A Phase II Trial of Varenicline for the Treatment of Cocaine Dependence

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT01680887
• Collaborator: (none)
• Enrollment: 156
• Location: 1
• Arms: 2
• Duration (Months): 82
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

This is a double-blind placebo-controlled clinical trial (n = 156) of varenicline for the treatment of cocaine dependence that utilizes contingency management to promote treatment attendance.

Condition or Disease	Intervention/Treatment	Phase
Cocaine Dependence	Drug: Varenicline; Drug: Placebo	Phase 2

Detailed Description

Background: Varenicline is a medication approved for the treatment of Tobacco Use Disorder. It is a partial agonist at α2β4 nicotinic acetyl choline receptors and a full agonist at α7 nicotinic acetyl choline receptors. By its effects on cholinergic activity at α7 and α2β4 receptors, varenicline may reduce dopaminergic and glutamatergic activity in the midbrain, and reduce symptoms of Cocaine Use Disorder. A preliminary trial of varenicline in human cocaine users suggested that varenicline treatment was associated with reductions in cocaine use. The current trial was intended to confirm these promising preliminary results.

Methods: This was a 12-week, double blind, placebo controlled parallel group clinical trial involving 156 DSM IV cocaine dependent subjects. Subjects received 2 mg of varenicline or identical placebo each day along with weekly individual cognitive behavioral relapse prevention psychotherapy. The primary outcome measure was cocaine use measured by by thrice weekly urine drug screens. Additional outcome measures included cocaine withdrawal symptoms measured by the Cocaine Selective Severity Assessment (CSSA) End of study cocaine abstinence was analyzed using a Chi-square test.

Study Design

• Study Type: Interventional
• Actual Enrollment: 156 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II, Randomized, Double-Blind Trial of Varenicline for the Treatment of Cocaine Dependence
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Jan 1, 2018
• Actual Study Completion Date: Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Varenicline Oral 1.0 mg BID.	Drug: Varenicline; Other Names: Chantix
Placebo Comparator: Placebo Oral 1.0 mg BID.	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Report no Cocaine Use and Have no Cocaine Positive Urine Drug Screens in the Chantix Group Versus the Placebo Group Comparator During the Last Three Weeks of the Trial [weeks 11,12,13 of the trial]

   Number of subjects with cocaine abstinence as measured through three-times-weekly urine benzoylecgonine (BE) levels in urine drug screen (UDS) and self-reports of use from the Time Line Follow Back. UDS results and TLFB reports combined to yield weekly use/no-use indicators for each week of treatment.

Secondary Outcome Measures

1. Average Weekly Cocaine Craving Scores Varenicline Group Versus the Placebo Group Comparator [Once per week in weeks 2 through 13]

   As measured by average weekly scores for cocaine craving on the brief substance craving scale combining cocaine craving frequency, intensity and duration. Minimum value 0 maximum value 12 higher scores indicate worse craving.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Males and females, 18 to 65 years old.

2. Meets DSM-IV criteria for Cocaine Dependence, as determined by the Structured Clinical Interview for DSM-IV (SCID).

3. Live within a commutable distance of the Treatment Research Center (TRC) at the Penn/VA Center for Studies of Addiction, University of Pennsylvania. We define this to be a distance within the service area of Septa, within an hour drive, or a distance that both the patient and Principal Investigator (PI) find acceptable.

4. Understands and signs the informed consent.

Exclusion Criteria:

1. Current DSM-IV diagnosis of any psychoactive substance dependence other than cocaine, alcohol, or nicotine dependence, as determined by the SCID.

2. Subject is, in the investigator's opinion, at risk of requiring medical detoxification for alcohol dependence during the study.

3. Concomitant treatment with psychotropic medications.

4. Current gambling problems. This will be assessed by the patient's self-report.

5. Patients mandated to treatment based upon a legal decision or as a condition of employment who will use participation in this study to fulfill to their court mandated treatment requirement.This will be assessed by the patient's self-report.

6. Current severe psychiatric symptoms, e.g., psychosis, dementia, suicidal or homicidal ideation, mania or depression requiring antidepressant therapy in the opinion of the Principal Investigator (PI).

7. Use of any investigational medication within the past 30 days.

8. Subject has serious heart, lung, kidney, immune system, GI tract (ulcerative colitis, regional enteritis, or gastrointestinal bleeding) disease.

9. Current use of naltrexone, disulfiram, modafinil, stimulants, haloperidol, benzodiazepines or anticonvulsants.

10. Known hypersensitivity to varenicline.

11. Patients with known AIDS or other serious illnesses that may require hospitalization during the study.

12. Female subjects who are pregnant or lactating, or female subjects of child-bearing potential who are not using acceptable methods of birth control. Acceptable methods of birth control include:

13. barrier (diaphragm or condom) with spermicide

14. intrauterine progesterone contraceptive system

15. levonorgestrel implant

16. medroxyprogesterone acetate contraceptive injection

17. oral contraceptives

18. tubal ligation.

19. Patients with impaired renal function as indicated by corrected creatinine clearance below 60 ml/min as determined by the modified Cockcroft equation (CDC, 1986).

20. Clinical laboratory tests (CBC, blood chemistries, urinalysis) outside normal limits that are clinically unacceptable to the Medical Director. EKG 1st degree heart block, sinus tachycardia, left axis deviation, and nonspecific ST or T wave changes are allowed; liver function tests [LFTs] <5 x ULN are acceptable).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania Treatment Research Center	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania

Investigators

• Principal Investigator: Kyle M Kampman, MD, University of Pennsylvania

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 28, 2019

More Information

Additional Information:

• University of Pennsylvania Center for Studies of Addictions

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01680887
• Other Study ID Numbers: 814643
• First Posted: Sep 7, 2012
• Last Update Posted: Aug 6, 2019
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by University of Pennsylvania: Cocaine dependence
• Additional relevant MeSH terms: Cocaine-Related Disorders; Varenicline

Study Results

Participant Flow

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	Oral 1.0 mg BID. Varenicline	Oral 1.0 mg BID. Placebo
Period Title: Overall Study
STARTED	80	76
COMPLETED	51	52
NOT COMPLETED	29	24

Baseline Characteristics

Arm/Group Title	Varenicline	Placebo	Total
Arm/Group Description	Oral 1.0 mg BID. Varenicline	Oral 1.0 mg BID. Placebo	Total of all reporting groups
Overall Participants	80	76	156
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	80 100%	75 98.7%	155 99.4%
>=65 years	0 0%	1 1.3%	1 0.6%
Sex: Female, Male (Count of Participants)
Female	18 22.5%	16 21.1%	34 21.8%
Male	62 77.5%	60 78.9%	122 78.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	68 85%	68 89.5%	136 87.2%
White	12 15%	8 10.5%	20 12.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	80 100%	76 100%	156 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Report no Cocaine Use and Have no Cocaine Positive Urine Drug Screens in the Chantix Group Versus the Placebo Group Comparator During the Last Three Weeks of the Trial
Description	Number of subjects with cocaine abstinence as measured through three-times-weekly urine benzoylecgonine (BE) levels in urine drug screen (UDS) and self-reports of use from the Time Line Follow Back. UDS results and TLFB reports combined to yield weekly use/no-use indicators for each week of treatment.
Time Frame	weeks 11,12,13 of the trial

Outcome Measure Data

Analysis Population Description

all subject

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	Oral 1.0 mg BID. Varenicline	Oral 1.0 mg BID. Placebo
Measure Participants	80	76
Count of Participants [Participants]	6 7.5%	7 9.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Varenicline, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.403
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Average Weekly Cocaine Craving Scores Varenicline Group Versus the Placebo Group Comparator
Description	As measured by average weekly scores for cocaine craving on the brief substance craving scale combining cocaine craving frequency, intensity and duration. Minimum value 0 maximum value 12 higher scores indicate worse craving.
Time Frame	Once per week in weeks 2 through 13

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Varenicline	Placebo
Arm/Group Description	Oral 1.0 mg BID. Varenicline	Oral 1.0 mg BID. Placebo
Measure Participants	80	76
Mean (Standard Deviation) [score on a scale]	1.12 (0.82)	0.99 (0.71)

Adverse Events

Time Frame	17 weeks
Adverse Event Reporting Description	Adverse events were queried at each visit.
Arm/Group Title	Varenicline		Placebo
Arm/Group Description	varenicline 2 mg daily		Identical placebo capsules
All Cause Mortality
	Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/80 (0%)		0/76 (0%)
Serious Adverse Events
	Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/80 (7.5%)		6/76 (7.9%)
Cardiac disorders
chest pain, cocaine induced	1/80 (1.3%)	1	0/76 (0%)	0
mitral valve replacement	0/80 (0%)	0	1/76 (1.3%)	1
chest pain	1/80 (1.3%)	1	0/76 (0%)	0
Gastrointestinal disorders
Lower abdominal mass	1/80 (1.3%)	1	0/76 (0%)	0
gastroenteritis	0/80 (0%)	0	1/76 (1.3%)	1
nausea	1/80 (1.3%)	1	0/76 (0%)	0
General disorders
gunshot wound	0/80 (0%)	0	1/76 (1.3%)	1
Psychiatric disorders
Cocaine use disorder exacerbation	1/80 (1.3%)	1	0/76 (0%)	0
Substance induced depression	0/80 (0%)	0	1/76 (1.3%)	1
oiate detoxification	1/80 (1.3%)	1	0/76 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary edema	0/80 (0%)	0	1/76 (1.3%)	1
Vascular disorders
orthostatic hypotension	0/80 (0%)	0	1/76 (1.3%)	1
Other (Not Including Serious) Adverse Events
	Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	80/80 (100%)		67/76 (88.2%)
Blood and lymphatic system disorders
elevated blood pressure	14/80 (17.5%)		11/76 (14.5%)
Gastrointestinal disorders
diarrhea	9/80 (11.3%)		14/76 (18.4%)
abdominal pain	11/80 (13.8%)		9/76 (11.8%)
nausea	19/80 (23.8%)		5/76 (6.6%)
flatulence	6/80 (7.5%)		5/76 (6.6%)
General disorders
headache	15/80 (18.8%)		11/76 (14.5%)
toothache	8/80 (10%)		7/76 (9.2%)
fatigue	5/80 (6.3%)		7/76 (9.2%)
lightheadedness	4/80 (5%)		6/76 (7.9%)
Musculoskeletal and connective tissue disorders
aches and pains	20/80 (25%)		23/76 (30.3%)
Nervous system disorders
vivid dreams	11/80 (13.8%)		2/76 (2.6%)
Respiratory, thoracic and mediastinal disorders
upper respiratory tract infection	26/80 (32.5%)		27/76 (35.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.