Clinical trial NCT01594957: Pharmacokinetics of LCQ908 in Patients With Hepatic Impairment
Official title: An Open-label, Single Dose, Parallel-group Study to Evaluate the Pharmacokinetics of LCQ908 in Patients With Mild, Moderate and Severe Hepatic Impairment Compared to Age, Gender and Weight-matched Healthy Volunteers.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: LCQ908,
Hepatic Impairment,
Pharmacokinetics
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-05-09
Enrollment: 53
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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


Eligibility criteria: Inclusion criteria:

Individuals with hepatic impairment only

• Hepatic impairment evidenced by a Child-Pugh score

* Mild hepatic impairment defined Child-Pugh Class A (5-6 points)
* Moderate hepatic impairment defined Child-Pugh Class B (7-9 points)
* Severe hepatic impairment defined Child-Pugh Class C (10-15 points).

Healthy subjects only

• Good health determined.

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 hepatic impairment

* History of drug or alcohol abuse within 3 months prior to dosing.
* History or presence of significant uncontrolled disease of any major organ class.
* Any surgical or medical condition other than hepatic impairment which might alter the drug metabolism.

Healthy subjects

* History or presence of significant uncontrolled disease of any major organ class.
* Any surgical or medical condition other than hepatic impairment which might alter the drug metabolism.
* 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 for part I of the study
timeFrame: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
measure: Area under the plasma concentration-time profile from time zero extrapolated to infinite time [AUC(0-inf)] of LCQ908 for part I of the study
timeFrame: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
measure: Maximum plasma concentration of LCQ908 (Cmax) for Part I of the study
timeFrame: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
measure: The apparent systemic clearance (CL/F) of LCQ908 following extra vascular administration for Part I of the study
timeFrame: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
measure: Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (AUClast) of LCQ908 for Part II of the study
timeFrame: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
measure: Area under the plasma concentration-time profile from time zero extrapolated to infinite time [AUC(0-inf)] of LCQ908 for Part II of the study
timeFrame: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
measure: Maximum plasma concentration of LCQ908 (Cmax) for Part II of the study
timeFrame: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
measure: The apparent systemic clearance (CL/F) of LCQ908 following extra vascular administration for Part II of the study
timeFrame: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
Secondary outcomes:
measure: Number of participants with adverse events, serious adverse events and death (for both Part I and Part II)
timeFrame: Day 28
measure: Time to maximum plasma concentration of LCQ908 (Tmax) (for both Part I and Part II)
timeFrame: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
measure: The time required for the concentration of the drug to reach half of its original value (T1/2) (for both Part I and Part II)
timeFrame: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
measure: The apparent volume of distribution of LCQ908 during the terminal elimination phase following extra vascular administration (Vz/F) (for both Part I and Part II)
timeFrame: Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing and on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing
measure: LCQ908 protein binding: unbound area under curve (AUCu) of LCQ908 (for both Part I and Part II)
timeFrame: 10 and 24 hours post dose
measure: LCQ908 protein binding: unbound observed maximum plasma (Cmax) of LCQ908 (for both Part I and Part II)
timeFrame: 10 and 24 hours
measure: LCQ908 protein binding: unbound apparent systemic clearance from plasma (CL/Fu) following extra vascular administration (for both Part I and Part II)
timeFrame: 10 and 24 hours
Other outcomes:
Locations:
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Orlando
country: United States
facility: Novartis Investigative Site
state: Florida
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Hirano M, Meyers D, Golla G, Pal P, Pinot P, Lin T, Majumdar T, Rebello S, Sunkara G, Chen J. Effect of Hepatic Impairment on the Pharmacokinetics of Pradigastat, a Diacylglycerol Acyltransferase 1 (DGAT1) Inhibitor. Clin Pharmacokinet. 2015 Jul;54(7):761-70. doi: 10.1007/s40262-015-0235-9.