Evaluation of Renal Function Impairment on the Pharmacokinetics of LEE011

NCT02431481 | Completed Phase 1 FDA Drug

• 1 other identifier: CLEE011A2116
• Study Type: interventional
• Target: 38
• Locations: 4 countries
• Sites: 4

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.

Conditions

Normal Renal Function; Impaired Renal Function

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Secondary PK parameters of LEE011 when appropriate

  14 days

• PK parameters of LEQ803 (i.e., Cmax, AUClast, AUCinf, Tmax, T1/2)

  14 days

• Frequency of adverse events (AEs)

  From consent to 28 days post-dose

Study Arms (5)

Normal renal function

EXPERIMENTAL

Normal renal function; matched demography to renal impariment cohorts

Drug: LEE011

Severe renal impairment

EXPERIMENTAL

Severe decrease in GFR (15-29 ml/min)

Drug: LEE011

End Stage Renal Disease

EXPERIMENTAL

End stage renal disease not on dialysis; GFR \<15 ml/min

Drug: LEE011

Mild renal impairment

EXPERIMENTAL

Mild decrease in GFR (60-89 ml/min)

Drug: LEE011

Moderate renal impairment

EXPERIMENTAL

Moderate decrease in GFR (30-59 ml/min)

Drug: LEE011

Interventions

LEE011 DRUG

400 mg

End Stage Renal Disease; Mild renal impairment; Moderate renal impairment; Normal renal function; Severe renal impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (4)

DaVita Clinical Research

Minneapolis, Minnesota, 55404, United States

Location

Novartis Investigative Site

Sofia, 1612, Bulgaria

Location

Novartis Investigative Site

Prague, Czech Republic, 140 59, Czechia

Location

Novartis Investigative Site

Berlin, 14050, Germany

Location

Related Publications (1)

• Ji Y, Yartsev V, Quinlan M, Serra P, Wang Y, Chakraborty A, Miller M. Justifying Ribociclib Dose in Patients with Advanced Breast Cancer with Renal Impairment Based on PK, Safety, and Efficacy Data: An Innovative Approach Integrating Data from a Dedicated Renal Impairment Study and Oncology Clinical Trials. Clin Pharmacokinet. 2023 Mar;62(3):493-504. doi: 10.1007/s40262-022-01206-2. Epub 2023 Feb 17.

  PMID: 36800111 DERIVED

Related Links

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

MeSH Terms

Conditions

Renal Insufficiency

Interventions

ribociclib

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2015
• First Posted: May 1, 2015
• Study Start: October 23, 2015
• Primary Completion: September 14, 2017
• Study Completion: May 11, 2018
• Last Updated: December 19, 2020

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); CZ (1); US (1); BU (1)