Study of MGL-3196 in Patients With Heterozygous Familial... | NCT03038022

ID	Type	Description	Link
2016-002315-17	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
MGL-3196	Experimental	Study Drug	Drug: MGL-3196 (resmetirom)
Placebo	Placebo Comparator	Matching Placebo	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
MGL-3196 (resmetirom)	Drug	Oral	MGL-3196
Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mean Percent Change in LDL-C From Baseline To Week 12	LDL-C was determined by ultracentrifugation or direct measure. Least-squares (LS) mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.	Baseline up to Week 12

Secondary Outcomes

Measure	Description	Time Frame
Mean Change From Baseline to Week 12 of Free Thyroxine (T4)	T4 was assessed at each study visit.	Baseline up to Week 12
Mean Change From Baseline to Week 12 of Free Triiodothyronine (T3)	Free T3 was assessed at each study visit.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Must be willing to participate in the study and provide written informed consent;
Male and female adults ≥18 years of age;
Female participants of child bearing potential with negative serum pregnancy (beta human chorionic gonadotropin) test who are not breastfeeding, do not plan to become pregnant during the study, and agree to use effective birth control per locally agreed requirements; male participants who have sexual intercourse with a female partner of child bearing potential from the first dose of study drug until 1 month after study completion must either be surgically sterile (confirmed by documented azoospermia >90 days after the procedure) or agree to use a condom with spermicide. All male participants must agree not to donate sperm from the first dose of study drug until 1 month after study completion;
Must have a diagnosis of HeFH by genetic testing or by having met the diagnostic criteria for definite familial hypercholesterolemia outlined by the Simon Broome Register Group or World Health Organization/Dutch Lipid Network (score >8);
Must have had a fasting LDL-C (low density lipoprotein cholesterol) ≥2.6 mmol/L (100 mg/dL); and
Must be on a stable or maximally tolerated dose (≥4 weeks prior to screening) of an approved statin (rosuvastatin ≤40 mg daily, atorvastatin ≤80 mg daily), with or without ezetimibe. Patients intolerant to statins were allowed.

Exclusion Criteria:

Homozygous familial hypercholesterolemia
LDL or plasma apheresis within 2 months prior to randomization;
New York Heart Association class III or IV heart failure, or known left ventricular ejection fraction <30%;
Uncontrolled cardiac arrhythmia, including confirmed QT interval corrected using Fridericia's formula >450 msec for males and >470 msec for females at the screening electrocardiogram assessment;
Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft, or stroke within 3 months prior to randomization;
Type 1 diabetes, or newly diagnosed or uncontrolled type 2 diabetes (hemoglobin A1c >8%);
History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening; Note: Significant alcohol consumption is defined as average of >20 g/day in female participants and >30 g/day in male participants;
Hyperthyroidism;
Thyroid replacement therapy;
Hypothyroidism;
Evidence of chronic liver disease;
Hepatitis B, as defined by the presence of hepatitis B surface antigen;
Hepatitis C, as defined by the presence of hepatitis C virus (HCV) antibody (anti-HCV) and HCV ribonucleic acid (RNA). Participants with positive anti-HCV who test negative for HCV RNA at screening will be allowed to participate in the study;
Serum alanine aminotransferase >1.5 x upper limit of normal (ULN) (one repeat allowed);
Estimated glomerular filtration rate <60 mL/min;
Creatine kinase >3 x ULN (one repeat allowed);
History of biliary diversion;
Positive for human immunodeficiency virus infection;
History of malignant hypertension;
Systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg at screening or randomization and confirmed at an unscheduled visit;
Triglycerides >5.7 mmol/L (500 mg/dL) at screening and confirmed by repeat assessment;
Active, serious medical disease with likely life expectancy <2 years;
Active substance abuse, including inhaled or injection drugs within the year prior to screening;
Participation in an investigational new drug trial within the 30 days prior to randomization; or
Any other condition which, in the opinion of the Investigator, would impede compliance, hinder completion of the study, or compromise the well-being of the participants.

Name	Affiliation	Role
Rebecca Taub, MD	Madrigal Pharmaceuticals, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Madrigal Research Site		Aalborg			Denmark
Madrigal Research Site

PubMed Identifier	Type	Citation	Retractions
35331419	Derived	Hovingh GK, Klausen IC, Heggen E, McCarty K, Zhou R, Isaac BF, Taub R, Langslet G, Kastelein JJP. Resmetirom (MGL-3196) in Patients With Heterozygous Familial Hypercholesterolemia. J Am Coll Cardiol. 2022 Mar 29;79(12):1220-1222. doi: 10.1016/j.jacc.2022.01.023. No abstract available.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured pharmacokinetic (PK) assessments of MGL-3196 exposure.
FG001	Placebo

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 14, 2016	Nov 20, 2025

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00056.4± 12.38 BG00159.1± 11.33 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00039 BG00116 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Baseline Low-density Lipoprotein Cholesterol (LDL-C) (Direct measure or ultracentrifugation)

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG000131.4± 47.24 BG001137.0± 57.53 BG002

Statin Use

Count of Participants

Participants

Title

Denominators

Categories

Atorvastatin

Title	Measurements
	BG00040 BG00116 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Mean Percent Change in LDL-C From Baseline To Week 12

LDL-C was determined by ultracentrifugation or direct measure. Least-squares (LS) mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.

Modified Intent-to-Treat (mITT) population: all participants who were randomized in the study, received at least 2 weeks of study drug, and had a valid lipid measurement at Week 2 or later.

Posted

Least Squares Mean

Standard Error

percent change

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG00076 OG00137

Title

Denominators

Categories

Title	Measurements
	OG000-10.6± 2.59 OG0018.2± 3.71

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	LS mean difference in LDL-C between MGL-3196 and placebo.	ANOVA		<0.0001		Mean Difference (Net)	-18.8	Standard Error of the Mean	4.52	2-Sided	95	-27.8	-9.8					Superiority

Secondary

Mean Change From Baseline to Week 12 of Free Thyroxine (T4)

T4 was assessed at each study visit.

Safety population: all participants who were randomized in the study and received at least 1 dose of study drug.

Posted

Least Squares Mean

Standard Error

ng/dL

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Change From Baseline to Week 12 of Free Triiodothyronine (T3)

Free T3 was assessed at each study visit.

Safety population: all participants who were randomized in the study and received at least 1 dose of study drug.

Posted

Least Squares Mean

Standard Error

ng/L

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Change From Baseline to Week 12 of Thyrotropin (TSH)

TSH was assessed at each study visit.

Safety population: all participants who were randomized in the study and received at least 1 dose of study drug.

Posted

Least Squares Mean

Standard Error

mIU/L

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Change From Baseline to Week 12 of Thyroxine Binding Globulin (TBG)

TBG was assessed at all study visits except the Screening Visit.

Safety population: all participants who were randomized in the study and received at least 1 dose of study drug.

Posted

Least Squares Mean

Standard Error

mg/L

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Change From Baseline to Week 12 of Reverse Triiodothyronine (T3)

Reverse T3 was assessed at each study visit.

Safety population: all participants who were randomized in the study and received at least 1 dose of study drug.

Posted

Least Squares Mean

Standard Error

ng/dL

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 12

Non-HDL-C were determined by ultracentrifugation. LS mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor

Posted

Least Squares Mean

Standard Error

percent change

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured pharmacokinetic (PK) assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Percent Change In Triglycerides From Baseline To Week 12

Triglycerides were determined by ultracentrifugation. LS mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.

mITT population: all participants who were randomized in the study, received at least 2 weeks of study drug, and had a valid lipid measurement at Week 2 or later.

Posted

Least Squares Mean

Standard Error

percent change

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants

Secondary

Mean Percent Change In Lipoprotein(a) (Lp[a]) From Baseline To Week 12

Lp(a) was determined by ultracentrifugation. LS mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.

mITT population: all participants who were randomized in the study, received at least 2 weeks of study drug, and had a valid lipid measurement at Week 2 or later.

Posted

Least Squares Mean

Standard Error

percent change

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants

Secondary

Mean Percent Change in Apolipoprotein CIII From Baseline to Week 12

Apolipoprotein CIII was determined by ultracentrifugation. LS mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.

Posted

Least Squares Mean

Standard Error

percent change

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured pharmacokinetic (PK) assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Percent Change In Apolipoprotein B (ApoB) From Baseline To Week 12

ApoB was determined by ultracentrifugation. LS mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.

mITT population: all participants who were randomized in the study, received at least 2 weeks of study drug, and had a valid lipid measurement at Week 2 or later.

Posted

Least Squares Mean

Standard Error

percent change

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants

Secondary

Mean Percent Change in Apolipoprotein B/Apolipoprotein A1 (ApoB/ApoA1) Ratio From Baseline to Week 12

The ApoB/ApoA1 ratio was determined by ultracentrifugation. LS mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.

Posted

Least Squares Mean

Standard Error

percent change

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured pharmacokinetic (PK) assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Percent Change In Cholesterol/HDL-C Ratio From Baseline to Week 12

The Cholesterol/HDL-C Ratio was determined by ultracentrifugation. LS mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.

Posted

Least Squares Mean

Standard Error

percent change

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured pharmacokinetic (PK) assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Absolute Change in LDL-C From Baseline to Week 12

LDL-C was determined by ultracentrifugation or direct measure . Least-squares (LS) mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured pharmacokinetic (PK) assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in LDL-C at Week 2 and Week 4 in Patients in the 100 mg and the 60 mg Groups

Posted

Least Squares Mean

95% Confidence Interval

percent change

Baseline to Week 2 and Week 4

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured pharmacokinetic (PK) assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Percent Change in LDL-C From Baseline to Week 12 by Systemic Exposure Category

The effect on percent change in LDL-C from baseline to Week 12 was determined by patient exposure category (higher/lower). Patients taking MGL-3196 were categorized into lower and higher exposure groups. Patients in the higher exposure group must either have had estimated Week 2 AUC ≥5,000 mg∙h/L, or if Week 2 AUC <5,000 mg∙h/L but Week 4 pre-dose concentration >1.5 ng/mL (if on 60 mg MGL-3196). All other patients were in the lower exposure group.

mITT Population

Posted

Mean

Standard Error

percent change

Baseline to Week 12

ID	Title	Description
OG000	MGL-3196 Lower Exposure	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured pharmacokinetic (PK) assessments of MGL-3196 exposure.
OG001	MGL-3196 Higher Exposure	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured pharmacokinetic (PK) assessments of MGL-3196 exposure. Patients in the higher exposure group must either have had estimated Week 2 AUC ≥5,000 mg∙h/L, or if Week 2 AUC <5,000 mg∙h/L but Week 4 pre-dose concentration >1.5 ng/mL (if on 60 mg MGL-3196)

Secondary

Mean Change in Lipid Particle Concentration From Baseline To Week 12: Total LDL Particles

The effect of once-daily oral dosing of MGL-3196 versus placebo for 12 weeks in terms of change from baseline was assessed for LDL Particles.

Posted

Least Squares Mean

Standard Deviation

nmol/L

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Change in Lipid Particle Concentration From Baseline To Week 12: Small LDL Particles

The effect of once-daily oral dosing of MGL-3196 versus placebo for 12 weeks in terms of change from baseline was assessed for Small LDL Particles.

Posted

Least Squares Mean

Standard Deviation

nmol/L

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Change in Lipid Particle Concentration From Baseline To Week 12: Intermediate LDL Particles

The effect of once-daily oral dosing of MGL-3196 versus placebo for 12 weeks in terms of change from baseline was assessed for Intermediate LDL Particles.

Posted

Least Squares Mean

Standard Deviation

nmol/L

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Change in Lipid Particle Concentration From Baseline To Week 12: Large LDL Particles

The effect of once-daily oral dosing of MGL-3196 versus placebo for 12 weeks in terms of change from baseline was assessed for Large LDL Particles.

Posted

Least Squares Mean

Standard Deviation

nmol/L

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Change in Lipid Particle Concentration From Baseline To Week 12:Total Very Low-Density Lipoprotein (VLDL) and Chylomicron Particles

The effect of once-daily oral dosing of MGL-3196 versus placebo for 12 weeks in terms of change from baseline was assessed for VLDL and Chylomicron Particles.

Posted

Least Squares Mean

Standard Deviation

nmol/L

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Change in Lipid Particle Concentration From Baseline To Week 12: Total HDL Particles

The effect of once-daily oral dosing of MGL-3196 versus placebo for 12 weeks in terms of change from baseline was assessed for Total HDL Particles.

Posted

Least Squares Mean

Standard Deviation

micromol/L

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Change in Lipid Particle Concentration From Baseline To Week 12: LDL Particle Size

The effect of once-daily oral dosing of MGL-3196 versus placebo for 12 weeks in terms of change from baseline was assessed for LDL Particle size.

Posted

Least Squares Mean

Standard Deviation

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Change in Lipid Particle Concentration From Baseline To Week 12: VLDL Particle Size

The effect of once-daily oral dosing of MGL-3196 versus placebo for 12 weeks in terms of change from baseline was assessed for VLDL Particle Size.

Posted

Least Squares Mean

Standard Deviation

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Change in Lipid Particle Concentration From Baseline To Week 12: HDL Particle Size

The effect of once-daily oral dosing of MGL-3196 versus placebo for 12 weeks in terms of change from baseline was assessed for HDL Particle Size.

Posted

Least Squares Mean

Standard Deviation

Baseline up to Week 12

ID	Title	Description
OG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
OG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhea	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG00015 affected78 at risk EG0014 affected38 at risk
Nausea	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG00016 affected78 at risk EG0012 affected38 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0005 affected78 at risk EG0012 affected38 at risk
Flatulence	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0005 affected78 at risk EG0010 affected38 at risk
Vomiting	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0004 affected78 at risk EG0011 affected38 at risk
Abdominal Pain Upper	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0004 affected78 at risk EG0010 affected38 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0005 affected78 at risk EG0015 affected38 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected78 at risk EG0013 affected38 at risk
Muscle Spasms	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0004 affected78 at risk EG0010 affected38 at risk
Alanine aminotransferase increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0008 affected78 at risk EG0010 affected38 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0008 affected78 at risk EG0010 affected38 at risk
Hepatic enzyme increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0007 affected78 at risk EG0010 affected38 at risk
Nasopharyngitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG00010 affected78 at risk EG0016 affected38 at risk
Headache	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG00010 affected78 at risk EG0016 affected38 at risk
Dizziness	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0004 affected78 at risk EG0014 affected38 at risk
Fatigue	General disorders	MedDRA (19.0)	Systematic Assessment	EG0007 affected78 at risk EG0012 affected38 at risk
Night Sweats	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected78 at risk EG0012 affected38 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0002 affected78 at risk EG0012 affected38 at risk
Insomnia	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected78 at risk EG0012 affected38 at risk

ID	Title	Description
BG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.
BG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	MGL-3196	Participants randomized to MGL-3196 received 100 mg daily during the first 2 weeks, 60 mg daily during Weeks 2 to 4, and then either 60 or 100 mg daily to Week 12 based on Week 2 measured PK assessments of MGL-3196 exposure.	0	78	0	78	65	78
EG001	Placebo	Participants administered matching oral placebo once daily for 12 weeks.	0	38	1	38	28	38