A Study of Metyrapone and Oxazepam Combination Product (EMB-001) and Cocaine

A Phase 1b, Randomized, Double-Blinded, Multiple-Dose, Placebo Controlled, Crossover Study To Evaluate The Safety, Tolerability And Pharmacokinetic Effects Of A Metyrapone And Oxazepam Combination (EMB-001) When Co-Administered With Cocaine

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 Phase 1b cocaine interaction study is being conducted in order to assess the safety and PK of EMB-001 and cocaine in combination.

This is a single center, randomized, double-blinded, multiple-dose, PLB controlled, 2-period, 4-sequence, crossover study design.

After establishing eligibility approximately 16 subjects with cocaine use disorder will be randomized to one of four sequences.

Treatment periods will be separated by a 7-day in-patient washout period. EMB-001/PLB will be orally administered for 7 consecutive days, BID for 6 days (starting on Day 1 and Day 15) followed on the last day (Day 7 and Day 21) by one EMB-001/PLB oral dose in the morning. Infusion of 40 mg IV cocaine and IV saline-to-match cocaine infusion will be administered in a randomized order, 2 hours apart, starting 3 hours after the last morning EMB-001/PLB oral administration.

The subjects will be discharged from the research clinic 2 days after the last dose of cocaine, and will have a follow-up visit 7 days after last dose.

Inclusion Criteria:

• non-treatment-seeking cocaine users with a positive urine toxicology screen for cocaine at least once during screening
• have a medical history and physical examination that demonstrate no clinically significant contraindication for participating in the study
• males must use contraception; females must be of non-childbearing potential

Exclusion Criteria:

• drug allergies or reactions to metyrapone or benzodiazepines, or severe hypersensitivity reactions (like angioedema) to any drugs
• history of clinically significant adverse reaction to cocaine
• a low out-of-range serum cortisol value at screening or subjects who have a heightened likelihood of having adrenal insufficiency, or have signs or a history of adrenal insufficiency or confounders of the levels of cortisol and/or cortisol binding globulin
• treatment with glucocorticoids
• history of seizures, benzodiazepine use disorder, respiratory disease, neurologic or neuromuscular disease, liver disease or cardiovascular disease
• other psychiatric or substance use disorders of clinical significance, or suicidality
• clinically significant finding on medical history, physical examination, clinical laboratory tests, vital signs or ECGs
• use of any other drugs
• abnormal BP or HR
• positive urine drug screen at for alcohol or any drug other than marijuana (THC) or cocaine
• positive serology test results for HIV-1/HIV-2 Antibodies, Hepatitis B surface Antigen (HBsAg) or Hepatitis C Antibody (HCVAb)