Pharmacokinetic Study of Buparlisib in Subjects With Renal Impairment.

Novartis

Status and phase: Completed; Phase 1

Conditions: Renal Impairment

Treatments: Drug: Buparlisib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02048787

CBKM120C2113

2013-003384-64 (EudraCT Number)

Details and patient eligibility

About

To characterize the pharmacokinetics and safety of buparlisib following a single 50 mg oral dose in subjects with moderate and severe renal impairment.

Enrollment: 19 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Other than renal impairment, subjects should be in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, (except for additional inclusion criteria for renal impaired patients).

• Subjects must have a BMI between 18 kg/m2 and 34 kg/m2 and weight at least 50 kg and no more than 120 kg.

  • Additional criteria for renal impaired subjects: - Subjects must have stable renal disease without evidence of renal progressive disease defined as moderate renal impairment (eGFR 30-59 mL/min/1.73m2) or severe renal impairment (eGFR 15-29 mL/min/1.73m2).
  • Additional criteria for matched healthy control subjects: - Matched to at least one renal impaired subject by gender, race, age (± 10 years), and weight (± 20%).

• An estimated GFR as determined by MDRD equation within normal range as determined by eGFR ≥ 90 mL/min/1.73m2

Exclusion criteria

• Significant illness, including infections, or hospitalization within the 2 weeks prior to dosing, except for the renal impaired subjects who due to their renal disease may be affected by significant medical problems which require frequent hospitalizations.
• Any surgical or medical condition that may significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study
• Subject has a medical history of cardiac disease and/or clinically significant ECG abnormalities within 6 months prior to screening.
• Subject has an active or a history within 6 months prior to screening of clinically significant hematologic, endocrinologic, pulmonary, cardiovascular, hepatic, or allergic disease, medically documented (other than clinical conditions associated with renal impairment for the renal impaired subjects only).
• • Additional exclusion criteria for renal impaired subjects: - Severe albuminuria > 300 mg/day.
• Subjects undergoing any method of dialysis.
• Subjects with renal impairment due to hepatic disease (hepatorenal syndrome).
• Subjects with clinically significant abnormal findings, not consistent with clinical disease, upon physical examination, ECG or laboratory evaluation.
• Use of any prescription or non-prescription medication that has the potential to interact with buparlisib within two weeks prior to dosing or during the study.
• • Additional criteria for matched healthy control subjects: - Use of any prescription or non-prescription medication or vitamins during 14 days prior to dosing.

Other protocol-defined inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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19 participants in 3 patient groups

Moderate renal impairment group

Experimental group

Description:

Subjects with moderate renal impairment defined as eGFR of 30-59 mL/min/1.73m2 at screening can be enrolled in this group

Treatment:

Drug: Buparlisib

Severe renal impairment group

Experimental group

Description:

Subjects with severe renal impairment defined as eGFR of 15-29 mL/min/1.73m2 at screening can be enrolled in this group

Treatment:

Drug: Buparlisib

Matching healthy control group

Experimental group

Description:

Subjects with normal renal function defined as eGFR ≥ 90 mL/min/1.73m2 at screening and matching to the renal impaired subject based on gender, race, age, and weight can be enrolled in this group.

Treatment:

Drug: Buparlisib