Cocaine Use Disorder
Conditions
Brief 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). 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.
Interventions
Sponsors
National Institute on Drug Abuse (NIDA)
Embera NeuroTherapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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 * 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | 29 Days | Adverse event data (including clinically significant changes in laboratory values) will be compiled for EMB-001 and placebo cohorts. |
| Vital signs | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK Parameter EMB-001 | 21 days | Cmax (maximum concentration) of EMB-001 will be compared when taken alone and when taken with cocaine |
| PK Parameter Cocaine | 21 days | Cmax (maximum concentration) of cocaine will be compared when taken alone and when taken with EMB-001 |
Countries
United States
Outcome results
None listed