Evaluation of Renal Function Impairment on the Pharmacokinetics of LEE011

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

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.

Study Overview

• Status: Completed
• Conditions: Impaired Renal Function; Normal Renal Function
• Intervention / Treatment: Drug: LEE011

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1612
    • Novartis Investigative Site
• Czechia
  • Czech Republic
    • Praha 4, Czech Republic, Czechia, 140 59
      • Novartis Investigative Site
• Germany
  • Berlin, Germany, 14050
    • Novartis Investigative Site
• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Davita Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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
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
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CLEE011A2116 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2015
• Primary Completion (Actual): September 14, 2017
• Study Completion (Actual): May 11, 2018

Study Registration Dates

• First Submitted: April 2, 2015
• First Submitted That Met QC Criteria: April 27, 2015
• First Posted (Estimate): May 1, 2015

Study Record Updates

• Last Update Posted (Actual): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: CLEE011A2116

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No