A Study to Evaluate the Pharmacokinetics and Safety of INCB161734 in Participants With Impaired Renal Function and Participants on Hemodialysis

Korábbi kezelés

• History of uncontrolled or unstable cardiovascular, respiratory, renal, GI, endocrine, hematopoietic, psychiatric, or neurological disease within 6 months before screening.
  • History or current diagnosis of uncontrolled or significant cardiac disease indicating significant risk of safety for participation in the study, including but not limited to the following:
  • Recent myocardial infarction (within 6 months before check-in).
  • New York Heart Association Class III or IV congestive heart failure.
  • Unstable angina (within 6 months before check-in).
  • Clinically significant (symptomatic) cardiac arrhythmias (eg, sustained ventricular tachycardia, second or third degree atrioventricular block without a pacemaker).
  • Uncontrolled hypertension.
• Participants who have a current, functioning organ transplant or are on the national transplant list and expected to receive a transplant within 3 months.
• Current or recent (within 3 months before screening) clinically significant GI disease or surgery (including cholecystectomy [< 2 months]; excluding appendectomy and hernia repair) that could affect the absorption of study drug.
• Any major surgery within 4 weeks before screening. Note: This does not include procedure for HD.
• Blood transfusion within 4 weeks before check-in (Day -1).
• Positive test result for HBV, HCV, or HIV. Upon testing, HBV DNA and HCV RNA must be undetectable.
  • Note 1: Participants with no prior history of HBV infection who have been vaccinated against HBV and who have a positive HBsAg antibody test as the only evidence of prior exposure may participate in the study.
  • Note 2: Participants who have cleared a prior HBV infection (defined as HbsAg negative, HBsAb positive, or HBcAb positive) may be included at the discretion of the investigator.
• Receipt of any vaccine including but not limited to live (including attenuated), influenza, and SARS-CoV-2 vaccines within 3 months before the first dose of study drug.
• History of significant alcohol use, defined as regular alcohol consumption > 21 units per week for males and > 14 units for females, within 3 months before screening.
• 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 study.
• Treatment within 14 days or 5 half-lives (whichever is longer) before the first dose of study drug with an inducer or inhibitor of CYP3A4, P-gp, or BCRP (refer to the Drug Interaction Database Program for prohibited drugs).
• Tobacco or nicotine-containing product use of > 10 cigarettes per day within 1 month before screening.
• Use of prescription drugs (including hormonal contraceptives) within 14 days before study drug administration or nonprescription medications/products (including megadose vitamins, minerals, and phytotherapeutic, herbal, or plant-derived preparations as well as pre/probiotics) within 7 days of study drug administration
  • Note 1: Occasional acetaminophen, standard-dose ibuprofen, and standard-dose vitamins are permitted.
  • Note 2: Established therapy for renal disease, or the treatment of associated disorders, that has been stable for at least 7 days prior to study drug administration, is allowed if approved by the medical monitor and investigator.
• Excessive exercise (eg, Ironman, bi/triathlon) within 3 months before screening.
• Participants who had a change in disease status within 30 days before screening, as documented by the participant's medical history, that is deemed clinically significant by the investigator.
• Participants who have a history of paracentesis within 3 months prior to check-in.
• Participants who required new medication or an increase in dose for renal disease within 3 months prior to check-in.
• Esophageal banding within 3 months prior to check-in or required any other treatment for GI bleeding within 6 months prior to check-in.
  • Other protocol-defined Inclusion/Exclusion Criteria may apply.

Más betegség

• History of an autoimmune disease diagnosis (eg, myasthenia gravis).
• History of cardiovascular, cerebrovascular, peripheral vascular, or thrombotic disease or uncontrolled hypertension (systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg at screening, confirmed by repeat testing).
• Presence or history of a malabsorption syndrome possibly affecting drug absorption (eg, Crohn disease or chronic pancreatitis).
• History of malignancy within 5 years before screening, with the exception of cured basal cell or squamous cell carcinoma of the skin, ductal carcinoma in situ, or Gleason 6 prostate cancer.
• Chronic or current active infectious disease (including latent tuberculosis) requiring systemic antibiotic, antifungal, or antiviral treatment.
• Medical or self-reported history of alcoholism within 3 years before screening.
• Active infection requiring systemic therapy.
• History of any significant drug allergy (such as anaphylaxis or hepatotoxicity) deemed clinically relevant by the investigator.
• Known hypersensitivity or severe reaction to INCB161734, any excipients of INCB161734, or any KRAS inhibitors (refer to the IB).

Laborértékek

• Participants with laboratory values outside the accepted range for participants with severe renal impairment or ESRD at screening.
• Participants who have a history of unstable diabetes mellitus (as evidenced by hemoglobin A1c ≥ 10.0%). Medications for treatment of diabetes mellitus must be reviewed and approved by the investigator and medical monitor.

Egyéb

• Participants who have a 12-lead ECG abnormality at screening that, in the opinion of the investigator, increases the risks associated with participating in the study or may confound ECG data analysis.
• Confirmed resting pulse rate (up to 2 consecutive measurements) < 40 bpm or > 100 bpm at screening.
• Inability to undergo venipuncture or tolerate venous access, or inadequate veins for repeat venipuncture or venous access as determined by the investigator.
• Participants who are pregnant or lactating.

• Ability to comprehend and willingness to sign a written ICF for the study.
• Aged 18 to 85 years, inclusive, at the time of signing the ICF.
• Severe renal impairment or ESRD based on CKD-EPI (National Kidney Foundation).
  • Participants with impaired renal function should have stable renal function (ie, those with acute changes in renal function should not be enrolled in the study).
• Medical findings consistent with the degree of renal dysfunction, determined by medical history, physical examination, vital sign measurements, 12-lead ECGs, and clinical laboratory determinations at screening or check-in (as applicable). Participants with abnormal findings considered not clinically significant by the medical monitor or investigator are eligible.
• BMI of 18.0 to 43.0 kg/m2 (inclusive) at screening.
• Ability to swallow and retain oral tablets.
• Willingness to avoid pregnancy, breastfeeding, or fathering children.