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

NCT ID: NCT02856854

Last Updated: 2017-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-31
• Study Completion Date: 2017-07-25

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.

Conditions

Cocaine Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

EMB-001 (oral)

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).

Group Type: EXPERIMENTAL

EMB-001

Intervention Type: DRUG

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

Cocaine IV

Intervention Type: DRUG

Cocaine administered at doses of 20 and 40mg

Saline IV

Intervention Type: DRUG

Cocaine matched placebo

Placebo (oral)

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

EMB-001 matched placebo

Cocaine IV

Intervention Type: DRUG

Cocaine administered at doses of 20 and 40mg

Saline IV

Intervention Type: DRUG

Cocaine matched placebo

Interventions

EMB-001

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

Intervention Type: DRUG

Placebo

EMB-001 matched placebo

Intervention Type: DRUG

Cocaine IV

Cocaine administered at doses of 20 and 40mg

Intervention Type: DRUG

Saline IV

Cocaine matched placebo

Intervention Type: DRUG

Other Intervention Names

metyrapone and oxazepam; oral placebo; IV cocaine; IV saline

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)

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Embera NeuroTherapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Debra Kelsh, MD

Role: PRINCIPAL_INVESTIGATOR

Vince & Associates

Locations

Vince & Associates

Overland Park, Kansas, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 22236504 (View on PubMed)

Other Identifiers

U01DA038879

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ERL-002

Identifier Type: -

Identifier Source: org_study_id