Efficacy of Varenicline in Methadone-Stabilized Cocaine Users

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00567320
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH), US Department of Veterans Affairs (U.S. Fed)
• Enrollment: 31
• Location: 1
• Arms: 2
• Duration (Months): 29
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

Cocaine addiction continues to be an important public health problem in the US with a significant cost to the individual and society. Among substance abusers, cocaine use has been recognized as a significant problem especially in methadone-maintenance patients. In several studies, rates of cocaine use have been reported to range from 30 to over 60 percent of those in methadone maintenance programs (Condelli et al. 1991; Hunt et al. 1984; Kidorf and Stitzer 1993; Kosten et al. 1988). In these patients, cocaine use seems to be a predictor of poor clinical outcome (Hartel et al. 1995; Kosten et al. 1987a). The development of effective pharmacotherapies for cocaine use disorders, especially in the opioid-dependent population is of great importance. Unfortunately, such effective pharmacotherapies do not exist.

1. To determine the safety and tolerability of varenicline in cocaine-using methadone-stabilized subjects.

2. To determine if varenicline is efficacious in reducing cocaine-use in methadone-stabilized subjects.

Condition or Disease	Intervention/Treatment	Phase
Cocaine Dependence; Nicotine Dependence	Drug: Varenicline; Drug: Sugar pill or Placebo	N/A

Detailed Description

For this pilot study, we hope to recruit a total of 40 subjects, with 20 subjects in the varenicline group, and 20 into the placebo-control group. Assuming significant findings, these data will enable us to estimate a possible effect size for carrying-out a larger study. For preliminary analysis as a prelude to planning larger controlled studies, we will clinically require an effect size of 20% differences in the rates of cocaine positive urines or of self-reported cocaine use between the active medication and placebo groups. We will not adjust for these multiple comparisons to the placebo group since this is a pilot study, and use two-tailed significance level of 0.05 when we employ repeated measures analysis of variance (ANOVA) or Hierarchical Linear Modeling (HLM,see below) for statistical analysis over the 16-week study period.

An Amendment was made and a new Updated consent form to include new FDA findings for study medication Varenicline." Varenicline may also cause changes in behavior, agitation, depressed mood, suicidal ideation and suicidal behavior." Currently we have 30 subjects who have completed this study. This study is suspended due to these new concerns, Department of Veterans Affairs and the P.I. James Poling agreed.

Study has been published. (April 2011)

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Health Services Research
• Official Title: Efficacy of Varenicline in Methadone-Stabilized Cocaine Users
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Varenicline	Drug: Varenicline; Varenicline up to 2 mg a day; Other Names: Chantix
Active Comparator: Sugar Pill or Placebo Placebo is compared to active drug varenicline	Drug: Sugar pill or Placebo; Placebo; Other Names: Sugar pill

Outcome Measures

Primary Outcome Measures

1. Proportion of Cocaine Positive Urine Tests Per Week [Weekly Measures over 12 weeks]

   Urine samples were obtained thrice-weekly and analyzed for the presence of cocaine metabolites. Levels that exceeded 300 ng / ml on each individual urine test were considered positive. The primary outcome measure was the proportions of positive cocaine urine results per week that was calculated by using the total number of completed tests as the denominator and the total number of positive tests for that week as the numerator. This data was subjected to Hierarchical Linear Modeling (HLM) analysis using a total of 13 longitudinal results that included a baseline result (Week 0).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males and females between 18 and 55 years old will be eligible for this study. Females must not be pregnant as determined by pregnancy screening, nor breast feeding, and must be using acceptable birth control methods during study participation.

• Current opioid dependence as evidenced by documentation of prior treatment for opioid dependence or signs of withdrawal, self-reported history of opioid dependence for consecutive 12 month period and a positive urine for opiates.

• Subjects must fulfill Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for opioid dependence.

• Subjects must have a history of cocaine use, with a reported street cocaine use of a minimum of 1/2 gram during the preceding 30 days.

• Subjects must meet DSM-IV criteria for cocaine dependence or abuse, and have laboratory confirmation of recent cocaine use (positive urine for cocaine) during the month prior to study entry.

• Subjects must be treatment-seekers for opioid and cocaine use.

• Subjects must have smoked at least 10 cigarette per day for at least one year. Varenicline's safety has only been studied in smokers.

Exclusion Criteria:

• History of heart disease, left ventricular hypertrophy, ischemic ECG changes, chest pain, arrhythmia, hypertension.

• History of severe renal or hepatic diseases.

• History of psychosis, schizophrenia, bipolar or major depressive disorder.

• History of seizure disorder.

• Current diagnosis of alcohol, benzodiazepine and other drug abuse or dependence (other than opiates, cocaine, and nicotine).

• Current use of over-the-counter or prescription psychoactive drugs (antidepressant, anxiolytics, antipsychotics, mood stabilizers, psychostimulants).

• Liver function tests (ALT or AST) greater than 3 times normal.

• Known allergy to varenicline or methadone.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Veterans Hopsital	West Haven	Connecticut	United States	06516

Sponsors and Collaborators

• Yale University
• National Institute on Drug Abuse (NIDA)
• US Department of Veterans Affairs

Investigators

• Principal Investigator: James Poling, Ph.D., Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT00567320
• Other Study ID Numbers: 0702002337; R01DA021264; DPMC; MIRECC 000000000
• First Posted: Dec 4, 2007
• Last Update Posted: Apr 2, 2020
• Last Verified: Jan 1, 2013

• Keywords provided by Yale University: varenicline
• Additional relevant MeSH terms: Tobacco Use Disorder; Cocaine-Related Disorders; Varenicline

Study Results

Participant Flow

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	Varenicline 2 mg per day.	This is the Placebo condition
Period Title: Overall Study
STARTED	13	18
COMPLETED	13	18
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Varenicline	Placebo	Total
Arm/Group Description	Varenicline 2 mg per day.	This is the Placebo condition	Total of all reporting groups
Overall Participants	13	18	31
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.5 (12)	34.4 (12)	35.45 (12)
Sex: Female, Male (Count of Participants)
Female	2 15.4%	4 22.2%	6 19.4%
Male	11 84.6%	14 77.8%	25 80.6%
Region of Enrollment (participants) [Number]
United States	13 100%	18 100%	31 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Cocaine Positive Urine Tests Per Week
Description	Urine samples were obtained thrice-weekly and analyzed for the presence of cocaine metabolites. Levels that exceeded 300 ng / ml on each individual urine test were considered positive. The primary outcome measure was the proportions of positive cocaine urine results per week that was calculated by using the total number of completed tests as the denominator and the total number of positive tests for that week as the numerator. This data was subjected to Hierarchical Linear Modeling (HLM) analysis using a total of 13 longitudinal results that included a baseline result (Week 0).
Time Frame	Weekly Measures over 12 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat analysis of all subjects receiving medication

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	Varenicline 2 mg per day.	This is the Placebo condition
Measure Participants	13	16
Mean (Standard Deviation) [Proportion of cocaine positive]	.57 (.05)	.58 (.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Varenicline, Placebo
	Comments	HLM analysis of % of Cocaine Positive Urines per week over 12 weeks. Subjects were used as a Random variable, with medication dosing set to 'Fixed'.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.84
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Arm/Group Title	Varenicline		Placebo
Arm/Group Description	Varenicline 2 mg per day.		This is the Placebo condition
All Cause Mortality
	Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.