Phase 1 Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Multiple Oral Doses of MGL-3196 in Subjects With Varying Degrees of Hepatic Impairment and Healthy Matched Control Subjects

NCT04643795 | Completed Phase 1 FDA Drug

• 1 other identifier: MGL-3196-10
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Hepatic Impairment; NASH - Nonalcoholic Steatohepatitis; Cirrhosis, Liver

Outcome Measures

Primary Outcomes (5)

• 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

Study Arms (4)

40 mg MGL-3196 Tablet

EXPERIMENTAL

Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated

Drug: MGL-3196

60 mg MGL-3196 Tablet

EXPERIMENTAL

Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated

Drug: MGL-3196

80 mg MGL-3196 Tablet

EXPERIMENTAL

Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated

Drug: MGL-3196

100 mg MGL-3196 Tablet

EXPERIMENTAL

Multiple cohorts (normal, varying hepatic impairment, NASH non-cirrhosis, and NASH cirrhosis) evaluated

Drug: MGL-3196

Interventions

MGL-3196 DRUG

Once daily oral dose for 6 days

100 mg MGL-3196 Tablet; 40 mg MGL-3196 Tablet; 60 mg MGL-3196 Tablet; 80 mg MGL-3196 Tablet

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Considered by the Investigator to be healthy, based on medical and surgical history, physical examination including vital signs, 12-lead ECG, and laboratory test results
• Match demographically with a subject in the hepatically impaired population according to gender, BMI (±20%), and age (±10 years)
• In subjects with hepatic impairment:
• Considered by the Investigator to be clinically stable with respect to underlying HI, based on medical and surgical history, physical examination including vital signs, 12-lead ECG, and laboratory test results
• In subjects with NASH:
• Confirmed diagnosis of NASH suggested by historical data, which include a previous liver biopsy within the last 5 years prior to randomization with evidence of NASH.
• BMI ≥18 kg/m2

You may not qualify if:

• 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:
• Systolic blood pressure outside the range of 90 to 150 mmHg, diastolic blood pressure outside the range of 40 to 95 mmHg or heart rate outside the range of 40 to 100 beats per minute (bpm)
• History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) within 6 months prior to screening
• In subjects with hepatic impairment:
• Any non-hepatic acute or chronic condition (including, but not limited to, poorly controlled diabetes and encephalopathy Grade ≥3) that, in the opinion of the Investigator, would limit the subject's ability to complete and/or participate in the study
• Acute exacerbation of HI or unstable hepatic function, as determined by the Investigator, 30 days prior to study drug administration
• Has had a Transjugular Intrahepatic Portosystemic Shunt (TIPS) procedure performed

Sponsors & Collaborators

• Madrigal Pharmaceuticals, Inc.: lead

Study Sites (3)

Madrigal Research Center

Orlando, Florida, 32809, United States

Location

Madrigal Research Center

Saint Paul, Minnesota, 55114, United States

Location

Madrigal Research Center

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Liver Cirrhosis

Interventions

resmetirom

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2020
• First Posted: November 25, 2020
• Study Start: October 25, 2018
• Primary Completion: August 4, 2021
• Study Completion: August 4, 2021
• Last Updated: October 5, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)