Renal Impairment
Conditions
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.
Interventions
DRUG100 mg Resmetirom Tablet
Once daily oral dose for 6 days
Sponsors
Madrigal Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma pharmacokinetics - Cmax | 8 days | Cmax after administration |
| Plasma pharmacokinetics - Tmax | 8 days | Tmax after administration |
| Plasma pharmacokinetics - AUC(0-Last) | 8 days | AUC(0-Last) after administration |
| Plasma pharmacokinetics - t1/2 | 8 days | t1/2 after administration |
Secondary
| Measure | Time frame |
|---|---|
| Effect on the incidence of adverse events | 13 days |
Countries
United States
Outcome results
None listed