Single Dose Crossover Comparative Bioavailability and Food Effect Study of Two EMB-001 Formulations

Phase 1

Completed

• Conditions: Cocaine Use Disorder
• Interventions: Drug: Original formulation EMB-001; Drug: New formulation EMB-001

• Registration Number: NCT03404817
• Lead Sponsor: Embera NeuroTherapeutics, Inc.

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-01-12
• Study First Submitted QC: 2018-01-12
• Study First Posted: 2018-01-19
• Study Start: 2018-03-01
• Status Verified: 2018-06
• Primary Completion: 2018-06-07
• Study Completion: 2018-06-07
• Last Update Submitted: 2018-06-07
• Last Update Posted: 2018-06-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sequence 2	Original formulation EMB-001	Subjects will receive investigational product (IP) once each Period as a single dose under fasted or fed conditions as follows: Period 1: EMB-001 original formulation under fed conditions Period 2: EMB-001 new formulation under fed conditions Period 3: EMB-001 new formulation under fasted conditions
Sequence 2	New formulation EMB-001	Subjects will receive investigational product (IP) once each Period as a single dose under fasted or fed conditions as follows: Period 1: EMB-001 original formulation under fed conditions Period 2: EMB-001 new formulation under fed conditions Period 3: EMB-001 new formulation under fasted conditions
Sequence 1	Original formulation EMB-001	Subjects will receive investigational product (IP) once each Period as a single dose under fasted or fed conditions as follows: Period 1: EMB-001 new formulation under fed condition Period 2: EMB-001 new formulation under fasted conditions Period 3: EMB-001 original formulation under fed conditions
Sequence 3	New formulation EMB-001	Subjects will receive investigational product (IP) once each Period as a single dose under fasted or fed conditions as follows: Period 1: EMB-001 new formulation under fasted conditions Period 2: EMB-001 original formulation under fed conditions Period 3: EMB-001 new formulation under fed conditions
Sequence 1	New formulation EMB-001	Subjects will receive investigational product (IP) once each Period as a single dose under fasted or fed conditions as follows: Period 1: EMB-001 new formulation under fed condition Period 2: EMB-001 new formulation under fasted conditions Period 3: EMB-001 original formulation under fed conditions
Sequence 3	Original formulation EMB-001	Subjects will receive investigational product (IP) once each Period as a single dose under fasted or fed conditions as follows: Period 1: EMB-001 new formulation under fasted conditions Period 2: EMB-001 original formulation under fed conditions Period 3: EMB-001 new formulation under fed conditions

Primary Outcome Measures

Name	Time	Method
Time to Maximum Concentration (Tmax) of EMB-001	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.	Tmax is the time elapsed from the time of drug administration to maximum plasma concentration.
Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of EMB-001	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.	The AUC0-inf is calculated in a plot of concentration of drug in blood plasma against time and extrapolated to infinity.
Apparent Half-Life (t1/2) of EMB-001	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.	Half-life is defined as the time required for the drug plasma concentration to be reduced to half.
Maximum Observed Concentration (Cmax) of EMB-001	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.	Cmax is the maximum observed concentration of drug in blood plasma.

Secondary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)	21 days	Adverse event data (including clinically significant changes in laboratory values) will be compiled for EMB-001.

Trial Locations

Locations (1)

Collaborative Neuroscience Network, LLC; 🇺🇸 Long Beach, California, United States