Drug Interaction Study of MGL-3196 With Rosuvastatin and Simvastatin

NCT02542969 | Completed Phase 1

• 1 other identifier: MGL-3196-03
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether MGL-3196 alters the pharmacokinetics of rosuvastatin and/or simvastatin in healthy male subjects and female subjects not of child-bearing potential.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• Area under the curve from the time of dosing extrapolated to infinity (AUC(0-inf)) of Rosuvastatin as affected by MGL-3196

  72 hours

• AUC(0-inf) of Simvastatin as affected by MGL-3196

  24 hours

Study Arms (1)

Treatment

OTHER

Simvastatin followed by Rosuvastatin then MGL-3196 daily followed by separate co-administration of Simvastatin and Rosuvastatin

Drug: Simvastatin; Drug: Rosuvastatin; Drug: MGL-3196

Interventions

Simvastatin DRUG

Also known as: Zocor

Treatment

Rosuvastatin DRUG

Also known as: Crestor

Treatment

MGL-3196 DRUG

Also known as: VIA-3196

Treatment

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 follicle stimulating hormone (FSH) at screening.
• If male and non-vasectomized, must agree to use a condom with spermicide or abstain from sexual intercourse during the study 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.

You may not qualify if:

• 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 aspartate aminotransferase (AST), alanine aminotransferase (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 creatine kinase (CK) at screening (one repeat test allowed).
• Gilbert's syndrome.
• Positive screening test for HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody.
• Abnormal screening ECG: including machine-read QTc \>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.
• 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.

Sponsors & Collaborators

• Madrigal Pharmaceuticals, Inc.: lead
• Celerion: collaborator

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

Simvastatin; Rosuvastatin Calcium; resmetirom

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Gerri Poss, MD

  Celerion

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2015
• First Posted: September 7, 2015
• Study Start: September 1, 2015
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: September 2, 2022

Record last verified: 2015-09

Locations

US (1)