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

NCT02856854 | Completed Phase 1 DMC

• 2 other identifiers: ERL-002U01DA038879
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Cocaine Use Disorder

Outcome Measures

Primary Outcomes (3)

• 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.

  29 Days

• Vital signs

  Blood Pressure (BP) and heart rate (HR) measures during saline infusions will be compared to HR and BP after cocaine infusion (40 mg). Changes in BP and HR induced by cocaine infusion along with EMB-001 will be compared to those with EMB-001-matched placebo.

  29 days

• ECGs

  Changes in ECG readings during saline infusion will be compared to those taken during cocaine infusion along with EMB-001 will be compared to those with EMB-001-matched placebo.

  29 days

Secondary Outcomes (4)

• PK Parameter EMB-001

  21 days

• PK Parameter Cocaine

  21 days

• PK Parameter EMB-001

  21 days

• PK Parameter Cocaine

  21 days

Study Arms (2)

EMB-001 (oral)

EXPERIMENTAL

EMB-001 will be orally administered for 7 consecutive days, twice daily for 6 days followed on the last day by one EMB-001 oral dose (QD) in the morning. Three hours later Cocaine IV or Saline IV will be administered followed 2 hours by the other (saline or cocaine).

Drug: EMB-001; Drug: Cocaine IV; Drug: Saline IV

Placebo (oral)

PLACEBO COMPARATOR

PLB-to-match EMB-001 will be orally administered for 7 consecutive days, BID for 6 days, followed on the last day by one PLB oral dose in the morning. Three hours later Cocaine IV or Saline IV will be administered followed 2 hours by the other (saline or cocaine).

Drug: Placebo; Drug: Cocaine IV; Drug: Saline IV

Interventions

EMB-001 DRUG

EMB-001 is a combination of metyrapone (720mg per dose in this study) and oxazepam (24mg per dose in this study)

Also known as: metyrapone and oxazepam

EMB-001 (oral)

Placebo DRUG

EMB-001 matched placebo

Also known as: oral placebo

Placebo (oral)

Cocaine IV DRUG

Cocaine administered at doses of 20 and 40mg

Also known as: IV cocaine

EMB-001 (oral); Placebo (oral)

Saline IV DRUG

Cocaine matched placebo

Also known as: IV saline

EMB-001 (oral); Placebo (oral)

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Embera NeuroTherapeutics, Inc.: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Vince & Associates

Overland Park, Kansas, 66212, United States

Location

Related Publications (1)

• 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.

  PMID: 22236504 BACKGROUND

MeSH Terms

Interventions

Metyrapone; Oxazepam; Cocaine; Sodium Chloride

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Debra Kelsh, MD

  Vince & Associates

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2016
• First Posted: August 5, 2016
• Study Start: July 1, 2016
• Primary Completion: February 17, 2017
• Study Completion: July 25, 2017
• Last Updated: August 1, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Every three months- blinded results
• Access Criteria: A DSMB report is prepared an submitted via NIDA.

Locations

US (1)