Effect of Hepatic Impairment on LDK378 Pharmacokinetics

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

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

Study Overview

• Status: Completed
• Conditions: Normal Hepatic Function; Impaired Hepatic Function
• Intervention / Treatment: Drug: LDK378

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • DaVita Clinical Research-Denver
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail. Clinical Research, LLC
    • Miami, Florida, United States, 33126
      • Clinical Research of Miami, INC CLDK378A2110
    • Orlando, Florida, United States, 32086
      • Orlando Clinical Research Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Davita Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal Hepatic Function; Subjects with normal hepatic function	Drug: LDK378; Oral LDK378 750 mg once
Experimental: Mild Hepatic Impairment; Subjects with mild hepatic impairment	Drug: LDK378; Oral LDK378 750 mg once
Experimental: Moderate Hepatic Impairment; Subjects with moderate hepatic impairment	Drug: LDK378; Oral LDK378 750 mg once
Experimental: Severe Hepatic Impairment; Subjects with severe hepatic impairment	Drug: LDK378; Oral LDK378 750 mg once

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LDK378 pharmacokinetic parameters (Tmax)	Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects	18 Days
LDK378 pharmacokinetic parameters ( Cmax)	Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects	18 Days
LDK378 pharmacokinetic parameters ( AUClast)	Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects	18 Days
LDK378 pharmacokinetic parameters (AUCinf)	Evaluate the pharmacokinetics of a single dose of LDK378 in subjects with impaired hepatic function as compared to healthy subjects	18 Days
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	18 Days
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	18 Days
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	18 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with Adverse events	Safety will be determined by the frequency of adverse events and the frequency of laboratory toxicities.	after informed consent is signed, 30 days after last dose
Plasma protein binding of LDK378	Plasma protein binding of LDK378	Day 1 predose, Day 1 6 hours postdose

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: September 23, 2013
• First Submitted That Met QC Criteria: September 23, 2013
• First Posted (Estimate): September 25, 2013

Study Record Updates

• Last Update Posted (Actual): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: pharmacokinetics; hepatic impairment; LDK378
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Ceritinib
• Other Study ID Numbers: CLDK378A2110