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

Smoking Cessation Clinical Trial

Official title:

Cytisine as a Smoking Cessation Agent: Improving Adherence Through a Better Understanding of Pharmacokinetics and Dose Response

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02585024
• Other study ID #: AMRF reference 1 1 15 011
• Status: Terminated
• Phase: Phase 1
• Start date: February 2016
• Est. completion date: March 2019

Study information

• Verified date: March 2019
• Source: University of Auckland, New Zealand
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

see above

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 35
• Est. completion date: March 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.)

Related Conditions & MeSH terms

• Smoking Cessation

Intervention

Drug:
• Cytisine

Locations

Country	Name	City	State
New Zealand	Soo Hee Jeong	Auckland

Sponsors (1)

Lead Sponsor	Collaborator
University of Auckland, New Zealand

Country where clinical trial is conducted

New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exposure (AUC)	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.	Arms 1-3: 24 hours; Arms 4-6: 24 hours, and up to Day 5
Secondary	Nicotine and cotinine concentrations	Plasma nicotine and cotinine concentrations will be measured along with cytisine concentrations (from the same plasma samples)	Arms 1-3: 24 hours; Arms 4-6: 24 hours, and up to Day 5
Secondary	Craving for cigarettes	The brief Questionnaire on Smoking Urges will be administered	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	Blood pressure	Systolic and diastolic blood pressure (mm Hg) will be measured with a blood pressure monitor	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	Heart rate	Heart rate (beats per minute) will be simultaneously measured with blood pressure using a blood pressure monitor	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	Respiratory rate	Respiratory rate (breaths per minute) will be measured along with blood pressure and heart rate	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