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

Renal Impairment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06397872
• Other study ID #: MGL-3196-21
• Status: Enrolling by invitation
• Phase: Phase 1
• Start date: March 5, 2024
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2024
• Source: Madrigal Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 28
• Est. completion date: December 31, 2024
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• 100 mg Resmetirom Tablet
Once daily oral dose for 6 days

Locations

Country	Name	City	State
United States	Madrigal Research Center	Chicago	Illinois
United States	Madrigal Research Center	Orlando	Florida
United States	Madrigal Research Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Madrigal Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma pharmacokinetics - Cmax	Cmax after administration	8 days
Primary	Plasma pharmacokinetics - Tmax	Tmax after administration	8 days
Primary	Plasma pharmacokinetics - AUC(0-Last)	AUC(0-Last) after administration	8 days
Primary	Plasma pharmacokinetics - t1/2	t1/2 after administration	8 days
Secondary	Effect on the incidence of adverse events		13 days