A Study to Determine the Relative Bioavailability of Two New Relacorilant Capsule Variants

A Phase 1, Randomized, Open-label, Crossover Study to Determine the Relative Bioavailability of Relacorilant Administered as 3×100-mg Softgel Capsules, 3×100 mg Hard Shell Capsules, and 6×50-mg Hard-shell Capsules in Healthy Adult Subjects

This is an open-label, randomized, 3 treatment, 3-period, 6-sequence, crossover study conducted at a single study center to characterize the relative bioavailability of relacorilant administered as 3×100-mg softgel capsules (Treatment A), 3×100 mg hard-shell capsules (Treatment B), and 6×50-mg hard shell capsules (Treatment C/reference) in healthy, fasted, adult subjects.

Eligible subjects will participate in 3 treatment periods. During each treatment period, subjects will receive a single 300-mg relacorilant dose. An equal number of subjects will be randomized to each of 6 sequences.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Relacorilant (3x100 mg softgel capsules); Drug: Relacorilant (3x100 mg hard-shell capsules); Drug: Relacorilant (6x50mg hard-shell capsules)

Detailed Description

This is an open-label, randomized, 3 treatment, 3-period, 6-sequence, crossover study. Eligible subjects will participate in 3 treatment periods. During each treatment period, subjects will receive a single 300-mg relacorilant dose. An equal number of subjects will be randomized to each of 6 sequences (i.e., ABC, BCA, CAB, BAC, ACB, and CBA):

(A) relacorilant single 300 mg dose (3×100-mg softgel capsules) following a minimum 10 hour fast (Test 1) (B) relacorilant single 300 mg dose (3×100-mg hard-shell capsules) following a minimum 10-hour fast (Test 2) (C) relacorilant single 300 mg dose (6×50-mg hard-shell capsules) following a minimum 10 hour fast (Reference) Subjects will be admitted to the Clinical Research Unit (CRU) on the morning of Day -1 of each period following an 8-hour fast for baseline assessments and will remain confined until Day 3 of each period. After dosing in Period 1 and Period 2, subjects will undergo minimum 14 day washouts between doses of study drug. Subjects will then receive the next relacorilant dose in their randomized sequence in Period 2 and Period 3, respectively. Subjects will attend an outpatient Follow-up Visit 14±2 days after the last dose of study drug in Period 3 (or Early Termination Visit).

Blood samples will be collected before dosing and at intervals up to 120 hours after relacorilant dose in Periods 1, 2 and 3.

Safety and tolerability will be monitored using AEs, clinical laboratory evaluations, 12-lead ECG recordings, vital signs, and physical examinations.

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

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Able to understand the purpose and risks of the study; willing and able to adhere to scheduled visits, treatment plans, laboratory tests, and other study evaluations and procedures.
• Give written informed consent.
• Be males or nonpregnant, nonlactating females judged to be in good health, based on the results of medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory findings.
• Have a body mass index (BMI) between 18 and 32 kg/m2, inclusive, and a body weight more than 50 kg (110 pounds).
• Be a nonsmoker. Use of nicotine or nicotine-containing products must be discontinued at least 90 days prior to the first dose of study drug.
• Be willing to comply with study restrictions
• Have suitable veins for multiple venipuncture/cannulation.

• Female subjects must be either of nonchildbearing potential (i.e., postmenopausal or permanently sterilized) or use highly effective contraception with low user-dependency.

  • The only acceptable method of highly effective contraception with low user-dependency is an intrauterine device (IUD). Use of hormonal contraception (by any route, including intrauterine hormone releasing systems) or hormone replacement therapy is NOT acceptable.

Exclusion Criteria:

• Be an employee or immediate family member of the Clinical Research Unit or Corcept.
• Have been previously enrolled in any study of relacorilant.
• Have multiple drug allergies or be allergic to any of the components of relacorilant.
• Have a condition that could be aggravated by glucocorticoid blockade (e.g., asthma, any chronic inflammatory condition).
• Have a history of malabsorption syndrome or previous gastrointestinal surgery, with the exception of appendectomy and cholecystectomy, which could affect drug absorption or metabolism.
• Current, or previous within a 1-year period, alcohol or substance abuse.
• In the 2 calendar months before first study drug administration, have donated/lost blood or plasma in excess of 400 mL.
• In the 30 days before first study drug administration, have participated in another clinical trial of a new chemical entity or a prescription medicine.
• Have a positive test for alcohol or drugs of abuse at screening or first admission.

• Have clinically relevant abnormal findings on vital signs, physical examination, laboratory screening tests, or 12-lead ECG, at screening and/or before first study drug administration, including but not limited to**:

  • QT interval corrected for heart rate (QTc) using Fridericia's equation (QTcF) >450 ms (from mean of 3 supine ECGs, performed at least 2 minutes apart)
  • Stage 2 or higher hypertension (supine/semi-recumbent systolic blood pressure [SBP] >160 mmHg, diastolic blood pressure [DBP] >100 mmHg; based on mean of duplicate values recorded at least 2 minutes apart)
  • Stage 1 hypertension (supine/semi-recumbent SBP 140-160 mmHg, DBP 90-100 mmHg; based on mean of duplicate values recorded at least 2 minutes apart) associated with indication for treatment i.e., evidence of end-organ damage, diabetes, or a 10-year cardiovascular risk, estimated using a standard calculator, (e.g., QRISK2-2016) greater than 20%
  • Estimated glomerular filtration rate <60 mL/minute/1.73 m2, estimated using the Chronic Kidney Disease Epidemiology Collaboration method (Levey 2009)
  • Hypokalemia (potassium below lower limit of normal)
  • Alanine aminotransferase (ALT), aspartate amino transferase (AST), and/or gamma- glutamyl transferase (GGT) >1.5 times the upper limit of normal (ULN)
  • Seropositive for hepatitis B, hepatitis C, or human immunodeficiency (HIV) viruses **For purposes of qualifying any given subject for study participation, out-of-range values may be repeated once.
• Have any medical or social reasons for not participating in the study raised by their primary care physician.
• Have any other condition that might increase the risk to the individual or decrease the chance of obtaining satisfactory data, as assessed by the Investigator.
• Taken any prohibited prior medication within protocol designated timeframes, such as or including any glucocorticoid, strong inducers, inhibitors or substrates of CYP enzymes involved in drug-drug-interactions, hormonal contraception or hormone replacement therapy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Relacorilant 3x100mg softgel capsules; Relacorilant (3x100 mg softgel capsules)	Drug: Relacorilant (3x100 mg softgel capsules); A single relacorilant 300mg dose (3x100 mg softgel capsules) will be given once on Day 1 of one of three treatment periods.; Other Names: CORT125134
Experimental: Relacorilant 3x100mg hard-shell capsules; Relacorilant (3x100 mg hard-shell capsules)	Drug: Relacorilant (3x100 mg hard-shell capsules); A single relacorilant 300mg dose (3x100 mg hard-shell capsules) will be given once on Day 1 of one of three treatment periods.; Other Names: CORT125134
Experimental: Relacorilant 6x50mg hard-shell capsules; Relacorilant (6x50mg hard-shell capsules)	Drug: Relacorilant (6x50mg hard-shell capsules); A single relacorilant 300mg dose (6x50mg hard-shell capsules) will be given once on Day 1 of one of three treatment periods.; Other Names: CORT125134

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz)	Ratio of population geometric means (GMR) of AUC0-tz for Test 1 (relacorilant 3×100-mg softgel capsules) and Reference (relacorilant 6×50-mg hard-shell capsules) and for Test 2 (relacorilant 3×100-mg hard-shell capsules) and Reference (relacorilant 6×50-mg hard-shell capsules)	pre-dose to 120 hours post-dose in Periods 1 -3.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under plasma concentration-time curve extrapolated to infinity (AUCinf)	Ratio of population geometric means (GMR) of AUCinf for Test 1 (relacorilant 3×100-mg softgel capsules) and Reference (relacorilant 6×50-mg hard-shell capsules and for Test 2 (relacorilant 3×100-mg hard-shell capsules) and Reference (relacorilant 6×50-mg hard-shell capsules)	pre-dose to 120 hours post-dose in Periods 1-3
Maximum plasma concentration (Cmax)	Ratio of population geometric means (GMR) of Cmax for Test 1 (relacorilant 3×100-mg softgel capsules) and Reference (relacorilant 6×50-mg hard-shell capsules) and for Test 2 (relacorilant 3×100-mg hard-shell capsules) and Reference (relacorilant 6×50-mg hard-shell capsules)	pre-dose to 120 hours post-dose in Periods 1-3
Time to Maximum plasma concentration (Tmax)	Ratio of population geometric means (GMR) of Tmax for Test 1 (relacorilant 3×100-mg softgel capsules) and Reference (relacorilant 6×50-mg hard-shell capsules) and for Test 2 (relacorilant 3×100-mg hard-shell capsules) and Reference relacorilant 6×50-mg hard-shell capsules)	pre-dose to 120 hours post-dose in Periods 1-3
Adverse Events	Incidence of treatment emergent adverse events	up to 30 days after the last dose of study drug

Collaborators and Investigators

• Sponsor: Corcept Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2018
• Primary Completion (Actual): July 16, 2018
• Study Completion (Actual): July 25, 2018

Study Registration Dates

• First Submitted: May 17, 2018
• First Submitted That Met QC Criteria: May 17, 2018
• First Posted (Actual): May 30, 2018

Study Record Updates

• Last Update Posted (Actual): September 7, 2018
• Last Update Submitted That Met QC Criteria: September 5, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Inflammatory Agents; Cortisone
• Other Study ID Numbers: CORT125134-127

Drug and device information, study documents

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