Effects of EVT 302 With or Without NRT on Craving and Withdrawal in Healthy Male Smokers Deprived of Cigarettes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00622752
Recruitment Status : Completed
First Posted : February 25, 2008
Last Update Posted : June 17, 2008
Information provided by:
Evotec Neurosciences GmbH

Brief Summary:
This randomised, placebo-controlled study is designed to explore the effects of EVT 302 both with and without concomitant nicotine replacement therapy (NRT) on craving and withdrawal in smokers after short term deprivation of cigarettes.

Condition or disease Intervention/treatment Phase
Smoking Cessation Drug: EVT 302, 10 mg Drug: placebo Drug: Nicotine replacement therapy (NRT) Device: NRT placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Randomized, Placebo- and NRT -Controlled Phase II Study to Assess the Effects of EVT 302 Alone and in Combination With NRT on Craving and Withdrawal in Healthy Male Smokers Deprived of Cigarettes
Study Start Date : February 2008
Actual Primary Completion Date : May 2008
Actual Study Completion Date : May 2008

Arm Intervention/treatment
Experimental: 1
EVT 302, 10 mg
Drug: EVT 302, 10 mg
2 X EVT 302, 5 mg tablets

Experimental: 2
EVT 302, 10 mg + NRT patch, 21 mg
Drug: EVT 302, 10 mg
2 X EVT 302, 5 mg tablets

Drug: Nicotine replacement therapy (NRT)
NRT patch containing 21 mg of nicotine

Experimental: 3
NRT patch, 21 mg
Drug: Nicotine replacement therapy (NRT)
NRT patch containing 21 mg of nicotine

Placebo Comparator: 4
Placebo to match EVT 302 and placebo patch to match NRT patch
Drug: placebo
2 X placebo tablets to match EVT 302 5 mg

Device: NRT placebo
Medically inert plaster cut to match the NRT plaster

Primary Outcome Measures :
  1. Reduction in Craving and withdrawal [ Time Frame: Within 12 hours of the last cigarette ]

Secondary Outcome Measures :
  1. CogState Cognitive test Battery [ Time Frame: 12 hours post last cigarette ]
  2. Breath carbon monoxide levels [ Time Frame: 12 hours post last cigarette ]
  3. Salivary cotinine levels [ Time Frame: 12 hours post last cigarette ]
  4. Clinical safety lab tests [ Time Frame: Up to 7 days post dose ]
  5. Assessment of adverse events [ Time Frame: Up to 7 days post dose ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male subjects between 18 and 55 years of age, inclusive
  • BMI between 18 and 30, minimum weight of 50 kg
  • Negative urine drug & alcohol screen
  • Able to comply with tyramine-restricted diet
  • Smoking of ≥17 and ≤34 cigarettes per day for the past year and have not tried to quit smoking in the 3 months prior to screening
  • Subjects are willing and able to quit for about 12 hours in each of three subsequent study periods
  • Previous experience of craving following smoking cessation
  • Breath CO between 15 ppm and 20 ppm and cotinine in saliva and plasma at least 250 ng/mL at screening
  • Liver function test results not above 1.5 times the upper normal limit (UNL) at screening visit and at re-assessment during the study.

Exclusion Criteria:

  • Participation in another clinical study within 60 days of screening
  • Evidence of active significant psychiatric or neurological disease or dependency other than cigarettes
  • Are known to have or are a carrier of the hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, has a positive result to the human immunodeficiency virus-1 and/or 2 (HIV-1 and/or HIV-2) antibodies
  • Known hypersensitivity to MAO inhibitors or any substance that is contained in the study formulations
  • Known allergy to plasters or NRT patches
  • Previous participation in another study with EVT 302
  • Currently receiving treatment for smoking cessation
  • Current use of tobacco products other than cigarettes
  • Require treatment with any medication
  • Subject with a clinically relevant abnormal 12-lead ECG recording or QTcB/F >430 ms
  • Use of a prescription medicine within 14 days or 5 half-lives, whichever is the longer, of the start of dosing, or use of an over-the-counter medication during the 7 days before the study, including herbal remedies, but excluding paracetamol and vitamin supplements (provided intake does not exceed the daily recommended allowance)
  • Subjects must not be planning to father a child or donate sperm, during the study and 3 months after the end of the study. Acceptable methods of contraception comprise barrier contraception and a medically accepted contraceptive method for the female partner (intra-uterine device with spermicide, hormonal contraceptive since at least 2 month)
  • Daily consumption of more than 5 cups of tea or coffee, or more than 1.0 litre of xanthine-containing drinks
  • Recent myocardial infarction, unstable or worsening angina pectoris, prince metal angina, severe arrhythmias, recent stroke.
  • Creatinine clearance (CLR) calculated according to the formula by Modification of Diet in Renal Disease (MDRD) of <80 mL/min

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00622752

PAREXEL International GmbH, Clinical Pharmacology Research Unit
Berlin, Germany, 14050
Sponsors and Collaborators
Evotec Neurosciences GmbH
Principal Investigator: Alla Radicke, MD Parexel International GmbH, Clinical Pharmacology Research Unit

Responsible Party: Doris Greiling, Clinical Development Programme Manager, Evotec Neurosciences GmbH Identifier: NCT00622752     History of Changes
Other Study ID Numbers: EVT 302/3011
EUDRACT No.: 2007-006236-63
First Posted: February 25, 2008    Key Record Dates
Last Update Posted: June 17, 2008
Last Verified: June 2008

Keywords provided by Evotec Neurosciences GmbH:
Smoking cessation

Additional relevant MeSH terms:
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action