Eligibility |
Inclusion Criteria:
- Healthy males or females aged 18 to 55 years, inclusive
- A male subject is eligible to participate if he does not have a female partner who is
pregnant or who intends to become pregnant during the study. Male subjects must agree
to use contraception starting at Screening, during the treatment period, and for at
least 100 days after the last dose of Investigational Product (IP), and refrain from
donating sperm during this period.
- Female subjects of childbearing potential must agree to use contraception starting at
Screening, during the treatment period, and for at least 30 days after the last dose
of IP.
- Body mass index (BMI) = 18 kg/m2 and = 32 kg/m2 at Screening
- Japanese subjects must have been born in Japan and not have lived outside of Japan >
10 years at the time of Screening, have both parents and grandparents of ethnic
Japanese origin, and have not significantly modified their diets since leaving Japan.
- Caucasian subjects must be of European or Latin American descent (i.e., White).
- Capable of giving signed informed consent, able to understand and comply with protocol
requirements, instructions, and protocol related restrictions, and likely to complete
the study as planned.
Exclusion Criteria:
- Any known pre-existing medical or psychiatric condition that could interfere with the
subject's ability to provide informed consent or participate in study conduct, or that
may confound study findings including, but not limited to a history of clinically
significant gastrointestinal, hematologic, renal, hepatic, bronchopulmonary,
neurological, psychiatric, or cardiovascular disease
- a. History of Gilbert's Syndrome
- b. History of depression
- c. History of any allergy that, in the opinion of the Investigator, contraindicates
participation in the trial
- Any positive finding on the Columbia-Suicide Severity Rating Scale (C-SSRS).
- Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding
volume drawn at Screening) of 50 mL to 499 mL of blood within 30 days or more than 499
mL within 56 days prior to Day 1
- Participation in an investigational drug, vaccine, or device study within 30 days
before IP administration or 90 days for a biologic study
- Evidence of previous myocardial infarction
- a. Any conduction abnormality (including but not specific to atrioventricular block
[2nd degree or higher], Wolff Parkinson White syndrome [unless curative ablation
treatment]).
- b. Sinus pauses > 3 seconds.
- c. Any significant arrhythmia which, in the opinion of the Investigator and Medical
Monitor, will interfere with the safety for the individual subject.
- d. Non-sustained or sustained ventricular tachycardia (= 3 consecutive ventricular
ectopic beats).
- Abnormal blood pressure, either low (defined as < 90 mmHg systolic and/or < 50 mmHg
diastolic) or high (defined as > 140 mmHg systolic and/or > 90 mmHg diastolic)
- Clinically significant abnormalities in laboratory test results (including hepatic and
renal panels, complete blood count, coagulation, chemistry panel, and urinalysis)
- a. Positive serology for hepatitis B, hepatitis C virus, or human immunodeficiency
virus
- b. Estimated glomerular filtration rate < 80 mL/min/1.73 m2
- c. Aspartate aminotransferase, alanine aminotransferase values greater than 1.5 x
upper limit of normal.
- d. Positive urine test for drugs of abuse
- e. Positive alcohol test (breath, saliva, or urine)
- Use of prescription or nonprescription drugs including high dose vitamins, dietary
supplements (including St. John's Wort) within 7 days or 5 half-lives of the
prescription or nonprescription drug (whichever was longer) prior to the first dose of
IP product, unless in the opinion of the Investigator and Sponsor, the medication
would not interfere with the study outcomes or compromise subject safety.
- Subject unable to abstain from consumption of tryptophan-rich foods 48 hours prior to
admission to the clinic through the Follow-up visit
- Consumption of grapefruit or Seville oranges or their juices within the 7 days prior
to dosing until collection of the final PK sample.
- Use of medications associated with QT prolongation within 30 days prior to dosing and
during the study. A list of prohibited medications is provided in an appendix to the
protocol.
- Subjects unable to abstain from alcohol for 72 hours prior to the start of dosing
through collection of their final PK sample
- Subjects with a clinical history of or current alcohol abuse defined as an average
weekly intake of more than 21 units for males or 15 units for females (1 unit = 340 mL
beer, 115 mL wine, or 43 mL spirits).
- Subjects with a clinical history of or current illicit drug use which, in the opinion
of the Investigator, would interfere with the subject's ability to complete the study
and could compromise subject safety and/or the results of the study.
- Subjects unable to abstain from caffeine, xanthine, or strenuous exercise for 72 hours
prior to dosing until collection of their final PK sample.
- Subjects who have smoked or used tobacco or nicotine-containing products or
cannabidiol and related products (in all forms) within 3 months prior to the Screening
visit and who are unwilling to refrain from cannabidiol and related products, smoking,
tobacco use, or use of nicotine products and all for the entire duration of the study
(through the Follow-up visit)
- History of hypersensitivity to rodatristat ethyl, any its components, or any
components in the placebo preparation.
- Employed as site personnel directly involved with this study
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