have severe renal impairment
-have had an adverse reaction to varenicline or cytisine

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



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis
As this is an exploratory study, no formal statistical power was required.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/10/2012
Actual
16/11/2012
Date of last participant enrolment
Anticipated
Actual
25/01/2013
Date of last data collection
Anticipated
Actual
30/06/2014
Sample size
Target
12
Accrual to date
Final
11
Recruitment outside Australia
Country [1] 4739 0
New Zealand
State/province [1] 4739 0

Funding & Sponsors
Funding source category [1] 286446 0
University
Name [1] 286446 0
University of Auckland
Country [1] 286446 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
Private Bag 92019
Auckland, 1142
Country
New Zealand
Secondary sponsor category [1] 285233 0
None
Name [1] 285233 0
Address [1] 285233 0
Country [1] 285233 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288526 0
Health and Disabilities Ethics Committee Northern X
Ethics committee address [1] 288526 0
Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington 6011
Ethics committee country [1] 288526 0
New Zealand
Date submitted for ethics approval [1] 288526 0
Approval date [1] 288526 0
30/06/2011
Ethics approval number [1] 288526 0
NTX/11/05/038

Summary
Brief summary
Smoking is the most significant cause of lost healthy life in New Zealand. Smoking cessation dramatically reduces the risk of smoking–related diseases such as cardiovascular disease and cancer and is thus a key strategy for reducing health inequalities. Medicines currently available in New Zealand to help people stop smoking, such as nicotine replacement therapy (NRT), bupropion, nortriptyline and varenicline, are not used by many smokers (at least 70% of whom want to quit) because of low acceptability, side effects, cost and contraindications. Cytisine, an alkaloid found in plants such as Golden Rain and the New Zealand Kowhai, may address some of these concerns. Cytisine is a partial agonist at the nicotinic acetylcholine receptor (nAChR) and is thought to act by attenuating unpleasant tobacco withdrawal symptoms while simultaneously making smoking less rewarding. It has been used in Central and Eastern Europe for several decades. Evidence from three placebo-controlled trials conducted several decades ago in Eastern Europe suggests that cytisine is effective. However, these trials reported limited safety data, and no other human data are available in the literature. With cytisine appearing promising as a smoking cessation aid, it is essential to obtain human pharmacokinetic, dose response and adverse effects data to inform future studies.
Trial website
Trial related presentations / publications
Jeong S., Tingle M., Sheridan J., Newcombe D. (2014). Cytisine Pharmacokinetics in Humans. Oral presentation at the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT)- NZ Annual Meeting, Queenstown, New Zealand.

Jeong S., Tingle M., Sheridan J., Newcombe D. (2014). Cytisine - What happens to it in the body? Oral presentation at Society for Research on Nicotine and Tobacco (SRNT) Annual Meeting Pre-conference Workshop titled Cytisine: A Globally Affordable Treatment for Tobacco Dependence? Seattle, USA.

Jeong S., Newcombe D., Sheridan J., Tingle M. (2013). Cytisine as a smoking cessation aid: measuring craving, withdrawal and mood over a course of treatment. Oral presentation at the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT)- NZ Annual Meeting, Queenstown, New Zealand.
Public notes

Contacts
Principal investigator
Name 36502 0
A/Prof Janie Sheridan
Address 36502 0
School of Pharmacy
University of Auckland
Private Bag 92019
Auckland 1142
Country 36502 0
New Zealand
Phone 36502 0
+6499235247
Fax 36502 0
Email 36502 0
[email protected]
Contact person for public queries
Name 36503 0
A/Prof Janie Sheridan
Address 36503 0
School of Pharmacy
University of Auckland
Private Bag 92019
Auckland 1142
Country 36503 0
New Zealand
Phone 36503 0
+6499235247
Fax 36503 0
Email 36503 0
[email protected]
Contact person for scientific queries
Name 36504 0
A/Prof Janie Sheridan
Address 36504 0
School of Pharmacy
University of Auckland
Private Bag 92019
Auckland 1142
Country 36504 0
New Zealand
Phone 36504 0
+6499235247
Fax 36504 0
Email 36504 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbasePlasma concentrations of cytisine, a commercially available plant-based alkaloid, in healthy adult smokers taking recommended doses for smoking cessation.2018https://dx.doi.org/10.1080/00498254.2017.1409916
N.B. These documents automatically identified may not have been verified by the study sponsor.