A Study to Evaluate EMB 001 in Subjects With Cocaine Use Disorder

Study Overview
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Brief Summary
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EMB-001 is a combination of 2 drugs: the cortisol synthesis inhibitor, metyrapone (Metopirone®), and the benzodiazepine receptor agonist, oxazepam (original trade name Serax®; now marketed as oxazepam (generic) only). This is a Phase 2 study in approximately 80 adult subjects with moderate-to-severe Cocaine Use Disorder (CUD).

Detailed Description
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This study is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, study to compare the safety and efficacy of EMB-001 with a placebo control in approximately 80 subjects with moderate-to-severe CUD. Subjects will receive investigational medicinal product (IMP) during a 12-week, double-blind Treatment Period (Week 2 through Week 13) and a 1-week, double-blind Taper Period (Week 14). After undergoing study procedures during the Screening and Baseline Periods, subjects who meet inclusion and exclusion criteria will then be randomized in a 1:1 ratio (n=40/arm) to one of the following for the Treatment Period (weeks 2 - 13) on Study Day 8: EMB-001 720 mg metyrapone/24 mg oxazepam mg BID, for a total daily dose of 1440 mg metyrapone and 48 mg oxazepam (Active Group) Placebo BID, (Placebo Group) During the Taper Period (week 14), subjects in the Active Group will receive EMB-001 240/8 mg BID; and the Placebo Group will continue to receive placebo. Both groups will change from taking three capsules BID (twice daily) to one capsule BID (twice daily). There will be a follow-up visit for safety assessments at Week 18.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Study to Evaluate the Safety and Efficacy of EMB 001 in Subjects With Moderate-to-Severe Cocaine Use Disorder

Conditions
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Cocaine Use Disorder

Intervention / Treatment
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* Drug: EMB-001
* Drug: EMB-001 Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Provide written informed consent prior to any study procedures 18 to 65 years of age DSM-5 diagnosis of moderate-to-severe CUD Seeking treatment for CUD. Subjects with past rehabilitation attempts are eligible if the most recent rehabilitation attempt ended at least 30 days prior to Screening Female subjects must be of non-childbearing potential Male subjects must agree to use accepted contraceptive regimens during the study and for at least 90 days after the last dose of the study drug Key Exclusion Criteria: Any significant current medical conditions Known hypersensitivity to or intolerance of oxazepam, metyrapone, or any benzodiazepine, or severe hypersensitivity reaction (e.g., angioedema) to any drug Heightened likelihood of having adrenal insufficiency in the investigator's or designees' opinion Current court-mandated treatment requirement for a substance-use disorder Current DSM-5 moderate-to-severe substance use disorder, other than CUD, tobacco or caffeine Current DSM-5 opioid or benzodiazepine use disorder of any severity

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: EMB-001 Active<br>EMB-001 Combination product of 720 mg metyrapone/24 mg oxazepam mg by mouth twice per day for 12 weeks followed by a 1 week taper | Drug: EMB-001<br>* 720 mg metyrapone/24 mg oxazepam mg BID<br>|
| Placebo Comparator: EMB-001 Placebo<br>EMB-001 Placebo by mouth twice per day for 12 weeks followed by a 1 week taper | Drug: EMB-001 Placebo<br>* Inactive comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Continuous Abstinence from Cocaine Use | The Primary Endpoint is the Proportion of Subjects That Successfully Achieve Abstinence From Cocaine During the Last Three Weeks of Treatment using the Timeline Follow Back; days of abstinence, confirmed by Urine benzoylecgonine (BE) | Week 11 to Week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | Adverse event data (including clinically significant changes in laboratory values) will be compiled for EMB-001 and placebo cohorts. | 13 weeks | 
| Reduction in cocaine-use days | Self-report weekly cocaine non-use days by Timeline Follow-Back | Week 2 to Week 13 | 
| Urine confirmation of cocaine use | Qualitative urine BE levels twice per week | Week 2 to Week 13 | 
| Reduction in total Cocaine Craving Questionnaire-Brief score | The Cocaine Craving Questionnaire-Brief (CCQ-B) assesses current cocaine craving in routine clinical practice. The CCQ-B is a 10 item questionnaire and items are scored on a one to seven scale. Total responses are then divided by 10 to achieve a total craving score between 1.0 (least craving) to 7.0 (most craving). | Week 2 to Week 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cocaine