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

Embera NeuroTherapeutics

Status and phase: Completed; Phase 1

Conditions: Cocaine Use Disorder

Treatments: Drug: New formulation EMB-001; Drug: Original formulation EMB-001

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT03404817

ERL-PK001

U01DA038879 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Enrollment: 9 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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9 participants in 3 patient groups

Sequence 1

Active Comparator group

Description:

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

Treatment:

Drug: Original formulation EMB-001

Drug: New formulation EMB-001

Sequence 2

Active Comparator group

Description:

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

Treatment:

Drug: Original formulation EMB-001

Drug: New formulation EMB-001

Sequence 3

Active Comparator group

Description:

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

Treatment:

Drug: Original formulation EMB-001

Drug: New formulation EMB-001