Clinical trial NCT04831996: To Evaluate the Safety, and Pharmacokinetics of Parscaclisib in Participants With Normal Renal Function and Renal Impairment.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Malignancies
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2021-04-05
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 82
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetics Parameter Groups1-4 : Cmax of parsaclisib
timeFrame: 4 Days
measure: Pharmacokinetics Parameter Groups 1-4 : AUC 0-∞ of parsaclisib
timeFrame: 4 Days
measure: Pharmacokinetics Parameter Groups 1-4 : AUC(0-t) of parsaclisib
timeFrame: 4 Days
measure: Pharmacokinetics Parameter Group 5: Cmax of parsaclisib
timeFrame: 4 Days for period 1 and 2
measure: Pharmacokinetics Parameter Group 5 : AUC 0-∞ of parsaclisib
timeFrame: 4 Days for period 1 and 2
measure: Pharmacokinetics Parameter Group 5: AUC(0-t) of parsaclisib
timeFrame: 4 Days for period 1 and 2
Secondary outcomes:
measure: Number of Treatment Emergent Adverse Events (TEAE) Groups 1-4
timeFrame: up to 11 Days
measure: Pharmacokinetics Parameter Groups 1-4 : tmax of parsaclisib
timeFrame: 4 Days
measure: Pharmacokinetics Parameter Groups 1-4 : t1/2 of parsaclisib
timeFrame: 4 Days
measure: Pharmacokinetics Parameter Groups 1-4 : CL/F of parsaclisib
timeFrame: 4 Days
measure: Pharmacokinetics Parameter Groups 1-4 : Vz/F of parsaclisib
timeFrame: 4 Days
measure: Pharmacokinetics Parameter Group 5 : tmax of parsaclisib
timeFrame: 4 Days for period 1 and 2
measure: Pharmacokinetics Parameter Group 5 : t1/2 of parsaclisib
timeFrame: 4 Days for period 1 and 2
measure: Pharmacokinetics Parameter Group 5 : CL/F of parsaclisib
timeFrame: 4 Days for period 1 and 2
measure: Pharmacokinetics Parameter Group 5 : Vz/F of parsaclisib
timeFrame: 4 Days for period 1 and 2
measure: Pharmacokinetics Parameter Group 5 during Dialysis - : AUC1-5 of parsaclisib
timeFrame: 4 Days for period 1 and 2
measure: Number of Treatment Emergent Adverse Events (TEAE) Group 5
timeFrame: up to 18 Days
Other outcomes:
Locations:
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Hialeah
country: United States
facility: Clinical Pharmacology of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Saint Paul
country: United States
facility: Prism Research
state: Minnesota
Study officials:
References: