Clinical trial NCT04249323: Single and Multiple Ascending Dose Study of CORT113176 in Healthy Participants
Official title: A Phase 1 Adaptive Dose, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally Administered CORT113176 in Healthy Subjects, With an Optional Pharmacological Effects Cohort
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Adults
Lead sponsor: Corcept Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-01-30
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This is a 3-part, first-in-human study of single ascending doses (SAD; Part 1) and multiple ascending doses (MAD; Part 2) of CORT113176 in healthy participants; Part 3 is an optional part to investigate whether CORT113176 ameliorates the effects of prednisone on various pharmacodynamic (PD) endpoints. The 3 parts may not be conducted entirely sequentially provided that this is justified by pharmacokinetic (PK) and safety data obtained from completed cohorts. The first MAD cohort will not start until data are available from at least 2 SAD levels to allow MAD administration in the fasted state, or until after a food-effect cohort has been dosed in the SAD phase to allow MAD administration in the fed state. The expected exposure for the daily MAD level at steady state (taking into consideration potential accumulation on repeat dosing) must not exceed the highest exposure considered to be safe and well tolerated during preceding SAD cohorts.


Eligibility criteria: Inclusion Criteria:

* Body mass index (BMI) 18.0 to 30.0 kg/m\^2, inclusive
* Body weight ≤102 kg
* Willing to consume a high-fat breakfast, including pork
* Agrees to adhere to the contraception requirements of the protocol
* Additional criteria apply.

Exclusion Criteria:

* Received any investigational drug or device in a clinical research study within the last 90 days
* History of any drug or alcohol abuse in the last 2 years; a confirmed positive drugs of abuse test result
* Regular alcohol consumption; a confirmed positive alcohol breath test at screening
* Current smoker; a confirmed positive breath carbon monoxide reading; current user of e-cigarettes or nicotine replacement products in the last 6 months
* Female of childbearing potential, pregnant or breastfeeding
* Have a pregnant partner
* Clinically significant abnormal clinical chemistry, hematology, or urinalysis result
* Positive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), or human immunodeficiency virus (HIV)
* Active renal or hepatic disease
* History of clinically significant cardiovascular, renal, hepatic, endocrine, metabolic, respiratory, gastrointestinal, neurological, or psychiatric disorder
* Any form of cancer in the last 5 years (exceptions apply)
* History of adrenal insufficiency
* Have a condition that could be aggravated by glucocorticoid and/or mineralocorticoid blockade
* Currently using glucocorticoids or a history of systemic glucocorticoid use in the last 12 months or 3 months for inhaled products
* Additional criteria apply.

Primary outcomes:
measure: Number of Participants with One or More Adverse Events
timeFrame: Part 1 SAD Cohorts: up to Day 9; Part 2 MAD Cohorts: up to Day 23; Part 3 Cohort: up to Day 19
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of CORT113176
timeFrame: Before dosing and at pre-specified time points up to Day 9 (Part 1 SAD Cohorts), up to Day 23 (Part 2 MAD Cohorts), or Days 10-19 (Part 3 Cohort)
measure: Time of Cmax (Tmax) of CORT113176
timeFrame: Before dosing and at pre-specified time points up to Day 9 (Part 1 SAD Cohorts), up to Day 23 (Part 2 MAD Cohorts), or Days 10-19 (Part 3 Cohort)
measure: Apparent Elimination Half-life (t1/2) of Plasma CORT113176
timeFrame: Before dosing and at pre-specified time points up to Day 9 (Part 1 SAD Cohorts), up to Day 23 (Part 2 MAD Cohorts), or Days 10-19 (Part 3 Cohort)
measure: Area Under the Plasma Concentration-time Curve (AUC) of CORT113176
timeFrame: Before dosing and at pre-specified time points up to Day 9 (Part 1 SAD Cohorts), up to Day 23 (Part 2 MAD Cohorts), or Days 10-19 (Part 3 Cohort)
measure: Serum Cortisol
timeFrame: Predose on Days 1 and 14 (Part 2 MAD Cohorts)
measure: Serum Adrenocorticotropic Hormone (ACTH)
timeFrame: Predose on Days 1 and 14 (Part 2 MAD Cohorts)
Other outcomes:
Locations:
city: Ruddington
country: United Kingdom
facility: Quotient Sciences
state: Nottingham
Study officials:
affiliation: Quotient Sciences
name: Sharan Sidhu, MBChb, BAO, MRCS, MFPM
role: PRINCIPAL_INVESTIGATOR
References: