Study to Evaluate the Effects of a Cytochrome P450 2C19 Inhibitor on the Pharmacokinetics of Miricorilant

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the pharmacokinetics (PK) of miricorilant in the presence and absence of the strong cytochrome P450 [(CYP) 2C19] inhibitor, fluvoxamine, in healthy participants. Participants will receive a single dose of miricorilant under fed conditions with a standard breakfast after an overnight fast alone and in combination with once-daily doses of fluvoxamine. Blood samples will be collected at regular intervals for PK and safety analysis between admission and discharge from the clinical unit.

Official Title
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A Phase 1, Open-Label, Fixed-Sequence Crossover Study to Evaluate the Effect of a Strong Inhibitor of Cytochrome P450 2C19 on the Pharmacokinetics of Miricorilant in Healthy Subjects

Conditions
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Antipsychotic Induced Weight Gain, Non-alcoholic Steatohepatitis (NASH)

Intervention / Treatment
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* Drug: Miricorilant
* Drug: Fluvoxamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to understand a written informed consent Willing and able to comply with all study requirements including potential CYP 2C19 genotyping analysis Male participants must agree to use an adequate method of contraception Healthy men or non-pregnant, non-lactating healthy women of non-childbearing potential Body mass index of 19.0 to 32.0 kg/m^2 Body weight ≥50 kg. Exclusion Criteria: Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients Presence or history of clinically significant allergy requiring treatment. Hay fever is allowed unless it is active. Significant skin disease, including rash, food allergy, eczema, psoriasis, or urticaria History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease (except cholecystectomy), bleeding disorder, neurological or psychiatric disorder, as judged by the Investigator Poor venous access that limits phlebotomy Evidence of current SARS-CoV-2 infection Clinically significant abnormal clinical chemistry, hematology, or urinalysis as judged by the Investigator. Participants with Gilbert's Syndrome are allowed. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results Evidence of renal impairment at screening Positive highly sensitive serum pregnancy test at screening or admission. Those who are pregnant or lactating will be excluded. A woman is considered of childbearing potential unless she is permanently sterile or is postmenopausal. Clinically-significant ECG abnormalities or vital sign abnormalities at screening or at baseline Have received any study drug in a clinical research study within 30 days (or 5 half-lives if longer) prior to first dose of study medication Are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies (other than up to 2 g per day acetaminophen or COVID-19 vaccines) in the 14 days before study drug administration. Exceptions may apply. 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 Are taking, or have taken, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors within 3 months before study drug administration History of any drug or alcohol abuse in the past 2 years Regular alcohol consumption in men >21 units per week and women >14 units per week (1 unit = 12 oz 1 bottle/can of beer, 1 oz 40% spirit, or 5 oz glass of wine) Confirmed positive alcohol urine test at screening or admission Current smokers and those who have smoked within the last 12 months Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months Positive drugs of abuse test result Male participants with pregnant or lactating partners Donation of blood within 2 months or donation of plasma within 7 days prior to first dose of study medication Are, or are immediate family members of a study site or Sponsor employee Failure to satisfy the investigator of fitness to participate for any other reason.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Miricorilant - Fluvoxamine/Miricorilant<br>Participants will receive a single oral dose of miricorilant 600 mg on Days 1 and 10 and a single oral dose of fluvoxamine 50 mg on Days 4 to 12. | Drug: Miricorilant<br>* Miricorilant 6 x 100 mg coated tablets<br>* Other names: CORT118335;Drug: Fluvoxamine<br>* Fluvoxamine 50 mg tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration of miricorilant (Cmax) |  | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Days 1 and 10 | 
| Area under the curve from time zero to the time of last measurable plasma concentration of miricorilant (AUC0-last) |  | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Days 1 and 10 | 
| Area under the curve from time zero extrapolated to infinity of plasma concentration of miricorilant (AUC0-inf) |  | Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Days 1 and 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with one or more treatment-emergent adverse events (TEAEs) |  | Up to 30 days after study drug administration | 
| Number of participants with one or more serious adverse events (SAEs) |  | Up to 30 days after study drug administration | 
| Number of participants with a clinically-significant vital sign abnormality |  | Up to Day 13 | 
| Number of participants with a clinically-significant laboratory test abnormality |  | Up to Day 13 |