A Randomized, Double-Blind, Placebo-Controlled, 2-Way Crossover, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Danavorexton in Healthy Subjects Undergoing Opioid-Induced Respiratory Depression

1. In the opinion of the investigator, the subject is capable of understanding
and complying with protocol requirements.
2. The subject reviews, and signs and dates an informed (electronic) consent
form, in addition to any required privacy authorization, before the initiation
of any study procedure.
3. The subject is male and aged 18 to 55 years, inclusive, at the screening
visit.
4. The subject is a current nonsmoker who has not used tobacco- or
nicotine-containing products (eg, nicotine patch) for at least 6 months before
the administration of the study drug.
5. The subject has regular sleep-wake habits (eg, routinely spends 6.5 to 9
hours in bed nightly) and regularly goes to bed between 9:00 PM and 1:00 AM, as
determined by investigator interviews.
6. A male subject must meet the following birth control requirements:
a) For a male subject who is sterile: no restrictions are required for a
vasectomized male subject, provided the subject is at least 1-year
postbilateral vasectomy procedure before the first dose of the study drug. If a
vasectomy procedure was performed less than 1 year before the first dose of the
study drug, the male subject must follow the same restrictions as a male that
has not had a vasectomy/sterilization (below). Appropriate documentation of
surgical procedures should be provided.
b) For a male subject who is nonsterilized: if sexually active with a female
partner of childbearing potential, the subject must agree to use an appropriate
method of contraception, including a condom with or without spermicidal cream
or jelly. These precautions will begin from the administration of the study
drug until 5 half-lives plus 90 days after the administration of the study drug.
c) Male subjects must agree to not donate sperm from the time of study drug
administration until 5 half lives plus 90 days after the administration of the
study drug.
7. The subject has a BMI >=18 and <=32 kg/m2 at the screening visit.
8. The subject must be judged to be in good health based on results of safety
laboratory tests (biochemistry, hematology, and urinalysis testing) performed
at the screening visit and on medical history, physical examination, vital-sign
measurements, and 12-lead ECG performed at screening and baseline assessments.
9. The subject has no history of hypertension or use of antihypertensive
medication. BP must be <140 mmHg (systolic) and <90 mmHg (diastolic); subjects
will have a heart rate within the range of 50 to 90 beats per minute at the
screening visit. BP will be averaged over 3 readings that are done 10 minutes
apart.
10. The subject agrees to refrain from taking excluded medications, vitamins,
supplements or dietary products listed in Section 7.3 of the protocol during
the study.

- The subject has received treatment with another investigational drug within 3
months before screening, or the subject participated in more than 4
investigational drug studies within 1 year before screening.
- The subject received immunotherapy within the past year.
- The subject has facial hair that could interfere with the seal of a facemask
(per investigator or site staff judgment), and is unwilling to shave it off
before check-in.
- The subject has a positive test result for hepatitis B surface antigen, HCV,
HIV antibody/antigen, or syphilis serum reaction test at screening. Note:
subjects with positive HBV or HCV serology may be enrolled if quantitative
polymerase chain reaction for HBV or HCV viral RNA is negative.
- The subject has a risk of suicide according to endorsement of Item 4 or 5 of
the C-SSRS at the screening visit or has made a suicide attempt in the previous
6 months.
- The subject has a positive alcohol or drug screen at screening or check-in,
has a history of alcohol consumption exceeding 2 standard drinks per day on
average within the 12 months before screening, or has a history of opioid abuse.
- The subject has caffeine consumption of more than 400 mg/day for 2 weeks
before screening (1 serving of coffee is approximately equivalent to 100 mg of
caffeine).
- The subject has a screening ECG with a QT interval with Fridericia correction
method (QTcF) >450 ms.