Pharmacokinetics of LCQ908 in Patients With Renal Impairment - Full Text View

Purpose

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

Condition	Intervention	Phase
Renal Impairment	Drug: LCQ908	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Pharmacokinetics Study Intervention Model: Parallel Assignment Masking: Open Label
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.

Further study details as provided by Novartis:

Primary Outcome Measures:

Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (AUClast) of LCQ908 [ Time Frame: 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 ] [ Designated as safety issue: No ]
Area under the plasma concentration-time profile from time zero extrapolated to infinite time [AUC(0-inf)] of LCQ908 [ Time Frame: 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 ] [ Designated as safety issue: No ]
Maximum plasma concentration (Cmax) of LCQ908 [ Time Frame: 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Number of participants with adverse events (AEs), serious adverse events (SAEs) and death [ Time Frame: Day 29 ] [ Designated as safety issue: Yes ]
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.
The apparent systemic clearance (CL/F) of LCQ908 following extra vascular administration [ Time Frame: 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 ] [ Designated as safety issue: No ]
Time to maximum plasma concentration of LCQ908 [ Time Frame: 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 ] [ Designated as safety issue: No ]
The time required for the concentration of the drug to reach half of its original value [ Time Frame: 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 ] [ Designated as safety issue: No ]
Apparent volume of distribution of LCQ908 during the terminal elimination phase following extra vascular administration [ Time Frame: 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 ] [ Designated as safety issue: No ]
LCQ908 protein binding: unbound area under curve (AUCc) of LCQ908 [ Time Frame: 10 and 24 hours ] [ Designated as safety issue: No ]
LCQ908 protein binding: unbound observed maximum plasma (Cmax) of LCQ908 [ Time Frame: 10 and 24 hours ] [ Designated as safety issue: No ]
LCQ908 protein binding: unbound apparent systemic clearance from plasma (CL/Fu) following extra vascular administration [ Time Frame: 10 and 24 hours ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	May 2012
Estimated Study Completion Date:	January 2013
Estimated Primary Completion Date:	January 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01558323

Contacts

Contact: Novartis Pharmaceuticals

+1(862)778-8300

Locations

United States, Florida
Novartis Investigative Site	Recruiting
Orlando, Florida, United States, 32809
United States, Tennessee
Novartis Investigative Site	Not yet recruiting
Knoxville, Tennessee, United States, 37920

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01558323 History of Changes
Other Study ID Numbers:	CLCQ908B2102
Study First Received:	March 14, 2012
Last Updated:	November 20, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Novartis:

LCQ908, Renal Impairment, Pharmacokinetics

Additional relevant MeSH terms:

Renal Insufficiency
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on May 19, 2013