Pharmacokinetic Study of Buparlisib in Subjects With Renal Impairment.

December 6, 2020 updated by: Novartis Pharmaceuticals

An Open-label, Single Dose, Multicenter Study to Evaluate the Pharmacokinetics and Safety of 50 mg Oral Buparlisib in Subjects With Moderate and Severe Renal Impairment Compared to Matched Control Healthy Volunteers.

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
19

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bulgaria
      • Sofia, Bulgaria, 1612
        • Novartis Investigative Site
  • Czechia
      • Praha 4, Czechia, 140 59
        • Novartis Investigative Site
  • Germany
      • Berlin, Germany, 14050
        • Novartis Investigative Site
  • Romania
      • Bucuresti, Romania
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Moderate renal impairment group
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
Subjects will receive a single dose of 50 mg buparlisib.
Other Names:
  • BKM120
Experimental: Severe renal impairment group
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
Subjects will receive a single dose of 50 mg buparlisib.
Other Names:
  • BKM120
Experimental: Matching healthy control group
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
Subjects will receive a single dose of 50 mg buparlisib.
Other Names:
  • BKM120

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Plasma pharmacokinetic (PK) parameter Cmax
Time Frame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
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
Time Frame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
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
Time Frame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
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
Time Frame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
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
Time Frame: 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
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Plasma PK parameter Tmax
Time Frame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
Measurement of effect of renal impairment on PK of buparlisib by assessment of the PK parameter Tmax (time to reach maximum plasma concentration), directly determined from the plasma concentration-time profile.
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
Time Frame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
Measurement of effect of renal impairment on PK of buparlisib by assessment of the PK parameter T1/2 (terminal half-life).
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
Time Frame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
Measurement of effect of renal impairment on PK of buparlisib by assessment of the PK parameter Vz/F (the apparent volume of distribution following extravascular administration).
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
Time Frame: predose, 1 hour post-dose
Measurement of effect of renal impairment on plasma protein binding. Fraction of buparlisib unbound will be determined (Fu).
predose, 1 hour post-dose
Unbound plasma PK parameter Cmax,u
Time Frame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
Measurement of effect of renal impairment on PK of buparlisib by assessment of the PK parameter Cmax,u (Cmax,u is the observed maximum unbound plasma concentration following administration).
predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
Unbound plasma PK parameter AUCinf,u
Time Frame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
Measurement of effect of renal impairment on PK of buparlisib by assessment of the PK parameters AUCinf,u (AUCinf,u is the area under the unbound plasma concentration-time curve extrapolated to infinity).
predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
Unbound plasma PK parameter Vu/F
Time Frame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
Measurement of effect of renal impairment on PK of buparlisib by assessment of the PK parameter Vu/F (the apparent unbound drug volume of distribution following extravascular administration).
predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
Unbound plasma PK parameter CLu/F
Time Frame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
Measurement of effect of renal impairment on PK of buparlisib by assessment of the PK parameter CLu/F (the unbound systemic clearance from plasma).
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 Ae0-t
Time Frame: 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
Measurement of effect of renal impairment on PK of buparlisib by assessment of the urine PK parameter Ae0-t (the amount of unchanged buparlisib excreted into the urine from time 0 to a defined point in time).
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
Relationship between PK parameters Cmax, AUCinf, AUC0-t, CL/F, urine CLR and renal function.
Time Frame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
Determination of the relationship between the primary PK parameters (Cmax, AUCinf, AUC0-t, CL/F and urine PK parameter CLR) and renal function parameters eGFR (estimated glomerular filtration rate using the equation from the Modification of Diet in Renal Disease (MDRD) study).
predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
Adverse Events severity and frequency
Time Frame: Baseline Day 1 to 30 days post-dose
Assessment of safety and tolerability of a single dose buparlisib in renal impaired subjects compared with healthy control subjects by assessing the frequency and severity of Adverse Events based on the CTCAE criteria.
Baseline Day 1 to 30 days post-dose
Change from baseline in laboratory parameters
Time Frame: From baseline Day 1 to 30 days post-dose
Assessment of safety and tolerability of a single dose buparlisib in renal impaired subjects compared with healthy control subjects by assessing the change from baseline in hematological and biochemical laboratory parameters.
From baseline Day 1 to 30 days post-dose
Change from baseline in ECG parameters
Time Frame: From baseline Day 1 to 30 days post-dose
Assessment of safety and tolerability of a single dose buparlisib in renal impaired subjects compared with healthy control subjects by assessing the change from baseline in ECG parameters.
From baseline Day 1 to 30 days post-dose
Unbound plasma PK parameter AUC0-t,u
Time Frame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
Measurement of effect of renal impairment on PK of buparlisib by assessment of the PK parameters AUC0-t,u (AUC0-t,u is the area under the unbound plasma concentration-time curve from time zero to time t).
predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 20, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 28, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 29, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 9, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 6, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CBKM120C2113
  • 2013-003384-64 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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