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

Study Overview
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Brief Summary
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To characterize the pharmacokinetics of LCI699 following a single oral dose in adult subjects with various degrees of impaired renal 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 LCI699 in Subjects With Varying Degrees of Impaired Renal Function Compared to Subjects With Normal Renal Function

Conditions
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Renal Impairment

Intervention / Treatment
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* Drug: osilodrostat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Weight must be ≥50 kg and BMI must be between 18-35 kg/m2 Subjects must have stable renal disease without evidence of progressive decline in renal function (stable renal disease is defined as no significant change, such as, stable eGFR <90 mL/min, for 12 weeks prior to study entry) Other than renal impairment, subjects must be stable and appropriately managed relative to chronic diseases (such as diabetes and hypertension) Exclusion Criteria: History of any surgical or medical condition other than renal impairment which might significantly alter the absorption, distribution, metabolism or excretion of drugs. Subjects with ongoing alcohol or drug abuse within 1 month prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations. Subjects with screening 12-lead ECG QTcF of > 450 msec for males or > 460 msec for female History of diabetes mellitus (Type 1 or 2) or blood glucose of >125 mg/dl at screening Subjects with potassium levels greater than the upper limit of normal (>ULN) Other protocol defined Inclusion/Exclusion 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 4 day treatment period ( a single 30 mg dose of LCI699 (Day 1) with 4 days of PK smple collection | Drug: osilodrostat<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK in plasma) of a single dose of 30 mg osilodrostat: AUClast | To assess the influence of renal impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of renal impairment compared to subjects with normal renal function. | Pre-dose (Day 0), and at timepoints 05.1,1.5,2,3,4,6,8,12,24,36,28 and 72 hours post dose | 
| Pharmacokinetics (PK in plasma) of a single dose of 30 mg osilodrostat: AUCinf | To assess the influence of renal impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of renal impairment compared to subjects with normal renal function. | Pre-dose (Day 0), and at timepoints 05.1,1.5,2,3,4,6,8,12,24,36,28 and 72 hours post dose | 
| Pharmacokinetics (PK in plasma) of a single dose of 30 mg osilodrostat: Cmax | To assess the influence of renal impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of renal impairment compared to subjects with normal renal function. | Pre-dose (Day 0), and at timepoints 05.1,1.5,2,3,4,6,8,12,24,36,28 and 72 hours post dose | 
| Pharmacokinetics (PK in urine) of a single dose of 30 mg osilodrostat: CL/F | To assess the influence of renal impairment on the pharmacokinetics (PK) of LCI699i in subjects with varying degrees of renal impairment compared to subjects with normal renal function. | Pre-dose (Day 0), and at timepoints 05.1,1.5,2,3,4,6,8,12,24,36,28 and 72 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The relationship between PK parameters (, T1/2, V2/F and urine AeOt) |  | Pre-dose (Day 0), and at timepoints 05.1,1.5,2,3,4,6,8,12,24,36,28 and 72 hours post dose | 
| Number of participants with adverse events |  | Pre-treatment, during treatment (Day1) and 30 days post treatment | 

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