Single and Multiple Rising Dose Study of Safety and PK of Metyrapone/Oxazepam Combination (EMB-001)

This study is a Phase 1, double blind, single and multiple rising dose tolerance study of
EMB-001 (metyrapone/oxazepam combination) in otherwise healthy adults who have tobacco use
disorder. There will be 3 cohorts, each with 8 subjects (6 active: 2 placebo), for a total
of 24 subjects. During the treatment period, subjects will receive a single dose of EMB 001
on Day 1, followed 24 hours later by the start of multiple doses twice daily for 7 days, and
then a final morning dose on the last dosing day (Day 9). This design allows for
characterization of EMB-001 single dose PK for 24 hours, followed by assessment of repeat
dose PK in the multiple-dose phase. Safety will be assessed after the single dose and
repeated dosing. Effects of study drug on smoking and craving cigarettes will be assessed at
the end of repeated dosing. Later studies may also assess the efficacy of this drug
combination in treating cocaine use disorder, tobacco use disorder, and/or other disorders.

Inclusion Criteria:

- Males and females of Non-Childbearing Potential age 18-65

- Have provided written informed consent prior to any study procedures

- Are willing and able to comply with all aspects of the protocol

- Normal or clinically acceptable screening electrocardiogram (ECG)

- Normal blood pressure (systolic: 90-140 mmHg; diastolic 50-90 mmHg) and heart rate
(50-100 bpm)

- Smoke at least 10 cigarettes per day (for approximately 1 year or longer)

- Body mass index > 18.5 and < 35

Exclusion Criteria:

- Known hypersensitivity to or intolerance of oxazepam or metyrapone, or any
benzodiazepine

- Subjects with a low out-of-range serum cortisol value at screening or subjects who,
in the investigator's opinion, have a heightened likelihood of having adrenal
insufficiency.

- Subjects who have a positive urine drug screen for illegal drugs or other drugs with
a high potential for abuse (other than nicotine).

- Inability to communicate or cooperate with the investigator

- History of drug dependence (except nicotine) or psychiatric illness within the past 2
years.

- Subjects with any history of adrenal insufficiency or other adrenal, hypothalamic, or
pituitary disorders.

- History of asthma or other respiratory disease, neurologic or neuromuscular disease,
or hypotension or cardiovascular disease, that may, in the opinion of the
investigator, impact any study procedures or measures, or compromise the safety of
the subject.

- Other severe, acute, or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with trial participation or
investigational product administration or may interfere with the interpretation of
trial results and, in the judgment of the Investigator or Sponsor, would make the
subject inappropriate for entry into this trial.