A Study to Evaluate the Effects of Hepatic Impairment on the Pharmacokinetics of Relacorilant

An Open-label, Multiple-dose, Adaptive Design Study to Evaluate the Effects of Hepatic Impairment on the Pharmacokinetics of Relacorilant

The primary objective of this multiple-dose, adaptive design study is to evaluate the effect of hepatic impairment on the pharmacokinetics (PK) of relacorilant relative to healthy matched control male and female subjects (Part 1).

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: Relacorilant

Detailed Description

If an obvious effect of moderate hepatic impairment on exposure to relacorilant is observed in Part 1, optional Part 2 of the study will be conducted. In Part 2, the effect of mild hepatic impairment on the PK of relacorilant will be evaluated, using control data from the same healthy control subjects who were matched to the subjects in Part 1.

Secondary objectives of the study are 1) evaluation of the effect of hepatic impairment on the PK of relacorilant metabolites, and 2) evaluation of safety and tolerability of relacorilant on healthy subjects and those with hepatic impairment.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Clinical Pharmacology of Miami, LLC
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Able to understand the purpose and risks of the study and is willing and able to adhere to scheduled visits, treatment plans, laboratory tests, and other study evaluations and procedures
• Provide written informed consent before any study-specific procedure is performed
• Male or a nonpregnant, nonlactating female judged to be in good health, except for allowance of health conditions consistent with hepatic impairment
• Body mass index (BMI) between 18 and 32 kg/m^2, inclusive, and a body weight more than 50 kg (110 pounds)
• Estimated glomerular filtration rate (eGFR) ≥80 mL/minute/1.73 m^2
• Suitable veins for multiple venipuncture/cannulation
• Agrees to limit smoking or use of tobacco or nicotine-containing products to less than 5 cigarettes or uses per day
• Willing to comply with study restrictions as described in the protocol
• Female subject is of either nonchildbearing potential (ie, postmenopausal or permanently sterilized) or uses highly effective contraception with low user-dependency, as described in the protocol.

Subjects with normal hepatic function must also satisfy the following inclusion criteria:

• Clinical laboratory results within the reference range at Screening and Day -1, unless considered not clinically significant by the Principal Investigator
• Negative screening results for hepatitis B surface antigen, hepatitis C virus antibody, and HIV antibodies.

Subjects with moderate or mild hepatic impairment must also satisfy the following inclusion criteria:

• Documented parenchymal hepatic disease
• Liver dysfunction of moderate (Child-Pugh Class B [score of 7 to 9]; Part 1) or mild (Child-Pugh Class A [score of 5 to 6]; Part 2) severity
• Stable hepatic impairment defined as no clinically significant change in disease status within the last 30 days
• On a stable dose of medication and/or treatment regimen at least 2 weeks before study drug dosing
• If a subject has nonhepatic abnormal clinical laboratory results, these results are considered not clinically relevant by the Principal Investigator (or designee) and the medical monitor.

Exclusion Criteria:

• An employee or immediate family member of the Clinical Research Unit (CRU) or the Sponsor
• Has been previously enrolled in any study of relacorilant
• Has multiple clinically significant drug allergies or is allergic to any of the components of relacorilant
• Has a condition that could be aggravated by excessive glucocorticoid receptor antagonism. Subjects with inactive seasonal hay fever or childhood asthma may be included.
• Has a history of malabsorption syndrome or previous gastrointestinal surgery that could affect drug absorption or metabolism
• Has Gilberts syndrome
• Has current or previous (within a 1-year period) alcohol or substance abuse and/or dependence
• Has evidence of acute viral hepatitis in the 3 calendar months before the first dose of study drug
• In the 2 calendar months before the first dose of study drug, subject has: donated/lost blood or plasma in excess of 400 mL, or received an investigational drug
• Has a positive result for alcohol or drugs of abuse at Screening or upon admission to the CRU
• Has clinically relevant abnormal vital signs, physical examination, laboratory tests, or 12-lead ECG findings at Screening and/or before the first dose of study drug, other than those associated with chronic hepatic impairment
• Has taken any prohibited prior medication, as described in the protocol
• Has any other condition that might increase the risk to the individual or decrease the chance of obtaining satisfactory data, as assessed by the Principal Investigator.

Additional exclusion criteria for subjects with moderate or mild hepatic impairment:

• Has hepatic encephalopathy of Grade 2 that has not been controlled with medication for the previous 3 calendar months before Screening or of Grade 3 or higher within the previous 3 calendar months before Screening, regardless of use of medication for the treatment of hepatic encephalopathy
• Has a history of liver transplantation, hepatocellular carcinoma, portosystemic shunt, or acute liver disease (eg, caused by infection or drug toxicity).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: No Hepatic Impairment; Subjects with no hepatic impairment will receive relacorilant 300 mg once daily on Days 1 through 10.	Drug: Relacorilant; Relacorilant 300 mg (3 X 100 mg softgel capsules) for oral administration; Other Names: CORT125134
Experimental: Moderate Hepatic Impairment; Subjects with moderate hepatic impairment (Child-Pugh Class B) will receive relacorilant 300 mg once daily on Days 1 through 10.	Drug: Relacorilant; Relacorilant 300 mg (3 X 100 mg softgel capsules) for oral administration; Other Names: CORT125134
Experimental: Mild Hepatic Impairment; Subjects with mild hepatic impairment (Child-Pugh Class A) will receive relacorilant 300 mg once daily on Days 1 through 10.	Drug: Relacorilant; Relacorilant 300 mg (3 X 100 mg softgel capsules) for oral administration; Other Names: CORT125134

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum concentration of plasma relacorilant during the dosing interval (Cmax)	Predose and at serial time points up to 24 hours after dosing on Day 10
Area under the concentration-time curve of plasma relacorilant from time zero to the end of the dosing interval (24 hours) (AUCt)	Predose and at serial time points up to 24 hours after dosing on Day 10

Secondary Outcome Measures

Outcome Measure	Time Frame
Cmax of relacorilant plasma metabolites	Predose and at serial time points up to 24 hours after dosing on Day 10
AUCt of relacorilant plasma metabolites	Predose and at serial time points up to 24 hours after dosing on Day 10
Number of subjects with one or more treatment-emergent adverse events	Up to Day 20
Number of subjects with one or more treatment-emergent adverse events by severity	Up to Day 20

Collaborators and Investigators

• Sponsor: Corcept Therapeutics
• Investigators: Study Director: Joseph Custodio, Corcept Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2020
• Primary Completion (Actual): December 14, 2020
• Study Completion (Actual): December 14, 2020

Study Registration Dates

• First Submitted: October 17, 2023
• First Submitted That Met QC Criteria: October 17, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: CORT125134-128

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No