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Effect of Hepatic Impairment on LDK378 Pharmacokinetics

Primary Purpose

Normal Hepatic Function, Impaired Hepatic Function

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

LDK378

About this trial

This is an interventional treatment trial for Normal Hepatic Function focused on measuring LDK378, pharmacokinetics, hepatic impairment

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria (all groups):

Male Subjects between 18-70 years of age
Female subjects between 18-70 years of age who are postmenopausal or sterile
Body Mass Index (BMI) of 18.0- 36.0 kg/m2, with body weight ≥ 50 kg.

Inclusion (group mild, moderate and severe hepatic impairment):

- Subjects with confirmed cirrhosis

Exclusion Criteria (all groups):

impaired cardiac function
concurrent severe and/or uncontrolled medical conditions

Exclusion Criteria (moderate, mild and severe groups):

Clinical evidence of severe ascites
Use of PPIs within 10 days prior to 2 days after LDK378 dosing

Sites / Locations

DaVita Clinical Research-Denver
Avail. Clinical Research, LLC
Clinical Research of Miami, INC CLDK378A2110
Orlando Clinical Research Center
DaVita Clinical Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Normal Hepatic Function

Mild Hepatic Impairment

Moderate Hepatic Impairment

Severe Hepatic Impairment

Arm Description

Subjects with normal hepatic function

Subjects with mild hepatic impairment

Subjects with moderate hepatic impairment

Subjects with severe hepatic impairment

Outcomes

Primary Outcome Measures

LDK378 pharmacokinetic parameters (Tmax)

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

LDK378 pharmacokinetic parameters ( Cmax)

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

LDK378 pharmacokinetic parameters ( AUClast)

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

LDK378 pharmacokinetic parameters (AUCinf)

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

LDK378 pharmacokinetic parameters (T1/2)

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

LDK378 pharmacokinetic parameters (CL/F)

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

LDK378 pharmacokinetic parameters (Vz/F)

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

Secondary Outcome Measures

Number of subjects with Adverse events

Safety will be determined by the frequency of adverse events and the frequency of laboratory toxicities.

Plasma protein binding of LDK378

Full Information

NCT ID

NCT01950481

First Posted

September 23, 2013

Last Updated

December 16, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01950481

Brief Title

Effect of Hepatic Impairment on LDK378 Pharmacokinetics

Official Title

A Phase I, Open Label, Multi-center, Single Dose Study to Evaluate the Pharmacokinetics of LDK378 in Subjects With Hepatic Impairment Compared to Subjects With Normal Hepatic Function

Study Type

Interventional

2. Study Status

Record Verification Date

December 2016

Overall Recruitment Status

Completed

Study Start Date

January 2014 (undefined)

Primary Completion Date

September 2016 (Actual)

Study Completion Date

September 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Pharmacokinetics and safety of 750 mg of LDK378 given once orally in subjects with impaired hepatic function and healthy subjects with normal hepatic function.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Normal Hepatic Function, Impaired Hepatic Function

Keywords

LDK378, pharmacokinetics, hepatic impairment

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

36 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Normal Hepatic Function

Arm Type

Experimental

Arm Description

Subjects with normal hepatic function

Arm Title

Mild Hepatic Impairment

Arm Type

Experimental

Arm Description

Subjects with mild hepatic impairment

Arm Title

Moderate Hepatic Impairment

Arm Type

Experimental

Arm Description

Subjects with moderate hepatic impairment

Arm Title

Severe Hepatic Impairment

Arm Type

Experimental

Arm Description

Subjects with severe hepatic impairment

Intervention Type

Drug

Intervention Name(s)

LDK378

Intervention Description

Oral LDK378 750 mg once

Primary Outcome Measure Information:

Title

LDK378 pharmacokinetic parameters (Tmax)

Description

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

Time Frame

18 Days

Title

LDK378 pharmacokinetic parameters ( Cmax)

Description

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

Time Frame

18 Days

Title

LDK378 pharmacokinetic parameters ( AUClast)

Description

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

Time Frame

18 Days

Title

LDK378 pharmacokinetic parameters (AUCinf)

Description

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

Time Frame

18 Days

Title

LDK378 pharmacokinetic parameters (T1/2)

Description

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

Time Frame

18 Days

Title

LDK378 pharmacokinetic parameters (CL/F)

Description

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

Time Frame

18 Days

Title

LDK378 pharmacokinetic parameters (Vz/F)

Description

Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects

Time Frame

18 Days

Secondary Outcome Measure Information:

Title

Number of subjects with Adverse events

Description

Safety will be determined by the frequency of adverse events and the frequency of laboratory toxicities.

Time Frame

after informed consent is signed, 30 days after last dose

Title

Plasma protein binding of LDK378

Description

Plasma protein binding of LDK378

Time Frame

Day 1 predose, Day 1 6 hours postdose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria (all groups): Male Subjects between 18-70 years of age Female subjects between 18-70 years of age who are postmenopausal or sterile Body Mass Index (BMI) of 18.0- 36.0 kg/m2, with body weight ≥ 50 kg. Inclusion (group mild, moderate and severe hepatic impairment): - Subjects with confirmed cirrhosis Exclusion Criteria (all groups): impaired cardiac function concurrent severe and/or uncontrolled medical conditions Exclusion Criteria (moderate, mild and severe groups): Clinical evidence of severe ascites Use of PPIs within 10 days prior to 2 days after LDK378 dosing

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

DaVita Clinical Research-Denver

City

Lakewood

State/Province

Colorado

ZIP/Postal Code

80228

Country

United States

Facility Name

Avail. Clinical Research, LLC

City

DeLand

State/Province

Florida

ZIP/Postal Code

32720

Country

United States

Facility Name

Clinical Research of Miami, INC CLDK378A2110

City

Miami

State/Province

Florida

ZIP/Postal Code

33126

Country

United States

Facility Name

Orlando Clinical Research Center

City

Orlando

State/Province

Florida

ZIP/Postal Code

32086

Country

United States

Facility Name

DaVita Clinical Research

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55404

Country

United States

12. IPD Sharing Statement

Links:

URL

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=16555

Description

Results for CLDK378A2110 can be found on the Novartis Clinical Trial Results Website

Learn more about this trial

Effect of Hepatic Impairment on LDK378 Pharmacokinetics

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