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A Phase 1 Study of Osilodrostat (LCI699) in Healthy Volunteers and Subjects With Impaired Hepatic Function

Primary Purpose

Hepatic Impairment

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
osilodrostat
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatic Impairment focused on measuring Hepatic impairment,, osilodrostat,, LCI699

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Weight ≥50 kg and BMI between 18-38kg/m2.
  • Stable liver cirrhosis and evidence of hepatic impairment.
  • Free of significant medical disorders unrelated to underlying hepatic impairment

Exclusion Criteria:

  • History of any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs
  • Subjects with ongoing alcohol or drug abuse
  • Symptoms or history of encephalopathy (Grade 2 or above)
  • History or presence of liver disease or liver injury (healthy volunteers only)
  • History or presence of impaired renal function
  • Clinical evidence of severe ascites.
  • Total Bilirubin > 6 mg/dL,
  • Subjects with a serum free cortisol test results that is below the lower limit of normal (based on central laboratory) during the screening period
  • Concomitant use of a drug that is a strong inducer of the CYP3A4/5 pathway

Other protocol-defined inclusion/exclusion criteria may apply -

Sites / Locations

  • University of Miami / Clinical Research Services, Inc. Boynton Beach
  • Orlando Clinical Research Center
  • DaVita Clinical Research

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

osilodrostat (LCI699)

Arm Description

Each participant will undergo a 28-day screening/baseline period (day -28 to day -1), followed by a 5 day treatment period (a single 30 mg dose of LCI699 ( Day 1) with 5 days of PK sample collection).

Outcomes

Primary Outcome Measures

Pharmacokinetics (PK) of a single dose of 30 mg osilodrostat: AUClast
To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.
PK of a single dose of 30 mg osilodrostat: AUCinf
To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.
PK of a single dose of 30 mg osilodrostat: Cmax
To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.
PK of a single dose of 30 mg osilodrostat: T1/2
To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.
PK of a single dose of 30 mg osilodrostat: CL/F
To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.
PK of a single dose of 30 mg osilodrostat: Vz/F
To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.

Secondary Outcome Measures

The relationship between PK parameters (Cmax and AUC) and baseline hepatic function parameters namely; total bilirubin, albumin, INR (or prothrombin, if INR unavailable)
To evaluate the relationship between hepatic function parameters and pharmacokinetics.
Number of participants with adverse events (AEs)
This will be assessed using laboratory abnormalities, ECG and vital sign assessments of a single 30 mg dose of LCI699

Full Information

First Posted
February 23, 2015
Last Updated
December 16, 2020
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02372084
Brief Title
A Phase 1 Study of Osilodrostat (LCI699) in Healthy Volunteers and Subjects With Impaired Hepatic Function
Official Title
A Phase I, Open-label, Multi-center, Single Dose, Parallel Group Study to Evaluate the Pharmacokinetics and Safety of Osilodrostat (LCI699) in Subjects With Impaired Hepatic Function Compared to Subjects With Normal Hepatic Function
Study Type
Interventional

2. Study Status

Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
April 21, 2015 (Actual)
Primary Completion Date
May 19, 2016 (Actual)
Study Completion Date
May 19, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
To assess the pharmacokinetics of a single oral dose of osilodrostat (LCI699) 30 mg in subjects with mild, moderate and severe hepatic impairment compared with subjects with normal hepatic function.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Impairment
Keywords
Hepatic impairment,, osilodrostat,, LCI699

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
osilodrostat (LCI699)
Arm Type
Experimental
Arm Description
Each participant will undergo a 28-day screening/baseline period (day -28 to day -1), followed by a 5 day treatment period (a single 30 mg dose of LCI699 ( Day 1) with 5 days of PK sample collection).
Intervention Type
Drug
Intervention Name(s)
osilodrostat
Other Intervention Name(s)
LCI699
Primary Outcome Measure Information:
Title
Pharmacokinetics (PK) of a single dose of 30 mg osilodrostat: AUClast
Description
To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.
Time Frame
Predose (Day 0) , and at timepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.
Title
PK of a single dose of 30 mg osilodrostat: AUCinf
Description
To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.
Time Frame
Predose (Day 0) , and at imepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.
Title
PK of a single dose of 30 mg osilodrostat: Cmax
Description
To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.
Time Frame
Predose (Day 0) , and at timepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.
Title
PK of a single dose of 30 mg osilodrostat: T1/2
Description
To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.
Time Frame
Predose (Day 0) , and at timepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.
Title
PK of a single dose of 30 mg osilodrostat: CL/F
Description
To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.
Time Frame
Predose (Day 0) , and at timepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.
Title
PK of a single dose of 30 mg osilodrostat: Vz/F
Description
To assess the influence of hepatic impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of hepatic impairment compared to subjects with normal hepatic function.
Time Frame
Predose (Day 0) , and timepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.
Secondary Outcome Measure Information:
Title
The relationship between PK parameters (Cmax and AUC) and baseline hepatic function parameters namely; total bilirubin, albumin, INR (or prothrombin, if INR unavailable)
Description
To evaluate the relationship between hepatic function parameters and pharmacokinetics.
Time Frame
Predose ( Day 0) and at timepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.
Title
Number of participants with adverse events (AEs)
Description
This will be assessed using laboratory abnormalities, ECG and vital sign assessments of a single 30 mg dose of LCI699
Time Frame
Pre-treatment, during treatment (Day 1) and 30 days post treatment.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Weight ≥50 kg and BMI between 18-38kg/m2. Stable liver cirrhosis and evidence of hepatic impairment. Free of significant medical disorders unrelated to underlying hepatic impairment Exclusion Criteria: History of any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs Subjects with ongoing alcohol or drug abuse Symptoms or history of encephalopathy (Grade 2 or above) History or presence of liver disease or liver injury (healthy volunteers only) History or presence of impaired renal function Clinical evidence of severe ascites. Total Bilirubin > 6 mg/dL, Subjects with a serum free cortisol test results that is below the lower limit of normal (based on central laboratory) during the screening period Concomitant use of a drug that is a strong inducer of the CYP3A4/5 pathway Other protocol-defined inclusion/exclusion criteria may apply -
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
University of Miami / Clinical Research Services, Inc. Boynton Beach
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Orlando Clinical Research Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
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=16087
Description
Novartis results database

Learn more about this trial

A Phase 1 Study of Osilodrostat (LCI699) in Healthy Volunteers and Subjects With Impaired Hepatic Function

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