Effect of Hepatic Impairment on LDE225..

A Phase I, Open Label, Multi-center, Single Dose Study to Evaluate the Pharmacokinetics of LDE225 in Healthy Subjects With Normal Hepatic Function and Subjects With Impaired Hepatic Function.

This study is to evaluate the pharmacokinetics and safety of 800 mg of LDE225 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: LDE225

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
• Bulgaria
  • Sofia, Bulgaria, 1612
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 14050
    • Novartis Investigative Site
• Israel
  • Tel-Aviv, Israel, 64239
    • Novartis Investigative Site
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Div. of Clinical Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria (all groups):

• Male and sterile or postmenopausal female age ≥18 to ≤70 years old.
• Normal Vital signs

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

-Subjects with confirmed cirrhosis

Exclusion (all groups):

• Woman of childbearing potential and pregnant or lactating females or male not using condom
• Risk factors for torsades de pointes
• Clinically significant cardio-vascular disease
• severe or uncontrolled medical conditions
• Smokers consuming greater than 10 cigarettes or equivalent nicotine containing products per day.
• Use of investigational drugs (i.e. participation in any clinical investigation)

Exclusion for moderate, mild and severe groups:

• Symptoms or history of encephalopathy
• Clinical evidence of severe ascites

Exclusion Criteria:

-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LDE225	Drug: LDE225; LDE225

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LDE225A pharmacokinetic parameter Tmax	Evaluate the pharmacokinetics of a single dose of LDE225 in subjects with impaired hepatic function as compared to healthy subjects for an 8 weeks follow up period	8 weeks
LDE225A pharmacokinetic parameter Cmax	Evaluate the pharmacokinetics of a single dose of LDE225 in subjects with impaired hepatic function as compared to healthy subjects for an 8 weeks follow up period	8 weeks
LDE225A pharmacokinetic parameter AUClast	Evaluate the pharmacokinetics of a single dose of LDE225 in subjects with impaired hepatic function as compared to healthy subjects for an 8 weeks follow up period	8 weeks
LDE225A pharmacokinetic parameter AUCinf	Evaluate the pharmacokinetics of a single dose of LDE225 in subjects with impaired hepatic function as compared to healthy subjects for an 8 weeks follow up period	8 weeks
LDE225A pharmacokinetic parameter T1/2	Evaluate the pharmacokinetics of a single dose of LDE225 in subjects with impaired hepatic function as compared to healthy subjects for an 8 weeks follow up period	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of abnormal safety laboratory parameters	Laboratory assessments	8 weeks
Plasma protein binding of LDE225	Plasma protein binding of LDE225	1 day
Occurrence of changes in ECGs	ECGs	8 weeks
Occurrence of adverse event	follow up on any adverse event	8 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CLDE225A2113 from Novartis Clinical Trials website

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: January 8, 2013
• First Submitted That Met QC Criteria: January 8, 2013
• First Posted (Estimate): January 10, 2013

Study Record Updates

• Last Update Posted (Actual): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Pharmacokinetics; PK; Postmenopausal women; mild hepatic impairment; moderate hepatic impairment; LDE225; normal hepatic function; severe hepatic impairment
• Other Study ID Numbers: CLDE225A2113