Cocaine Dependence
Conditions
Keywords
Cocaine, Addiction, Dependence, Treatment
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.
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.
Interventions
DRUGvigabatrin
Tablets twice a day for 9 weeks
DRUGplacebo
tablets twice daily for 9 weeks
Sponsors
Catalyst Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
01/08-01/09 at 11 US research trial sites.
Pre-assignment details
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)
Participants by arm
| Arm | Count |
|---|---|
| CPP-109 Vigabatrin CPP-109 tablets, 500 mg. 3 Tablets bid. | 92 |
| Placebo Matching Placebo Tablets. 3 tablets bid. | 94 |
| Total | 186 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative | 1 | 1 |
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Incarceration | 3 | 2 |
| Overall Study | Lost to Follow-up | 25 | 29 |
| Overall Study | Other | 5 | 4 |
| Overall Study | Protocol noncompliance | 7 | 6 |
| Overall Study | Withdrawal by Subject | 6 | 5 |
Baseline characteristics
| Characteristic | CPP-109 Vigabatrin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 44.6 years STANDARD_DEVIATION 7.62 | 45.0 years STANDARD_DEVIATION 8.33 | 44.8 years STANDARD_DEVIATION 7.92 |
| Region of Enrollment United States | 92 participants | 94 participants | 186 participants |
| Sex: Female, Male Female | 32 Participants | 30 Participants | 62 Participants |
| Sex: Female, Male Male | 60 Participants | 64 Participants | 124 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 73 / 92 | 81 / 94 |
| serious Total, serious adverse events | 6 / 92 | 0 / 94 |
Outcome results
Primary
Proportion of Subjects in Each Treatment Group Abstinent During the Last 2 Weeks of Treatment.
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
Population: intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CPP-109 Vigabatrin Tablets, 500 mg | Proportion of Subjects in Each Treatment Group Abstinent During the Last 2 Weeks of Treatment. | 7 participants |
| Matching Placebo Tablets | Proportion of Subjects in Each Treatment Group Abstinent During the Last 2 Weeks of Treatment. | 5 participants |
Post Hoc
Medication Compliance
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CPP-109 Vigabatrin Tablets, 500 mg | Medication Compliance | Number of Vigabatrin Completers Analyzed | 61 participants |
| CPP-109 Vigabatrin Tablets, 500 mg | Medication Compliance | Number Medication Compliant | 24 participants |