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Evaluation of Renal Function Impairment on the Pharmacokinetics of LEE011

Primary Purpose

Normal Renal Function, Impaired Renal Function

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

LEE011

About this trial

This is an interventional treatment trial for Normal Renal Function

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

DaVita Clinical Research
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Normal renal function

Severe renal impairment

End Stage Renal Disease

Mild renal impairment

Moderate renal impairment

Arm Description

Normal renal function; matched demography to renal impariment cohorts

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

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

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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.

Full Information

NCT ID

NCT02431481

First Posted

April 2, 2015

Last Updated

December 16, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02431481

Brief Title

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

2. Study Status

Record Verification Date

February 2019

Overall Recruitment Status

Completed

Study Start Date

October 23, 2015 (Actual)

Primary Completion Date

September 14, 2017 (Actual)

Study Completion Date

May 11, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Normal Renal Function, Impaired Renal Function

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

38 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Normal renal function

Arm Type

Experimental

Arm Description

Normal renal function; matched demography to renal impariment cohorts

Arm Title

Severe renal impairment

Arm Type

Experimental

Arm Description

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

Arm Title

End Stage Renal Disease

Arm Type

Experimental

Arm Description

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

Arm Title

Mild renal impairment

Arm Type

Experimental

Arm Description

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

Arm Title

Moderate renal impairment

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

LEE011

Intervention Description

400 mg

Primary Outcome Measure Information:

Title

Primary Pharmacokinetics (PK) parameters of LEE011 when appropriate

Description

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

Time Frame

14 days

Secondary Outcome Measure Information:

Title

Secondary PK parameters of LEE011 when appropriate

Description

Time Frame

14 days

Title

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

Description

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

Time Frame

14 days

Title

Frequency of adverse events (AEs)

Description

Time Frame

From consent to 28 days post-dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

DaVita Clinical Research

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55404

Country

United States

Facility Name

Novartis Investigative Site

City

Sofia

ZIP/Postal Code

1612

Country

Bulgaria

Facility Name

Novartis Investigative Site

City

Praha 4

State/Province

Czech Republic

ZIP/Postal Code

140 59

Country

Czechia

Facility Name

Novartis Investigative Site

City

Berlin

ZIP/Postal Code

14050

Country

Germany

12. IPD Sharing Statement

Plan to Share IPD

Links:

URL

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17418

Description

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

Learn more about this trial

Evaluation of Renal Function Impairment on the Pharmacokinetics of LEE011

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