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.
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.