To Evaluate the Safety, and Pharmacokinetics of Parscaclisib in Participants With Normal Hepatic Function and Hepatic Impairment.

Phase 1

Completed

• Conditions: Advanced Malignancies
• Interventions: Drug: parsaclisib

• Registration Number: NCT04831944
• Lead Sponsor: Incyte Corporation

Brief Summary

The purpose of the study is to evaluate the pharmacokinetics and safety of parsaclisib in participants With normal hepatic function and participants with hepatic impairment.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-03-29
• Study First Submitted: 2021-04-02
• Study First Submitted QC: 2021-04-02
• Study First Posted: 2021-04-05
• Primary Completion: 2022-03-10
• Study Completion: 2022-03-11
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-25
• Last Update Posted: 2022-08-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

• Participants with hepatic impairment.
• Participants eligible for Group 4 should be in good health.
• Participants eligible for Groups 1 through 3 may have medical findings consistent with their degree of hepatic dysfunction.
• Participants with abnormal findings considered not clinically significant by the investigator are eligible.
• Body mass index within the range of 18.0 to 40.0 kg/m2 (inclusive) at screening.
• Willingness to avoid pregnancy or fathering children.

Exclusion Criteria

• Evidence of rapidly deteriorating hepatic function.
• Participants with serum calcium and phosphorus levels over the upper limits of the institutional normal ranges.
• History or current diagnosis of uncontrolled or significant cardiac disease indicating significant risk of safety for participation in the study, including any of the following:
• Participants who have a current, functioning organ transplant or have a scheduled organ transplant in the next 6 weeks from check-in.
• History of malignancy within 5 years of 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 gastrointestinal disease or surgery (cholecystectomy and appendectomy are allowed) that could impact the absorption of study drug.
• Participants with severe ascites or an encephalopathy ≥ Grade 2.
• Any major surgery within 4 weeks of screening.
• Donation of blood to a blood bank within 4 weeks of screening (within 2 weeks for plasma only).
• Blood transfusion within 4 weeks of check-in. Current or recent history (within 30 days before screening) of a clinically significant bacterial, fungal, parasitic, or mycobacterial infection, or currently receiving systemic antibiotics. Current clinically significant viral infection at screening or check-in.
• Positive serology for hepatitis B virus (eg, hepatitis B surface antigen) or human immunodeficiency virus. Participants whose results are compatible with immunity due to infection or prior immunization for hepatitis B may be included at the discretion of the investigator.
• History of alcoholism within 3 months of screening.
• Positive breath test for ethanol or positive 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) of study drug administration 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) of study drug administration with strong or moderate inducer or potent inhibitor of CYP3A4.
• 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 first dose administration.)
• Known hypersensitivity or severe reaction to parsaclisib or excipients of parsaclisib.
• History of any significant drug allergy (such as anaphylaxis or hepatotoxicity) deemed clinically relevant by the investigator. Inability to be venipunctured or tolerate venous access.
• Participants eligible for Group 4 who have a history or presence of liver disease or liver injury as indicated by an abnormal clinically significant liver function profile at screening or check-in.
• Participants eligible for Group 4 who have a positive test for hepatitis C virus.
• Participants eligible for Group 4 who used tobacco- or nicotine-containing products within 6 months of screening.
• Women who are pregnant or breastfeeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Group 1 : Severe hepatic impairment	parsaclisib	Child Pugh (CP) assessment score of 10-14 points
Treatment Group 2 : Moderate hepatic impairment	parsaclisib	Child Pugh (CP) assessment score of 7-9 points
Treatment Group 3 : Mild hepatic impairment	parsaclisib	Child Pugh (CP) assessment score of 5-6 points
Treatment Group 4 : Normal hepatic impairment	parsaclisib	Normal hepatic function

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics Parameter : Cmax of parsaclisib	5 Days	Maximum Observed Plasma Concentration of parsaclisib
Pharmacokinetics Parameter : AUC 0-∞ of parsaclisib	5 Days	Area Under the Concentration-time Curve From 0 to Infinity of parsaclisib
Pharmacokinetics Parameter : AUC(0-t) of parsaclisib	5 Days	Area Under the concentration- time curve up to the last measurable concentration of parsaclisib

Secondary Outcome Measures

Name	Time	Method
Number of Treatment Emergent Adverse Events (TEAE)	Up to10 Days	Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
Pharmacokinetics Parameter : tmax of parsaclisib	5 Days	Time to reach maximum plasma concentration of parsaclisib
Pharmacokinetics Parameter : CL/F of parsaclisib	5 Days	Oral dose clearance of parsaclisib
Pharmacokinetics Parameter : t1/2 of parsaclisib	5 Days	Apparent terminal phase disposition half-life of parsaclisib
Pharmacokinetics Parameter : Vz/F of parsaclisib	5 Days	Apparent oral dose volume of distribution of parsaclisib

Trial Locations

Locations (5)

Orange County Research Center; 🇺🇸 Tustin, California, United States

Inland Empire Liver Foundation; 🇺🇸 Rialto, California, United States

Orlando Clinical Research Center; 🇺🇸 Orlando, Florida, United States

Clinical Pharmacology of Miami; 🇺🇸 Hialeah, Florida, United States

Texas Liver Institute Tli the Liver Institute of South Texas List Downtown Office; 🇺🇸 San Antonio, Texas, United States