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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: osilodrostat

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

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami / Clinical Research Services, Inc. Boynton Beach
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Davita Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 -

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: osilodrostat (LCI699); 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).	Drug: osilodrostat; Other Names: LCI699

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.
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.	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.
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.	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.
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.	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.
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.	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.
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.	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 Measures

Outcome Measure	Measure Description	Time Frame
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.	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.
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	Pre-treatment, during treatment (Day 1) and 30 days post treatment.

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Novartis results database

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2015
• Primary Completion (Actual): May 19, 2016
• Study Completion (Actual): May 19, 2016

Study Registration Dates

• First Submitted: February 23, 2015
• First Submitted That Met QC Criteria: February 23, 2015
• First Posted (Estimate): February 26, 2015

Study Record Updates

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

More Information

Terms related to this study

• Keywords: LCI699; Hepatic impairment,; osilodrostat,
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: CLCI699C2103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No