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

NCT ID: NCT06397872

Last Updated: 2025-10-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-06
• Study Completion Date: 2024-12-31

Brief Summary

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.

Conditions

Renal Impairment

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Severe renal impairment

Group Type: EXPERIMENTAL

100 mg Resmetirom Tablet

Intervention Type: DRUG

Once daily oral dose for 6 days

Normal Healthy Match

Matched to severe renal impairment

Group Type: EXPERIMENTAL

100 mg Resmetirom Tablet

Intervention Type: DRUG

Once daily oral dose for 6 days

Interventions

100 mg Resmetirom Tablet

Once daily oral dose for 6 days

Intervention Type: DRUG

Other Intervention Names

Rezdiffra, MGL-3196

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Madrigal Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Geoff Rezvani

Role: STUDY_DIRECTOR

Madrigal Pharmaceuticals, Inc.

Locations

Madrigal Research Center

Orlando, Florida, United States

Madrigal Research Center

Tampa, Florida, United States

Madrigal Research Center

Chicago, Illinois, United States

Countries

United States

Other Identifiers

MGL-3196-21

Identifier Type: -

Identifier Source: org_study_id