NCT03335956

CORT125281 Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD)

A Double-blind, Randomised, Placebo-controlled Study of the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of SAD and MAD of CORT125281 in Healthy Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (actual)
• Sponsor: Corcept Therapeutics · Industry
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

This initial Phase I study will evaluate the dose-related safety and tolerability pharmacokinetics (PK) of CORT125281, and CORT125324 (active metabolite), and pharmacodynamics (PD) after single and multiple ascending oral doses of CORT125281 in healthy subjects.

Detailed description

Separate single-and multiple-ascending dose (SAD and MAD) parts will be conducted. Throughout each part of the study, safety, pharmacological (PD) and PK effects will be assessed. Safety and tolerability will be assessed using adverse event (AE) monitoring, measurement of vital signs, recording 12-lead electrocardiogram (ECG), physical examination and clinical laboratory safety tests. Blood samples will be collected at intervals for assay of plasma concentration of CORT125281 and CORT125324. The SAD part of the study is double-blind, randomized and placebo-controlled with respect to CORT125281. Two cohorts, each of 9 subjects, will receive three sequential single doses of the investigational medicinal product (IMP), either CORT125281 at the assigned dose level or placebo, in a partial within-subject crossover manner. The starting dose is CORT125281, 40 mg; the rules for determining later doses are detailed within the protocol. The PD effects of CORT125281 will be examined by testing its ability to ameliorate the pharmacological effects of a concomitantly administered dose of prednisone. The MAD part of the study will be double-blind, randomized, placebo-controlled and parallel-group with respect to CORT125281. Up to four cohorts of 8 subjects, randomized so that 6 receive CORT125281 and 2 receive placebo, will participate in the study, so that up to four dose levels of CORT125281 are studied in total. An exploratory assessment will be made of the effect of repeated doses of CORT125281 on exposure to pioglitazone, probe substrate for CYP2C8. Each subject will be admitted on Day-1 for baseline assessments. On Day1, subjects will receive a single oral dose of pioglitazone, 15mg. From Day3 to Day16 (14 days), subjects will be dosed daily with IMP (CORT125281 at the selected dose or placebo). On Day13, subjects will receive a second dose of pioglitazone, 15 mg.

Conditions

• Healthy

Interventions

Type	Name	Description
DRUG	CORT125281, 40mg, fasted	CORT125281 is supplied as capsules for oral dosing
DRUG	Prednisone 25mg, fasted	Challenge Agent, Dose and Route of Administration: Standard release 25 mg tablets, orally administered
DRUG	Placebo oral capsule, fasted	Reference Therapy, Dose and Route of Administration: Placebo capsule, orally administered
DRUG	Pioglitazone 15mg Tablet	Probe Substrate, Dose and Route of Administration: 15 Mg tablet, orally administered
DRUG	Placebo oral capsule, fed	Reference Therapy, Dose and Route of Administration: Placebo capsule, orally administered
DRUG	Prednisone 25mg, fed	Challenge Agent, Dose and Route of Administration: Standard release 25 mg tablets, orally administered
DRUG	CORT125281, 120mg, fasted	CORT125281 is supplied as capsules for oral dosing
DRUG	CORT125281, 360mg, fasted	CORT125281 is supplied as capsules for oral dosing
DRUG	CORT125281, 720mg, fasted	CORT125281 is supplied as capsules for oral dosing
DRUG	CORT125281, 360mg, fed	CORT125281 is supplied as capsules for oral dosing
DRUG	CORT125281, 360mg	CORT125281 is supplied as capsules for oral dosing twice, 12 hours apart, fasted (morning) and after evening meal
DRUG	CORT125281, 120mg	CORT125281 is supplied as capsules for oral dosing once daily
DRUG	CORT125281, 180mg	CORT125281 is supplied as capsules for oral dosing twice daily
DRUG	CORT125281, 240mg	CORT125281 is supplied as capsules for oral dosing twice daily
DRUG	CORT125281, 360mg	CORT125281 is supplied as capsules for oral dosing once daily
DRUG	Placebo oral capsule	Reference Therapy, Dose and Route of Administration: Placebo capsule, orally administered twice, 12 hours apart, fasted (morning) and after evening meal
DRUG	Placebo oral capsule	Reference Therapy, Dose and Route of Administration: Placebo capsule, orally administered, twice daily
DRUG	Placebo oral capsule	Reference Therapy, Dose and Route of Administration: Placebo capsule, orally administered, once daily

Timeline

• Start date: 2017-09-21
• Primary completion: 2018-05-31
• Completion: 2018-06-25
• First posted: 2017-11-08
• Last updated: 2018-07-26

Locations

1 site across 1 country: United Kingdom