| Eligibility |
Inclusion Criteria:
- Classification 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, as determined by medical history, physical
examination, vital signs, 12-lead ECGs, and clinical laboratory determinations at
screening and Day -1 (Groups 2 through 4) or Period 1 Day -1 (Group 5).
- 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:
- History of uncontrolled or unstable cardiovascular, respiratory, hepatic, GI,
endocrine, hematopoietic, psychiatric, and/or neurological disease within 6 months of
screening or evidence of rapidly deteriorating renal function.
- Current, functioning organ transplant or a cheduled 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 GI disease or surgery (cholecystectomy and
appendectomy are allowed) that could impact the absorption of study drug.
- Eligible for Group 1 and have a history of renal disease or renal injury as indicated
by an abnormal, clinically significant renal function profile at screening or Day -1.
- Eligible for Groups 2 through 5 and have had a change in disease status within 30 days
of screening, as documented by the participant's medical history and 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, including any of the
following:
1. Recent myocardial infarction (within 6 months of check-in)
2. New York Heart Association Class III or IV congestive heart failure
3. Unstable angina (within 6 months of check-in)
4. Clinically significant (symptomatic) cardiac arrhythmias (eg, sustained
ventricular tachycardia, second- or third-degree atrioventricular block without a
pacemaker)
5. Uncontrolled hypertension
- 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 and symptomatic for HBV, HCV, or HIV. Participants whose results are
compatible with prior immunization for or immunity due to infection with HBV may be
included at the discretion of the investigator.
- Eligible for Group 1 and have a history of using tobacco- or nicotine-containing
products within 6 months of screening.
- Eligible for Groups 2 through 5 and 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.
- History of alcohol dependency within 3 months of screening.
- Positive breath test for ethanol or positive urine or saliva screen for drugs of abuse
(confirmed by repeat test) at screening or check-in that are 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 15 days or 5 half-lives (whichever is longer)
before the first dose of study drug with moderate and potent inducers or inhibitors of
CYP3A4 (refer to the Drug Interaction Database Program [University of Washington
School of Pharmacy 2002] for prohibited drugs).
- Consumption of Seville oranges, grapefruit or grapefruit juice, pomelos, exotic citrus
fruits, grapefruit hybrids, or fruit juices within 72 hours before the first dose of
study drug.
- Eligible for Group 1 and have used prescription drugs within 14 days of study drug
administration or nonprescription medications/products (including vitamins, minerals,
and hytotherapeutic/herbal/plant-derived preparations) within 7 days of study drug
administration. However, occasional use of acetaminophen and ibuprofen is permitted
(see Section 6.6.1).
- Eligible for Groups 2 through 5 and have used 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, currently
receiving systemic antibiotics, or having a 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.
- Eligible for Group 5 and not expected to continue HD treatment for the duration of the
study.
- Women who are pregnant or breastfeeding.
- Use of hormonal contraception
- QTcF > 450 milliseconds for Groups 1 through 3 and QTcF > 470 milliseconds for Group
4.
- Eligible for Group 1 and have abnormal LFT values, defined as aspartate
aminotransferase, alanine aminotransferase, and serum (total and direct) bilirubin, as
well as amylase and lipase above the upper limit of the normal range at screening.
- Eligible for Groups 2 through 4 and have values outside the normal ranges for LFTs;
however, values may be acceptable if they are consistent with the participant's renal
condition (if stable for 1 month prior to screening) and if the investigator (or
designee) and the sponsor feel that the results are not clinically significant (based
on age and renal impairment status).
- Receipt of live (including attenuated) vaccines within 3 months of check-in 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 INCB054707 or excipients of INCB054707
(refer to the IB).
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