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

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

To characterize the pharmacokinetics of LCI699 following a single oral dose in adult subjects with various degrees of impaired renal function.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: osilodrostat

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1612
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 14050
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: osilodrostat ( LCI699); 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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CLCI699C2104 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2015
• Primary Completion (Actual): March 21, 2016
• Study Completion (Actual): March 21, 2016

Study Registration Dates

• First Submitted: March 20, 2015
• First Submitted That Met QC Criteria: March 20, 2015
• First Posted (Estimate): March 26, 2015

Study Record Updates

• Last Update Posted (Actual): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Renal impairment, osilodrostat, LCI699
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: CLCI699C2104; 2014-003528-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No