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

Cocaine Use Disorder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02856854
• Other study ID #: ERL-002
• Secondary ID: U01DA038879
• Status: Completed
• Phase: Phase 1
• First received: July 22, 2016
• Last updated: July 31, 2017
• Start date: July 2016
• Est. completion date: July 25, 2017

Study information

• Verified date: July 2017
• Source: Embera NeuroTherapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: July 25, 2017
• Est. primary completion date: February 17, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 55 Years

Eligibility

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)

Related Conditions & MeSH terms

• Cocaine Use Disorder

Intervention

Drug:
• EMB-001
EMB-001 is a combination of metyrapone (720mg per dose in this study) and oxazepam (24mg per dose in this study)
• Placebo
EMB-001 matched placebo
• Cocaine IV
Cocaine administered at doses of 20 and 40mg
• Saline IV
Cocaine matched placebo

Locations

Country	Name	City	State
United States	Vince & Associates	Overland Park	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Embera NeuroTherapeutics, Inc.	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	PK Parameter EMB-001	Cmax (maximum concentration) of EMB-001 will be compared when taken alone and when taken with cocaine	21 days
Secondary	PK Parameter Cocaine	Cmax (maximum concentration) of cocaine will be compared when taken alone and when taken with EMB-001	21 days
Secondary	PK Parameter EMB-001	AUC (area under the curve) of EMB-001 will be compared when taken alone and when taken with cocaine	21 days
Secondary	PK Parameter Cocaine	AUC (area under the curve) of Cocaine will be compared when taken alone and when taken with EMB-001	21 days