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The purpose of this study is to directly characterize the pharmacokinetic (PK) profiles of MGL-3196 and its major metabolite (MGL-3623) following administration of multiple oral doses (QD x 6 days) in subjects with varying degrees of hepatic impairment (HI) compared to healthy matched control subjects with normal hepatic function, including a subset of NASH subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 40 mg MGL-3196 Tablet | Experimental | Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated |
|
| 60 mg MGL-3196 Tablet | Experimental | Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated |
|
| 80 mg MGL-3196 Tablet | Experimental | Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated |
|
| 100 mg MGL-3196 Tablet | Experimental | Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MGL-3196 | Drug | Once daily oral dose for 6 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Plasma pharmacokinetics - Cmax | Cmax after administration | 16 days |
| Plasma pharmacokinetics - Tmax | Tmax after administration | 16 days |
| Plasma pharmacokinetics - AUC (0-last) | AUC (0-last) after administration | 16 days |
| Plasma pharmacokinetics - t1/2 | t1/2 after administration | 16 days |
| Effect on the incidence of adverse events | 16 days |
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Inclusion Criteria:
Capable of understanding and willing and able to sign written informed consent
Male or female, between 18 and 85 years of age (inclusive)
BMI between 18 and 45 kg/m2 (inclusive)
In healthy subjects with normal hepatic function:
In subjects with hepatic impairment:
In subjects with NASH:
Exclusion Criteria:
Any clinically significant concomitant disease or condition (including treatment for such conditions) that, in the opinion of the Investigator, could either interfere with the study drug, pose an unacceptable risk to the subject, or compromise interpretation of study data
Gilbert's syndrome
Pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function that could interfere with the absorption, metabolism, and/or excretion of study drug
eGFR <60 mL/min/1.73 m2 based on Modification of Diet in Renal Disease (MDRD) equation
Received an investigational drug or device from another study within 30 days (or 5 half-lives, whichever is longer) prior to study drug administration
In healthy subjects with normal hepatic function:
In subjects with hepatic impairment:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Madrigal Research Center | Orlando | Florida | 32809 | United States | ||
| Madrigal Research Center |
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| Saint Paul |
| Minnesota |
| 55114 |
| United States |
| Madrigal Research Center | San Antonio | Texas | 78229 | United States |
| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| D008103 | Liver Cirrhosis |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C588408 | resmetirom |
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