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

Primary Purpose

Cocaine Use Disorder, Tobacco Use Disorder

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

metyrapone & oxazepam

Placebo

About this trial

This is an interventional treatment trial for Cocaine Use Disorder

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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:

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.

Sites / Locations

Collaborative Neuroscience Network, LLC
Pennington Biomedical Research Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Low Dose (Cohort 1)

Medium Dose (Cohort 2)

High Dose (Cohort 3)

Arm Description

Subjects will receive capsules containing no active pharmaceutical ingredients.

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

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT02406066

First Posted

April 16, 2014

Last Updated

July 21, 2016

Sponsor

Embera NeuroTherapeutics, Inc.

Collaborators

National Institute on Drug Abuse (NIDA)

1. Study Identification

Unique Protocol Identification Number

NCT02406066

Brief Title

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

Official Title

Phase 1 Combined Single and Multiple Rising Dose Study of the Safety and Pharmacokinetics of Metyrapone/Oxazepam Combination (EMB-001)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2016

Overall Recruitment Status

Completed

Study Start Date

March 2015 (undefined)

Primary Completion Date

December 2015 (Actual)

Study Completion Date

June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Embera NeuroTherapeutics, Inc.

Collaborators

National Institute on Drug Abuse (NIDA)

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cocaine Use Disorder, Tobacco Use Disorder

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Subjects will receive capsules containing no active pharmaceutical ingredients.

Arm Title

Low Dose (Cohort 1)

Arm Type

Active Comparator

Arm Description

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

Arm Title

Medium Dose (Cohort 2)

Arm Type

Active Comparator

Arm Description

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

Arm Title

High Dose (Cohort 3)

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

metyrapone & oxazepam

Other Intervention Name(s)

Cohort 1

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

metyrapone & oxazepam

Other Intervention Name(s)

Cohort 2

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

metyrapone & oxazepam

Other Intervention Name(s)

Cohort 3

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

All Cohorts

Intervention Description

Each cohort will have 2 subjects receiving placebo

Primary Outcome Measure Information:

Title

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)

Description

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 Outcome Measure Information:

Title

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

Description

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 Pre-specified Outcome Measures:

Title

Craving/addiction measures

Description

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

Time Frame

These will be assessed at baseline and on Study Day 9

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gary Connor, RN

Organizational Affiliation

Embera NeuroTherapeutics, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Collaborative Neuroscience Network, LLC

City

Long Beach

State/Province

California

ZIP/Postal Code

90806

Country

United States

Facility Name

Pennington Biomedical Research Center

City

Baton Rouge

State/Province

Louisiana

ZIP/Postal Code

70808

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.emberaneuro.com/

Description

Sponsor: Embera NeuroTherapeutics

Learn more about this trial

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

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