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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03540836
• Other study ID #: CORT125134-127
• Status: Completed
• Phase: Phase 1
• Start date: May 24, 2018
• Est. completion date: July 25, 2018

Study information

• Verified date: August 2018
• Source: Corcept Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: July 25, 2018
• Est. primary completion date: July 16, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Celerion	Tempe	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Corcept Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Adverse Events	Incidence of treatment emergent adverse events	up to 30 days after the last dose of study drug