A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Multiple Oral Doses (6 Days) of 100 mg Resmetirom in Subjects With Severe Renal Impairment and in Matched Healthy Control Subjects With Normal Renal Function

A Phase 1, Multi-center, Open-label Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Multiple Oral Doses (6 Days) of 100 mg Resmetirom in Subjects With Severe Renal Impairment and in Matched Healthy Control Subjects With Normal Renal Function

The purpose of this study is to directly characterize the pharmacokinetic (PK) profiles of resmetirom and its major metabolite (MGL-3623) following oral administration of 100 mg resmetirom (QD x 6 days) in subjects with severe renal impairment (RI) compared to healthy matched control subjects with normal renal function.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: 100 mg Resmetirom Tablet

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Madrigal Research Center
    • Tampa, Florida, United States, 33603
      • Madrigal Research Center
  • Illinois
    • Chicago, Illinois, United States, 60643
      • Madrigal Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Capable of understanding the informed consent and willing and able to provide written informed consent.

Subjects with Severe Renal Impairment

• Body weight > 50 kg, BMI between 18.0 to 45.0 kg/m2, inclusive, at the screening visit.
• Impaired renal function with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, determined using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation at the screening visit and not requiring dialysis.
• Stable renal function with no clinically significant change in renal status at least 29 days prior to first dosing and is not currently or has not been previously on dialysis for at least 1 year.
• With exception of the known renal disease and stable comorbidities, is in otherwise good health, in the opinion of the Investigator, based on medical history, physical examination, vital sign measurements, ECG, and clinical laboratory tests performed at the screening and Day -1 visits.

Matched Healthy Control Subjects

• Must match the BMI (within ± 20%) of a subject with severe RI.
• Must match the age (± 10 years) and sex of a subject with severe RI.
• Normal renal function with eGFR ≥ 90 mL/min/1.73 m2, determined using the CKD-EPI creatinine equation (2021) at the screening and Day -1 visit.
• Must be in good health as determined by medical history, physical examination, vital sign measurements, ECG, and clinical laboratory tests at the screening and Day -1 visits.

Exclusion Criteria:

All Subjects

• Gilbert's syndrome.
• Pre-existing condition interfering with normal gastrointestinal anatomy or motility, or hepatic function that could interfere with the absorption, metabolism, and/or excretion of study drug (cholecystectomy is allowed).

Subjects with Severe Renal Impairment

• TSH < 0.3 or > 7 mIU/L at the screening or Day -1 visit.
• Evidence or history of clinically significant hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, neurological, or psychiatric disease, except for stable comorbidities.
• Has had a failed renal transplant or has had a nephrectomy.
• Has end stage renal disease requiring dialysis.
• Systolic blood pressure outside the range of 80 to 170 mmHg, diastolic blood pressure outside the range of 40 to 100 mmHg, or heart rate outside the range of 40 to 100 bpm at the screening or Day -1 visit.

Healthy Matched Control Subjects

• Current or recent (< 6 months from the screening visit) hepatobiliary disease; or serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), or direct bilirubin value greater than the upper limit of reference range at the screening or Day -1 visit.
• TSH outside normal range.
• Evidence or history of clinically significant hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, renal, hepatic, neurological, or psychiatric disease.
• Systolic blood pressure outside the range of 90 to 160 mmHg, diastolic blood pressure outside the range of 40 to 95 mmHg, or heart rate outside the range of 40 to 100 bpm at the screening or Day -1 visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Severe renal impairment	Drug: 100 mg Resmetirom Tablet; Once daily oral dose for 6 days; Other Names: Rezdiffra, MGL-3196
Experimental: Normal Healthy Match; Matched to severe renal impairment	Drug: 100 mg Resmetirom Tablet; Once daily oral dose for 6 days; Other Names: Rezdiffra, MGL-3196

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma pharmacokinetics - Cmax	Cmax after administration	8 days
Plasma pharmacokinetics - Tmax	Tmax after administration	8 days
Plasma pharmacokinetics - AUC(0-Last)	AUC(0-Last) after administration	8 days
Plasma pharmacokinetics - t1/2	t1/2 after administration	8 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Effect on the incidence of adverse events	13 days

Collaborators and Investigators

• Sponsor: Madrigal Pharmaceuticals, Inc.
• Investigators: Study Director: Geoff Rezvani, Madrigal Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2024
• Primary Completion (Actual): September 16, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: April 30, 2024
• First Submitted That Met QC Criteria: April 30, 2024
• First Posted (Actual): May 3, 2024

Study Record Updates

• Last Update Posted (Estimated): October 14, 2025
• Last Update Submitted That Met QC Criteria: October 10, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; resmetirom
• Other Study ID Numbers: MGL-3196-21

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No