Clinical trial NCT02856854: A Study of Metyrapone and Oxazepam Combination Product (EMB-001) and Cocaine
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cocaine Use Disorder
Lead sponsor: Embera NeuroTherapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2016-08-05
Enrollment: 18
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
timeFrame: 29 Days
measure: Vital signs
timeFrame: 29 days
measure: ECGs
timeFrame: 29 days
Secondary outcomes:
measure: PK Parameter EMB-001
timeFrame: 21 days
measure: PK Parameter Cocaine
timeFrame: 21 days
measure: PK Parameter EMB-001
timeFrame: 21 days
measure: PK Parameter Cocaine
timeFrame: 21 days
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Vince & Associates
state: Kansas
Study officials:
affiliation: Vince & Associates
name: Debra Kelsh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kablinger AS, Lindner MA, Casso S, Hefti F, DeMuth G, Fox BS, McNair LA, McCarthy BG, Goeders NE. Effects of the combination of metyrapone and oxazepam on cocaine craving and cocaine taking: a double-blind, randomized, placebo-controlled pilot study. J Psychopharmacol. 2012 Jul;26(7):973-81. doi: 10.1177/0269881111430745. Epub 2012 Jan 11.