Pharmacokinetics of LCQ908 in Patients With Hepatic Impairment

NCT01594957 | Completed Phase 1

• 1 other identifier: CLCQ908B2101
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Hepatic Impairment

Keywords

LCQ908,; Hepatic Impairment,; Pharmacokinetics

Outcome Measures

Primary Outcomes (8)

• 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

  This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers. Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.

  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

• 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

  This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers. Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.

  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

• Maximum plasma concentration of LCQ908 (Cmax) for Part I of the study

  This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers. Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.

  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

• The apparent systemic clearance (CL/F) of LCQ908 following extra vascular administration for Part I of the study

  This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers. Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.

  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

• 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

  This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers. Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.

  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

• 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

  This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers. Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.

  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

• Maximum plasma concentration of LCQ908 (Cmax) for Part II of the study

  This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers. Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.

  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

• The apparent systemic clearance (CL/F) of LCQ908 following extra vascular administration for Part II of the study

  This outcome applies to Part I of study involving mild and moderate hepatic impairment as well as healthy volunteers. Blood will be collected on Day 1 (treatment day) within 60 minutes prior to dosing, then, 1,2,4,6,8,10,12 hours after the dosing followed by additional blood draws on Days 2, 3, 4, 5, 6,7, 10, 13, 17, 21 and 28 post dosing.

  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 (7)

• Number of participants with adverse events, serious adverse events and death (for both Part I and Part II)

  Day 28

• Time to maximum plasma concentration of LCQ908 (Tmax) (for both Part I and Part II)

  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

• 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)

  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

• 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)

  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

• LCQ908 protein binding: unbound area under curve (AUCu) of LCQ908 (for both Part I and Part II)

  10 and 24 hours post dose

Study Arms (3)

LCQ908 (mild hepatic impairment plus healthy volunteers)

EXPERIMENTAL

Healthy subjects will be matched pair-wise by, sex, race, age (±10 years) and weight (±20%) to subjects with mild hepatic impairment and will receive a single dose of LCQ908.

Drug: LCQ908

LCQ908 (moderate hepatic impairment plus healthy volunteers)

EXPERIMENTAL

Healthy subjects will be matched pair-wise by, sex, race, age (±10 years) and weight (±20%) to subjects with moderate hepatic impairment and will receive a single dose of LCQ908.

Drug: LCQ908

LCQ908 (severe hepatic impairment plus healthy volunteers)

EXPERIMENTAL

Healthy subjects will be matched pair-wise by, sex, race, age (±10 years) and weight (±20%) to subjects with severe hepatic impairment and will receive a single dose of LCQ908.

Drug: LCQ908

Interventions

LCQ908 DRUG

Participants will receive a single oral dose of LCQ908

LCQ908 (mild hepatic impairment plus healthy volunteers); LCQ908 (moderate hepatic impairment plus healthy volunteers); LCQ908 (severe hepatic impairment plus healthy volunteers)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (2)

Novartis Investigative Site

Miami, Florida, 33136, United States

Location

Novartis Investigative Site

Orlando, Florida, 32809, United States

Location

Related Publications (1)

• 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.

  PMID: 25633714 DERIVED

Related Links

• Results for CCLCQ908B2101 can be found on the Novartis Clinical Trial Results Website

MeSH Terms

Interventions

pradigastat

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2012
• First Posted: May 9, 2012
• Study Start: April 1, 2012
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: December 19, 2020

Record last verified: 2013-05

Locations

US (2)