Study in Healthy Subjects to Determine the Effect of an Inhibitor on Exposure to Relacorilant and Its Metabolites

NCT03512548 | Completed Phase 1 FDA Drug

• 1 other identifier: CORT125134-124
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Area under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz)

  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)

  predose to 96 hrs postdose in Part 1 and predose to 24 hrs after last dose in Part 2

Secondary Outcomes (3)

• 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

• Maximum plasma concentration (Cmax)

  predose to 96 hrs postdose in Part 1 and predose to 24 hrs after last dose in Part 2

• Number and Severity of Treatment Emergent Adverse Events

  up to 7 weeks in Part 1 and up to 7 weeks in Part 2

Study Arms (5)

Part 1 Period 1

EXPERIMENTAL

Part 1 Period 1: Relacorilant 350mg will be given once on Day 1

Drug: Relacorilant 350mg

Part 1 Period 2

EXPERIMENTAL

Part 1 Period 2: Itraconazole 200mg will be given for three days

Drug: Itraconazole

Part 1 Period 3

EXPERIMENTAL

Part 1 Period 3: Relacorilant 350mg will be given once with concomitant itraconazole and itraconazole will continue for three additional days

Drug: Relacorilant 350mg; Drug: Itraconazole

Part 2 Period A

EXPERIMENTAL

Part 2 Period A: Relacorilant 300mg will be given once daily for 10 days

Drug: Relacorilant 300mg

Part 2 Period B

EXPERIMENTAL

Part 2 Period B: Relacorilant 300mg will be given once daily in combination with itraconazole 200mg once daily for 10 days

Drug: Itraconazole; Drug: Relacorilant 300mg

Interventions

Relacorilant 350mg DRUG

Relacorilant 350mg

Also known as: CORT125134

Part 1 Period 1; Part 1 Period 3

Itraconazole DRUG

Itraconazole 200 mg

Also known as: Sporanox

Part 1 Period 2; Part 1 Period 3; Part 2 Period B

Relacorilant 300mg DRUG

Relacorilant 300mg

Also known as: CORT125134

Part 2 Period A; Part 2 Period B

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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\*\*:
• 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)

Sponsors & Collaborators

• Corcept Therapeutics: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

relacorilant; Itraconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Officials

• Joseph Custodio, PhD

  Corcept Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2018
• First Posted: April 30, 2018
• Study Start: April 10, 2018
• Primary Completion: July 29, 2019
• Study Completion: August 23, 2019
• Last Updated: March 24, 2020

Record last verified: 2020-03

Locations

US (1)