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CompletedNCT02856854Updated Aug 1, 2017

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

A Phase 1 interventional study of EMB-001 and Placebo in Cocaine Use Disorder, sponsored by Embera NeuroTherapeutics, Inc.. Completed at 1 site in United States. Open to participants aged 21 Years to 55 Years. Per ClinicalTrials.gov, last updated 2017-08-01.

Sponsored by Embera NeuroTherapeutics, Inc. · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
18
Allocation
Randomized
Ages
21 Years to 55 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Cocaine Use Disorder
03

Who can participate

Ages eligible
21 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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)
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
18 participants (actual)

Study arms

  • 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 · Drug: Cocaine IV · Drug: Saline IV

  • 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 · Drug: Cocaine IV · Drug: Saline IV

Interventions

  • DrugEMB-001

    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

  • DrugPlacebo

    EMB-001 matched placebo

    Also known as: oral placebo

  • DrugCocaine IV

    Cocaine administered at doses of 20 and 40mg

    Also known as: IV cocaine

  • DrugSaline IV

    Cocaine matched placebo

    Also known as: IV saline

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 29 Days

  2. 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.

    Time frame: 29 days

  3. 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.

    Time frame: 29 days

Secondary outcomes

  1. PK Parameter EMB-001

    Cmax (maximum concentration) of EMB-001 will be compared when taken alone and when taken with cocaine

    Time frame: 21 days

  2. PK Parameter Cocaine

    Cmax (maximum concentration) of cocaine will be compared when taken alone and when taken with EMB-001

    Time frame: 21 days

  3. PK Parameter EMB-001

    AUC (area under the curve) of EMB-001 will be compared when taken alone and when taken with cocaine

    Time frame: 21 days

  4. PK Parameter Cocaine

    AUC (area under the curve) of Cocaine will be compared when taken alone and when taken with EMB-001

    Time frame: 21 days

06

Study locations

1 site
  • Vince & Associates
    Overland Park, Kansas 66212, United States
07

References and documents

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. PubMed 22236504 ↗

Individual participant data

Plan to share: Yes — 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 information: Study protocol, Csr

08

Registry details

Key details

Study ID
NCT02856854
Lead sponsor
Embera NeuroTherapeutics, Inc.
Collaborators
National Institute on Drug Abuse (NIDA)
Responsible party
Sponsor
First posted
Aug 5, 2016
Start date
Jul 2016
Primary completion
Feb 17, 2017
Completion
Jul 25, 2017
Last update
Aug 1, 2017

Study contacts

Debra Kelsh, MD
principal investigator · Vince & Associates

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2017. You cannot join it, but the record below documents what was studied.

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