| Eligibility |
Inclusion Criteria:
- Ability to comprehend and willingness to sign a written ICF for the study.
- Healthy adult participants aged 19 to 55 years at screening.
- Body mass index between 18.0 and 32.0 kg/m2, inclusive, at screening. Note: Only up to
25% of the participants in each cohort may be enrolled with a body mass index > 30 to
= 32.0 kg/m2.
- No clinically significant findings on screening evaluations (clinical, laboratory, and
ECG).
- Ability to swallow and retain oral medication.
- Willingness to avoid pregnancy or fathering children based on the criteria below.
- Male participants with reproductive potential must agree to take appropriate
precautions to avoid fathering children (with at least 99% certainty) and not
have a partner that is currently pregnant from screening through follow-up.
Permitted methods that are at least 99% effective in preventing pregnancy should
be communicated to the participants and their understanding confirmed.
- Female participants who are WOCBP must have a negative serum pregnancy test at
screening and a negative serum or urine pregnancy test at check-in before the
first dose on Day -1 and must agree to take appropriate precautions to avoid
pregnancy (with at least 99% certainty) from screening through follow-up.
Permitted methods that are at least 99% effective in preventing pregnancy should
be communicated to the participants and their understanding confirmed.
- Female participants of nonchildbearing potential (ie, surgically sterile with a
hysterectomy and/or bilateral oophorectomy OR = 12 months of amenorrhea and at
least 51 years of age and FSH compatible with postmenopausal status) are
eligible.
Exclusion Criteria:
- History of uncontrolled or unstable cardiovascular, respiratory, renal,
gastrointestinal, endocrine, hematopoietic, psychiatric, and/or neurological disease
within 6 months of screening.
- History of cardiovascular, cerebrovascular, peripheral vascular or thrombotic disease
or uncontrolled hypertension (blood pressure > 140/90 mmHg confirmed by repeat
testing).
- Resting pulse < 45 bpm or > 100 bpm, confirmed by repeat testing.
- History or presence of an abnormal ECG before initial dose administration that, in the
investigator's opinion, is clinically significant, such as a QTcF interval > 450
milliseconds.
- Presence of a malabsorption syndrome possibly affecting drug absorption (eg, Crohn's
disease or chronic pancreatitis).
- Hemoglobin, WBC count, platelet count, or absolute neutrophil count less than
laboratory lower limit of normal at screening or at check-in, confirmed by repeat
testing.
- Hepatic transaminases (ALT and AST), ALP, or total bilirubin > 1.25 × the
laboratory-defined ULN at screening and check-in, confirmed by repeat testing (except
participants with Gilbert's disease, for which total bilirubin must be = 2.0 × ULN).
- History of malignancy within 5 years of screening, with the exception of cured basal
cell or squamous cell carcinoma of the skin, ductal carcinoma in situ, or Gleason 6
prostate cancer.
- Current or recent (within 3 months of screening) clinically significant
gastrointestinal disease or surgery (including cholecystectomy) that could affect the
absorption of study drug except that appendectomy will be allowed.
- Any major surgery within 4 weeks of screening.
- Donation of blood to a blood bank or in a clinical study (except a screening visit)
within 4 weeks of screening (within 2 weeks for plasma only).
- Blood transfusion within 4 weeks of check-in.
- Chronic or current active infectious disease requiring systemic antibiotic,
antifungal, or antiviral treatment (includes latent treated tuberculosis).
- Positive test for hepatitis B virus, HCV, or HIV. Participants whose results are
compatible with prior immunization or immunity due to infection for hepatitis B may be
included at the discretion of the investigator.
- History of alcoholism within 3 months of screening.
- Positive urine or breath test for ethanol or positive urine screen for drugs of abuse
that are not otherwise explained by permitted concomitant medications or diet.
- Current treatment or treatment within 30 days or 5 half-lives (whichever is longer)
before the first dose of study drug with another investigational medication or current
enrollment in another investigational drug Protocol.
- Current treatment or treatment within 30 days or 5 half-lives (whichever is longer)
before the first dose of study drug with an inducer or inhibitor of cytochrome P450
3A4, P-glycoprotein, or breast cancer resistance protein.
- Current use of prohibited medication.
- History of any significant drug allergy (such as anaphylaxis or hepatotoxicity) deemed
clinically relevant by the investigator.
- Known hypersensitivity or severe reaction to ruxolitinib or any excipients of
ruxolitinib.
- Inability to undergo venipuncture or tolerate venous access.
- Inability or unlikeliness of the participant to comply with the dose schedule and
study evaluations, in the opinion of the investigator.
- Use of tobacco- or nicotine-containing products within 1 month of screening and
throughout the study.
- Use of prescription drugs within 14 days of study drug administration or
nonprescription medications/products (including vitamins, minerals, and
phytotherapeutic/herbal/plant derived preparations) within 7 days of study drug
administration and throughout the study except for permitted medications during the
study.
- Women who are pregnant or breastfeeding.
- Any condition that would, in the investigator's judgment, interfere with full
participation in the study, including administration of study drug and attending
required study visits; pose a significant risk to the participant; or interfere with
interpretation of study data.
- eGFR < 90 mL/min/1.73 m2 based on the site's standard formula.
- Any condition that would jeopardize the safety of the participant or compliance with
the Protocol.
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