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

This study has been completed.
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Embera NeuroTherapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT02856854
First received: July 22, 2016
Last updated: July 31, 2017
Last verified: July 2017
  Purpose

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.


Condition Intervention Phase
Cocaine Use Disorder Drug: EMB-001 Drug: Placebo Drug: Cocaine IV Drug: Saline IV Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Embera NeuroTherapeutics, Inc.:

Primary Outcome Measures:
  • Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: 29 Days ]
    Adverse event data (including clinically significant changes in laboratory values) will be compiled for EMB-001 and placebo cohorts.

  • Vital signs [ Time Frame: 29 days ]
    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.

  • ECGs [ Time Frame: 29 days ]
    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.


Secondary Outcome Measures:
  • PK Parameter EMB-001 [ Time Frame: 21 days ]
    Cmax (maximum concentration) of EMB-001 will be compared when taken alone and when taken with cocaine

  • PK Parameter Cocaine [ Time Frame: 21 days ]
    Cmax (maximum concentration) of cocaine will be compared when taken alone and when taken with EMB-001

  • PK Parameter EMB-001 [ Time Frame: 21 days ]
    AUC (area under the curve) of EMB-001 will be compared when taken alone and when taken with cocaine

  • PK Parameter Cocaine [ Time Frame: 21 days ]
    AUC (area under the curve) of Cocaine will be compared when taken alone and when taken with EMB-001


Enrollment: 18
Study Start Date: July 2016
Study Completion Date: July 25, 2017
Primary Completion Date: February 17, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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).
Drug: EMB-001
EMB-001 is a combination of metyrapone (720mg per dose in this study) and oxazepam (24mg per dose in this study)
Other Name: metyrapone and oxazepam
Drug: Cocaine IV
Cocaine administered at doses of 20 and 40mg
Other Name: IV cocaine
Drug: Saline IV
Cocaine matched placebo
Other Name: IV saline
Placebo Comparator: 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).
Drug: Placebo
EMB-001 matched placebo
Other Name: oral placebo
Drug: Cocaine IV
Cocaine administered at doses of 20 and 40mg
Other Name: IV cocaine
Drug: Saline IV
Cocaine matched placebo
Other Name: IV saline

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

Ages Eligible for Study:   21 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02856854

Locations
United States, Kansas
Vince & Associates
Overland Park, Kansas, United States, 66212
Sponsors and Collaborators
Embera NeuroTherapeutics, Inc.
National Institute on Drug Abuse (NIDA)
Investigators
Principal Investigator: Debra Kelsh, MD Vince & Associates
  More Information

Publications:
Responsible Party: Embera NeuroTherapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02856854     History of Changes
Other Study ID Numbers: ERL-002
U01DA038879 ( U.S. NIH Grant/Contract )
Study First Received: July 22, 2016
Last Updated: July 31, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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).
Supporting Materials: Study Protocol
Clinical Study Report (CSR)
Time Frame: Every three months- blinded results
Access Criteria: A DSMB report is prepared an submitted via NIDA.

Additional relevant MeSH terms:
Cocaine
Oxazepam
Metyrapone
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Vasoconstrictor Agents
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Antimetabolites
Enzyme Inhibitors
Hypnotics and Sedatives
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents

ClinicalTrials.gov processed this record on August 18, 2017