Clinical trial NCT02372084: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: Hepatic impairment,
osilodrostat,
LCI699
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-02-26
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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 -

Primary outcomes:
measure: Pharmacokinetics (PK) of a single dose of 30 mg osilodrostat: AUClast
timeFrame: 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.
measure: PK of a single dose of 30 mg osilodrostat: AUCinf
timeFrame: 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.
measure: PK of a single dose of 30 mg osilodrostat: Cmax
timeFrame: 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.
measure: PK of a single dose of 30 mg osilodrostat: T1/2
timeFrame: 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.
measure: PK of a single dose of 30 mg osilodrostat: CL/F
timeFrame: 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.
measure: PK of a single dose of 30 mg osilodrostat: Vz/F
timeFrame: 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:
measure: The relationship between PK parameters (Cmax and AUC) and baseline hepatic function parameters namely; total bilirubin, albumin, INR (or prothrombin, if INR unavailable)
timeFrame: 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.
measure: Number of participants with adverse events (AEs)
timeFrame: Pre-treatment, during treatment (Day 1) and 30 days post treatment.
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami / Clinical Research Services, Inc. Boynton Beach
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Minneapolis
country: United States
facility: DaVita Clinical Research
state: Minnesota
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: