Evaluation of Renal Function Impairment on the Pharmacokinetics of LEE011

Novartis

Status and phase: Completed; Phase 1

Conditions: Impaired Renal Function; Normal Renal Function

Treatments: Drug: LEE011

Study type: Interventional

Funder types: Industry

Identifiers

NCT02431481

CLEE011A2116

Details and patient eligibility

About

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.

Enrollment: 38 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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38 participants in 5 patient groups

Normal renal function

Experimental group

Description:

Normal renal function; matched demography to renal impariment cohorts

Treatment:

Drug: LEE011

Severe renal impairment

Experimental group

Description:

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

Treatment:

Drug: LEE011

End Stage Renal Disease

Experimental group

Description:

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

Treatment:

Drug: LEE011

Mild renal impairment

Experimental group

Description:

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

Treatment:

Drug: LEE011

Moderate renal impairment

Experimental group

Description:

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

Treatment:

Drug: LEE011