A Phase 1 Study of Osilodrostat (LCI699) in Healthy Volunteers and Subjects With Impaired Hepatic Function
- Registration Number
- NCT02372084
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 33
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description osilodrostat (LCI699) osilodrostat 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).
- Primary Outcome Measures
Name Time Method 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.
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.
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.
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.
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.
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
Name Time Method 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.
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
Trial Locations
- Locations (3)
University of Miami / Clinical Research Services, Inc. Boynton Beach
🇺🇸Miami, Florida, United States
Orlando Clinical Research Center
🇺🇸Orlando, Florida, United States
DaVita Clinical Research
🇺🇸Minneapolis, Minnesota, United States
University of Miami / Clinical Research Services, Inc. Boynton Beach🇺🇸Miami, Florida, United States