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

NCT02372084 | Completed Phase 1 FDA Drug

• 1 other identifier: CLCI699C2103
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 3

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.

Conditions

Hepatic Impairment

Keywords

Hepatic impairment,; osilodrostat,; LCI699

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (2)

• The relationship between PK parameters (Cmax and AUC) and baseline hepatic function parameters namely; total bilirubin, albumin, INR (or prothrombin, if INR unavailable)

  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)

  Pre-treatment, during treatment (Day 1) and 30 days post treatment.

Study Arms (1)

osilodrostat (LCI699)

EXPERIMENTAL

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

Interventions

osilodrostat DRUG

Also known as: LCI699

osilodrostat (LCI699)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

University of Miami / Clinical Research Services, Inc. Boynton Beach

Miami, Florida, 33136, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

DaVita Clinical Research

Minneapolis, Minnesota, 55404, United States

Location

Related Links

• Novartis results database

MeSH Terms

Interventions

Osilodrostat

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2015
• First Posted: February 26, 2015
• Study Start: April 21, 2015
• Primary Completion: May 19, 2016
• Study Completion: May 19, 2016
• Last Updated: December 19, 2020

Record last verified: 2020-05

Locations

US (3)