Eligibility Details:
Inclusion Criteria
- Participants must be 18 to 55 years of age inclusive, at the time of signing the
informed consent.
- Participants who are healthy as determined by the investigator or medically qualified
designee based on a medical evaluation including medical history, physical
examination, laboratory tests, and cardiac monitoring (history and ECG).
- Body weight >=50.0 kilogram (kg) (110 pounds [lbs]) for men and >=45.0 kg (99 lbs) for
women and body mass index within the range 18.5 to 31.0 kg per square meter (kg/m^2)
(inclusive).
- Contraceptive use by men or women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies.
Male participants: Males shall not engage in intercourse while confined in the clinic.
There is no need for an extended period of double barrier use or prolonged abstinence
after study discharge. Female participants: 1. A female participant is eligible to
participate if she is not pregnant or breastfeeding, and at least 1 of the following
conditions applies: a. not a woman of childbearing potential (WOCBP); or Is a WOCBP
and using a nonhormonal contraceptive method that is highly effective, with a failure
rate of <1 percent (%), for 28 days before intervention, during the intervention
period, and for at least 28 days after the last dose of study intervention. The
investigator should evaluate the effectiveness of the contraceptive method in
relationship to the first dose of study intervention. 2. A WOCBP must have a negative
highly sensitive serum pregnancy test at Screening and Day -1. 3. Additional
requirements for pregnancy testing during and after study intervention.
- The investigator is responsible for review of medical history, menstrual history, and
recent sexual activity to decrease the risk for inclusion of a woman with an early
undetected pregnancy.
- Capable of giving signed informed consent, which includes compliance with the
requirements and restrictions.
Exclusion Criteria
- Current or chronic history of liver disease or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A pre-existing condition interfering with normal gastrointestinal (GI) anatomy or
motility (example [e.g.], gastroesophageal reflux disease, gastric ulcers, gastritis),
hepatic and/or renal function, that could interfere with the absorption, metabolism,
and/or excretion of the study intervention or render the participant unable to take
oral study intervention.
- Prior cholecystectomy surgery (prior appendectomy is acceptable).
- Any history of significant underlying psychiatric disorder, including, but not limited
to, schizophrenia, bipolar disorder with or without psychotic symptoms, other
psychotic disorders, or schizotypal (personality) disorder.
- Any history of major depressive disorder with or without suicidal features, or anxiety
disorders that required medical intervention (pharmacologic or not) such as
hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient
treatment. Participants with other conditions such as adjustment disorder or dysthymia
that have required shorter term medical therapy (<6 months) without inpatient
treatment and are currently well-controlled clinically or resolved may be considered
for entry after discussion and agreement with the Medical Monitor.
- Any pre-existing physical or other psychiatric condition (including alcohol or drug
abuse), which, in the opinion of the investigator (with or without psychiatric
evaluation), could interfere with the participant's ability to comply with the dosing
schedule and protocol evaluations or which might compromise the safety of the
participant.
- Medical history of cardiac arrhythmias, prior myocardial infarction in the past 3
months, or cardiac disease or a family or personal history of long QT syndrome.
- Presence of hepatitis B surface antigen at Screening or within 3 months prior to
starting study intervention.
- Positive hepatitis C antibody test result at Screening or within 3 months prior to
starting study intervention and positive on reflex to hepatitis C ribonucleic acid
(RNA).
- Positive Human immunodeficiency virus (HIV)-1 and -2 antigen/antibody immunoassay at
Screening.
- ALT >1.5 times upper limit of normal (ULN). A single repeat of ALT is allowed within a
single Screening period to determine eligibility.
- Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin
is fractionated and direct bilirubin <35%). A single repeat of any laboratory
abnormality is allowed within a single Screening period to determine eligibility.
- Any acute laboratory abnormality at Screening which, in the opinion of the
investigator, should preclude participation in the study of an investigational
compound.
- Any Grade 2 to 4 laboratory abnormality at Screening, with the exception of creatine
phosphokinase (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides),
and ALT (described above), will exclude a participant from the study unless the
investigator can provide a compelling explanation for the laboratory result(s) and has
the assent of the sponsor. A single repeat of any laboratory abnormality is allowed
within a single Screening period to determine eligibility.
- A positive test result for drugs of abuse (including marijuana), alcohol, or cotinine
(indicating active current smoking) at Screening or before the first dose of study
intervention.
- Unable to refrain from the use of prescription or nonprescription drugs including
vitamins, herbal and dietary supplements (including Saint John's wort) within 7 days
(or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is
longer) prior to the first dose of study intervention and for the duration of the
study.
- Treatment with any vaccine within 30 days prior to receiving study intervention.
- Unwillingness to abstain from excessive consumption of any food or drink containing
grapefruit and grapefruit juice, Seville oranges, blood oranges, or pomelos or their
fruit juices within 7 days prior to the first dose of study intervention(s) until the
end of the study.
- Participation in another concurrent clinical study or prior clinical study (with the
exception of imaging trials) prior to the first dosing day in the current study: 30
days, 5 half-lives, or twice the duration of the biological effect of the study
intervention (whichever is longer).
- Where participation in the study would result in donation of blood or blood products
in excess of 500 milliliter (mL) within 56 days.
- Any positive (abnormal) response confirmed by the investigator on a screening
clinician- or qualified designee-administered Columbia Suicide Severity Rating Scale
(C-SSRS).
- Any significant arrhythmia or ECG finding (e.g., prior myocardial infarction in the
past 3 months, symptomatic bradycardia, non-sustained or sustained atrial arrhythmias,
non-sustained or sustained ventricular tachycardia, second-degree atrioventricular
block Mobitz Type II, third-degree atrioventricular block, complete heart block, or
conduction abnormality) which, in the opinion of the investigator or Medical Monitor,
will interfere with the safety for the individual participant.
- Exclusion criteria for Screening ECG (a single repeat is allowed for eligibility
determination): Heart rate: <50 or >100 beats per minute and QTcF interval: >450
millisecond.
- History of regular alcohol consumption within 6 months of the study defined as an
average weekly intake of >14 units. One unit is equivalent to 8 grams of alcohol: a
half pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL)
measure of spirits.
- Unable to refrain from tobacco or nicotine-containing products within 3 months prior
to Screening.
- History of sensitivity to any of the study medications, or components thereof or a
history of drug or other allergy that, in the opinion of the investigator or medical
monitor, contraindicates their participation.
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-no
