Clinical trial NCT06555081: A Study to Evaluate the Bioequivalence of Ruxolitinib Extended Release (XR) Tablets With Ruxolitinib Immediate Release (IR) Tablets Administered Orally in Healthy Participants
Official title: Bioequivalence of Ruxolitinib XR Tablets With Ruxolitinib IR Tablets Administered Orally in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: INCB018424
Ruxolitinib
Healthy Participants
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2024-08-15
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: INCB018424 pharmacokinetic (PK) in Plasma
timeFrame: Up to Day 16
Secondary outcomes:
measure: Number of participants with Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to Day 33
measure: Additional INCB018424 pharmacokinetic (PK) in Plasma
timeFrame: Up to Day 16
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion Clinical Research Unit
state: Arizona
Study officials:
affiliation: Incyte Corporation
name: Incyte Medical Monitor
role: STUDY_DIRECTOR
References: