| Eligibility |
Inclusion Criteria
1. Participants aged 18 years or older (or the minimum age of consent in accordance with
local regulations) at screening.
2. Healthy female participants of nonchildbearing potential and/or male participants who
are overtly healthy as determined by medical evaluation including medical history,
physical examination, and laboratory tests.
3. BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).
Exclusion Criteria:
Medical Conditions:
1. Evidence or history of clinically significant hematological, renal, endocrine,
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or
allergic disease (including drug allergies, but excluding untreated, asymptomatic,
seasonal allergies at the time of dosing).
- Any condition possibly affecting drug absorption (eg, gastrectomy,
cholecystectomy).
- History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV,
HBsAg, HBcAb, or HCVAb. Hepatitis B vaccination is allowed.
- Hypersensitivity to any component of the formulations
2. Other medical or psychiatric condition including recent (within the past year) or
active suicidal ideation/behavior or laboratory abnormality or other conditions or
situations related to COVID-19 pandemic (eg, Contact with positive case, residence, or
travel to an area with high incidence) that may increase the risk of study
participation or, in the investigator's judgment, make the participant inappropriate
for the study.
Prior/Concomitant Therapy:
3. Use of prescription or nonprescription drugs, dietary and herbal supplements within 7
days or 5 half lives (whichever is longer) prior to the first dose of study
intervention. (Refer to Section 6.9 Prior and Concomitant Therapy for additional
details).
4. Current use of any prohibited concomitant medication(s) or participant
unwilling/unable to use a permitted concomitant medication(s). Refer to Section 6.9
Prior and Concomitant Therapy.
Prior/Concurrent Clinical Study Experience:
5. Previous administration with an investigational product (drug or vaccine) within 6
months (or as determined by the local requirement) or 5 half-lives preceding the first
dose of study intervention used in this study (whichever is longer).
Diagnostic Assessments:
6. A positive urine drug test.
7. Screening seated BP =140 mm Hg (systolic) or =90 mm Hg (diastolic), following at least
5 minutes of seated rest. If BP is =140 mm Hg (systolic) or =90 mm Hg (diastolic), the
BP should be repeated 2 more times and the average of the 3 BP values should be used
to determine the participant's eligibility.
8. Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may
affect participant safety or interpretation of study results (eg, QTcF >450 ms,
complete LBBB, signs of an acute or indeterminate age myocardial infarction, ST-T
interval changes suggestive of myocardial ischemia, second or third degree AV block,
or serious bradyarrhythmias or tachyarrhythmias). If the uncorrected QT interval is
>450 ms, this interval should be rate-corrected using the Fridericia method only and
the resulting QTcF should be used for decision making and reporting. If QTcF exceeds
450 ms, or QRS exceeds 120 ms, the ECG should be repeated twice and the average of the
3 QTcF or QRS values used to determine the participant's eligibility.
Computer-interpreted ECGs should be overread by a physician experienced in reading
ECGs before excluding a participant.
9. Participants with ANY of the following abnormalities in clinical laboratory tests at
screening, as assessed by the study specific laboratory and confirmed by a single
repeat test, if deemed necessary:
- AST or ALT level = 1.5 × ULN;
- Total bilirubin level =1.5 × ULN; participants with a history of Gilbert's
syndrome may have direct bilirubin measured and would be eligible for this study
provided the direct bilirubin level is = ULN.
Other Exclusion Criteria:
10. History of alcohol abuse or binge drinking and/or any other illicit drug use or
dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5
(male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule,
alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1
ounce (30 mL) of 40% spirit, or 3 ounces (90 mL) of wine).
11. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more
within 60 days prior to dosing.
12. History of sensitivity to heparin or heparin induced thrombocytopenia.
13. Unwilling or unable to comply with the criteria in the Lifestyle Considerations
section of this protocol.
14. Investigator site staff directly involved in the conduct of the study and their family
members, site staff otherwise supervised by the investigator, and sponsor and sponsor
delegate employees directly involved in the conduct of the study and their family
members.
15. Use of tobacco or nicotine-containing products in excess of the equivalent of 5
cigarettes per day.
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