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

Hepatic Impairment Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02372084
• Other study ID #: CLCI699C2103
• Status: Completed
• Phase: Phase 1
• Start date: April 21, 2015
• Est. completion date: May 19, 2016

Study information

• Verified date: May 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: May 19, 2016
• Est. primary completion date: May 19, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 -

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• osilodrostat

Locations

Country	Name	City	State
United States	University of Miami / Clinical Research Services, Inc. Boynton Beach	Miami	Florida
United States	DaVita Clinical Research	Minneapolis	Minnesota
United States	Orlando Clinical Research Center	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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	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.
Secondary	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.

External Links

•   Novartis results database