Drug Interaction Study of MGL-3196 With Clopidogrel

A Single Center, Open-Label, Drug Interaction Study of MGL-3196 With Clopidogrel in Healthy Subjects

The purpose of this study is to determine whether the single and multiple-dose pharmacokinetics (PK) of MGL-3196 are affected by co-administration with clopidogrel in healthy subjects.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 20
• 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: 18 years to 55 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)

• Female subjects must:

  • Be non-pregnant and non-lactating
  • For females of non-childbearing potential, female must have undergone one of the following sterilization procedures at least 6 months prior to first dosing: hysterscopic fertilization bilateral salpingectomy, tubal occlusion, hysterectomy, bilateral oophorectomy
  • For postmenopausal women, are considered postmenopausal if amenorrheic for at least 12 months without an alternative medical cause
  • For females of childbearing potential, must one of the following birth control methods: surgical sterilization of partner, hormonal contraceptives no prone to drug-drug interactions, hormonal oral contraceptive agents such as normal and low dose combined pills or progesterone only pills, physical barrier method (eg, male condom) in addition to spermicide, non-hormonal intrauterine device for at least 3 months prior to first dosing, total abstinence from sexual intercourse for at least 3 months prior to first dosing and through study completion
• 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 14 days beyond the last dose of study drug. No restrictions required for vasectomized male provided his vasectomy has been performed 3 months or more prior to Day 1. A male who has been vasectomized less than 3 months prior to study start must follow the same procedure as a non-vasectomized male.

Exclusion Criteria:

• Any clinically significant abnormal findings on physical examination, clinical laboratory tests or 12-lead ECG.
• Evidence or history of clinically significant hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, renal, hepatic, neurological or psychiatric disease.
• 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 per site standard procedures.
• 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 (Cholecystectomy is allowed).
• Abnormal screening ECG: including machine-read QTcF >450 msec in men and QTcF > 470 msec in women (confirmed by manual over read) 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, thyroid medication, 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.
• Participation in another clinical trial of an investigational drug (or medical device) within the last 30 days prior to the Day 1, or who have been exposed to more than four new chemical entities within 12 months prior to Day 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MGL-3196 100 mg tablet plus Clopidogrel 75 mg tablet	Drug: MGL-3196; Administered orally on the morning of Day 1; Multiple-dose administration of 100 mg MGL-3196 on Day 6 until Day 14; Drug: Clopidogrel; After one-day washout period after Day 1, loading dose of 300 mg clopidogrel administered on Day 3 and then, at approximately the same time each morning, 75 mg clopidogrel administered on Days 4 to 11

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC from the time of dosing of clopidogrel as affected by single and multiple daily dosing with MGL-3196 100 mg/day in healthy subjects	14 days
Pharmacokinetics (Cmax) of clopidogrel as affected by chronic dosing with MGL-3196 100 mg/day in healthy subjects	14 days

Collaborators and Investigators

• Sponsor: Madrigal Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2019
• Primary Completion (Actual): August 30, 2019
• Study Completion (Actual): September 14, 2019

Study Registration Dates

• First Submitted: December 10, 2020
• First Submitted That Met QC Criteria: December 10, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): December 28, 2020
• Last Update Submitted That Met QC Criteria: December 23, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: MGL-3196-12

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