Evaluation of Renal Function Impairment on the Pharmacokinetics of LEE011

Impaired Renal Function Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02431481
• Other study ID #: CLEE011A2116
• Status: Completed
• Phase: Phase 1
• Start date: October 23, 2015
• Est. completion date: May 11, 2018

Study information

• Verified date: February 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: May 11, 2018
• Est. primary completion date: September 14, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Impaired Renal Function
• Normal Renal Function
• Renal Insufficiency

Intervention

Drug:
• LEE011
400 mg

Locations

Country	Name	City	State
Bulgaria	Novartis Investigative Site	Sofia
Czechia	Novartis Investigative Site	Praha 4	Czech Republic
Germany	Novartis Investigative Site	Berlin
United States	DaVita Clinical Research	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Bulgaria,  Czechia,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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

External Links

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