Clinical trial NCT02048787: Pharmacokinetic Study of Buparlisib in Subjects With Renal Impairment.
Official 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Keywords: Renal impairment
Healthy volunteers
Clinical pharmacology study
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-01-29
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Plasma pharmacokinetic (PK) parameter Cmax
timeFrame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
measure: Plasma PK parameter AUCinf
timeFrame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
measure: Plasma PK parameter AUC0-t
timeFrame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
measure: Plasma PK parameter CL/F
timeFrame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
measure: Urine PK parameter CLR
timeFrame: 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:
measure: Plasma PK parameter Tmax
timeFrame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
measure: Plasma PK parameter T1/2
timeFrame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
measure: Plasma PK parameter Vz/F
timeFrame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
measure: Plasma Protein Binding
timeFrame: predose, 1 hour post-dose
measure: Unbound plasma PK parameter Cmax,u
timeFrame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
measure: Unbound plasma PK parameter AUCinf,u
timeFrame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
measure: Unbound plasma PK parameter Vu/F
timeFrame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
measure: Unbound plasma PK parameter CLu/F
timeFrame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
measure: Urine PK parameter Ae0-t
timeFrame: 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
measure: Relationship between PK parameters Cmax, AUCinf, AUC0-t, CL/F, urine CLR and renal function.
timeFrame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
measure: Adverse Events severity and frequency
timeFrame: Baseline Day 1 to 30 days post-dose
measure: Change from baseline in laboratory parameters
timeFrame: From baseline Day 1 to 30 days post-dose
measure: Change from baseline in ECG parameters
timeFrame: From baseline Day 1 to 30 days post-dose
measure: Unbound plasma PK parameter AUC0-t,u
timeFrame: predose, 10, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144, 192, 240 hours post-dose
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Praha 4
country: Czechia
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bucuresti
country: Romania
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: