| Eligibility |
Inclusion Criteria:
1. Willing and able to give written informed consent and to comply with the requirements
of the study for its duration.
2. Healthy adult males or females aged 18 to 55 years, inclusive. As determined by the
Investigator, healthy subjects are defined as individuals free from clinically
significant illness or disease as determined by their medical history, physical
examination, vital signs, cardiac monitoring, and clinical laboratory test results.
3. 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.
4. Female subjects of childbearing potential must agree to use contraception.
5. Body mass index (BMI) within 18.0 kg/m2 to 33.0 kg/m2, inclusively.
Exclusion Criteria:
1. Female who is lactating.
2. Positive pregnancy test at the Screening visit or check-in or planning to become
pregnant within the next 6 months.
3. Pulse rate less than 40 beats per minute (bpm) or more than 100 bpm at the Screening
visit or check-in.
4. A sustained supine systolic blood pressure > 140 mm Hg or < 90 mmHg or a supine
diastolic blood pressure > 90 mmHg or < 50 mmHg at the Screening visit, check-in, or
prior to dosing.
5. History of significant hypersensitivity to rodatristat ethyl, moxifloxacin, or any
related products (including excipients of the formulations) as well as severe
hypersensitivity reactions (like angioedema) to any drugs.
6. As determined by the Investigator, 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 (including
cholecystectomy), hematologic, renal, hepatic, bronchopulmonary, neurological,
psychiatric, endocrine, immunologic, dermatologic or cardiovascular disease,
including:
1. History of Gilbert's Syndrome
2. History of depression
3. History of any allergy that, in the opinion of the Investigator, contraindicates
participation in the trial
7. An uninterpretable or abnormal Screening ECG indicating a second or third degree
atrioventricular block, presence of out-of-range cardiac interval (heart rate [HR] <
40 bpm, PR < 110 msec, PR > 200 msec, QRS < 60 msec, QRS >110 msec and
Fridericia-corrected QT interval (QTcF) > 450 msec for males and > 470 msec for
females) on the ECG at the Screening visit or other clinically significant ECG
abnormalities, unless deemed non significant by an investigator.
8. History of risk factors for torsades de pointes, including unexplained syncope, known
long QT syndrome, heart failure, myocardial infarction, angina, or clinically
significant abnormal laboratory assessments including hypokalemia, hypercalcemia, or
hypomagnesemia. Subjects will also be excluded if there is a family history of long QT
syndrome or Brugada syndrome.
9. Clinically significant abnormalities in laboratory test results, as determined by the
Investigator, (including hepatic and renal panels, complete blood count, coagulation,
chemistry panel, and urinalysis) at the Screening visit or check-in that are confirmed
by a repeat reading .
1. Positive serology for hepatitis B virus (HBV), hepatitis C virus (HCV), or human
immunodeficiency virus (HIV)
2. Estimated glomerular filtration rate < 80 mL/min/1.73 m2 at the Screening visit,
calculated using the Cockcroft-Gault formula
3. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) values greater
than upper limit of normal (ULN). A single repeat measurement is allowed for
eligibility determination
4. Positive urine test for drugs of abuse at the Screening visit or check-in
5. Positive alcohol test (breath) at the Screening visit or check-in
6. Positive pregnancy test at the Screening visit or check-in
10. Presence of unstable cardiovascular disease, including recent myocardial infarction or
cardiac arrhythmia.
11. 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 = 11 oz
beer, 4 oz wine, or 1 oz spirits).
12. Subjects with a clinical history of or current illicit drug use which, in the opinion
of the Investigator, would interfere with the subjects ability to complete the study
and could compromise subject safety and/or the results of the study.
13. Any clinically significant illness, including viral syndromes, in the 28 days prior to
dosing.
14. Use of prescription or nonprescription drugs, (with exception of contraceptive and
acetaminophen allowed), including high-dose vitamins, dietary supplements (including
St. John's Wort) within 14 days or 5 half-lives of the prescription or nonprescription
drug (whichever is longer) prior to the first dose of study drug, through to the final
Follow-up visit, unless in the opinion of the Investigator and Sponsor, the medication
would not interfere with the study outcomes or compromise subject safety.
15. Consumption of grapefruit and/or pomelo and Seville oranges or their juices within the
7 days prior to dosing and until collection of the final lab sample.
16. Use of medications associated with QT prolongation within 30 days prior to dosing and
during the study.
17. Any other clinically significant abnormalities in laboratory test results at the
Screening visit or check-in, or any other medical, psychological, or social condition
that that would, in the opinion of an investigator, increase the subject's risk of
participation, jeopardize complete participation in the study, or compromise
interpretation of study data.
18. Previous intake of rodatristat ethyl in the last 6 months before Day 1.
19. Participation in another investigational drug, vaccine, or device study or treated
with an investigational drug within 30 days or 5 half-lives, whichever is longer,
before dosing, or 90 days for a biologic.
20. Donation of plasma within 7 days prior to dosing or donation or loss of blood
(excluding volume drawn at the Screening visit) of 50 mL to 499 mL of blood within 30
days or more than 499 mL within 56 days prior to dosing.
21. Is an employee of the Investigator or study center with direct involvement in the
proposed study or other studies under the direction of that Investigator or study
center, as well as a family member of the employee or Investigator.
22. Subjects who have smoked or used tobacco or nicotine containing products within 3
months prior to the Screening visit and who are unwilling to refrain from smoking,
tobacco use, or use of nicotine products for the entire duration of the study (through
the Follow-up visit).
23. Subjects unable to abstain from caffeine, xanthine, or strenuous exercise for 72 hours
prior to dosing until collection of the final lab sample.
24. Showing suicidal tendency as per the Columbia Suicide Severity Rating Scale (C SSRS)
administered at the Screening visit or prior to dosing.
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