Impaired Renal Function, Normal Renal Function
Conditions
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.
Interventions
DRUGLEE011
400 mg
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Pharmacokinetics (PK) parameters of LEE011 when appropriate | 14 days | 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
| Measure | Time frame | Description |
|---|---|---|
| Secondary PK parameters of LEE011 when appropriate | 14 days | 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) | 14 days | 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) | From consent to 28 days post-dose | 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. |
Countries
Bulgaria, Czechia, Germany, United States
Outcome results
None listed