Clinical trial NCT03404817: Single Dose Crossover Comparative Bioavailability and Food Effect Study of Two EMB-001 Formulations
Official title: Single Dose Crossover Comparative Bioavailability and Food Effect Study of Two EMB-001 Formulations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cocaine Use Disorder
Lead sponsor: Embera NeuroTherapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2018-01-19
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 3-period, 3-sequence crossover evaluating 3 treatments

* Treatment-1: new formulation under fed conditions
* Treatment-2: new formulation under fasted conditions
* Treatment-3: original formulation under fed conditions
Primary purpose: OTHER

Brief summary: This is a study of EMB-001 (a combination of two FDA-approved drugs, metyrapone and oxazepam) in healthy adults.This is a Phase 1, single dose, 3-period, 3-sequence, crossover study in 9 healthy male and female (not of childbearing potential) volunteers. The study will evaluate the bioavailability and food effect of a new formulation of EMB-001 relative to the original formulation of EMB 001.

During the study, a total of 9 eligible subjects will be randomized in a 1:1:1 ratio to each of 3 treatment sequences


Eligibility criteria: Inclusion Criteria:

1. Provide written informed consent prior to any study procedures.
2. Age 18 to 60 and able to read and write English
3. Females must be of non-childbearing potential. Evidence of non-childbearing potential includes documented surgical sterilization (hysterectomy or bilateral oophorectomy) or being postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over age 45 in the absence of other biological or physiological cause. In addition, women must have a documented serum follicle stimulating hormone (FSH) level \>40 mIU/mL.
4. Light smokers (\<10 cigarettes per day), non-smokers, or ex-smokers
5. Body mass index ≥18.5 and \<30 kg/m2
6. Able to take oral medications and willing to adhere to medication regimen during the study
7. No clinically relevant abnormal physical findings at the Screening examination
8. Electrocardiogram without clinically significant abnormality at Screening
9. Normal blood pressure (BP) and heart rate (systolic BP 90 to 140 mmHg; diastolic BP 50 to 90 mmHg; heart rate 50 to 100 beats per minute)
10. No clinically relevant abnormal laboratory findings (general biochemistry, hematology, urinalysis, endocrinology \[cortisol\]) at Screening
11. Adequate organ function at screening as defined by:

    1. Serum aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN; unless the increased AST is assessed by the Investigator as due to hemolysis and/or hepatic iron deposition); and alanine aminotransferase (ALT) ≤ 2.5 × ULN (unless the increased ALT is assessed by the Investigator as due to hepatic iron deposition).
    2. Normal or elevated levels of serum bilirubin. Serum bilirubin \>2× ULN is acceptable if the elevation is attributed to hemolysis with or without Gilbert's syndrome.
    3. Serum creatinine ≤ 1.25 × ULN. If serum creatinine \> 1.25 × ULN, then 24-hour measured or calculated (Cockcroft-Gault) glomerular filtration rate ≥ 60 mL/min.
    4. Absolute neutrophil count (ANC) ≥ 1.2 × 109/L.
    5. Platelet count ≥ 100 × 109/L.
    6. Activated partial thromboplastin time (aPTT) and international normalized ratio ≤ 1.25 × ULN, unless the patient is receiving therapeutic anticoagulants.

Exclusion Criteria:

1. Any significant current medical conditions (neurological, cardiovascular \[including hypertension\], endocrine, thyroid, renal, liver), seizures, delirium or hallucinations, or other unstable medical conditions
2. Known hypersensitivity to or intolerance of oxazepam or metyrapone, or any benzodiazepine
3. Subjects that have confounders of the levels of cortisol and/or cortisol binding globulin, including but not limited to: consuming estrogens, selective estrogen receptor modulators, or herbal/natural estrogen-like compounds; low serum albumin or total protein at screening; history of cirrhosis; hyperthyroidism; other thyroid disease that is untreated and not well-controlled; nephrotic syndrome or other protein-losing enteropathies.
4. Current DSM-5 substance use disorder. Mild tobacco, marijuana, or alcohol use are allowed.
5. Participants who have a positive test result at intake appointment on urine drug screens conducted for illicit drugs, including cannabis.
6. Treatment with an investigational drug or biologic within the 30 days preceding the first dose of study medication or plans to take another investigational drug or biologic within 30 days of study completion (including the follow-up visit)
7. Women of childbearing potential.
8. Have positive serology test results at Screening for human immunodeficiency (HIV) 1/HIV 2 antibodies, Hepatitis B surface antigen (HBsAg) or Hepatitis C Antibody (HCVAb) before Day -2 of this study.
9. Suicidal, homicidal thoughts and behaviors, or evidence of current severe mental illness such as schizophrenia, bipolar disorder or others that may interfere with subject safety or data integrity
10. Use of serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor antidepressants in the 30 days prior to Period 1 or during the study.
11. Use of any prescription, over-the-counter, or herbal medications, vitamins, or mineral supplements within 14 days prior to administration of their first study medication dose

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of EMB-001
timeFrame: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 hours post drug administration in each Period.
measure: Maximum Observed Concentration (Cmax) of EMB-001
timeFrame: Periods 1-3, pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 hours post drug administration in each Period.
measure: Time to Maximum Concentration (Tmax) of EMB-001
timeFrame: Periods 1-3, pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 hours post drug administration in each Period.
measure: Apparent Half-Life (t1/2) of EMB-001
timeFrame: Periods 1-3, pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 hours post drug administration in each Period.
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
timeFrame: 21 days
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
Study officials:
affiliation: Embera NeuroTherapeutics, Inc.
name: Mike Detke, MD
role: STUDY_DIRECTOR
References: