Clinical trial NCT04672512: Single and Multiple Ascending Dose Study of CORT125329 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 CORT125329 in Healthy Subjects, With an Optional Pharmacological Effects Cohort
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Corcept Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-12-17
Enrollment: 115
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: The purpose of this study is to evaluate the dose-related safety, tolerability, pharmacokinetics (PK) and pharmacological effects (PD) of CORT125329 after single and multiple ascending oral doses of CORT125329 lipid capsule formulations in healthy participants.

Detailed description: This is a 3-part, single-center study of single and multiple ascending doses of CORT125329 in healthy participants.

Part 1 will be a double-blind, randomized, placebo-controlled assessment of single ascending doses (SAD) of CORT125329 lipid capsule formulations. Participants will be enrolled sequentially into 1 of up to 8 cohorts, each containing 8 participants.

Part 2 will be double-blind, randomized, placebo-controlled assessments of multiple oral ascending doses (MAD) of CORT125329 lipid capsule formulations. Participants will be enrolled sequentially into 1 of up to 4 cohorts, each containing 8 participants.

Optional Part 3 will be an open-label, 2-way fixed sequence cross-over study and will serve as proof of PD (glucocorticoid receptor modulation) for CORT125329 lipid capsule formulations. Participants will be enrolled in a single cohort of 10 participants.

Throughout the study, routine safety tests will be performed. In selected parts of the study, assessments of PK (CORT125329), changes in serum cortisol and plasma adrenocorticotrophic hormone (ACTH), and changes in hematological and bone biomarkers will be measured.

Eligibility criteria: Inclusion Criteria:

* Body mass index of 18.0 to 30.0 kg/m\^2
* Weight of ≤102 kg
* Must agree to adhere to the contraception requirements
* Additional criteria apply.

Exclusion Criteria:

* Received any investigational medicinal product in a clinical research study within the 90 days
* History of any drug or alcohol abuse in the past 2 years
* Regular alcohol consumption
* Current smokers and those who have smoked within the last 6 months
* Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 6 months
* Females of childbearing potential including those who are pregnant or lactating (all female subjects must have a negative pregnancy test at screening and admission)
* Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the Investigator
* Confirmed positive drugs of abuse test result
* Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
* Active renal and/or hepatic disease
* History of clinically significant cardiovascular, renal, hepatic, endocrine, metabolic, respiratory, GI, neurological or psychiatric disorder, as judged by the Investigator
* Any form of cancer within the last 5 years (exceptions apply)
* History and/or symptoms of adrenal insufficiency
* History of clinically significant gastrointestinal disease
* Has a condition that could be aggravated by glucocorticoid antagonism
* Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
* Presence or history of clinically significant allergy requiring treatment
* Donation or loss of greater than 400 mL of blood or plasma within the previous 3 months
* Are taking, or have taken, any prescribed, over-the-counter drug (other than 4 g per day paracetamol), vitamins or herbal remedies within 14 days before the study (exceptions may apply on a case by case basis)
* Are currently using glucocorticoids or have a history of systemic glucocorticoid use at any dose within the last 12 months or 3 months for inhaled products
* Additional criteria apply.

Primary outcomes:
measure: Percentage of Participants with One or More Adverse Events
timeFrame: SAD Cohorts: up to Day 11; MAD Cohorts: up to Day 23; PD Effect Cohort: up to Day 2 in Period 1 and up to Day 11 in Period 2
measure: Percentage of Participants with One or More Serious Adverse Events
timeFrame: SAD Cohorts: up to Day 11; MAD Cohorts: up to Day 23; PD Effect Cohort: up to Day 2 in Period 1 and up to Day 11 in Period 2
measure: Percentage of Participants Discontinued from the Study Due to an Adverse Event
timeFrame: SAD Cohorts: up to Day 11; MAD Cohorts: up to Day 23; PD Effect Cohort: up to Day 2 in Period 1 and up to Day 11 in Period 2
Secondary outcomes:
measure: Plasma Pharmacokinetics (PK) of CORT125329: Maximum Observed Concentration (Cmax)
timeFrame: SAD Cohorts: before dosing and at prespecified time points up to Day 11; MAD Cohorts: before dosing and at prespecified time points up to Day 23; PD Effect Cohort: before dosing and at prespecified time points up to Day 11 in Period 2
measure: Plasma PK of CORT125329: Elapsed Time from Dosing at which the Analyte was First Quantifiable in a Concentration vs Time Profile (tlag)
timeFrame: SAD Cohorts: before dosing and at prespecified time points up to Day 11; MAD Cohorts: before dosing and at prespecified time points up to Day 23; PD Effect Cohort: before dosing and at prespecified time points up to Day 11 in Period 2
measure: Plasma PK of CORT125329: Time from Dosing at which Cmax was Apparent (Tmax)
timeFrame: SAD Cohorts: before dosing and at prespecified time points up to Day 11; MAD Cohorts: before dosing and at prespecified time points up to Day 23; PD Effect Cohort: before dosing and at prespecified time points up to Day 11 in Period 2
measure: Plasma PK of CORT125329: Apparent Elimination Half-life (t1/2)
timeFrame: SAD Cohorts: before dosing and at prespecified time points up to Day 11; MAD Cohorts: before dosing and at prespecified time points up to Day 23; PD Effect Cohort: before dosing and at prespecified time points up to Day 11 in Period 2
measure: Plasma PK of CORT125329: Area Under the Curve from Zero Time to the Last Measurable Concentration (AUC0-last)
timeFrame: SAD Cohorts: before dosing and at prespecified time points up to Day 11; PD Effect Cohort: before dosing and at prespecified time points up to Day 11 in Period 2
measure: Plasma PK of CORT125329: Area Under the Curve During a Dosing Interval (AUC0-tau)
timeFrame: MAD Cohorts: before dosing and at prespecified time points up to Day 15
measure: Plasma PK of CORT125329: Area Under the Curve from Zero Time Extrapolated to Infinity (AUC0-inf)
timeFrame: SAD Cohorts: before dosing and at prespecified time points up to Day 11; PD Effect Cohort: before dosing and at prespecified time points up to Day 11 in Period 2
measure: Serum Cortisol
timeFrame: MAD Cohorts: before dosing in the morning of Days 1 and 14 and in the evening of Days -1 and 14
measure: Plasma Adrenocorticotrophic Hormone (ACTH)
timeFrame: MAD Cohorts: two samples taken before dosing in the morning of Days 1 and 14 and in the evening of Days -1 and 14
measure: Eosinophil Count
timeFrame: PD Effect Cohort: before dosing and at prespecified time points up to 24 hours after dosing in Period 1 and 2
measure: Lymphocyte Count
timeFrame: PD Effect Cohort: before dosing and at prespecified time points up to 24 hours after dosing in Period 1 and 2
measure: Neutrophil Count
timeFrame: PD Effect Cohort: before dosing and at prespecified time points up to 24 hours after dosing in Period 1 and 2
measure: Serum Osteocalcin
timeFrame: PD Effect Cohort: before dosing and at prespecified time points up to 24 hours after dosing in Period 1 and 2
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: