Effect of Relacorilant on the Pharmacokinetics of the Sensitive P-glycoprotein Substrate Dabigatran Etexilate in Healthy Participants

An Open-Label, Drug-Drug Interaction Study Designed to Evaluate the Effect of Relacorilant on the Pharmacokinetics of the Sensitive P-glycoprotein Substrate Dabigatran Etexilate in Healthy Subjects

The primary objective is to determine the effect of relacorilant on the pharmacokinetics (PK) of the sensitive P-glycoprotein (P-gp) substrate dabigatran etexilate.

Study Overview

• Status: Completed
• Conditions: Neoplasms; Cushing Syndrome
• Intervention / Treatment: Drug: Dabigatran Etexilate; Drug: Relacorilant

Detailed Description

The investigational medicinal product (IMP), relacorilant, and the non-investigational medicinal product (NIMP), dabigatran etexilate, will be used to evaluate the effect of relacorilant on the PK of the sensitive P-gp substrate, dabigatran etexilate in healthy participants. Participants will receive a single dose of dabigatran etexilate before and after administration of daily (QD) doses of relacorilant for 11 days. As all participants will receive the same treatments, the study will be open-label and no randomization is required.

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

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33126
      • Site 01

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must agree to use an adequate method of contraception
• Healthy men or non-pregnant, non-lactating healthy women of non-childbearing potential
• Body mass index (BMI) of 19.0 to 32.0 kg/m^2 as measured at screening
• Weight ≥50 kg at screening

Exclusion Criteria:

• Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
• Presence or history of clinically significant allergy requiring treatment, as judged by the Investigator.
• Significant serious skin disease, including rash, food allergy, eczema, psoriasis, or urticaria
• History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, bleeding disorder or abnormal bleeding, or clinically significant active bleeding, congenital or acquired clotting disorders, neurological or psychiatric disorder
• History of esophagitis, gastritis, gastroesophageal reflux surgery, or significant trauma or surgery within 1 month of IMP/NIMP administration
• Have poor venous access that limits phlebotomy
• Evidence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
• Clinically significant abnormal clinical chemistry, hematology or thrombocytopenia, coagulation or urinalysis
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results
• Evidence of renal impairment at screening
• Pregnant or lactating women
• Women of childbearing potential. A woman is considered of childbearing potential unless she is permanently sterile or is postmenopausal
• Participants who have received any IMP in a clinical research study within 5 half-lives or within 30 days prior to first dose.
• Participants who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies in the 14 days before IMP/NIMP administration.
• Participants who are currently using glucocorticoids or have a history of systemic glucocorticoid use at any dose within the last 12 months before IMP/NIMP administration, or 3 months for inhaled products
• Participants who are taking, or have taken, heparin, vitamin K antagonists or anti-platelet agents within 1 month before IMP/NIMP administration
• Participants who are taking, or have taken, selective serotonin re-uptake inhibitors, serotonin and norepinephrine re-uptake inhibitors within 3 months before IMP/NIMP administration
• History of any drug or alcohol abuse in the past 2 years
• A confirmed positive alcohol urine test at screening or admission
• Current smokers and those who have smoked within the last 12 months
• Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
• Positive drugs of abuse test result
• Male participants with pregnant or lactating partners
• Donation of blood within 2 months or donation of plasma within 7 days prior to first dose of study medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dabigatran Etexilate (NIMP) and Relacorilant (IMP); Following an overnight fast, participants will receive 75 mg dabigatran etexilate on Day 1, 400 mg dose of relacorilant QD on Days 3 to 13, and 75 mg dabigatran etexilate on Day 12. On Day 12, dabigatran etexilate will be dosed at approximately the same time as the relacorilant dose.	Drug: Dabigatran Etexilate; Dabigatran will be administered orally as a 75 mg capsule on Day 1 and Day 12.; Other Names: Pradaxa®; Drug: Relacorilant; Relacorilant will be administered orally as 4 X 100 mg capsules (400 mg) on Days 3 through 13.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Dabigatran When Administered With and Without Relacorilant	Up to Day 14
Area Under the Curve from Time 0 to the Time of Last Measurable Concentration (AUC0-last) of Dabigatran When Administered With and Without Relacorilant	Up to Day 14
Area Under the Curve from Time 0 Extrapolated to Infinity (AUC 0-inf) of Dabigatran When Administered With and Without Relacorilant	Up to Day 14

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma Concentrations of Relacorilant	Up to Day 6
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	Up to 30 days post final dose
Number of Participants with Clinically Significant Abnormalities in Blood Pressure and Heart Rate	Up to Day 14
Number of Participants with Clinically Significant Abnormalities in Electrocardiogram (ECG) Measurements	Up to Day 14
Number of Participants with Clinically Significant Abnormalities in Laboratory Safety Tests (Clinical Chemistry, Hematology, Urinalysis)	Up to Day 14

Collaborators and Investigators

• Sponsor: Corcept Therapeutics

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 25, 2022
• Primary Completion (ACTUAL): July 19, 2022
• Study Completion (ACTUAL): July 19, 2022

Study Registration Dates

• First Submitted: April 18, 2022
• First Submitted That Met QC Criteria: April 22, 2022
• First Posted (ACTUAL): April 27, 2022

Study Record Updates

• Last Update Posted (ESTIMATE): February 9, 2023
• Last Update Submitted That Met QC Criteria: February 7, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Cushing Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran
• Other Study ID Numbers: CORT125134-132

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
• product manufactured in and exported from the U.S.: No