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

NCT02585024 | Terminated Phase 1

• 1 other identifier: AMRF reference 1 1 15 011
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Smoking Cessation

Keywords

smoking; cytisine; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Nicotine and cotinine concentrations

  Arms 1-3: 24 hours; Arms 4-6: 24 hours, and up to Day 5

• Craving for cigarettes

  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

• Blood pressure

  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

  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

  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

Study Arms (6)

1.5 mg cytisine

EXPERIMENTAL

1.5 mg cytisine given as a single dose

Drug: Cytisine

3 mg cytisine

EXPERIMENTAL

3 mg cytisine given as a single dose

Drug: Cytisine

4.5 mg cytisine

EXPERIMENTAL

4.5 mg cytisine given as a single dose

Drug: Cytisine

1.5 mg cytisine six times a day

EXPERIMENTAL

1.5 mg (1 capsule) is given six times a day (0, 2, 4, 6, 8 and 10 hours) for 5 days

Drug: Cytisine

3 mg cytisine three times a day

EXPERIMENTAL

3 mg (2 capsules) are given three times a day (0, 4 and 8 hours) for 5 days

Drug: Cytisine

4.5 mg cytisine two times a day

EXPERIMENTAL

4.5 mg (3 capsules) are given two times a day (0 and 6 hours) for 5 days

Drug: Cytisine

Interventions

Cytisine DRUG

Also known as: Cytisine, Desmoxan

1.5 mg cytisine; 1.5 mg cytisine six times a day; 3 mg cytisine; 3 mg cytisine three times a day; 4.5 mg cytisine; 4.5 mg cytisine two times a day

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.)

Sponsors & Collaborators

• University of Auckland, New Zealand: lead

Study Sites (1)

Soo Hee Jeong

Auckland, 1072, New Zealand

Location

Related Publications (1)

• 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.

  PMID: 30526213 DERIVED

MeSH Terms

Conditions

Smoking Cessation; Smoking

Interventions

cytisine

Condition Hierarchy (Ancestors)

Health Behavior; Behavior

Study Officials

• Soo Hee Jeong, Phd

  University of Auckland, New Zealand

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 21, 2015
• First Posted: October 23, 2015
• Study Start: February 1, 2016
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: March 22, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1)