Effect of Hepatic Impairment on LDK378 Pharmacokinetics

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

Official Title
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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

Conditions
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Normal Hepatic Function, Impaired Hepatic Function

Intervention / Treatment
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* Drug: LDK378


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LDK378, pharmacokinetics, hepatic impairment