Pharmacokinetic Study of Buparlisib in Subjects With Renal Impairment.

NCT02048787 | Completed Phase 1

• 2 other identifiers: CBKM120C21132013-003384-64
• Study Type: interventional
• Target: 19
• Locations: 4 countries
• Sites: 4

Brief Summary

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

Conditions

Renal Impairment

Keywords

Renal impairment; Healthy volunteers; Clinical pharmacology study

Outcome Measures

Primary Outcomes (5)

• Plasma pharmacokinetic (PK) parameter Cmax

  Measurement of effect of renal impairment on PK of buparlisib by assessment of the maximum plasma concentration (PK parameter Cmax). Cmax directly determined from the plasma concentration-time profiles.

  predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose

• Plasma PK parameter AUCinf

  Measurement of effect of renal impairment on PK of buparlisib by assessment of the PK parameter AUCinf (area under the plasma concentration-time curve from time 0 to infinity). AUC determined from the plasma concentration-time profile using non-compartmental analysis.

  predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose

• Plasma PK parameter AUC0-t

  Measurement of effect of renal impairment on PK of buparlisib by assessment of the PK parameter AU0-t (area under the plasma-concentration time curve from timepoint 0 to time t). AUC determined from the plasma concentration-time profile using non-compartmental analysis.

  predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose

• Plasma PK parameter CL/F

  Measurement of effect of renal impairment on PK of buparlisib by assessment of the PK parameter CL/F (clearance).

  predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose

• Urine PK parameter CLR

  Measurement of effect of renal impairment on PK of buparlisib by assessment of the urine clearance CLR.

  predose, 0-4 h, 4-8 h, 8-12 h, 12-24 h, 24-48 h, 48-72 h, 72-96 h, 96-120 h, 120-144 h

Secondary Outcomes (14)

• Plasma PK parameter Tmax

  predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose

• Plasma PK parameter T1/2

  predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose

• Plasma PK parameter Vz/F

  predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose

• Plasma Protein Binding

  predose, 1 hour post-dose

• Unbound plasma PK parameter Cmax,u

  predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose

Study Arms (3)

Moderate renal impairment group

EXPERIMENTAL

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

Drug: Buparlisib

Severe renal impairment group

EXPERIMENTAL

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

Drug: Buparlisib

Matching healthy control group

EXPERIMENTAL

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.

Drug: Buparlisib

Interventions

Buparlisib DRUG

Subjects will receive a single dose of 50 mg buparlisib.

Also known as: BKM120

Matching healthy control group; Moderate renal impairment group; Severe renal impairment group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (4)

Novartis Investigative Site

Sofia, 1612, Bulgaria

Location

Novartis Investigative Site

Prague, 140 59, Czechia

Location

Novartis Investigative Site

Berlin, 14050, Germany

Location

Novartis Investigative Site

Bucharest, Romania

Location

Related Links

• Results can be found for CBKM120C2113 on the Novartis Clinical Trial Results Website

MeSH Terms

Conditions

Renal Insufficiency

Interventions

NVP-BKM120

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2014
• First Posted: January 29, 2014
• Study Start: March 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: December 9, 2020

Record last verified: 2015-12

Locations

DE (1); BU (1); RO (1); CZ (1)