Clincosm LogoSign in Get a demo

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

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02372084
Collaborator
(none)
33
Enrollment
3
Locations
1
Arm
12.9
Actual Duration (Months)
11
Patients Per Site
0.8
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
33 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Apr 21, 2015
Actual Primary Completion Date :
May 19, 2016
Actual Study Completion Date :
May 19, 2016

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Pharmacokinetics (PK) of a single dose of 30 mg osilodrostat: AUClast [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.]

      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.

    2. PK of a single dose of 30 mg osilodrostat: AUCinf [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.]

      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.

    3. PK of a single dose of 30 mg osilodrostat: Cmax [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.]

      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.

    4. PK of a single dose of 30 mg osilodrostat: T1/2 [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.]

      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.

    5. PK of a single dose of 30 mg osilodrostat: CL/F [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.]

      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.

    6. PK of a single dose of 30 mg osilodrostat: Vz/F [Predose (Day 0) , and timepoints 0.5, 1, 1.5, 2, 3,4, 6, 8, 12, 24, 36, 48, 72, 96 hours post dose.]

      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

    1. 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.]

      To evaluate the relationship between hepatic function parameters and pharmacokinetics.

    2. Number of participants with adverse events (AEs) [Pre-treatment, during treatment (Day 1) and 30 days post treatment.]

      This will be assessed using laboratory abnormalities, ECG and vital sign assessments of a single 30 mg dose of LCI699

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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 -

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Miami / Clinical Research Services, Inc. Boynton Beach Miami Florida United States 33136
    2 Orlando Clinical Research Center Orlando Florida United States 32809
    3 DaVita Clinical Research Minneapolis Minnesota United States 55404

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT02372084
    Other Study ID Numbers:
    • CLCI699C2103
    First Posted:
    Feb 26, 2015
    Last Update Posted:
    Dec 19, 2020
    Last Verified:
    May 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    Hepatic impairment,
    osilodrostat,
    LCI699
    Additional relevant MeSH terms:
    Liver Diseases

    Study Results

    No Results Posted as of Dec 19, 2020