A Study to Evaluate the Bioequivalence of Ruxolitinib Extended Release (XR) Tablets With Ruxolitinib Immediate Release (IR) Tablets Administered Orally in Healthy Participants

Bioequivalence of Ruxolitinib XR Tablets With Ruxolitinib IR Tablets Administered Orally in Healthy Participants

This study is conducted to determine the Bioequivalence of Ruxolitinib XR 55 mg Tablets With Ruxolitinib IR Tablets Administered Orally in Healthy Participants

Inclusion Criteria:

• Ability to comprehend and willingness to sign a written ICF for the study.

• Healthy adult participants aged 18 to 55 years, inclusive at screening.

• Body mass index between 18.0 and 32.0 kg/m2, inclusive, at screening. Note: Only up to 25% of the participants 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 < 40 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 > 460 msec for males and > 470 msec for females.
• 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.
• History of significant alcohol use within 3 months before screening, defined as regular alcohol consumption > 21 units per week for males and > 14 units for females (1 unit = 8 oz of beer or a 25-mL shot of 40% spirit, 1.5 to 2 units = a 125-mL glass of wine, depending on type).
• 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 as assessed by the investigator.
• 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 14 days of screening and throughout the study.
• Use of prescription drugs (including oral contraceptives) within 14 days of study drug administration or nonprescription medications/products (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 at screening or check-in.
• 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 < 80 mL/min/1.73 m2 at screening, based on the site's standard formula.
• Any condition that would jeopardize the safety of the participant or compliance with the Protocol.