Relacorilant Food Effect Study in Healthy Subjects
- Conditions
- Food-drug InteractionHealthy
- Interventions
- Registration Number
- NCT03442621
- Lead Sponsor
- Corcept Therapeutics
- Brief Summary
This is an open-label, randomized, single-dose, 3-period crossover, Williams' design, food-interaction (fasted and fed arms) study conducted in healthy subjects.
- Detailed Description
This food-interaction study will be conducted in healthy subjects. Each subject will have a screening visit (within the 21 days prior to the first study drug administration to confirm eligibility), 3 single-dose treatment periods separated by a 7- to 14- day washout between doses, and an outpatient end-of-study follow-up visit 14 +/- 2 days after the last dose of study medication. During each treatment period, subjects will receive a single 350-mg relacorilant dose. Based on randomization to 1 of 6 sequences, each subject will receive the relacorilant dose once after a 10.5 hour fast; once 30 minutes after the start of a high-fat meal; and once 30 minutes after the start of a moderate meal.
During the first treatment period only, regardless of randomized sequence, subjects will report to the clinical research unit on the morning of Day -1 for baseline laboratory assessments and to collect samples for assay of messenger ribonucleic acid (mRNA) expression of glucocorticoid-modulated genes to explore the normal range over the day in healthy subjects. For the subsequent 2 treatment periods, subjects will report to the CRU on the evening of Day -1.
Blood samples for assay of plasma concentration of relacorilant and its main metabolites will be collected pre-dose and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, 72, and 96 hours post-dose. Subjects and will remain in the clinic until after the 24-hour blood samples are collected and then be discharged and scheduled to return for the later samples.
Additional samples will be collected for possible future pharmacogenomic analysis.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
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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.
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Give written informed consent.
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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.
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Have a body mass index (BMI) between 18 and 32 kg/m2, inclusive, and a body weight more than 50 kg (110 pounds).
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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.
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Be willing to comply with study restrictions
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Have suitable veins for multiple venipuncture/cannulation.
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Female subjects must be either of nonchildbearing potential (ie, 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.
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Be an employee or immediate family member of the Clinical Research Unit or Corcept.
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Have been previously enrolled in any study of relacorilant.
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Have multiple drug allergies, or be allergic to any of the components of relacorilant.
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Have a condition that could be aggravated by glucocorticoid blockade (eg, asthma, any chronic inflammatory condition).
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Have a history of gastric bypass surgery.
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Have a history of malabsorption syndrome or previous gastrointestinal surgery, with the exception of appendectomy and cholecystectomy, which could affect drug absorption or metabolism.
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Current alcohol or substance abuse.
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In the 2 calendar months before first study drug administration, have donated/lost blood or plasma in excess of 400 mL.
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In the 30 days before first study drug administration, have participated in another clinical trial of a new chemical entity or a prescription medicine.
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Have a positive test for alcohol or drugs of abuse at screening or first admission.
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Have a positive test for exogenous glucocorticoids at screening.
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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 ie, evidence of end-organ damage, diabetes, or a 10-year cardiovascular risk, estimated using a standard calculator, (eg, QRISK2-2016) greater than 20%
- Glomerular filtration rate, estimated using the chronic kidney disease epidemiology (collaboration) (CKD-EPI) method (eGFR; Levey 2009) <60 mL/minute/1.73 m2
- Hypokalemia (potassium below lower limit of normal)
- Alanine aminotransferase (ALT), aspartate amino transferase (AST), and/or gamma- glutamyltransferase (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.
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Have any medical or social reasons for not participating in the study raised by their primary care physician.
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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.
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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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Relacorilant Fasted Relacorilant Fasted Relacorilant Fasted Relacorilant with a high fat breakfast Relacorilant with a high fat breakfast Relacorilant with a high fat breakfast Relacorilant with a moderate breakfast Relacorilant with a moderate breakfast Relacorilant with a moderate breakfast
- Primary Outcome Measures
Name Time Method Area under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz) predose to 96 hrs postdose Ratio of population geometric means (GMR) for Test 1 (standard high fat breakfast) and Reference (fasted) and for Test 2 (standard moderate breakfast) and Reference for relacorilant areas under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz)
- Secondary Outcome Measures
Name Time Method Area under plasma concentration-time curve extrapolated to infinity (AUCinf) predose to 96 hrs postdose Ratio of population geometric means (GMR) for Test 1 (standard high fat breakfast) and Reference (fasted) and for Test 2 (standard moderate breakfast) and Reference for relacorilant areas under plasma concentration-time curve extrapolated to infinity (AUCinf)
Maximum plasma concentration (Cmax) predose to 96 hrs postdose Ratio of population geometric means (GMR) for Test 1 (standard high fat breakfast) and Reference (fasted) and for Test 2 (standard moderate breakfast) and Reference for relacorilant maximum plasma concentration (Cmax).
ECGs up to 9 weeks Safety and tolerability measure by number of subjects who experience potential clinically significant changes in ECGs
Vital Signs up to 9 weeks Safety and tolerability measure by number of subjects who experience potential clinically significant changes in vital signs
Physical Examinations up to 9 weeks Safety and tolerability measure by number of subjects who experience potential clinically significant changes in physical exams
Adverse Events up to 9 weeks Safety and tolerability measure by number of subjects who experience adverse events
Safety Labs up to 9 weeks Safety and tolerability measure by number of subjects who experience potential clinically significant changes in safety labs
Trial Locations
- Locations (1)
Celerion
đŸ‡ºđŸ‡¸Tempe, Arizona, United States