Clinical trial NCT02431481: Evaluation of Renal Function Impairment on the Pharmacokinetics of LEE011
Official title: A Phase I, Open Label, Multicenter, Parallel-group, Single Dose Two-staged Study to Evaluate the Pharmacokinetics and Safety of a Single 400 mg Oral Dose of LEE011 in Subjects With Varying Degrees of Impaired Renal Function Compared to Matched Healthy Volunteers With Normal Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Normal Renal Function
Impaired Renal Function
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-05-01
Enrollment: 38
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: TREATMENT

Brief summary: The purpose of this study is to characterize the PK and safety profile of LEE011 following a single oral dose in adult subjects with various degrees of renal impairment compared to a matched group of healthy subjects with normal renal function.


Eligibility criteria: Inclusion Criteria (All Subjects):

* Male or female (sterile or postmenopausal) subjects between 18-75 (both inclusive) years of age and healthy as determined by absence of clinically significant deviation from normal in medical history, physical examination, vital signs, electrocardiograms, and clinical laboratory determinations (except for renal impaired subjects).
* Subjects must have a BMI between 18 kg/m2 and 38 kg/m2 and weight at least 50 kg and no more than 120 kg.
* Additional inclusion criteria for subjects with normal renal function:

  * An absolute GFR as determined by MDRD equation and conversion within normal range as determined by GFR \> 90 mL/min

Inclusion Criteria (for subjects with impaired renal function):

- Subjects must have documented stable renal disease without evidence of renal progressive disease (stable renal disease is defined as no significant change, such as a stable absolute GFR, for 4 weeks prior to study entry.

Exclusion Criteria (All Subjects):

* Subject has received a renal transplant at any time in the past and is on immunosuppressant therapy
* History or presence of impaired cardiac function
* Any surgical or medical condition that may significantly alter the absorption, distribution, metabolism, or excretion of drugs
* Administration of CYP3A4/5 inhibitors or inducers or CYP3A4 substrates with narrow therapeutic windows
* Administration of medications that prolong the QT interval
* Subject has a history of immunodeficiency diseases, including HIV, as confirmed by (HIV-1, HIV-2) test
* Receipt of investigational product in another clinical trial within 4 weeks of dosing

Exclusion Criteria (for subjects with impaired renal function):

* Severe albuminuria \> 300 mg/day
* Subjects undergoing any method of dialysis
* Subjects with renal impairment due to hepatic disease (hepatorenal syndrome)

Other protocol-defined Inclusion/Exclusion may apply.

Primary outcomes:
measure: Primary Pharmacokinetics (PK) parameters of LEE011 when appropriate
timeFrame: 14 days
Secondary outcomes:
measure: Secondary PK parameters of LEE011 when appropriate
timeFrame: 14 days
measure: PK parameters of LEQ803 (i.e., Cmax, AUClast, AUCinf, Tmax, T1/2)
timeFrame: 14 days
measure: Frequency of adverse events (AEs)
timeFrame: From consent to 28 days post-dose
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: DaVita Clinical Research
state: Minnesota
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Praha 4
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Berlin
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: