Vigabatrin for Treatment of Cocaine Dependence

• Sponsor: Catalyst Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00611130
• Collaborator: (none)
• Enrollment: 186
• Locations: 11
• Arms: 2
• Duration (Months): 57
• Patients Per Site: 16.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The objective of this study is to demonstrate that a larger proportion of vigabatrin-treated subjects than placebo-treated subjects will be cocaine-free in the last 2 weeks of treatment.

Condition or Disease	Intervention/Treatment	Phase
Cocaine Dependence	Drug: vigabatrin; Drug: placebo	Phase 2

Detailed Description

Cocaine addiction, a serious public health concern associated with significant medical, social, and economic consequences, is difficult to treat using traditional psychosocial and behavioral therapies. Despite testing of a number of different agents for cocaine dependency, there remains no proven pharmacologic treatment for cocaine addiction.

The addictive properties of cocaine have been associated with its actions on mesotelencephalic dopamine reward pathways in the central nervous system (CNS). Cocaine administration increases the levels of dopamine, a neurotransmitter associated with sensations of pleasure and reward. Therefore, blocking cocaine-induced increases in dopamine levels represents a valid pharmaceutical approach to the treatment of cocaine addiction.

Another neurotransmitter, gamma-aminobutyric acid (GABA), suppresses striatal dopamine release, and attenuates cocaine-induced increases in extracellular and synaptic dopamine levels in the striatum and nucleus accumbens in animal models of drug dependence. Significant elevation of brain GABA levels may reduce cocaine-stimulated dopamine release and dampen the sensations of pleasure and reward. Thus, drugs that potentiate or enhance GABA-ergic transmission are candidates for the treatment of cocaine addiction.

Study Design

• Study Type: Interventional
• Actual Enrollment: 186 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Vigabatrin for Treatment of Cocaine Dependence: A Phase II Study
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 3 Vigabatrin Tablets, 500 mg, bid, for 9 weeks	Drug: vigabatrin; Tablets twice a day for 9 weeks; Other Names: CPP-109, VGB, GVG
Placebo Comparator: 2 3 Placebo Tablets, bid, for 9 weeks	Drug: placebo; tablets twice daily for 9 weeks

Outcome Measures

Primary Outcome Measures

1. Proportion of Subjects in Each Treatment Group Abstinent During the Last 2 Weeks of Treatment. [Week 13]

   Number of subjects in the CPP-109 Vigabatrin Group vs. Number in Placebo Group abstinent from using cocaine during Weeks 11 and 12 of the Treatment Phase.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Able to understand the study and provide written informed consent.

• Male or female at least 18 years of age.

• Meets DSM-IV (Diagnostic and Statistical Manual of Mental Disorders Fourth Edition) criteria for cocaine dependence as primary diagnosis, as determined by the Substance Abuse module of SCID (Structured Clinical Interview for DSM-IV).

• Provide at least one urine sample that is positive for cocaine according to a rapid screening test.

• Seeking treatment for cocaine dependence.

• Have normal visual fields.

• Be in generally good health based on history, physical examination, electrocardiogram and laboratory findings.

• If female of childbearing potential, use acceptable contraceptive methods. (oral contraceptives (the pill), IUDs, contraceptive implants under the skin, contraceptive rings or patches or injections, diaphragms with spermicide, and condoms with spermicide). Surgical sterilization by tubal ligation or hysterectomy is acceptable

Exclusion Criteria:

• Has current dependence, as determined by the SCID, on any psychoactive substance other than cocaine, alcohol, nicotine, or marijuana or physiologic dependence on alcohol requiring medical detoxification.

• Has any serious medical or psychiatric illness and/or clinically significant abnormal laboratory value, which in the judgment of the Principal Investigator or his/her designee would make study participation unsafe, or would make treatment compliance difficult or put the study staff at undue risk.

• Be under court mandate to obtain treatment.

• Be enrolled in an opiate substitution treatment program within 2 months of randomization.

• Has ever taken vigabatrin in the past.

• Is pregnant or lactating.

• Has clinically significant ophthalmologic disease, which would preclude safety monitoring or is undergoing treatment for ocular disease.

• Has received a drug with known major organ toxicity, including retinotoxicity within 30 days of randomization.

• Is currently participating in, or has been enrolled in another clinical trial within the last 30 days.

• Be anyone who, in the judgment of the investigator, would not be expected to attend regular study visits or to complete the study protocol, due to imminent relocation from the clinic area, legal difficulties, work-related problems, transportation, etc.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Addiction Treatment Clinic	Little Rock	Arkansas	United States
2	St. Luke's Hospital Addiction Pharmacology Research Laboratory	San Francisco	California	United States	94110
3	Friends Research Institute	Torrance	California	United States
4	Operation PAR	Largo	Florida	United States
5	Segal Institute for Clinical Research	North Miami	Florida	United States	33161
6	Johns Hopkins Bayview Medical Center Center for Chemical Dependence	Baltimore	Maryland	United States
7	Boston University School of Medicine	Boston	Massachusetts	United States
8	New York University Mental Health and Addictive Disorders Research Program	New York	New York	United States
9	Cincinnati Addiction Research Center (CinARC)	Cincinnati	Ohio	United States
10	Dayton Veterans Affairs Medical Center	Dayton	Ohio	United States
11	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States

Sponsors and Collaborators

• Catalyst Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Eugene Somoza, MD, PhD, University of Cincinnati

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Catalyst Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT00611130
• Other Study ID Numbers: CPP-01004
• First Posted: Feb 8, 2008
• Last Update Posted: Apr 13, 2016
• Last Verified: Mar 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Catalyst Pharmaceuticals, Inc.: Cocaine; Addiction; Dependence; Treatment
• Additional relevant MeSH terms: Cocaine-Related Disorders; Vigabatrin

Study Results

Participant Flow

Recruitment Details	01/08-01/09 at 11 US research trial sites.
Pre-assignment Detail	After Informed Consent obtained, subjects entered a 2-4 week Screening/Baseline Phase to determine whether all Inclusion/Exclusion Criteria were met. Randomization strata included gender, primary method of cocaine administration (snort or intravenous/smoke) & use in last 30 days (≤18 days or >18 days)

Arm/Group Title	CPP-109 Vigabatrin	Placebo
Arm/Group Description	CPP-109 tablets, 500 mg. 3 Tablets bid.	Matching Placebo Tablets. 3 tablets bid.
Period Title: Overall Study
STARTED	92	94
Completed 12 Week Treatment Phase	61	64
COMPLETED	43	47
NOT COMPLETED	49	47

Baseline Characteristics

Arm/Group Title	CPP-109 Vigabatrin	Placebo	Total
Arm/Group Description	CPP-109 tablets, 500 mg. 3 Tablets bid.	Matching Placebo Tablets. 3 tablets bid.	Total of all reporting groups
Overall Participants	92	94	186
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.6 (7.62)	45.0 (8.33)	44.8 (7.92)
Sex: Female, Male (Count of Participants)
Female	32 34.8%	30 31.9%	62 33.3%
Male	60 65.2%	64 68.1%	124 66.7%
Region of Enrollment (participants) [Number]
United States	92 100%	94 100%	186 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Subjects in Each Treatment Group Abstinent During the Last 2 Weeks of Treatment.
Description	Number of subjects in the CPP-109 Vigabatrin Group vs. Number in Placebo Group abstinent from using cocaine during Weeks 11 and 12 of the Treatment Phase.
Time Frame	Week 13

Outcome Measure Data

Analysis Population Description

intent-to-treat

Arm/Group Title	CPP-109 Vigabatrin Tablets, 500 mg	Matching Placebo Tablets
Arm/Group Description	Vigabatrin Tablets, 1.5 g bid po, 12 weeks, computerized cognitive behavioral therapy plus contingency management.Subjects proceeded to a 12 week Treatment Phase, including a 2 week dose escalation period, a 9 week maintenance period (3.0 gm/day of vigabatrin) and a 1 week medication taper period. Finally, subjects then proceeded to a 12 week follow-up period. Subjects attended clinic visits 3 times per week (typically on Monday, Wednesday, and Friday) for efficacy and safety assessments and for treatment during the Screening/Baseline Phase and the 12 week Treatment Phase. Subjects returned for follow up visits at Weeks 13, 16, 20 and 24.	Subjects proceeded to a 12 week Treatment Phase,receiving 3 tablets bid po Finally, subjects then proceeded to a 12 week follow-up period. Subjects attended clinic visits 3 times per week (typically on Monday, Wednesday, and Friday) during the Screening/Baseline Phase and the 12 week Treatment Phase. Subjects returned for follow up visits at Weeks 13, 16, 20 and 24.
Measure Participants	92	94
Number [participants]	7 7.6%	5 5.3%

2. Post-Hoc Outcome

Title	Medication Compliance
Description	Using retained urine samples and prior to unblinding, up to 12 specimens/ subject were analyzed for vigabatrin levels. Compliance assessment based on > or = 70% of urines in subjects assigned to vigabatrin having quantitative levels of vigabatrin indicaticative of taking drug within the last 24 hours of clinic visit.
Time Frame	Week 2, 4, 6 & 9-11

Outcome Measure Data

Analysis Population Description

Completers were defined as those who attended the scheduled Week 13 visit or the third visit of Week 12 and who also had provided urines during Weeks 11 & 12.

Arm/Group Title	Treatment Phase Completers
Arm/Group Description	Up to 12 urine specimens out of 37 collected during the Treatment Phase completers were analyzed for vigabatrin levels.
Measure Participants	125
Number of Vigabatrin Completers Analyzed	61 66.3%
Number Medication Compliant	24 26.1%

Adverse Events

Arm/Group Title	CPP-109 Vigabatrin Tablets, 500 mg		Matching Placebo Tablet
Arm/Group Description	Vigabatrin Tablets, 1.5 g bid po, 12 weeks. Subjects proceeded to a 12 week Treatment Phase, including a 2 week dose escalation period, a 9 week maintenance period (3.0 gm/day of vigabatrin), and a 1 week medication taper period. Finally, subjects then proceeded to a 12 week follow-up period. Subjects were scheduled for clinic visits 3 times per week (typically on Monday, Wednesday, and Friday) during the Screening/Baseline Phase and the 12 week Treatment Phase. Subjects returned for follow up visits at Weeks 13, 16, 20 and 24.		Subjects proceeded to a 12 week Treatment Phase,receiving 3 tablets bid po Finally, subjects then proceeded to a 12 week follow-up period. Subjects were scheduled for clinic visits 3 times per week (typically on Monday, Wednesday, and Friday) during the Screening/Baseline Phase and the 12 week Treatment Phase. Subjects returned for follow up visits at Weeks 13, 16, 20 and 24.
All Cause Mortality
	CPP-109 Vigabatrin Tablets, 500 mg		Matching Placebo Tablet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	CPP-109 Vigabatrin Tablets, 500 mg		Matching Placebo Tablet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/92 (6.5%)		0/94 (0%)
Cardiac disorders
Tachycardia	1/92 (1.1%)		0/94 (0%)
Hepatobiliary disorders
Hepatitis, acute	1/92 (1.1%)		0/94 (0%)
Infections and infestations
Meningitis & Pneumonia	1/92 (1.1%)		0/94 (0%)
Injury, poisoning and procedural complications
Gun shot wound, road traffic accident & tibia fracture	2/92 (2.2%)		0/94 (0%)
Psychiatric disorders
Drug Abuse & Major Depression	2/92 (2.2%)		0/94 (0%)
Other (Not Including Serious) Adverse Events
	CPP-109 Vigabatrin Tablets, 500 mg		Matching Placebo Tablet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	73/92 (79.3%)		81/94 (86.2%)
Eye disorders
Photopsia	8/92 (8.7%)		1/94 (1.1%)
Blurred vision	6/92 (6.5%)		6/94 (6.4%)
Visual disturbance	6/92 (6.5%)		3/94 (3.2%)
Gastrointestinal disorders
Constipation	5/92 (5.4%)		5/94 (5.3%)
Diarrhea	14/92 (15.2%)		15/94 (16%)
Nausea	9/92 (9.8%)		17/94 (18.1%)
Stomach discomfort	3/92 (3.3%)		7/94 (7.4%)
Toothache	2/92 (2.2%)		7/94 (7.4%)
Vomiting	1/92 (1.1%)		7/94 (7.4%)
General disorders
Fatigue	7/92 (7.6%)		9/94 (9.6%)
Infections and infestations
Nasopharyngitis	17/92 (18.5%)		17/94 (18.1%)
Investigations
ALT decreased	7/92 (7.6%)		0/94 (0%)
CPK increased	6/92 (6.5%)		3/94 (3.2%)
Weight increased	5/92 (5.4%)		3/94 (3.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/92 (5.4%)		7/94 (7.4%)
Back pain	8/92 (8.7%)		10/94 (10.6%)
Pain in extremity	0/92 (0%)		6/94 (6.4%)
Nervous system disorders
Headache	10/92 (10.9%)		26/94 (27.7%)
Somnolence	5/92 (5.4%)		5/94 (5.3%)
Dizziness	3/92 (3.3%)		6/94 (6.4%)
Psychiatric disorders
Anxiety	1/92 (1.1%)		6/94 (6.4%)
Insomnia	7/92 (7.6%)		3/94 (3.2%)

Limitations/Caveats

Lack of subject medication compliance, site-to-site variability in medication compliance possibly indicative of differing site capabilities to attract subjects sufficiently motivated to stop using cocaine.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.