A Study to Evaluate EMB 001 in Subjects With Cocaine Use Disorder

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Study to Evaluate the Safety and Efficacy of EMB 001 in Subjects With Moderate-to-Severe Cocaine Use Disorder

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 is a Phase 2 study in approximately 80 adult subjects with moderate-to-severe Cocaine Use Disorder (CUD).

Study Overview

• Status: Completed
• Conditions: Cocaine Use Disorder
• Intervention / Treatment: Drug: EMB-001; Drug: EMB-001 Placebo

Detailed Description

This study is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, study to compare the safety and efficacy of EMB-001 with a placebo control in approximately 80 subjects with moderate-to-severe CUD. Subjects will receive investigational medicinal product (IMP) during a 12-week, double-blind Treatment Period (Week 2 through Week 13) and a 1-week, double-blind Taper Period (Week 14).

After undergoing study procedures during the Screening and Baseline Periods, subjects who meet inclusion and exclusion criteria will then be randomized in a 1:1 ratio (n=40/arm) to one of the following for the Treatment Period (weeks 2 - 13) on Study Day 8:

• EMB-001 720 mg metyrapone/24 mg oxazepam mg BID, for a total daily dose of 1440 mg metyrapone and 48 mg oxazepam (Active Group)
• Placebo BID, (Placebo Group)

During the Taper Period (week 14), subjects in the Active Group will receive EMB-001 240/8 mg BID; and the Placebo Group will continue to receive placebo. Both groups will change from taking three capsules BID (twice daily) to one capsule BID (twice daily).

There will be a follow-up visit for safety assessments at Week 18.

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gary Connor, RN; Phone Number: 207-281-2652; Email: gconnor@emberaneuro.com

Study Locations

• United States
  • California
    • San Diego, California, United States, 92092
      • Pacific Treatment and Research Center, Department of Psychiatry, University of California, San Diego, School of Medicine
  • Florida
    • Miami, Florida, United States, 33161
      • Segal Trials
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • U PENN- Perelman School of Medicine
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Provide written informed consent prior to any study procedures
• 18 to 65 years of age
• DSM-5 diagnosis of moderate-to-severe CUD
• Seeking treatment for CUD. Subjects with past rehabilitation attempts are eligible if the most recent rehabilitation attempt ended at least 30 days prior to Screening
• Female subjects must be of non-childbearing potential
• Male subjects must agree to use accepted contraceptive regimens during the study and for at least 90 days after the last dose of the study drug

Key Exclusion Criteria:

• Any significant current medical conditions
• Known hypersensitivity to or intolerance of oxazepam, metyrapone, or any benzodiazepine, or severe hypersensitivity reaction (e.g., angioedema) to any drug
• Heightened likelihood of having adrenal insufficiency in the investigator's or designees' opinion
• Current court-mandated treatment requirement for a substance-use disorder
• Current DSM-5 moderate-to-severe substance use disorder, other than CUD, tobacco or caffeine
• Current DSM-5 opioid or benzodiazepine use disorder of any severity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: EMB-001 Active; EMB-001 Combination product of 720 mg metyrapone/24 mg oxazepam mg by mouth twice per day for 12 weeks followed by a 1 week taper	Drug: EMB-001; 720 mg metyrapone/24 mg oxazepam mg BID
Placebo Comparator: EMB-001 Placebo; EMB-001 Placebo by mouth twice per day for 12 weeks followed by a 1 week taper	Drug: EMB-001 Placebo; Inactive comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Continuous Abstinence from Cocaine Use	The Primary Endpoint is the Proportion of Subjects That Successfully Achieve Abstinence From Cocaine During the Last Three Weeks of Treatment using the Timeline Follow Back; days of abstinence, confirmed by Urine benzoylecgonine (BE)	Week 11 to Week 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	13 weeks
Reduction in cocaine-use days	Self-report weekly cocaine non-use days by Timeline Follow-Back	Week 2 to Week 13
Urine confirmation of cocaine use	Qualitative urine BE levels twice per week	Week 2 to Week 13
Reduction in total Cocaine Craving Questionnaire-Brief score	The Cocaine Craving Questionnaire-Brief (CCQ-B) assesses current cocaine craving in routine clinical practice. The CCQ-B is a 10 item questionnaire and items are scored on a one to seven scale. Total responses are then divided by 10 to achieve a total craving score between 1.0 (least craving) to 7.0 (most craving).	Week 2 to Week 13

Collaborators and Investigators

• Sponsor: Embera NeuroTherapeutics, Inc.
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Study Chair: Bruce McCarthy, MD, Embera NeuroTherapeutics, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2020
• Primary Completion (Actual): July 27, 2022
• Study Completion (Actual): October 15, 2022

Study Registration Dates

• First Submitted: August 3, 2020
• First Submitted That Met QC Criteria: August 5, 2020
• First Posted (Actual): August 6, 2020

Study Record Updates

• Last Update Posted (Actual): August 8, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: cocaine
• Additional Relevant MeSH Terms: Pathologic Processes; Disease
• Other Study ID Numbers: ERL-003; 5U01DA038879-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Every three months, the NIDA DSMB will convene to review the overall safety data, as well as data on safety summarized by treatment condition. As per NIH guidelines, the objective of these reviews will be to determine whether continued conduct of the trial poses any undue risk for participants. Blinded data tables, figures and/or listings will be provided to the Data Safety Monitoring Board (DSMB).
• IPD Sharing Time Frame: Every three months- blinded results
• IPD Sharing Access Criteria: A DSMB report is prepared an submitted via NIDA
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No