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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Corcept Therapeutics
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Area under the curve from time zero extrapolated to infinity of plasma concentration of miricorilant (AUC0-inf)
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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.
Arms & Interventions
Miricorilant - Fluvoxamine/Miricorilant
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.
Intervention: Miricorilant (Drug)
Miricorilant - Fluvoxamine/Miricorilant
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.
Intervention: Fluvoxamine (Drug)
Outcomes
Primary Outcomes
Area under the curve from time zero extrapolated to infinity of plasma concentration of miricorilant (AUC0-inf)
Time Frame: 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
Maximum observed plasma concentration of miricorilant (Cmax)
Time Frame: 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)
Time Frame: 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 Outcomes
- Number of participants with one or more treatment-emergent adverse events (TEAEs)(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 one or more serious adverse events (SAEs)(Up to 30 days after study drug administration)
- Number of participants with a clinically-significant laboratory test abnormality(Up to Day 13)