A Phase 1, Open-Label, Single-Sequence Crossover Study in Healthy Subjects to Determine the Effect of an Inhibitor of Cytochrome P450 3A on Exposure to Relacorilant and Its Main Metabolites
Overview
- Phase
- Phase 1
- Intervention
- Relacorilant 350mg
- Conditions
- Healthy
- Sponsor
- Corcept Therapeutics
- Enrollment
- 52
- Locations
- 1
- Primary Endpoint
- Area under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This is an open label, single sequence, crossover study. In Part 1, eligible subjects will participate in 3 treatment periods, in which they will receive the following treatments in turn: 1) In Period 1, a single 350-mg dose of relacorilant administered alone, 2) In Period 2, once daily 200-mg doses of itraconazole administered for 3 days; 3) In Period 3, single 350-mg dose of relacorilant administered with a concomitant 200-mg dose of itraconazole and continued once daily 200-mg doses of itraconazole for three additional days.
If Part 2 is conducted, eligible subjects will participate in 2 treatment periods, in which they will receive the following treatments in turn: 1) In Period A, once daily 300-mg doses of relacorilant alone for 10 days; 2) In Period B, once daily 300-mg doses of relacorilant in combination with once daily 200-mg doses of itraconazole for 10 days.
Detailed Description
This is an open label, single sequence, crossover study. In Part 1, eligible subjects will participate in 3 treatment periods, in which they will receive the following treatments in turn: 1) In Period 1, a single 350-mg dose of relacorilant administered alone, 2) In Period 2, once daily 200-mg doses of itraconazole administered for 3 days; 3) In Period 3, single 350-mg dose of relacorilant administered with a concomitant 200-mg dose of itraconazole and continued once daily 200-mg doses of itraconazole for three additional days. Part 2 of the study may be conducted if the results of Part 1 indicate that itraconazole has a clinically meaningful effect on exposure to relacorilant and metabolites. If Part 2 is conducted, eligible subjects will participate in 2 treatment periods, in which they will receive the following treatments in turn: 1) In Period A, once daily 300-mg doses of relacorilant alone for 10 days; 2) In Period B, once daily 300-mg doses of relacorilant in combination with once daily 200-mg doses of itraconazole for 10 days. Blood samples will be collected before dosing and at intervals up to 96 hours after relacorilant dose in Part 1, and up to 24 hours after the last dose of relacorilant in each study period in Part 2. In Part 1 only, additional samples will be collected during the itraconazole dosing to confirm exposure. Safety and tolerability will be monitored using AEs, clinical laboratory evaluations, 12-lead ECG recordings, vital signs, and and physical examinations. Subjects will be admitted to the Clinical Research Unit (CRU) on the morning of Day -1 following an 8-hour fast for baseline assessments and will remain confined until completion of procedures. Each subject will have a follow-up (FU) visit 14 ± 2 days (Part 1) or 7 ± 2 days (Part 2) after the last dose of relacorilant.
Investigators
Eligibility Criteria
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 (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.
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 and/or itraconazole.
- •Have a condition that could be aggravated by glucocorticoid blockade (eg, 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 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\*\*:
Arms & Interventions
Part 1 Period 1
Part 1 Period 1: Relacorilant 350mg will be given once on Day 1
Intervention: Relacorilant 350mg
Part 1 Period 2
Part 1 Period 2: Itraconazole 200mg will be given for three days
Intervention: Itraconazole
Part 1 Period 3
Part 1 Period 3: Relacorilant 350mg will be given once with concomitant itraconazole and itraconazole will continue for three additional days
Intervention: Relacorilant 350mg
Part 1 Period 3
Part 1 Period 3: Relacorilant 350mg will be given once with concomitant itraconazole and itraconazole will continue for three additional days
Intervention: Itraconazole
Part 2 Period A
Part 2 Period A: Relacorilant 300mg will be given once daily for 10 days
Intervention: Relacorilant 300mg
Part 2 Period B
Part 2 Period B: Relacorilant 300mg will be given once daily in combination with itraconazole 200mg once daily for 10 days
Intervention: Itraconazole
Part 2 Period B
Part 2 Period B: Relacorilant 300mg will be given once daily in combination with itraconazole 200mg once daily for 10 days
Intervention: Relacorilant 300mg
Outcomes
Primary Outcomes
Area under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz)
Time Frame: predose to 96 hrs postdose in Part 1 and predose to 24 hrs after last dose in Part 2
Ratio of population geometric means (GMR) for Reference (following oral administration of relacorilant alone) and Test (following the same dose given to subjects concomitantly with itraconazole) areas under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz)
Secondary Outcomes
- Area under plasma concentration-time curve extrapolated to infinity (AUCinf)(predose to 96 hrs postdose in Part 1; AUCinf not calculated in Part 2 due to steady state evaluation)
- Number and Severity of Treatment Emergent Adverse Events(up to 7 weeks in Part 1 and up to 7 weeks in Part 2)
- Maximum plasma concentration (Cmax)(predose to 96 hrs postdose in Part 1 and predose to 24 hrs after last dose in Part 2)