Single and Multiple Dose Study of Miricorilant (CORT118335) Tablet Formulations in Healthy Participants

Study Overview
=================
Brief Summary
-----------------
This study will assess the safety, tolerability, and pharmacokinetics (PK) of miricorilant (CORT118335) tablet formulations following single and multiple oral administration in healthy participants.

Detailed Description
-----------------
Cohort 1 will evaluate safety, tolerability, and PK of single doses of a 150-mg and a new 300-mg tablet formulation of miricorilant. Cohort 1 treatment will be randomized and open label. Optional Cohorts 2 and 3 will evaluate single- and repeated-dose administration of miricorilant using a formulation, dose, and dose-regimen determined after interim evaluation of PK and safety data from previous cohorts. Cohort 2 and 3 treatments will be randomized, blinded, and placebo controlled.

Official Title
-----------------
A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of Miricorilant Tablet Formulations Following Single and Multiple Oral Doses in Healthy Participants

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Miricorilant 300 mg tablets
* Drug: Miricorilant 150 mg tablets
* Drug: Placebo 150 mg tablets


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Body mass index (BMI) of 18.0 to 30.0 kg/m^2 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 last 90 days Male participants who have pregnant or lactating partners History of any drug or alcohol abuse in the past 2 years Regular alcohol consumption: a confirmed positive alcohol breath test at screening or admission Current smokers and those who have smoked or used e-cigarettes or nicotine replacement products within the last 6 months Females of childbearing potential including those who are pregnant or lactating (all female subjects must have a negative serum pregnancy test at screening and a negative urine pregnancy test at 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, chronic respiratory, neurological or psychiatric disorder, as judged by the Investigator Any form of cancer within the last 2 years (exceptions apply) History and/or symptoms of adrenal insufficiency Regularly consumes liquorice or other glycyrrhetic acid derivatives History of clinically significant gastrointestinal disease Currently using glucocorticoids or have a history of systemic glucocorticoid use within the last 12 months or 3 months for inhaled products Presence or history of clinically significant allergy requiring treatment Donation or loss of greater than 400 mL of blood within the previous 3 months Taking, or have taken, any prescribed, over-the-counter drug (other than up to 4 g per day paracetamol) or vitamins/herbal remedies within 14 days. Exceptions may apply on a case by case basis Additional criteria apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Miricorilant 900 mg (Regimen A1)<br>Participants will receive a single oral dose of miricorilant 900 mg (3 X 300 mg) after breakfast on Day 1. Cohort 1 treatment will be randomized and open label. | Drug: Miricorilant 300 mg tablets<br>* Miricorilant 300 mg tablets for oral administration<br>* Other names: CORT118335;|
| Experimental: Cohort 1: Miricorilant 300 mg (Regimen A2)<br>Participants will receive a single oral dose of miricorilant 300 mg (2 X 150 mg) after breakfast on Day 1. Cohort 1 treatment will be randomized and open label. | Drug: Miricorilant 150 mg tablets<br>* Miricorilant 150 mg tablets for oral administration<br>* Other names: CORT118335;|
| Experimental: Cohort 2: Miricorilant (Regimen B1 and B2)<br>Participants will receive a single oral dose of miricorilant 900 mg (6 X 150 mg) after breakfast on Day 1 (Regimen B1). After a minimum 7-day washout, participants will receive miricorilant 900 mg (6 X 150 mg) qd for 14 days (Regimen B2). Day 1 treatment in Regimen B2 will be in the fasted state; the remaining doses will follow breakfast. Cohort 2 treatments will be randomized and blinded. | Drug: Miricorilant 150 mg tablets<br>* Miricorilant 150 mg tablets for oral administration<br>* Other names: CORT118335;|
| Placebo Comparator: Cohort 2: Placebo (Regimen B1 and B2)<br>Participants will receive a single oral dose of placebo matching miricorilant 900 mg (6 X 150 mg) after breakfast on Day 1 (Regimen B1). After a minimum 7-day washout, participants will receive placebo matching miricorilant 900 mg (6 X 150 mg) qd for 14 days (Regimen B2). Day 1 treatment in Regimen B2 will be in the fasted state; the remaining doses will follow breakfast. Cohort 2 treatments will be randomized and blinded. | Drug: Placebo 150 mg tablets<br>* Placebo to match miricorilant 150 mg tablets for oral administration<br>|
| Experimental: Cohort 3: Miricorilant (Regimen C1 and C2)<br>Participants will receive two oral doses (morning and evening) of miricorilant 1350 mg (9 X 150 mg) after a meal on Day 1 (Regimen C1). After a minimum 7-day washout, participants will receive miricorilant 750 mg (5 X 150 mg) after breakfast for 14 days and miricorilant 600 mg (4 X 150 mg) in the evening after a meal for 13 days (Regimen C2). Cohort 3 treatments will be randomized and blinded. | Drug: Miricorilant 150 mg tablets<br>* Miricorilant 150 mg tablets for oral administration<br>* Other names: CORT118335;|
| Placebo Comparator: Cohort 3: Placebo (Regimen C1 and C2)<br>Participants will receive two oral doses (morning and evening) of placebo matching miricorilant 1350 mg (9 X 150 mg) after a meal on Day 1 (Regimen C1). After a minimum 7-day washout, participants will receive placebo matching miricorilant 750 mg (5 X 150 mg) after breakfast for 14 days and placebo matching miricorilant 600 mg (4 X 150 mg) in the evening after a meal for 13 days (Regimen C2). Cohort 3 treatments will be randomized and blinded. | Drug: Placebo 150 mg tablets<br>* Placebo to match miricorilant 150 mg tablets for oral administration<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with One or More Adverse Events |  | Up to 7±2 days after the last dose (up to approximately Day 9 for Cohort 1 and up to approximately Day 23 for Cohorts 2 and 3) | 
| Percentage of Participants with One or More Serious Adverse Events |  | Up to 7±2 days after the last dose (up to approximately Day 9 for Cohort 1 and up to approximately Day 23 for Cohorts 2 and 3) | 
| Percentage of Participants Discontinued from the Study due to an Adverse Event |  | Up to 7±2 days after the last dose (up to approximately Day 9 for Cohort 1 and up to approximately Day 23 for Cohorts 2 and 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Pharmacokinetics (PK) of Miricorilant: Elapsed Time from Dosing at which the Analyte was First Quantifiable in a Concentration vs Time Profile (tlag) |  | Single-dose regimens: before dosing and at pre-specified time points up to 72 hours after dosing (Day 4) | 
| Plasma PK of Miricorilant: Maximum Observed Concentration (Cmax) |  | Single-dose regimens: before dosing and at pre-specified time points up to 72 hours after dosing (Day 4); Repeated-dose regimens: before dosing and at pre-specified time points up to 72 hours after final dose (Day 17) | 
| Plasma PK of Miricorilant: Time from Dosing at which Cmax was Apparent (Tmax) |  | Single-dose regimens: before dosing and at pre-specified time points up to 72 hours after dosing (Day 4); Repeated-dose regimens: before dosing and at pre-specified time points up to 72 hours after final dose (Day 17) | 
| Plasma PK of Miricorilant: Apparent Elimination Half-life (t1/2) |  | Single-dose regimens: before dosing and at pre-specified time points up to 72 hours after dosing (Day 4); Repeated-dose regimens: before dosing and at pre-specified time points up to 72 hours after final dose (Day 17) | 
| Plasma PK of Miricorilant: Area Under the Curve from Time Zero to the Last Measurable Concentration (AUC0-last) |  | Single-dose regimens: before dosing and at pre-specified time points up to 72 hours after dosing (Day 4) | 
| Plasma PK of Miricorilant: Area Under the Curve from Time Zero to 24 Hours Postdose (AUC0-24) |  | Repeated-dose regimens: before dosing and at pre-specified time points up to 72 hours after final dose (Day 17) |