- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02406066
Single and Multiple Rising Dose Study of Safety and PK of Metyrapone/Oxazepam Combination (EMB-001)
July 21, 2016 updated by: Embera NeuroTherapeutics, Inc.
Phase 1 Combined Single and Multiple Rising Dose Study of the Safety and Pharmacokinetics of Metyrapone/Oxazepam Combination (EMB-001)
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
24
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
California
-
Long Beach, California, United States, 90806
- Collaborative Neuroscience Network, LLC
-
-
Louisiana
-
Baton Rouge, Louisiana, United States, 70808
- Pennington Biomedical Research Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 63 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
Subjects will receive capsules containing no active pharmaceutical ingredients.
|
Each cohort will have 2 subjects receiving placebo
Other Names:
|
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
|
6 subjects will receive active study drug (a low dose combination of metyrapone & oxazepam) and 2 subjects will receive placebo.
Other Names:
6 subjects will receive active study drug (a medium dose combination of metyrapone & oxazepam) and 2 subjects will receive placebo.
Other Names:
6 subjects will receive active study drug (a high dose combination of metyrapone & oxazepam) and 2 subjects will receive placebo.
Other Names:
|
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
|
6 subjects will receive active study drug (a low dose combination of metyrapone & oxazepam) and 2 subjects will receive placebo.
Other Names:
6 subjects will receive active study drug (a medium dose combination of metyrapone & oxazepam) and 2 subjects will receive placebo.
Other Names:
6 subjects will receive active study drug (a high dose combination of metyrapone & oxazepam) and 2 subjects will receive placebo.
Other Names:
|
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
|
6 subjects will receive active study drug (a low dose combination of metyrapone & oxazepam) and 2 subjects will receive placebo.
Other Names:
6 subjects will receive active study drug (a medium dose combination of metyrapone & oxazepam) and 2 subjects will receive placebo.
Other Names:
6 subjects will receive active study drug (a high dose combination of metyrapone & oxazepam) and 2 subjects will receive placebo.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
Time Frame: Daily on Days 1-12, and on Day 17. Study Completion occurs on Day 17.
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetics (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.
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Craving/addiction measures
Time Frame: These will be assessed at baseline and on Study Day 9
|
Exploratory efficacy endpoints will include the following craving and addiction measures:
|
These will be assessed at baseline and on Study Day 9
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Director: Gary Connor, RN, Embera NeuroTherapeutics, Inc.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2015
Primary Completion (Actual)
December 1, 2015
Study Completion (Actual)
June 1, 2016
Study Registration Dates
First Submitted
April 16, 2014
First Submitted That Met QC Criteria
April 1, 2015
First Posted (Estimate)
April 2, 2015
Study Record Updates
Last Update Posted (Estimate)
July 22, 2016
Last Update Submitted That Met QC Criteria
July 21, 2016
Last Verified
July 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Chemically-Induced Disorders
- Pathologic Processes
- Substance-Related Disorders
- Disease
- Tobacco Use Disorder
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Enzyme Inhibitors
- Antimetabolites
- Tranquilizing Agents
- Psychotropic Drugs
- Hypnotics and Sedatives
- Anti-Anxiety Agents
- GABA Modulators
- GABA Agents
- Metyrapone
- Oxazepam
Other Study ID Numbers
- ERL-001
- 5R01DA030932-04 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Tobacco Use Disorder
-
Washington University School of MedicineNational Cancer Institute (NCI); National Institutes of Health (NIH)CompletedSmoking | Smoking Cessation | Tobacco Use | Tobacco Smoking | Tobacco Use Cessation | Nicotine Dependence | Tobacco Dependence | Smoking, Tobacco | Nicotine Use Disorder | Nicotine Dependence, Cigarettes | Smoking, Cigarette | Nicotine Dependence Tobacco Product | Tobacco; Use, Rehabilitation | Smoking (Tobacco) Addiction and other conditionsUnited States
-
Johns Hopkins UniversityNational Institute on Drug Abuse (NIDA)RecruitingTobacco Use | Tobacco Smoking | Tobacco Use Disorder | Tobacco Use Cessation | Tobacco DependenceUnited States
-
Harvard School of Public Health (HSPH)Beacon Communities; The Community BuildersEnrolling by invitationTobacco Use | Tobacco Smoking | Tobacco Use Disorder | Tobacco Use Cessation | Second Hand Tobacco SmokeUnited States
-
University of California, San FranciscoNational Institute on Minority Health and Health Disparities (NIMHD)CompletedSmoking | Smoking Cessation | Tobacco Use | Tobacco Smoking | Tobacco Use Disorder | Tobacco Use Cessation | Tobacco Dependence | Smoking, Tobacco | Smoking, CigaretteUnited States
-
University of California, San FranciscoTobacco Related Disease Research ProgramCompletedSmoking | Smoking Cessation | Tobacco Use | Tobacco Smoking | Tobacco Use Disorder | Tobacco Use Cessation | Tobacco Dependence | Smoking, Tobacco | Smoking, CigaretteUnited States
-
New York State Psychiatric InstituteTerminatedSmoking | Smoking Cessation | Tobacco Use | Tobacco Smoking | Tobacco Use Disorder | Nicotine Dependence | Cigarette Smoking | Tobacco Dependence | Nicotine Use Disorder | Smoking, CigaretteUnited States
-
Rutgers, The State University of New JerseyNational Institute on Drug Abuse (NIDA)CompletedSchizophrenia | Schizoaffective Disorder | Tobacco Use | Tobacco Smoking | Tobacco Use Disorder | Tobacco Use CessationUnited States
-
University of PennsylvaniaFood and Drug Administration (FDA)Completed
-
University of Kansas Medical CenterCompletedTobacco Use Disorder/Cigarette SmokingUnited States
-
Ottawa Hospital Research InstituteCompletedTobacco Use Disorder | Tobacco Use Cessation | Tobacco Dependence
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States