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

NCT02406066 | Completed Phase 1

• 2 other identifiers: ERL-0015R01DA030932-04
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Cocaine Use Disorder; Tobacco Use Disorder

Outcome Measures

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.

  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)

  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

  These will be assessed at baseline and on Study Day 9

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Subjects will receive capsules containing no active pharmaceutical ingredients.

Drug: Placebo

Low Dose (Cohort 1)

ACTIVE COMPARATOR

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

Medium Dose (Cohort 2)

ACTIVE COMPARATOR

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

High Dose (Cohort 3)

ACTIVE COMPARATOR

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

metyrapone & oxazepam DRUG

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

Low Dose (Cohort 1)

Placebo DRUG

Each cohort will have 2 subjects receiving placebo

Also known as: All Cohorts

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Embera NeuroTherapeutics, Inc.: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (2)

Collaborative Neuroscience Network, LLC

Long Beach, California, 90806, United States

Location

Pennington Biomedical Research Center

Baton Rouge, Louisiana, 70808, United States

Location

Related Links

• Sponsor: Embera NeuroTherapeutics

MeSH Terms

Conditions

Tobacco Use Disorder

Interventions

Metyrapone; Oxazepam; KPNA1 protein, human

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Gary Connor, RN

  Embera NeuroTherapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2014
• First Posted: April 2, 2015
• Study Start: March 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: June 1, 2016
• Last Updated: July 22, 2016

Record last verified: 2016-07

Locations

US (2)