Single and Multiple Ascending Dose Study of CORT125329 in Healthy Participants

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04672512
• Other study ID #: CORT125329-140
• Secondary ID: 2020-001741-38
• Status: Completed
• Phase: Phase 1
• Start date: October 23, 2020
• Est. completion date: January 17, 2022

Study information

• Verified date: February 2022
• Source: Corcept Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 115
• Est. completion date: January 17, 2022
• Est. primary completion date: January 17, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• CORT125329 lipid capsule formulation
CORT125329 lipid capsule formulation 1 or 2 for oral administration
• Placebo
Placebo matching CORT125329 lipid capsule formulation 1 or 2 for oral administration
• Prednisone
Prednisone tablet for oral administration

Locations

Country	Name	City	State
United Kingdom	Quotient Sciences	Ruddington	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
Corcept Therapeutics

Country where clinical trial is conducted

United Kingdom, 

Outcome

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