NCT03315338

First-in-human Study in Healthy Subjects

A Phase I Adaptive Dose, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacological Effects of Orally Administered CORT118335 in Healthy Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 143 (actual)
• Sponsor: Corcept Therapeutics · Industry
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

Summary

This initial Phase I study will evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending doses of CORT118335, the effect of concomitant administration with food on exposure to CORT118335, and its pharmacological effect in healthy subjects.

Detailed description

This is a 5-part, single-center study of single and multiple ascending doses of CORT118335 in healthy subjects. Parts I and 4 of the study are double-blind, randomized, placebo-controlled assessments of single-ascending doses (SAD) of CORT118335. Subjects will be enrolled sequentially into 1 of up 8 cohorts (Part 1, Cohorts A to D \[Cohorts E to G have been cancelled\]; Part 4, Cohorts A to D), each containing 8 subjects. Within each cohort, 6 subjects will be randomly assigned to receive a single dose of CORT118335 and 2 subjects will be randomly assigned to receive a single dose of matching placebo. Part 2 Cohort A, food-effect, will be an open-label 2-way crossover study in one cohort of 12 subjects, randomized in a 1:1 ratio to receive a single dose of CORT118335 once after an overnight fast and once after a high-fat breakfast or the alternate sequence, over 2 study periods separated by a washout of at least 7 days/5 half-lives. Part 2 Cohort B, PD cohort, will be a double-blind, randomized, placebo-controlled, 3-way cross-over study and will serve as proof of pharmacological effect (GR modulation) for CORT118335. Subjects will be randomized in a 1:1:1 ratio to receive placebo, and two dose levels of CORT118335 in one of three treatment sequences across 3 study periods separated by washouts of at least 7 days/5 half-lives. On each occasion, the ability of CORT118335 to ameliorate the pharmacological effects of a single dose of prednisone will be measured. Parts 3 and 5 are double-blind, randomized, placebo-controlled assessments of multiple oral ascending doses of CORT118335. Subjects will be enrolled sequentially into 1 of up to 4 cohorts (Part 1 Cohort A \[Cohorts B to D have been cancelled; Part 5 Cohorts A to C), each containing 12 subjects. Within each cohort, 9 subjects will be randomly assigned to receive CORT118335 and 3 subjects to receive matching placebo daily for 14 days. Different formulations of CORT118335 will be used in Parts 1, 2 and 3, and in Parts 4 and 5.

Conditions

• Healthy

Interventions

Type	Name	Description
DRUG	CORT118335, 25 mg	CORT118335 is supplied as capsules for oral dosing
DRUG	Prednisone Oral Tablet	Challenge Agent, Dose and Route of Administration: Standard release 1x20mg and 1x5mg (25mg total) dose, orally administered.
DRUG	Glucose	75 g in 300 mL solution, orally administered
DRUG	Placebo oral suspension	Reference Therapy, Dose and Route of Administration: Placebo suspension, orally administered.
DRUG	CORT118335, 75mg	CORT118335 is supplied as capsules for oral dosing
DRUG	CORT118335, 225mg	CORT118335 is supplied as capsules for oral dosing
DRUG	CORT118335, 675mg	CORT118335 is supplied as capsules for oral dosing
DRUG	CORT118335, 600mg	CORT118335 is supplied as capsules for oral dosing
DRUG	CORT118335, 630mg	CORT118335 is supplied as capsules for oral dosing
DRUG	CORT118335, 375mg	CORT118335 is supplied as capsules for oral dosing
DRUG	CORT118335, 100mg	CORT118335 is supplied as a suspension for oral dosing
DRUG	CORT118335, 300mg	CORT118335 is supplied as a suspension for oral dosing
DRUG	CORT118335, 900mg	CORT118335 is supplied as a suspension for oral dosing
DRUG	CORT118335, 150mg	CORT118335 is supplied as a suspension for oral dosing
DRUG	CORT118335, 1500mg	CORT118335 is supplied as a suspension for oral dosing
DRUG	Placebo oral capsule	Placebo capsules, orally administered
DRUG	CORT118335, dose to be determined	CORT118335 is supplied as suspension for oral dosing

Timeline

• Start date: 2017-09-15
• Primary completion: 2019-02-22
• Completion: 2019-02-22
• First posted: 2017-10-20
• Last updated: 2019-05-24

Locations

1 site across 1 country: United Kingdom