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

• ClinicalTrials.gov Identifier: NCT02585024
• Recruitment Status: Terminated
• First Posted: October 23, 2015
• Last Update Posted: March 22, 2019
• Sponsor: University of Auckland, New Zealand
• Information provided by (Responsible Party): Natalie Walker, University of Auckland, New Zealand

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
Smoking Cessation	Drug: Cytisine	Phase 1

Detailed Description:

see above

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 35 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Cytisine as a Smoking Cessation Agent: Improving Adherence Through a Better Understanding of Pharmacokinetics and Dose Response
• Study Start Date: February 2016
• Actual Primary Completion Date: March 2019
• Actual Study Completion Date: March 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1.5 mg cytisine; 1.5 mg cytisine given as a single dose	Drug: Cytisine; Other Name: Cytisine, Desmoxan
Experimental: 3 mg cytisine; 3 mg cytisine given as a single dose	Drug: Cytisine; Other Name: Cytisine, Desmoxan
Experimental: 4.5 mg cytisine; 4.5 mg cytisine given as a single dose	Drug: Cytisine; Other Name: Cytisine, Desmoxan
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 Name: Cytisine, Desmoxan
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 Name: Cytisine, Desmoxan
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 Name: Cytisine, Desmoxan

Outcome Measures

Primary Outcome Measures :

1. Exposure (AUC) [ Time Frame: 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 :

1. Nicotine and cotinine concentrations [ Time Frame: 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)
2. Craving for cigarettes [ Time Frame: 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
3. Blood pressure [ Time Frame: 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
4. Heart rate [ Time Frame: 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
5. Respiratory rate [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.)

Contacts and Locations

Locations

New Zealand

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Natalie Walker, Associate Professor, University of Auckland, New Zealand
• ClinicalTrials.gov Identifier: NCT02585024
• Other Study ID Numbers: AMRF reference 1 1 15 011
• First Posted: October 23, 2015
• Last Update Posted: March 22, 2019
• Last Verified: March 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Natalie Walker, University of Auckland, New Zealand:

smoking; cytisine; Pharmacokinetics