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Completed

NCT Number: NCT02048787

Pharmacokinetic Study of Buparlisib in Subjects With Renal Impairment.

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

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Key information

Conditions

Renal Impairment Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Male Urogenital Diseases Renal Insufficiency Urogenital Diseases Urologic Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Novartis Investigative Site, Sofia, Bulgaria

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Buparlisib

Drug

Subjects will receive a single dose of 50 mg buparlisib.

Other names: BKM120

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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).

  5. 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.

Secondary outcomes

  1. 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.

  2. 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).

  3. 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).

  4. 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).

  5. 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).

  6. 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).

  7. 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).

  8. 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).

  9. 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).

  10. 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).

  11. 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.

  12. 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.

  13. 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.

  14. 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).

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

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.

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Jan 29, 2014
Registry last updated
Dec 9, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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