Clinical trial NCT01558323: Pharmacokinetics of LCQ908 in Patients With Renal Impairment
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Keywords: LCQ908, Renal Impairment, Pharmacokinetics
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-03-20
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This study will compare the pharmacokinetics of LCQ908 in subjects with varying degrees of renal impairment to healthy subjects


Eligibility criteria: 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.

Primary outcomes:
measure: Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (AUClast) of LCQ908
timeFrame: 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
measure: Area under the plasma concentration-time profile from time zero extrapolated to infinite time [AUC(0-inf)] of LCQ908
timeFrame: 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
measure: Maximum plasma concentration (Cmax) of LCQ908
timeFrame: 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 outcomes:
measure: Number of participants with adverse events (AEs), serious adverse events (SAEs) and death
timeFrame: Day 29
measure: The apparent systemic clearance (CL/F) of LCQ908 following extra vascular administration
timeFrame: 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
measure: Time to maximum plasma concentration of LCQ908
timeFrame: 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
measure: The time required for the concentration of the drug to reach half of its original value
timeFrame: 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
measure: Apparent volume of distribution of LCQ908 during the terminal elimination phase following extra vascular administration
timeFrame: 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
measure: LCQ908 protein binding: unbound area under curve (AUCc) of LCQ908
timeFrame: 10 and 24 hours
measure: LCQ908 protein binding: unbound observed maximum plasma (Cmax) of LCQ908
timeFrame: 10 and 24 hours
measure: LCQ908 protein binding: unbound apparent systemic clearance from plasma (CL/Fu) following extra vascular administration
timeFrame: 10 and 24 hours
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Novartis Investigative Site
state: Florida
city: Knoxville
country: United States
facility: Novartis Investigative Site
state: Tennessee
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: