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

A Phase 1, Open-Label Study to Evaluate the Pharmacokinetics and Safety of Parsaclisib in Participants With Normal Renal Function and Participants With Renal Impairment

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

Study Overview

• Status: Completed
• Conditions: Advanced Malignancies
• Intervention / Treatment: Drug: parsaclisib

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Florida
    • Hialeah, Florida, United States, 33014
      • Clinical Pharmacology of Miami
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Prism Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 82 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants will be classified at screening by renal function based on eGFR as calculated by the MDRD formula and requirement for HD (Group 5).
• Participants eligible for Group 5 with ESRD have received HD for at least 3 months prior to screening.
• Participants eligible for Group 1 should be in good health as determined by no clinically significant deviations from normal for medical history, physical examination, vital signs, 12-lead ECGs, or clinical laboratory determinations at screening or Day -1.
• Participants eligible for Groups 2 through 5 may have medical findings consistent with their degree of renal dysfunction.

• Participants with abnormal findings considered not clinically significant by the medical monitor or investigator are eligible.

  0Body mass index within the range 18.0 to 40.0 kg/m2 (inclusive) at screening.

• Willingness to avoid pregnancy or fathering children.
• Ability to swallow and retain oral medication.

Exclusion Criteria:

• History of uncontrolled or unstable cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematopoietic, psychiatric, and/or neurological disease within 6 months of screening. Evidence of rapidly deteriorating renal function.
• Participants who have a current, functioning organ transplant or have a scheduled organ transplant within 6 weeks after 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 eligible for Group 1 who have a history of renal disease or renal injury as indicated by an abnormal, clinically significant renal function profile at screening or Day -1.
• Participants eligible for Groups 2 through 5 who have had a change in disease status within 30 days of screening, as documented by the participant's medical history, deemed clinically significant by the investigator.
• History or current diagnosis of uncontrolled or significant cardiac disease indicating significant risk of safety for participation in the study.
• 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 Day -1 (for Groups 1 through 4) or Period 1, Day
• 1 (Group 5).
• Chronic or current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment.
• Positive test for HBV (HBsAg, HBsAg antibody, and hepatitis B core antibody), HCV (HCV antibody), or HIV. Participants whose results are compatible with prior immunization for HBV may be included at the discretion of the investigator.

Participants eligible for Group 1 who have used tobacco- or nicotine-containing products within 6 months of screening.

• Participants eligible for Groups 2 through 5 who 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 dosing days and abide by CRU restrictions.
• Positive breath test for ethanol or positive urine or serum 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 study.
• Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) of study drug administration with strong or moderate inducer or inhibitor of CYP3A4, P-gp,or BCRP.
• For participants eligible for Group 1, use of prescription drugs within 14 days of study drug administration or nonprescription medications/products (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) within 7 days of study drug administration. However, occasional paracetamol, ibuprofen, and standard-dose vitamins are permitted.
• For participants eligible for Groups 2 through 5, use of prescription drugs within 14 days of study drug administration, with the exception of established therapy for renal disease and the treatment of associated disorders that have been stable for at least 7 days prior to study drug administration, as approved by the investigator and in consultation with the sponsor's medical monitor.
• 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.
• 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.
• Participants eligible for Group 5 that are not expected to continue HD treatment for the duration of the study.
• Receipt of live (including attenuated) vaccines or anticipation of need for such a vaccine during the study (Note: nonlive or inactivated vaccines are allowed up to 2 weeks prior to the first dose of study drug).
• Known hypersensitivity or severe reaction to parsaclisib or excipients of parsaclisib.
• History of alcoholism within 3 months of screening.
• Women who are pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treat Group 1 : Normal Renal Function; eGFR: ≥ 90 mL/min/1.73 m^2	Drug: parsaclisib; parsaclisib will be administered orally after 8 hours of fasting.; Other Names: INCB050465
Experimental: Treat Group 2 : Mild Renal Impairment; eGFR: 60-89 mL/min/1.73 m^2	Drug: parsaclisib; parsaclisib will be administered orally after 8 hours of fasting.; Other Names: INCB050465
Experimental: Treat Group 3 : Moderate Renal Impairment; eGFR: 30-59 mL/min/1.73 m^2	Drug: parsaclisib; parsaclisib will be administered orally after 8 hours of fasting.; Other Names: INCB050465
Experimental: Treat Group 4 : Severe Renal Impairment; eGFR: 15-29 mL/min/1.73 m^2 and not on Hemo Dialysis	Drug: parsaclisib; parsaclisib will be administered orally after 8 hours of fasting.; Other Names: INCB050465
Experimental: Treat Group 5 : Kidney Failure; eGFR: < 15 mL/min/1.73 m^2 on Hemo Dialysis	Drug: parsaclisib; parsaclisib will be administered orally after 8 hours of fasting.; Other Names: INCB050465

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics Parameter Groups1-4 : Cmax of parsaclisib	Maximum Observed Plasma Concentration of parsaclisib	4 Days
Pharmacokinetics Parameter Groups 1-4 : AUC 0-∞ of parsaclisib	Area Under the Concentration-time Curve From 0 to Infinity of parsaclisib	4 Days
Pharmacokinetics Parameter Groups 1-4 : AUC(0-t) of parsaclisib	Area Under the concentration- time curve up to the last measurable concentration of parsaclisib	4 Days
Pharmacokinetics Parameter Group 5: Cmax of parsaclisib	Maximum Observed Plasma Concentration of parsaclisib	4 Days for period 1 and 2
Pharmacokinetics Parameter Group 5 : AUC 0-∞ of parsaclisib	Area Under the Concentration-time Curve From 0 to Infinity of parsaclisib	4 Days for period 1 and 2
Pharmacokinetics Parameter Group 5: AUC(0-t) of parsaclisib	Area Under the concentration- time curve up to the last measurable concentration of parsaclisib	4 Days for period 1 and 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment Emergent Adverse Events (TEAE) Groups 1-4	Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.	up to 11 Days
Pharmacokinetics Parameter Groups 1-4 : tmax of parsaclisib	Time to reach maximum plasma concentration of parsaclisib	4 Days
Pharmacokinetics Parameter Groups 1-4 : t1/2 of parsaclisib	Apparent terminal phase disposition half-life of parsaclisib	4 Days
Pharmacokinetics Parameter Groups 1-4 : CL/F of parsaclisib	Oral dose clearance of parsaclisib	4 Days
Pharmacokinetics Parameter Groups 1-4 : Vz/F of parsaclisib	Apparent oral dose volume of distribution of parsaclisib	4 Days
Pharmacokinetics Parameter Group 5 : tmax of parsaclisib	Time to reach maximum plasma concentration of parsaclisib	4 Days for period 1 and 2
Pharmacokinetics Parameter Group 5 : t1/2 of parsaclisib	Apparent terminal phase disposition half-life of parsaclisib	4 Days for period 1 and 2
Pharmacokinetics Parameter Group 5 : CL/F of parsaclisib	Oral dose clearance of parsaclisib	4 Days for period 1 and 2
Pharmacokinetics Parameter Group 5 : Vz/F of parsaclisib	Apparent oral dose volume of distribution of parsaclisib	4 Days for period 1 and 2
Pharmacokinetics Parameter Group 5 during Dialysis - : AUC1-5 of parsaclisib	Area Under the Concentration-time Curve From 1 to 5 hrs. of parsaclisib	4 Days for period 1 and 2
Number of Treatment Emergent Adverse Events (TEAE) Group 5	Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.	up to 18 Days

Collaborators and Investigators

• Sponsor: Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2021
• Primary Completion (Actual): July 8, 2022
• Study Completion (Actual): July 8, 2022

Study Registration Dates

• First Submitted: April 2, 2021
• First Submitted That Met QC Criteria: April 2, 2021
• First Posted (Actual): April 5, 2021

Study Record Updates

• Last Update Posted (Actual): August 17, 2022
• Last Update Submitted That Met QC Criteria: August 16, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: INCB 50465-109

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No