Healthy
Conditions
Brief summary
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.
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.
Interventions
DRUGRelacorilant (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.
DRUGRelacorilant (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.
DRUGRelacorilant (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.
Sponsors
Corcept Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz) | pre-dose to 120 hours post-dose in Periods 1 -3. | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under plasma concentration-time curve extrapolated to infinity (AUCinf) | pre-dose to 120 hours post-dose in Periods 1-3 | 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) |
| Maximum plasma concentration (Cmax) | pre-dose to 120 hours post-dose in Periods 1-3 | 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) |
| Time to Maximum plasma concentration (Tmax) | pre-dose to 120 hours post-dose in Periods 1-3 | 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) |
| Adverse Events | up to 30 days after the last dose of study drug | Incidence of treatment emergent adverse events |
Countries
United States
Outcome results
None listed