Pharmacokinetics of LCQ908 in Patients With Renal Impairment

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.

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

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: LCQ908

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Novartis Investigative Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LCQ908 (mild renal impairment plus healthy volunteers); 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; Participants will receive a single oral dose of LCQ908
Experimental: LCQ908 (moderate renal impairment plus healthy volunteers); 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; Participants will receive a single oral dose of LCQ908
Experimental: LCQ908 (severe renal impairment plus healthy volunteers); 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; Participants will receive a single oral dose of LCQ908

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CLCQ908B2102 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: March 14, 2012
• First Submitted That Met QC Criteria: March 19, 2012
• First Posted (Estimate): March 20, 2012

Study Record Updates

• Last Update Posted (Actual): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: LCQ908, Renal Impairment, Pharmacokinetics
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: CLCQ908B2102