Cocaine Use DisorderPhase 1NCT02856854
A Study of Metyrapone and Oxazepam Combination Product (EMB-001) and Cocaine
A Phase 1 study testing EMB-001, Cocaine IV and Saline IV in people with Cocaine Use Disorder, run by Embera NeuroTherapeutics, Inc. at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 21 to 55 years
- Conditions the study is for
- Cocaine Use Disorder
- What is being tested?
- EMB-001, Cocaine IV and Saline IV
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2016to 25 Jul 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1b, Randomized, Double-Blinded, Multiple-Dose, Placebo Controlled, Crossover Study To Evaluate The Safety, Tolerability And Pharmacokinetic Effects Of A Metyrapone And Oxazepam Combination (EMB-001) When Co-Administered With Cocaine
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.
- Conditions
- Cocaine Use Disorder
- Being tested
- EMB-001, Placebo, Cocaine IV, Saline IV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EMB-001Drug
Also called metyrapone and oxazepam
EMB-001 is a combination of metyrapone (720mg per dose in this study) and oxazepam (24mg per dose in this study)
PlaceboDrug
Also called oral placebo
EMB-001 matched placebo
Cocaine IVDrug
Also called IV cocaine
Cocaine administered at doses of 20 and 40mg
Saline IVDrug
Also called IV saline
Cocaine matched placebo
| Study group | Role | What they receive |
|---|---|---|
| EMB-001 (oral) | Experimental | 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). Receives: Drug: EMB-001; Drug: Cocaine IV; Drug: Saline IV |
| Placebo (oral) | Placebo comparator | 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). Receives: Drug: Placebo; Drug: Cocaine IV; Drug: Saline IV |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 29 Days
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.
Measured: 29 days
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.
Measured: 29 days
Secondary outcomes (4)
PK Parameter EMB-001
Cmax (maximum concentration) of EMB-001 will be compared when taken alone and when taken with cocaine
Measured: 21 days
PK Parameter Cocaine
Cmax (maximum concentration) of cocaine will be compared when taken alone and when taken with EMB-001
Measured: 21 days
PK Parameter EMB-001
AUC (area under the curve) of EMB-001 will be compared when taken alone and when taken with cocaine
Measured: 21 days
PK Parameter Cocaine
AUC (area under the curve) of Cocaine will be compared when taken alone and when taken with EMB-001
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2016 (estimated)
- Study startJul 2016
- Primary completion17 Feb 2017
- Study completion25 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cocaine Use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Embera NeuroTherapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Debra Kelsh, MD, Principal investigator, Vince & Associates
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02856854
- Sponsor's protocol ID
- ERL-002
- Other IDs
- U01DA038879
- Status last verified
- Jul 2017
- First submitted
- 22 Jul 2016
- Last updated
- 1 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- 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).
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
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Randomized, Double-Blinded, Multiple-Dose, Placebo Controlled, Crossover Study To Evaluate The Safety, Tolerability And Pharmacokinetic Effects Of A Metyrapone And Oxazepam Combination (EMB-001) When Co-Administered With Cocaine
- ClinicalTrials.gov ID
- NCT02856854
- Acronym / sponsor ID
- ERL-002
- Conditions
- Cocaine Use Disorder
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Embera NeuroTherapeutics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Jul 2016
- Primary completion
- 17 Feb 2017 (actual)
- Study completion
- 25 Jul 2017 (actual)
- First posted
- 5 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EMB-001 (oral) | Experimental | Drug: EMB-001, Drug: Cocaine IV, Drug: Saline IVEMB-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). |
| Placebo (oral) | Placebo comparator | Drug: Placebo, Drug: Cocaine IV, Drug: Saline IVPLB-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). |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EMB-001Also: metyrapone and oxazepamEMB-001 is a combination of metyrapone (720mg per dose in this study) and oxazepam (24mg per dose in this study) | Drug | EMB-001 (oral) |
| PlaceboAlso: oral placeboEMB-001 matched placebo | Drug | Placebo (oral) |
| Cocaine IVAlso: IV cocaineCocaine administered at doses of 20 and 40mg | Drug | EMB-001 (oral), Placebo (oral) |
| Saline IVAlso: IV salineCocaine matched placebo | Drug | EMB-001 (oral), Placebo (oral) |
Primary outcome
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Time frame: 29 Days
Adverse event data (including clinically significant changes in laboratory values) will be compiled for EMB-001 and placebo cohorts.
Vital signs
Time frame: 29 days
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.
ECGs
Time frame: 29 days
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.
4 secondary outcomes
PK Parameter EMB-001
Time frame: 21 days
PK Parameter Cocaine
Time frame: 21 days
PK Parameter EMB-001
Time frame: 21 days
PK Parameter Cocaine
Time frame: 21 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2017.
- Background: PubMed 22236504Kablinger 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.
- Individual participant dataSharing planned: 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).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Debra Kelsh, MD principal investigator
Vince & Associates
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing EMB-001, Cocaine IV and Saline IV in people with Cocaine Use Disorder, run by Embera NeuroTherapeutics, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) (time frame: 29 Days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02856854, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2017.