Evaluation of Renal Function Impairment on the Pharmacokinetics of LEE011

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Normal Renal Function, Impaired Renal Function

Intervention / Treatment
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* Drug: LEE011


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normal renal function<br>Normal renal function; matched demography to renal impariment cohorts | Drug: LEE011<br>* 400 mg<br>|
| Experimental: Severe renal impairment<br>Severe decrease in GFR (15-29 ml/min) | Drug: LEE011<br>* 400 mg<br>|
| Experimental: End Stage Renal Disease<br>End stage renal disease not on dialysis; GFR <15 ml/min | Drug: LEE011<br>* 400 mg<br>|
| Experimental: Mild renal impairment<br>Mild decrease in GFR (60-89 ml/min) | Drug: LEE011<br>* 400 mg<br>|
| Experimental: Moderate renal impairment<br>Moderate decrease in GFR (30-59 ml/min) | Drug: LEE011<br>* 400 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Pharmacokinetics (PK) parameters of LEE011 when appropriate | Primary composite PK parameters: Cmax, AUClast, AUCinf, and CL/F. To determine the impact of various degrees of renal impairment on primary PK parameters of LEE011 following a single 400mg oral dose | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary PK parameters of LEE011 when appropriate | Secondary composite PK parameters of LEE011: Tmax, T1/2, Vz/F, and CLr. To determine the impact of various degrees of renal impairment on secondary PK parameters of LEE011 following a single 400 mg oral dose | 14 days | 
| PK parameters of LEQ803 (i.e., Cmax, AUClast, AUCinf, Tmax, T1/2) | Composite PK parameters of LEQ803: Cmax, AUClast, AUCinf, Tmax, T1/2. To evaluate the PK profile of LEQ803 in subjects with various degrees of renal impairment following a single 400 mg oral dose | 14 days | 
| Frequency of adverse events (AEs) | Safety profile of a single dose of LEE011 in healthy subjects and subjects with varying degrees of hepatic function includes changes observed in physical examination, changes in vital signs, changes in electrocardiograms (ECGs), abnormal laboratory results. | From consent to 28 days post-dose |