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

Purpose

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

Condition	Intervention	Phase
Hepatic Impairment	Drug: LCQ908	Phase 1

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

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 for part I of the study [ Time Frame: 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 ] [ Designated as safety issue: No ]
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.
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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
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.
Maximum plasma concentration of LCQ908 (Cmax) for Part I of the study [ Time Frame: 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 ] [ Designated as safety issue: No ]
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.
The apparent systemic clearance (CL/F) of LCQ908 following extra vascular administration for Part I of the study [ Time Frame: 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 ] [ Designated as safety issue: No ]
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.
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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
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.
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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
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.
Maximum plasma concentration of LCQ908 (Cmax) for Part II of the study [ Time Frame: 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 ] [ Designated as safety issue: No ]
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.
The apparent systemic clearance (CL/F) of LCQ908 following extra vascular administration for Part II of the study [ Time Frame: 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 ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Number of participants with adverse events, serious adverse events and death (for both Part I and Part II) [ Time Frame: Day 28 ] [ Designated as safety issue: Yes ]
Adverse events 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. Serious adverse events 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 judgment of investigators represent significant hazards.
Time to maximum plasma concentration of LCQ908 (Tmax) (for both Part I and Part II) [ Time Frame: 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 ] [ Designated as safety issue: No ]
This outcome applies to Part I and II of the study involving mild and moderate hepatic impairment as well as healthy volunteers for Part I, severe hepatic impairment and healthy volunteers for Part II. 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 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) [ Time Frame: 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 ] [ Designated as safety issue: No ]
This outcome applies to Part I and II of the study involving mild and moderate hepatic impairment as well as healthy volunteers for Part I, severe hepatic impairment and healthy volunteers for Part II. 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 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) [ Time Frame: 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 ] [ Designated as safety issue: No ]
This outcome applies to Part I and II of the study involving mild and moderate hepatic impairment as well as healthy volunteers for Part I, severe hepatic impairment and healthy volunteers for Part II. 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 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) [ Time Frame: 10 and 24 hours post dose ] [ Designated as safety issue: No ]
This outcome applies to Part I and II of the study involving mild and moderate hepatic impairment as well as healthy volunteers for Part I, severe hepatic impairment and healthy volunteers for Part II. Blood will be collected 10 and 24 hours post dosing.
LCQ908 protein binding: unbound observed maximum plasma (Cmax) of LCQ908 (for both Part I and Part II) [ Time Frame: 10 and 24 hours ] [ Designated as safety issue: No ]
This outcome applies to Part I and II of the study involving mild and moderate hepatic impairment as well as healthy volunteers for Part I, severe hepatic impairment and healthy volunteers for Part II. Blood will be collected 10 and 24 hours post dosing.
LCQ908 protein binding: unbound apparent systemic clearance from plasma (CL/Fu) following extra vascular administration (for both Part I and Part II) [ Time Frame: 10 and 24 hours ] [ Designated as safety issue: No ]
This outcome applies to Part I and II of the study involving mild and moderate hepatic impairment as well as healthy volunteers for Part I, severe hepatic impairment and healthy volunteers for Part II. Blood will be collected 10 and 24 hours post dosing.

Estimated Enrollment:	60
Study Start Date:	April 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 hepatic impairment plus healthy volunteers) 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 Participants will receive a single oral dose of LCQ908
Experimental: LCQ908 (moderate hepatic impairment plus healthy volunteers) 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 Participants will receive a single oral dose of LCQ908
Experimental: LCQ908 (severe hepatic impairment plus healthy volunteers) 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 Participants will receive a single oral dose of LCQ908

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01594957

Contacts

Contact: Novartis Pharmaceuticals Study Director

862-778-8300

Locations

United States, Florida
Novartis Investigative Site	Recruiting
Miami, Florida, United States, 33136
Novartis Investigative Site	Not yet recruiting
Orlando, Florida, United States, 32809

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01594957 History of Changes
Other Study ID Numbers:	CLCQ908B2101
Study First Received:	May 7, 2012
Last Updated:	November 15, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Novartis:

LCQ908,
Hepatic Impairment,
Pharmacokinetics

Additional relevant MeSH terms:

Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on May 23, 2013