Study of Safety and Potential Efficacy of SYN117 in Cocaine Dependent Volunteers

Study Overview
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Brief Summary
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This study will assess the potential interaction and subjective effects between intravenous cocaine and SYN117 in non-treatment seeking cocaine dependant subjects

Official Title
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A Human Laboratory Assessment of the Safety and Potential Efficacy of SYN117 (Nepicastat) in Cocaine-dependent Volunteers Receiving Cocaine

Conditions
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Cocaine Dependence

Intervention / Treatment
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* Drug: SYN117 Placebo
* Drug: SYN117 80 mg
* Drug: SYN117 160 mg
* Drug: Cocaine 10mg
* Drug: Cocaine 20mg
* Drug: Cocaine 40mg
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: non treatment seeking cocaine dependent English speaking meet DSM IV TR criteria for cocaine dependence pulse 50-90bpm systolic BP 85-140 mmHg diastolic BP 45-90 mmHg essentially normal liver and kidney function blood tests ECG normal sign informed consent negative urine pregnancy test at screening and admission Exclusion Criteria: history or evidence of seizure disorder or brain injury previous medically adverse reaction to cocaine, including loss of consciousness, chest pain or epileptic seizure neurological disorders, organic brain disease, dementia psychiatric disorders such as psychosis, schizophrenia, bipolar disorder, major depression history of suicide attempts within past 3 months or suicidal ideation/plan history of clinically significant heart disease or hypertension family history in 1st degree relatives of early cardiovascular morbidity or mortality untreated or unstable medical conditions positive HIV test pregnant or nursing have asthma or are currently using alpha, beta agonists or theophylline or other sympathomimetics test positive for other drugs of abuse with the exception of cocaine, cocaine metabolites or marijuana any other illness, condition or use of psychotropic medications which preclude safe/successful completion of the study currently on parole

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: A<br>SYN117 placebo and Ascending doses of cocaine (10, 20, 40 mg) and placebo | Drug: SYN117 Placebo<br>* Placebo<br>Drug: Cocaine 10mg<br>* IV Cocaine 10mg<br>Drug: Cocaine 20mg<br>* IV Cocaine 20mg<br>Drug: Cocaine 40mg<br>* IV Cocaine 40mg<br>Drug: Saline<br>* IV Cocaine Placebo<br>|
| Experimental: B<br>Ascending doses of SYN117 (placebo, 80 mg, 160 mg) and ascending doses of cocaine (10 mg, 20 mg, 40 mg) and placebo | Drug: SYN117 80 mg<br>* SYN117 80 mg<br>Drug: SYN117 160 mg<br>* SYN117 160 mg<br>Drug: Cocaine 10mg<br>* IV Cocaine 10mg<br>Drug: Cocaine 20mg<br>* IV Cocaine 20mg<br>Drug: Cocaine 40mg<br>* IV Cocaine 40mg<br>Drug: Saline<br>* IV Cocaine Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the safety of treatment with SYN117 in cocaine-dependent volunteers by measuring hemodynamic and subjective effects of administration of ascending doses of cocaine(10mg, 20mg, 40mg)and placebo during treatment with ascending doses of SYN117. |  | inpatient 14 days with 2 week outpatient follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine tolerability by measuring adverse events |  | inpatient 14 days, 2 weeks post followup visit | 
| Determine subjective effects produced by self administration of cocaine or placebo |  | Days 4, 8, 12 and 13 | 
| Determine the effect of SYN117 of the pharmacokinetics of IV cocaine |  | Days 3 and 11 | 
| Determine if any baseline measures of impulsivity or drug use severity predict efficacy of SYN117 in reducing subjective effects of cocaine |  | Days 4, 8 and 12 |