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

Incyte

Status and phase: Enrolling; Phase 1

Conditions: Healthy Participants

Treatments: Drug: Ruxolitinib XR; Drug: Ruxolitinib IR

Study type: Interventional

Funder types: Industry

Identifiers

NCT06555081

INCB018424-154

Details and patient eligibility

About

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

Enrollment: 168 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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168 participants in 4 patient groups

Period 1: Dose Treatment A

Experimental group

Description:

Ruxolitinib IR will be administered at protocol defined dose.

Treatment:

Drug: Ruxolitinib IR

Period 1: Dose Treatment B

Experimental group

Description:

Ruxolitinib XR will be administered at protocol defined dose.

Treatment:

Drug: Ruxolitinib XR

Period 2: Dose Treatment A

Experimental group

Description:

Ruxolitinib IR will be administered at protocol defined dose.

Treatment:

Drug: Ruxolitinib IR

Period 2: Dose Treatment B

Experimental group

Description:

Ruxolitinib XR will be administered at protocol defined dose.

Treatment:

Drug: Ruxolitinib XR