Clinical trial NCT04994743: Safety, Tolerability, and Pharmacokinetic Study of CORT113176 in Healthy Participants
Official title: Multiple Dose Safety, Tolerability, Plasma and Cerebrospinal-Fluid Pharmacokinetic Study of Oral Doses of CORT113176
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Adults
Lead sponsor: Corcept Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-08-06
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a safety, tolerability, and pharmacokinetic study in 2 cohorts of healthy male participants with an option for an additional cohort. Cohorts 1 and 2 will receive once daily by mouth CORT113176 150 mg and 300 mg, respectively, for 14 days under fed conditions. Progression from Cohort 1 to Cohort 2 will be done based on the safety and tolerability outcome in Cohort 1 and after Cohort 1 has received the study drug for at least 7 days. The optional Cohort 3 may receive a higher dose that will not exceed CORT113176 450 mg once daily by mouth for 14 days under fed conditions. The progression from Cohort 2 to the optional cohort (Cohort 3) will be based on the same precautions as with the progression from Cohort 1 to Cohort 2. Each participant will undergo safety evaluations. Pharmacokinetics of CORT113176 will be assessed in plasma and cerebrospinal fluid (CSF) samples. Pharmacodynamic assessments will include the measurement of serum cortisol.


Eligibility criteria: Inclusion Criteria:

* Body mass index (BMI) of 18.0 to 30.0 kg/m\^2, inclusive
* Body weight ≤100 kg.
* Must agree to adhere to the requirements on contraception, exposure to sexual partners, and sperm donation as defined in the protocol
* Additional criteria apply.

Exclusion Criteria:

* Received any investigational drug in a clinical research study within the last 90 days
* History of alcohol abuse or drug addiction (including soft drugs like cannabis products) within past 5 years.
* Regular alcohol consumption
* Positive drug, nicotine (cotinine), or alcohol screen
* Current smokers, user of e-cigarettes and nicotine replacement products and those who have used these products within the last 3 months
* Have a pregnant partner
* Clinically significant abnormal clinical chemistry, hematology (including coagulation), or urinalysis
* Positive hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) results
* Positive nasopharyngeal polymerase chain reaction (PCR) test for severe acute respiratory syndrome Covid Virus-2 (SARS-CoV-2) on Day -1 or within 8 weeks prior to screening.
* Contact with COVID-19 positive (or suspected) persons within 14 days prior to first dose
* Active renal and/or hepatic disease
* History of clinically significant cardiovascular, renal, hepatic, endocrine, metabolic, respiratory, gastrointestinal (GI), neurological, or psychiatric disorder
* Abnormalities in brain and lumbar spine, or other medical or surgical conditions or clinically significant abnormal findings, for which lumbar puncture is contraindicated
* History of clinically significant back pain, back pathology and/or back injury
* History of significant active bleeding or coagulation disorder or have taken non-steroidal anti-inflammatory drugs or other drugs that affect coagulation or platelet function within 14 days prior to lumbar puncture
* Allergy to lidocaine (Xylocaine®) or its derivatives
* Any form of cancer within the 5 years (exceptions apply)
* History and/or symptoms of adrenal insufficiency
* Have a condition that could be aggravated by glucocorticoid antagonism
* Donation or loss of greater than 400 mL of blood within the previous 3 months
* 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: Number of Participants with One or More Adverse Events
timeFrame: Up to Day 28
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of CORT113176
timeFrame: Before dosing and a pre-specified time points up to Day 17
measure: Time of Cmax (Tmax) of Plasma CORT113176
timeFrame: Before dosing and a pre-specified time points up to Day 17
measure: Apparent Elimination Half-life (t1/2) of Plasma CORT113176
timeFrame: Before dosing and a pre-specified time points up to Day 17
measure: Area Under the Plasma Concentration-time Curve (AUC) of Plasma CORT113176
timeFrame: Before dosing and a pre-specified time points up to Day 17
measure: Cerebrospinal Fluid Concentration of CORT113176
timeFrame: Approximately 3 and 5 hours after dosing on Day 7
measure: Serum Concentration of Cortisol
timeFrame: Before and approximately 12 hours after dosing on Days 1, 7, and 14
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: Site 01
Study officials:
affiliation: Corcept Therapeutics
name: Hazel Hunt, Ph.D.
role: STUDY_DIRECTOR
References: