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

Advanced Malignancies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04831996
• Other study ID #: INCB 50465-109
• Status: Completed
• Phase: Phase 1
• Start date: May 4, 2021
• Est. completion date: July 8, 2022

Study information

• Verified date: August 2022
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: July 8, 2022
• Est. primary completion date: July 8, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 82 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Malignancies
• Renal Insufficiency

Intervention

Drug:
• parsaclisib
parsaclisib will be administered orally after 8 hours of fasting.

Locations

Country	Name	City	State
United States	Clinical Pharmacology of Miami	Hialeah	Florida
United States	Orlando Clinical Research Center	Orlando	Florida
United States	Prism Research	Saint Paul	Minnesota
United States	Orange County Research Center	Tustin	California

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics Parameter Groups1-4 : Cmax of parsaclisib	Maximum Observed Plasma Concentration of parsaclisib	4 Days
Primary	Pharmacokinetics Parameter Groups 1-4 : AUC 0-8 of parsaclisib	Area Under the Concentration-time Curve From 0 to Infinity of parsaclisib	4 Days
Primary	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
Primary	Pharmacokinetics Parameter Group 5: Cmax of parsaclisib	Maximum Observed Plasma Concentration of parsaclisib	4 Days for period 1 and 2
Primary	Pharmacokinetics Parameter Group 5 : AUC 0-8 of parsaclisib	Area Under the Concentration-time Curve From 0 to Infinity of parsaclisib	4 Days for period 1 and 2
Primary	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	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
Secondary	Pharmacokinetics Parameter Groups 1-4 : tmax of parsaclisib	Time to reach maximum plasma concentration of parsaclisib	4 Days
Secondary	Pharmacokinetics Parameter Groups 1-4 : t1/2 of parsaclisib	Apparent terminal phase disposition half-life of parsaclisib	4 Days
Secondary	Pharmacokinetics Parameter Groups 1-4 : CL/F of parsaclisib	Oral dose clearance of parsaclisib	4 Days
Secondary	Pharmacokinetics Parameter Groups 1-4 : Vz/F of parsaclisib	Apparent oral dose volume of distribution of parsaclisib	4 Days
Secondary	Pharmacokinetics Parameter Group 5 : tmax of parsaclisib	Time to reach maximum plasma concentration of parsaclisib	4 Days for period 1 and 2
Secondary	Pharmacokinetics Parameter Group 5 : t1/2 of parsaclisib	Apparent terminal phase disposition half-life of parsaclisib	4 Days for period 1 and 2
Secondary	Pharmacokinetics Parameter Group 5 : CL/F of parsaclisib	Oral dose clearance of parsaclisib	4 Days for period 1 and 2
Secondary	Pharmacokinetics Parameter Group 5 : Vz/F of parsaclisib	Apparent oral dose volume of distribution of parsaclisib	4 Days for period 1 and 2
Secondary	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
Secondary	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