Study in Healthy Subjects to Determine the Effect of Relacorilant on Exposure to Probe Substrates for Cytochrome P450s

NCT03457597 | Completed Phase 1 FDA Drug

• 1 other identifier: CORT125134-126
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-sequence, 3-period crossover study conducted in healthy subjects. Eligible subjects will participate in a single treatment period, in which they will receive the following treatments: Day 1, single doses of midazolam and metoprolol; Day 2, single doses of pioglitazone, tolbutamide, and omeprazole; Days 5 to 17, daily doses of relacorilant; Day 14, single doses of midazolam and metoprolol (with relacorilant); and, Day 15, single doses of pioglitazone, tolbutamide, and omeprazole (with relacorilant).

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 Day (following a single dose with each probe substrate given within a cocktail of probe substrates) and Test Day (following the same dose given to subjects after 10 or 11 days of daily dosing with relacorilant) areas under plasma concentration-time curve up to the last quantifiable sample (AUC0-tz)

  predose to 96 hrs postdose

Secondary Outcomes (7)

• Area under plasma concentration-time curve extrapolated to infinity (AUCinf)

  predose to 96 hrs postdose

• Maximum plasma concentration (Cmax)

  predose to 96 hrs postdose

• Adverse Events

  up to 8 weeks

• Safety Labs

  up to 8 weeks

• ECGs

  up to 8 weeks

Study Arms (3)

Period 1

EXPERIMENTAL

Period 1 (Study Days 1 to 4): Midazolam hydrochloride and metoprolol tartrate will be given once on Day 1. Pioglitazone hydrochloride, tolbutamide and omeprazole will be given once on Day 2

Drug: Midazolam hydrochloride; Drug: Metoprolol tartrate; Drug: Pioglitazone hydrochloride; Drug: Tolbutamide; Drug: Omeprazole

Period 2

EXPERIMENTAL

Period 2 (Study Days 5 to 13): Relacorilant will be given daily from Day 5 to Day 13.

Drug: Relacorilant

Period 3

EXPERIMENTAL

Period 3 (Study Days 14 to 17): Midazolam hydrochloride and metoprolol tartrate will be given once on Day 14. Pioglitazone hydrochloride, tolbutamide and omeprazole will be given once on Day 15. Relacorilant will be given daily from Day 14 to Day 17.

Drug: Midazolam hydrochloride; Drug: Metoprolol tartrate; Drug: Pioglitazone hydrochloride; Drug: Tolbutamide; Drug: Omeprazole; Drug: Relacorilant

Interventions

Midazolam hydrochloride DRUG

Midazolam hydrochloride 2.5 mg

Also known as: Versed

Period 1; Period 3

Metoprolol tartrate DRUG

Metoprolol tartrate 100 mg

Also known as: Lopressor

Period 1; Period 3

Pioglitazone hydrochloride DRUG

Pioglitazone hydrochloride 15 mg

Also known as: Actos

Period 1; Period 3

Tolbutamide DRUG

Tolbutamide 500 mg

Also known as: Orinase

Period 1; Period 3

Omeprazole DRUG

Omeprazole 20 mg

Also known as: Prilosec

Period 1; Period 3

Relacorilant DRUG

Relacorilant 350mg

Also known as: CORT125134

Period 2; Period 3

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.
• Have a condition that could be aggravated by glucocorticoid blockade (eg, asthma, any chronic inflammatory condition).
• Have a history of gastric bypass surgery.
• 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 a positive test for exogenous glucocorticoids at screening.
• 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%

Sponsors & Collaborators

• Corcept Therapeutics: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

Midazolam; Metoprolol; Pioglitazone; Tolbutamide; Omeprazole; relacorilant

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Thiazolidinediones; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Benzenesulfonamides; Sulfonamides; Amides; Sulfonylurea Compounds; Urea; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Pyridines; Benzimidazoles

Study Officials

• Kirsteen Donaldson, FFPM,DM,FRCP

  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: March 1, 2018
• First Posted: March 7, 2018
• Study Start: March 6, 2018
• Primary Completion: April 15, 2018
• Study Completion: April 28, 2018
• Last Updated: May 17, 2018

Record last verified: 2018-02

Locations

US (1)