Bioavailability Study of MGL-3196 Tablets Compared to Capsules

A Single Center, Open-Label, Single-Dose, Cross-over, Bioavailability Study of MGL-3196 Tablets Compared to Capsules in Healthy Subjects

The purpose of this study is to compare the pharmacokinetics of MGL-3196 capsules with MGL-3196 tablets in healthy male subjects and female subjects not of child-bearing potential.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: MGL-3196 Tablet; Drug: MGL-3196 Capsule

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must be willing and able to provide written informed consent.
• Healthy, non-smoking, male or female between the ages of 18 and 55 years inclusive.
• Body weight > 50 kg and BMI between 18 and 32 kg/m2 inclusive.
• if female, is of non-child bearing potential (i.e., surgically [bilateral oophorectomy, hysterectomy, hysteroscopic sterilization, or tubal ligation]. Or, is naturally sterile [>12 consecutive months without menses]) with verification by FSH at screening.
• If male and non-vasectomized, must agree to use a condom with spermicide or abstain from sexual intercourse from the first dose of study drug until 30 days beyond the last dose of study drug. No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to first dose of study drug. A male who has been vasectomized less than 4 months prior to study start must follow the same procedure as a non-vasectomized male.

Exclusion Criteria:

• Any clinically significant abnormal findings during physical examination including blood pressure, heart rate or rhythm, clinical laboratory tests or 12-lead ECG.
• Evidence or history of clinically significant hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, renal, hepatic, neurological or psychiatric disease.
• Thyroid stimulating hormone test at screening outside the normal range. Repeat testing is allowed once at the discretion of the Investigator.
• Current or recent (<6 months) hepatobiliary disease; or AST, ALT or direct bilirubin greater than the upper limit of reference range at screening. Repeat testing is allowed once at the discretion of the Investigator.
• Elevated CK at screening (one repeat test allowed).
• 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.
• Positive screening test for HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody.
• Abnormal screening ECG: including machine-read QTcF >450 msec (confirmed by manual over read), QRS >110 msec, intermittent bundle branch block, frequent premature atrial or premature ventricular contractions, or any rhythm other than normal sinus rhythm which is interpreted by the Investigator to be clinically significant.
• History of sensitivity to a similar study drug (e.g., Karo Bio KB2115 or Metabasis MB7811), or a history of important drug or other allergy (except for untreated, asymptomatic seasonal allergies at time of dosing) unless deemed not clinically significant by the Investigator.
• History of sensitivity to thyroid medication.
• History of intolerance to or adverse reaction to a statin, or history of myopathy including rhabdomyolysis.
• Intolerance to beta-blockers (beta-blocker treatment could be appropriate to alleviate tachycardia if observed).
• Participation in another clinical trial of an investigational drug (or medical device) within the last 30 days prior to the first dosing day, or who have been exposed to more than four new chemical entities within 12 months prior to the first dosing day.
• Donation of blood or blood loss in excess of 500 mL within 2 months prior to first dose of study drug.
• Use of prescription or non-prescription drugs, vitamins, herbal and dietary supplements within 7 days prior to the first dose of study drug.
• Use of St. John's Wort within 28 days before the first dose of study drug.
• Unwilling to forgo consumption of red wine, Seville oranges, grapefruit or grapefruit juice and/or pomelos, star fruit, grapefruit hybrids or other citrus juices from 5 days prior to the first dose of study drug and throughout the study.
• Subjects with a history of drug or alcohol abuse as defined by the Diagnostic and Statistical Manual 5th Edition.
• 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.
• Use of alcohol within 24 hours prior to screening, within 7 days before dosing, and throughout the study.
• Use of acetaminophen within 7 days before dosing and throughout the study.
• History of regular use of tobacco or nicotine containing products within the past 6 months relative to screening.
• Positive urine drug screen or alcohol test at screening or Day -1.
• Women who are pregnant or may become pregnant, or are nursing.
• Strenuous physical activity which could cause muscle aches or injury, including contact sports, at any time from 3 days prior to first dose of study drug until completion of the study.
• Excessive caffeine intake (>3 cups of coffee/day or equivalent).
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical disease (e.g., infectious disease) must not be enrolled.
• Any other sound medical, psychiatric, and /or social reason as determined by the Investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Capsule then Tablet; MGL-3196 Capsule on Day 1 followed by MGL-3196 Tablet on Day 5	Drug: MGL-3196 Tablet; MGL-3196 in Tablet form; Drug: MGL-3196 Capsule; MGL-3196 in Capsule form
Active Comparator: Tablet then Capsule; MGL-3196 Tablet on Day 1 followed by MGL-3196 Capsule on Day 5	Drug: MGL-3196 Tablet; MGL-3196 in Tablet form; Drug: MGL-3196 Capsule; MGL-3196 in Capsule form

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve from the time of dosing extrapolated to infinity (AUC(0-inf))	comparison between MGL-3196 capsules and MGL-3196 tablets	48 hours

Collaborators and Investigators

• Sponsor: Madrigal Pharmaceuticals, Inc.
• Collaborators: Celerion

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2018
• Primary Completion (Actual): February 17, 2018
• Study Completion (Actual): March 13, 2018

Study Registration Dates

• First Submitted: January 22, 2018
• First Submitted That Met QC Criteria: January 22, 2018
• First Posted (Actual): January 29, 2018

Study Record Updates

• Last Update Posted (Actual): September 18, 2019
• Last Update Submitted That Met QC Criteria: September 17, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: MGL-3196-08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No