Hepatic Insufficiency, Liver Diseases
Conditions
Keywords
hepatic impairment, liver impairment (moderate and severe)
Brief summary
This study is conducted to evaluate the pharmacokinetics and safety of INCB161734 in participants with hepatic impairment.
Interventions
DRUGINCB161734
single dose administered orally
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Ability to comprehend and willingness to sign a written ICF for the study. * Age 18 to 80 years (inclusive) at the time of signing the ICF. * Moderate or severe hepatic impairment based on Child-Pugh score. * Medical findings consistent with the degree of hepatic dysfunction, determined by medical history, physical examination, vital sign measurements, 12-lead ECGs, and clinical laboratory examinations at screening and check-in. * BMI of 18.0 to 44.0 kg/m2 (inclusive) at screening. * Ability to swallow and retain oral tablets. * Willingness to avoid pregnancy or fathering children.
Exclusion criteria
* In the opinion of the investigator, history of uncontrolled or unstable cardiovascular, respiratory, renal, GI, endocrine, hematopoietic, psychiatric, and/or neurological disease within 6 months before screening or evidence of rapidly deteriorating hepatic function. * History or current diagnosis of uncontrolled or significant cardiac disease indicating significant risk of safety for participation in the study. * Current, functioning organ transplant or on the national transplant list and expected to receive a transplant within 3 months. * History of an autoimmune disease diagnosis (eg, myasthenia gravis). * History of malignancy within 5 years before screening, with the exception of cured basal cell carcinoma, squamous cell carcinoma of the skin, ductal carcinoma in situ, or Gleason 6 prostate cancer. * History of clinically significant GI disease or surgery (cholecystectomy and appendectomy are allowed) that could impact the absorption of study drug. * Severe ascites (ascites requiring paracentesis more than twice every 4 weeks) or encephalopathy ≥ Grade 2 (precludes them from understanding and signing an ICF). * Any major surgery within 4 weeks before screening. * Donation of blood within 4 weeks before screening (within 2 weeks for plasma only). * Blood transfusion within 4 weeks before check-in (Day -1). * Current or recent history (within 30 days before screening) of a clinically significant bacterial, fungal, parasitic, or mycobacterial infection, or currently receiving systemic antibiotics or current clinically significant viral infection at screening or check-in (Day -1). * History of alcoholism within 3 months before screening. * Positive breath, urine, or blood test for ethanol or positive serum or urine screen for drugs of abuse that is not otherwise explained by permitted concomitant medications. * Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before study drug administration with another investigational medication or current enrollment in another investigational drug study. * Current treatment or treatment within 15 days or 5 half-lives (whichever is longer) before study drug administration with an inducer or inhibitor of CYP3A4, P-gp, or BCRP. * 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 before study drug administration. * Note 1: Occasional acetaminophen, standard-dose ibuprofen, and standard-dose vitamins are permitted. * Note 2: Established therapy for hepatic 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. * Consumption of alcohol within 1 month before screening. * Consumption of caffeine-containing foods and beverages within 3 days before check-in (Day -1). * Consumption of Seville oranges, grapefruits, pomelos, exotic citrus fruits, grapefruit hybrids, or fruit juices within 7 days before the first dose of study drug. * Current use of prohibited medication. * Receipt of live (including attenuated) vaccines or anticipation of need for such a vaccine during the study. (Note: Non-live or inactivated vaccines allowed up to 2 weeks before study drug administration.). * Known hypersensitivity or severe reaction to INCB161734 or excipients of INCB161734. * History of any significant drug allergy (such as anaphylaxis or hepatotoxicity) deemed clinically relevant by the investigator. * Inability to undergo venipuncture or tolerate venous access. * 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 the study data. * Currently smoke \> 10 cigarettes per day, or equivalent use of other tobacco- or nicotine-containing products, and are unwilling to refrain from tobacco or nicotine use on treatment days and abide by CRU restrictions. * Women who are pregnant or breastfeeding. * New medication requirement or an increase in dose for hepatic encephalopathy within 3 months prior to check-in. * Current portal systemic shunt. * Esophageal banding within 3 months prior to check-in or required any other treatment for GI bleeding within 6 months prior to check-in. Hemorrhoidal banding is permitted. Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK for plasma INCB161734: Cmax | Up to approximately 1.5 months | Defined as the maximum plasma concentration. |
| PK for plasma INCB161734: AUClast | Up to approximately 1.5 months | Defined as the area under the concentration-time curve from time zero to time of the last quantifiable concentration. |
| PK for plasma INCB161734: AUCinf | Up to approximately 1.5 months | Defined as the area under concentration-time curve from time zero extrapolated to infinity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment-Emergent Adverse Events (TEAEs) | Up to approximately 1.5 months and 15 days | Adverse events reported for the first time or worsening of a pre-existing event, occurring after first dose of study drug. |
| PK for plasma INCB161734: Tmax | Up to approximately 1.5 months | Defined as the time to maximum concentration. |
| PK for plasma INCB161734: t½ | Up to approximately 1.5 months | Defined as the terminal-phase half-life. |
| PK for plasma INCB161734: Tlast | Up to approximately 1.5 months | Defined as the time at which the last quantifiable concentration is observed. |
| PK for plasma INCB161734: CL/F | Up to approximately 1.5 months | Defined as the apparent clearance. |
| PK for plasma INCB161734: Vz/F | Up to approximately 1.5 months | Defined as the apparent volume of distribution. |
| PK for plasma INCB161734: AUCextrap% | Up to approximately 1.5 months | Defined as the percentage of area under the plasma concentration-time curve from time zero extrapolated to infinity obtained by forward extrapolation. |
Contacts
CONTACTIncyte Corporation Call Center (US)
CONTACTIncyte Corporation Call Center (ex-US)
STUDY_DIRECTORIncyte Medical Monitor
Incyte Corporation
Outcome results
None listed