CClinicalTrials.gg
CompletedNCT02406066Updated Jul 22, 2016

Single and Multiple Rising Dose Study of Safety and PK of Metyrapone/Oxazepam Combination (EMB-001)

A Phase 1 interventional study of metyrapone & oxazepam and metyrapone & oxazepam in Cocaine Use Disorder and Tobacco Use Disorder, sponsored by Embera NeuroTherapeutics, Inc.. Completed at 2 sites in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-07-22.

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

Phase
Phase 1
Study type
Interventional
Enrollment
24
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

This is a study of EMB-001 (a combination of two FDA-approved drugs, metyrapone and oxazepam) in otherwise healthy adults who are regular cigarette smokers. There will be 3 groups of 8 subjects; in each group, 6 subjects will get the drug combination and 2 will get placebo. Neither the subjects nor the study personnel will know who got drug and who got placebo (double-blind). In the first group the drug doses will be low, and they will be increased in the second and third groups. Subjects will receive a single dose on Day 1, followed 24 hours later by the start of doses twice daily for 7 days, and then a final morning dose on the last day. The levels of the drugs in the blood will be assessed by repeated blood draws after the first day and after the end of dosing. Safety will be assessed after the single dose and repeated dosing. Effects of study drug on smoking and craving cigarettes will be assessed at the end of repeated dosing. The hypothesis is that this drug combination will be safe, with relatively few side effects.

Read the detailed description

This study is a Phase 1, double blind, single and multiple rising dose tolerance study of EMB-001 (metyrapone/oxazepam combination) in otherwise healthy adults who have tobacco use disorder. There will be 3 cohorts, each with 8 subjects (6 active: 2 placebo), for a total of 24 subjects. During the treatment period, subjects will receive a single dose of EMB 001 on Day 1, followed 24 hours later by the start of multiple doses twice daily for 7 days, and then a final morning dose on the last dosing day (Day 9). This design allows for characterization of EMB-001 single dose PK for 24 hours, followed by assessment of repeat dose PK in the multiple-dose phase. Safety will be assessed after the single dose and repeated dosing. Effects of study drug on smoking and craving cigarettes will be assessed at the end of repeated dosing. Later studies may also assess the efficacy of this drug combination in treating cocaine use disorder, tobacco use disorder, and/or other disorders.

02

Conditions studied

  • Cocaine Use Disorder
  • Tobacco Use Disorder

Browse trials for

03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Males and females of Non-Childbearing Potential age 18-65
  • Have provided written informed consent prior to any study procedures
  • Are willing and able to comply with all aspects of the protocol
  • Normal or clinically acceptable screening electrocardiogram (ECG)
  • Normal blood pressure (systolic: 90-140 mmHg; diastolic 50-90 mmHg) and heart rate (50-100 bpm)
  • Smoke at least 10 cigarettes per day (for approximately 1 year or longer)
  • Body mass index > 18.5 and \< 35

Exclusion criteria

Exclusion Criteria:

  • Known hypersensitivity to or intolerance of oxazepam or metyrapone, or any benzodiazepine
  • Subjects with a low out-of-range serum cortisol value at screening or subjects who, in the investigator's opinion, have a heightened likelihood of having adrenal insufficiency.
  • Subjects who have a positive urine drug screen for illegal drugs or other drugs with a high potential for abuse (other than nicotine).
  • Inability to communicate or cooperate with the investigator
  • History of drug dependence (except nicotine) or psychiatric illness within the past 2 years.
  • Subjects with any history of adrenal insufficiency or other adrenal, hypothalamic, or pituitary disorders.
  • History of asthma or other respiratory disease, neurologic or neuromuscular disease, or hypotension or cardiovascular disease, that may, in the opinion of the investigator, impact any study procedures or measures, or compromise the safety of the subject.
  • Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the Investigator or Sponsor, would make the subject inappropriate for entry into this trial.
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
24 participants (actual)

Study arms

  • Placebo comparator
    Placebo

    Subjects will receive capsules containing no active pharmaceutical ingredients.

    Drug: Placebo

  • Active comparator
    Low Dose (Cohort 1)

    270 mg metyrapone and 12 mg oxazepam, given once for the single-dose phase of the study, followed by BID dosing for approximately one week

    Drug: metyrapone & oxazepam

  • Active comparator
    Medium Dose (Cohort 2)

    540 mg metyrapone and 24 mg oxazepam, given once for the single-dose phase of the study, followed by BID dosing for approximately one week

    Drug: metyrapone & oxazepam

  • Active comparator
    High Dose (Cohort 3)

    720 mg metyrapone and 24 mg oxazepam, given once for the single-dose phase of the study, followed by BID dosing for approximately one week

    Drug: metyrapone & oxazepam

Interventions

  • Drugmetyrapone & oxazepam

    6 subjects will receive active study drug (a low dose combination of metyrapone \& oxazepam) and 2 subjects will receive placebo.

    Also known as: Cohort 1

  • Drugmetyrapone & oxazepam

    6 subjects will receive active study drug (a medium dose combination of metyrapone \& oxazepam) and 2 subjects will receive placebo.

    Also known as: Cohort 2

  • Drugmetyrapone & oxazepam

    6 subjects will receive active study drug (a high dose combination of metyrapone \& oxazepam) and 2 subjects will receive placebo.

    Also known as: Cohort 3

  • DrugPlacebo

    Each cohort will have 2 subjects receiving placebo

    Also known as: All Cohorts

05

What researchers measure

Primary outcomes

  1. Safety/Tolerability based on multiple safety parameters (adverse events (AE), physical examinations, vital signs, 12-lead ECG, Sheehan Suicidality Tracking Scale (S STS) and laboratory tests)

    Safety will be assessed through monitoring of adverse events (AE), physical examinations, vital signs, 12-lead ECG, Sheehan Suicidality Tracking Scale (S STS) and laboratory tests.

    Time frame: Daily on Days 1-12, and on Day 17. Study Completion occurs on Day 17.

Secondary outcomes

  1. Pharmacokinetics (Plasma PK parameters will be serially assessed for oxazepam, metyrapone, and for the primary metabolite of metyrapone, metyrapol)

    Plasma PK parameters will be serially assessed for oxazepam, metyrapone, and for the primary metabolite of metyrapone, metyrapol.

    Time frame: After single- and multiple-dosing- Samples will be drawn on Day 1 and Day 10 at the following times Pre-dose, .25, .5, .75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, & 48 hours.

Other outcomes

  1. Craving/addiction measures

    Exploratory efficacy endpoints will include the following craving and addiction measures: 1. The Smoking Urges Questionnaire-Brief 2. Minnesota Nicotine Withdrawal Scale 3. Number of cigarettes smoked, breath carbon monoxide, and urine cotinine.

    Time frame: These will be assessed at baseline and on Study Day 9

06

Study locations

2 sites
  • Collaborative Neuroscience Network, LLC
    Long Beach, California 90806, United States
  • Pennington Biomedical Research Center
    Baton Rouge, Louisiana 70808, United States
07

References and documents

08

Registry details

Key details

Study ID
NCT02406066
Lead sponsor
Embera NeuroTherapeutics, Inc.
Collaborators
National Institute on Drug Abuse (NIDA)
Responsible party
Sponsor
First posted
Apr 2, 2015
Start date
Mar 2015
Primary completion
Dec 2015
Completion
Jun 2016
Last update
Jul 22, 2016

Study contacts

Gary Connor, RN
study director · Embera NeuroTherapeutics, Inc.

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2016. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion