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

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

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).

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.

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