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

Female subjects must be of non-childbearing potential.

Every three months, the NIDA DSMB will convene to review the overall safety data, as well as data on safety summarized by treatment condition. As per NIH guidelines, the objective of these reviews will be to determine whether continued conduct of the trial poses any undue risk for participants. Blinded data tables, figures and/or listings will be provided to the Data Safety Monitoring Board (DSMB).

Every three months- blinded results

A DSMB report is prepared an submitted via NIDA