Pharmacokinetics of LCQ908 in Patients With Renal Impairment

Study Overview
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Brief Summary
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This study will compare the pharmacokinetics of LCQ908 in subjects with varying degrees of renal impairment to healthy subjects

Official Title
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An Open-label, Parallel-group, Single Dose Study to Assess the Pharmacokinetics of LCQ908 in Patients With Mild, Moderate and Severe Renal Impairment Compared to Age, Gender and Weight-matched Healthy Volunteers.

Conditions
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Renal Impairment

Intervention / Treatment
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* Drug: LCQ908


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals with renal impairment only Estimated Creatinine Clearance (CLcr) by the Cockroft-Gault equation ≤80mL/min; Mild renal impairment defined as CLcr 50-80 mL/min Moderate renal impairment defined as CLcr 30-50 mL/min Severe renal impairment defined as CLcr <30 mL/min Healthy subjects only • Estimated CLcr by the Cockroft-Gault equation >80mL/min Exclusion Criteria: All Individuals A past medical history of clinically significant ECG abnormalities or a family history of a prolonged QT-interval syndrome. Female subjects must be of non child bearing potential or use an effective method of contraception. Individuals with renal impairment Renal transplant at any time. Subjects undergoing any method of dialysis (hemodialysis, peritoneal dialysis) within the last 3 months. History of clinically significant chronic or recurrent urinary tract infection active and requiring antibiotic treatment within the past 30 days. Any medication that is contraindicated in moderate or severe renally impaired population Healthy subjects History or presence of impaired renal function as indicated by clinically significantly abnormal creatinine or BUN and/or urea values, or abnormal urinary constituents (e.g., albuminuria) Evidence of urinary obstruction or difficulty in voiding at screening History or presence of hepatitis B or C and/or positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result at screening. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LCQ908 (mild renal impairment plus healthy volunteers)<br>Healthy subjects will be matched pair-wise by, sex, race, age (±15 years) and weight (±20%) to subjects with mild renal impairment and will receive a single 40 mg dose of LCQ908. | Drug: LCQ908<br>* Participants will receive a single oral dose of LCQ908<br>|
| Experimental: LCQ908 (moderate renal impairment plus healthy volunteers)<br>Healthy subjects will be matched pair-wise by, sex, race, age (±15 years) and weight (±20%) to subjects with moderate renal impairment and will receive a single 40 mg dose of LCQ908. | Drug: LCQ908<br>* Participants will receive a single oral dose of LCQ908<br>|
| Experimental: LCQ908 (severe renal impairment plus healthy volunteers)<br>Healthy subjects will be matched pair-wise by, sex, race, age (±15 years) and weight (±20%) to subjects with severe renal impairment and will receive a single 40 mg dose of LCQ908. | Drug: LCQ908<br>* Participants will receive a single oral dose of LCQ908<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (AUClast) of LCQ908 |  | Serial blood draws conducted on Day 1 (treatment day) followed by additional blood draws on Days 2-10,12, 14, 17, 21 and 29 post dosing | 
| Area under the plasma concentration-time profile from time zero extrapolated to infinite time [AUC(0-inf)] of LCQ908 |  | Serial blood draws conducted on Day 1 (treatment day) followed by additional blood draws on Days 2-10,12, 14, 17, 21 and 29 post dosing | 
| Maximum plasma concentration (Cmax) of LCQ908 |  | Serial blood draws conducted on Day 1 (treatment day) followed by additional blood draws on Days 2-10,12, 14, 17, 21 and 29 post dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs), serious adverse events (SAEs) and death | AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. SAEs are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital abnormalities or birth defects, or are other conditions which in the judgment of investigators represent significant hazards. | Day 29 | 
| The apparent systemic clearance (CL/F) of LCQ908 following extra vascular administration |  | Serial blood draws conducted on Day 1 (treatment day) followed by additional blood draws on Days 2-10,12, 14, 17, 21 and 29 post dosing | 
| Time to maximum plasma concentration of LCQ908 |  | Serial blood draws conducted on Day 1 (treatment day) followed by additional blood draws on Days 2-10,12, 14, 17, 21 and 29 post dosing | 
| The time required for the concentration of the drug to reach half of its original value |  | Serial blood draws conducted on Day 1 (treatment day) followed by additional blood draws on Days 2-10,12, 14, 17, 21 and 29 post dosing | 
| Apparent volume of distribution of LCQ908 during the terminal elimination phase following extra vascular administration |  | Serial blood draws conducted on Day 1 (treatment day) followed by additional blood draws on Days 2-10,12, 14, 17, 21 and 29 post dosing | 
| LCQ908 protein binding: unbound area under curve (AUCc) of LCQ908 |  | 10 and 24 hours | 
| LCQ908 protein binding: unbound observed maximum plasma (Cmax) of LCQ908 |  | 10 and 24 hours | 
| LCQ908 protein binding: unbound apparent systemic clearance from plasma (CL/Fu) following extra vascular administration |  | 10 and 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LCQ908, Renal Impairment, Pharmacokinetics