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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: osilodrostat


Participation Criteria
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Eligibility Criteria
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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 -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: osilodrostat (LCI699)<br>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<br> <br> * Other names: LCI699;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatic impairment,, osilodrostat,, LCI699