Pharmacokinetics of LCQ908 in Patients With Renal Impairment

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01558323
• Collaborator: (none)
• Enrollment: 58
• Locations: 2
• Arms: 3
• Duration (Months): 10
• Patients Per Site: 29
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Renal Impairment	Drug: LCQ908	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• 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 Start Date: May 1, 2012
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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]

2. 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]

3. 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

1. Number of participants with adverse events (AEs), serious adverse events (SAEs) and death [Day 29]

   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.

2. 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]

3. 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]

4. 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]

5. 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]

6. LCQ908 protein binding: unbound area under curve (AUCc) of LCQ908 [10 and 24 hours]

7. LCQ908 protein binding: unbound observed maximum plasma (Cmax) of LCQ908 [10 and 24 hours]

8. LCQ908 protein binding: unbound apparent systemic clearance from plasma (CL/Fu) following extra vascular administration [10 and 24 hours]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Orlando	Florida	United States	32809
2	Novartis Investigative Site	Knoxville	Tennessee	United States	37920

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01558323
• Other Study ID Numbers: CLCQ908B2102
• First Posted: Mar 20, 2012
• Last Update Posted: Dec 19, 2020
• Last Verified: Jan 1, 2014

• Keywords provided by Novartis Pharmaceuticals: LCQ908, Renal Impairment, Pharmacokinetics
• Additional relevant MeSH terms: Renal Insufficiency

Study Results

No Results Posted as of Dec 19, 2020