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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00749658
Other study ID # GCRC 10047
Secondary ID K01DA019446DPMC
Status Completed
Phase Phase 2/Phase 3
First received
Last updated
Start date November 2008
Est. completion date September 2010

Study information

Verified date October 2020
Source University of Minnesota
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The objective of this proposal is to elucidate effects of bupropion SR + varenicline on smoking-cessation related processes in early abstinence using a human laboratory model. A within-subjects design will be used to assess the additive effects of bupropion and varenicline in 48 treatment seeking smokers [bupropion SR (300 mg/day)+placebo, varenicline (2 mg/day+placebo, and bupropion SR (300 mg/day)+varenicline (2 mg/day)]. Outcomes include withdrawal and craving, cognition, stress tolerance, anxiety, the reinforcing effects of smoking, and smoking topography. Hypotheses: We hypothesize that greatest treatment effects will be observed in the bupropion SR+varenicline group followed by varenicline+placebo and bupropion SR+placebo groups.


Recruitment information / eligibility

Status Completed
Enrollment 121
Est. completion date September 2010
Est. primary completion date September 2010
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. 18 years and up. 2. Smoked at least 10 cigarettes/day for at least 1 year. 3. English speaking and reading. 4. Females who are of childbearing potential must practice effective contraception and meet the following criteria: 1. Are instructed to avoid pregnancy through 30 days after the last dose of study medication. 2. Have a negative urine pregnancy test at baseline. 3. Agree to use of the birth control methods listed: an oral contraceptive agent, an intrauterine device (IUD), an implantable contraceptive (e.g., Norplant), or an injectable contraceptive (e.g., Depo-Provera) for at least one month prior to entering the study and will continue its use through at least 30 days after the last dose of the study medication. A barrier method of contraception (e.g., condom or diaphragm with spermicide) while participating in the study and 30 days after the last dose of study medication. 5. Willingness to not use illicit drugs during study period including marijuana. Exclusion Criteria: 1. Any unstable medical condition. 2. Unstable angina, myocardial infarction, or coronary angioplasty within the past 3 months or an untreated cardiac dysrhythmia. 3. Personal history of seizures. 4. Closed head trauma with any loss of consciousness or amnesia in the last 5 years. 5. A history of closed head trauma with > 30 minutes of loss of consciousness or amnesia or resulting in skull fracture or subdural hematoma/brain contusion. 6. A history of psychosis, bipolar disorder, bulimia or anorexia nervosa. 7. Current depression as assessed by Center for Epidemiologic Studies Depression Scale (CES-D). 8. Medications that might affect the outcome measures of nicotine reward, cognition, anxiety, and stress will also be a basis for exclusion. These medications include psychotropic drugs (i.e., anti-psychotic, anti-depressant, anti-anxiety, or stimulant), anti- hypertensive agents (e.g., beta-blockers), and other drugs that can influence the outcome domains. 9. Active substance abuse other than nicotine. 10. Used an investigational drug within the last 30 days. 11. Are currently using a behavioral or pharmacologic tobacco treatment. 12. Use of bupropion or varenicline in the previous 30 days. 13. Current (past 14 days) use of antipsychotic or antidepressant medications. 14. An allergy to bupropion or varenicline. 15. Untreated hypertension or baseline systolic blood pressure > 180 or diastolic > 100. 16. Impaired kidney function (creatinine clearance < 30). 17. Having plans to leave the immediate geographical area within 2 months. 18. Unwillingness or inability to give written informed consent. -

Study Design


Intervention

Drug:
Bupropion
Form: tablet, Dosage, Frequency, Duration: Days 1-3, 150 mg, q.d., Days 4-11, 150 mg, b.i.d.
Varenicline
Form: tablet, Dosage, Frequency, Duration: Days 1-3, .5 mg, q.d., Days 4-7, .5 mg, b.i.d., Days 8-11, 1 mg, b.i.d.

Locations

Country Name City State
United States University of Minnesota, Tobacco Use Research Center Minneapolis Minnesota

Sponsors (3)

Lead Sponsor Collaborator
University of Minnesota National Institute on Drug Abuse (NIDA), Pfizer

Country where clinical trial is conducted

United States, 

References & Publications (34)

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Johnston AJ, Ascher J, Leadbetter R, Schmith VD, Patel DK, Durcan M, Bentley B. Pharmacokinetic optimisation of sustained-release bupropion for smoking cessation. Drugs. 2002;62 Suppl 2:11-24. Review. — View Citation

Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR; Varenicline Phase 3 Study Group. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):56-63. Erratum in: JAMA. 2006 Sep 20;296(11):1355. — View Citation

Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA, Hughes AR, Smith SS, Muramoto ML, Daughton DM, Doan K, Fiore MC, Baker TB. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med. 1999 Mar 4;340(9):685-91. — View Citation

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Killen JD, Robinson TN, Ammerman S, Hayward C, Rogers J, Stone C, Samuels D, Levin SK, Green S, Schatzberg AF. Randomized clinical trial of the efficacy of bupropion combined with nicotine patch in the treatment of adolescent smokers. J Consult Clin Psychol. 2004 Aug;72(4):729-35. — View Citation

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Kotlyar M, Brauer LH, al'absi M, Adson DE, Robiner W, Thuras P, Harris J, Finocchi ME, Bronars CA, Candell S, Hatsukami DK. Effect of bupropion on physiological measures of stress in smokers during nicotine withdrawal. Pharmacol Biochem Behav. 2006 Mar;83(3):370-9. Epub 2006 Mar 6. — View Citation

Krishnan-Sarin S, Meandzija B, O'Malley S. Naltrexone and nicotine patch smoking cessation: a preliminary study. Nicotine Tob Res. 2003 Dec;5(6):851-7. — View Citation

Mooney ME, Sofuoglu M. Bupropion for the treatment of nicotine withdrawal and craving. Expert Rev Neurother. 2006 Jul;6(7):965-81. Review. — View Citation

Nides M, Oncken C, Gonzales D, Rennard S, Watsky EJ, Anziano R, Reeves KR. Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Arch Intern Med. 2006 Aug 14-28;166(15):1561-8. — View Citation

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Rose JE, Levin ED. Concurrent agonist-antagonist administration for the analysis and treatment of drug dependence. Pharmacol Biochem Behav. 1992 Jan;41(1):219-26. Review. — View Citation

Shiffman S, Johnston JA, Khayrallah M, Elash CA, Gwaltney CJ, Paty JA, Gnys M, Evoniuk G, DeVeaugh-Geiss J. The effect of bupropion on nicotine craving and withdrawal. Psychopharmacology (Berl). 2000 Jan;148(1):33-40. — View Citation

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Warner C, Shoaib M. How does bupropion work as a smoking cessation aid? Addict Biol. 2005 Sep;10(3):219-31. Review. — View Citation

Williams J, Ziedonis DM. Naltrexone-bupropion combination therapy for protracted abstinence dysphoria. Am J Addict. 2003 May-Jun;12(3):270-2. — View Citation

* Note: There are 34 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Nicotine Withdrawal and Craving Subjects were analyzed by how they self reported withdrawal or craved cigarettes during treatment Subjects self reported during study visits along with surveys Change from Base line to 33 weeks
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