Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 2, Multi-Center, Double-Blind, Randomized, Placebo Controlled Study of MGL-3196 in Patients with Heterozygous Familial Hypercholesterolemia

    Summary
    EudraCT number
    		 2016-002315-17
    Trial protocol
    		 NO   DK   NL  
    Global end of trial date
    15 Jan 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Aug 2022
    First version publication date
    19 Aug 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MGL-3196-06
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03038022
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Madrigal Pharmaceuticals
    Sponsor organisation address
    200 Barr Harbor Drive, Conshohocken, PA, United States,
    Public contact
    Information, Madrigal Pharmaceuticals, Inc., +1 267-520-0252, info@madrgalpharma.com
    Scientific contact
    Information, Madrigal Pharmaceuticals, Inc., +1 267-520-0252, info@madrgalpharma.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    15 Jan 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    15 Jan 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Jan 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective was to determine the effect of once-daily oral dose of MGL-3196 and matching placebo after 12 weeks on the percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in participants with heterozygous familial hypercholesterolemia (HeFH).
    Protection of trial subjects
    This study was conducted in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 A placebo was used as a comparator to assess the safety and efficacy of the study drug.
    Actual start date of recruitment
    09 Feb 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 24
    Country: Number of subjects enrolled
    Norway: 43
    Country: Number of subjects enrolled
    Denmark: 49
    Worldwide total number of subjects
    116
    EEA total number of subjects
    116
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    81
    From 65 to 84 years
    35
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 137 participants diagnosed with HeFH were screened at 13 sites in Norway, Denmark and The Netherlands, of which 116 were randomized. Twenty-one participants failed screening, including 17 who failed to meet randomization criteria, 3 participants who withdrew, and 1 participant who was lost to follow-up.

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst
    Blinding implementation details
    Blinding was accomplished by providing visually indistinguishable MGL-3196 and placebo capsules. Packaging for MGL-3196 and placebo product was identical with the exception of a unique bottle identification number on the label.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MGL-3196
    Arm description
    		 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.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MGL-3196
    Investigational medicinal product code
    Other name
    Resmetirom
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received once-daily MGL-3196 hard gelatin capsule taken orally.

    Arm title
    		 Placebo
    Arm description
    		 Participants administered matching oral placebo once daily for 12 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received once-daily matching oral placebo.

    Number of subjects in period 1
    		MGL-3196 Placebo
    Started
    78
    38
    Received At Least 1 Dose of Study Drug
    78
    38
    Completed
    72
    36
    Not completed
    6
    2
         Adverse Event
    4
    2
         Withdrawal by Subject
    2
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    MGL-3196
    Reporting group description
    		 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.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants administered matching oral placebo once daily for 12 weeks.

    Reporting group values
    		 MGL-3196 Placebo Total
    Number of subjects
    		 78 38 116
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 56 25 81
        From 65-84 years
    		 22 13 35
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 56.4 ( 12.38 ) 59.1 ( 11.33 ) -
    Gender categorical
    Units: Subjects
        Female
    		 39 16 55
        Male
    		 39 22 61
    Race
    Units: Subjects
        Asian
    		 0 1 1
        White
    		 78 37 115
    Smoking
    Units: Subjects
        History of smoking
    		 4 3 7
        No history of smoking
    		 74 35 109
    Diabetes
    Units: Subjects
        History of diabetes
    		 3 4 7
        No history of diabetes
    		 75 34 109
    Hypertension
    Units: Subjects
        History of hypertension
    		 21 12 33
        No history of hypertension
    		 57 26 83
    ASCVD
    Units: Subjects
        History of ASCVD
    		 24 10 34
        No history of ASCVD
    		 54 28 82
    Ezetimibe
    Units: Subjects
        Participants using ezetimibe
    		 57 26 83
        Participants not using ezetimibe
    		 21 12 33
    Bile Acid Sequestrants
    Units: Subjects
        Participants using bile acid sequestrants
    		 6 4 10
        Participants not using bile acid sequestrants
    		 72 34 106
    Fish Oil or Omega-3
    Units: Subjects
        Participants using fish oil or Omega-3
    		 3 5 8
        Participants not using fish oil or Omega-3
    		 75 33 108
    PCSK9
    Units: Subjects
        Undergoing PCSK9 inhibitor treatment
    		 1 1 2
        Not undergoing PCSK9 inhibitor treatment
    		 77 37 114
    LDL Cholesterol ≥100 mg/dL
    Units: Subjects
        LDL Cholesterol <100 mg/dL
    		 15 12 27
        LDL Cholesterol ≥100 mg/dL
    		 63 26 89
    Lp(a) >10 nmol/L
    Units: Subjects
        Lp-a <10 nmol/L
    		 22 13 35
        Lp-a >10 nmol/L
    		 56 25 81
    HeFH
    Units: Subjects
        HeFH
    		 78 38 116
    Statin
    Units: Subjects
        None
    		 3 4 7
        Atorvastatin
    		 40 16 56
        Rosuvastatin
    		 34 17 51
        Pravastatin
    		 1 1 2
    BMI
    Units: kg/m^2
        arithmetic mean (standard deviation)
    		 28.51 ( 4.490 ) 27.69 ( 3.607 ) -
    Total Cholesterol
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 206.1 ( 54.74 ) 209.1 ( 57.97 ) -
    HDL Cholesterol
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 51.8 ( 13.92 ) 51.5 ( 13.00 ) -
    LDL-C (Screening)
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 137.1 ( 42.87 ) 140.3 ( 55.18 ) -
    LDL Cholesterol (Baseline - Direct)
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 131.4 ( 47.24 ) 137.0 ( 57.53 ) -
    LDL Cholesterol ≥100 mg/dL
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 142.2 ( 47.46 ) 153.6 ( 50.16 ) -
    Apolipoprotein B
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 106.9 ( 27.97 ) 111.1 ( 36.08 ) -
    Non-HDL Cholesterol
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 154.3 ( 54.25 ) 162.7 ( 68.73 ) -
    Apolipoprotein A1
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 144.3 ( 23.41 ) 144.4 ( 20.66 ) -
    Triglycerides
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 106.4 ( 57.93 ) 127.9 ( 89.27 ) -
    Lipoprotein-a
    Units: nmol/L
        arithmetic mean (standard deviation)
    		 84.3 ( 142.01 ) 67.6 ( 110.06 ) -
    Lp-a >10 nmol/L
    Units: nmol/L
        arithmetic mean (standard deviation)
    		 114.8 ( 157.70 ) 98.8 ( 125.25 ) -
    ApoB/ApoA1
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 0.757 ( 0.2306 ) 0.790 ( 0.3277 ) -
    Chol/HDL-C
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 4.184 ( 1.3620 ) 4.481 ( 2.1862 ) -
    Remnant Chol (Calc)
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 22.8 ( 10.34 ) 25.0 ( 15.16 ) -
    PCSK9
    Units: ng/mL
        arithmetic mean (standard deviation)
    		 571.37 ( 449.835 ) 595.05 ( 593.893 ) -
    Thyrotropin
    Units: mIU/L
        arithmetic mean (standard deviation)
    		 1.926 ( 1.0106 ) 2.226 ( 0.9998 ) -
    FT4
    Units: ng/dL
        arithmetic mean (standard deviation)
    		 1.134 ( 0.1506 ) 1.122 ( 0.1474 ) -
    FT3
    Units: ng/L
        arithmetic mean (standard deviation)
    		 3.06 ( 0.392 ) 3.05 ( 0.342 ) -
    Sex Hormone Binding Globulin
    Units: nmol/L
        arithmetic mean (standard deviation)
    		 56.017 ( 33.9798 ) 50.743 ( 26.7125 ) -
    Thyroxine Binding Globulin
    Units: mg/L
        arithmetic mean (standard deviation)
    		 18.10 ( 3.921 ) 16.88 ( 3.315 ) -
    Reverse T3
    Units: ng/dL
        arithmetic mean (standard deviation)
    		 14.76 ( 4.058 ) 14.98 ( 4.637 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    MGL-3196
    Reporting group description
    		 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.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants administered matching oral placebo once daily for 12 weeks.

    Primary: Percent Change In LDL-C From Baseline To Week 12

    		 Close Top of page
    End point title
    		 Percent Change In LDL-C From Baseline To Week 12
    End point description
    LDL-C was determined by ultracentrifugation. 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.
    End point type
    Primary
    End point timeframe
    Baseline to Week 12
    End point values
    		 MGL-3196 Placebo
    Number of subjects analysed
    76
    37
    Units: Percentage
        least squares mean (standard error)
    -10.6 ( 2.6 )
    8.2 ( 3.7 )
    Statistical analysis title
    		 Least Squares Mean Difference
    Comparison groups
    MGL-3196 v Placebo
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -18.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27.8
         upper limit
    		 -9.8
    Variability estimate
    Standard error of the mean

    Secondary: Percent Change In Triglycerides From Baseline To Week 12

    		 Close Top of page
    End point title
    		 Percent Change In Triglycerides From Baseline To Week 12
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 12
    End point values
    		 MGL-3196 Placebo
    Number of subjects analysed
    76
    37
    Units: Percentage
        least squares mean (standard error)
    -18.3 ( 3.2 )
    7.2 ( 4.6 )
    Statistical analysis title
    		 Least Squares Mean Difference
    Comparison groups
    Placebo v MGL-3196
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -25.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -36.7
         upper limit
    		 -14.2
    Variability estimate
    Standard error of the mean

    Secondary: Percent Change In Lp(a) From Baseline To Week 12

    		 Close Top of page
    End point title
    		 Percent Change In Lp(a) From Baseline To Week 12
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 12
    End point values
    		 MGL-3196 Placebo
    Number of subjects analysed
    76
    37
    Units: Percentage
        least squares mean (standard error)
    -21.8 ( 2.9 )
    4.4 ( 4.1 )
    Statistical analysis title
    		 Least Squares Mean Difference
    Comparison groups
    MGL-3196 v Placebo
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -26.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -36.2
         upper limit
    		 -16.4
    Variability estimate
    Standard error of the mean

    Secondary: Percent Change In ApoB From Baseline To Week 12

    		 Close Top of page
    End point title
    		 Percent Change In ApoB From Baseline To Week 12
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 12
    End point values
    		 MGL-3196 Placebo
    Number of subjects analysed
    76
    37
    Units: Percentage
        least squares mean (standard error)
    -14.2 ( 1.7 )
    3.8 ( 2.4 )
    Statistical analysis title
    		 Least Squares Mean Difference
    Comparison groups
    Placebo v MGL-3196
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.7
         upper limit
    		 -12.2
    Variability estimate
    Standard error of the mean

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to Week 12
    Adverse event reporting additional description
    Adverse event (AE) data are from the safety population. Although AEs for increased liver enzymes were reported in MGL-3196 participants, all elevations were asymptomatic and transient, related to absolute change in statin levels compared to baseline, and statistically significantly correlated with absolute change in statin, not MGL-3196.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    MGL-3196
    Reporting group description
    		 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.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants administered matching oral placebo once daily for 12 weeks.

    Serious adverse events
    		 MGL-3196 Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 38 (2.63%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 38 (2.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 MGL-3196 Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    65 / 78 (83.33%)
    28 / 38 (73.68%)
    Investigations
    Alanine aminotransferase (ALT) increased
    Additional description: Standard grading of ALT using CTCAE was not used by investigators. 7/8 AEs were mild (Grade [G] 1 >1XULN, <3XULN), clinically insignificant, asymptomatic, transient while remaining on IP; 1/8 AE was transient, asymptomatic G2 >3XULN, <5XULN.
         subjects affected / exposed
    8 / 78 (10.26%)
    0 / 38 (0.00%)
         occurrences all number
    8
    0
    Aspartate aminotransferase (AST) increased
    Additional description: Standard grading of AST using CTCAE was not used by investigators. All AEs were G1 (>1XULN, <3XULN), clinically insignificant, asymptomatic, transient while remaining on IP, associated with baseline elevations, alcohol or statin levels.
         subjects affected / exposed
    8 / 78 (10.26%)
    0 / 38 (0.00%)
         occurrences all number
    9
    0
    Hepatic enzyme increased
    Additional description: Standard CTCAE grading of liver enzymes was not used by investigators. 6/7 AEs: G1 (>1XULN, <3XULN) clinically insignificant and/or unconfirmed, transient while staying on IP; 1/7 AEs: ALT elevation off IP in FU period, resolved when statin withdrawn
         subjects affected / exposed
    7 / 78 (8.97%)
    0 / 38 (0.00%)
         occurrences all number
    7
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    2 / 78 (2.56%)
    2 / 38 (5.26%)
         occurrences all number
    2
    2
    Nervous system disorders
    Headache
         subjects affected / exposed
    10 / 78 (12.82%)
    6 / 38 (15.79%)
         occurrences all number
    13
    7
    Dizziness
         subjects affected / exposed
    4 / 78 (5.13%)
    4 / 38 (10.53%)
         occurrences all number
    4
    4
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    7 / 78 (8.97%)
    2 / 38 (5.26%)
         occurrences all number
    7
    2
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    15 / 78 (19.23%)
    4 / 38 (10.53%)
         occurrences all number
    22
    5
    Nausea
         subjects affected / exposed
    16 / 78 (20.51%)
    2 / 38 (5.26%)
         occurrences all number
    25
    3
    Abdominal Pain
         subjects affected / exposed
    5 / 78 (6.41%)
    2 / 38 (5.26%)
         occurrences all number
    5
    2
    Flatulence
         subjects affected / exposed
    5 / 78 (6.41%)
    0 / 38 (0.00%)
         occurrences all number
    7
    0
    Vomiting
         subjects affected / exposed
    4 / 78 (5.13%)
    1 / 38 (2.63%)
         occurrences all number
    6
    1
    Abdominal Pain Upper
         subjects affected / exposed
    4 / 78 (5.13%)
    0 / 38 (0.00%)
         occurrences all number
    5
    0
    Skin and subcutaneous tissue disorders
    Night Sweats
         subjects affected / exposed
    0 / 78 (0.00%)
    2 / 38 (5.26%)
         occurrences all number
    0
    2
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    1 / 78 (1.28%)
    2 / 38 (5.26%)
         occurrences all number
    1
    2
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    5 / 78 (6.41%)
    5 / 38 (13.16%)
         occurrences all number
    7
    6
    Arthralgia
         subjects affected / exposed
    2 / 78 (2.56%)
    3 / 38 (7.89%)
         occurrences all number
    3
    4
    Muscle Spasms
         subjects affected / exposed
    4 / 78 (5.13%)
    0 / 38 (0.00%)
         occurrences all number
    4
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    10 / 78 (12.82%)
    6 / 38 (15.79%)
         occurrences all number
    11
    6

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Nov 2016
    Amendment 1 (Denmark, The Netherlands, and Norway) - Added Exclusion Criteria #9 – Thyroid replacement therapy - Exclusion Criteria #10 – updated note regarding hypothyroidism - Exclusion Criteria #15 – changed eGFR rate from < 40 to < 60 mL/min - Treatment groups were changed from placebo, 80, and 120 mg to placebo and 100 mg and 60 mg groups. - The protocol employed an adaptive dose design. Participants, two-thirds of whom were randomized to MGL-3196 100 mg per day (one-third on placebo), received 100 mg for the first 2 weeks post-randomization, then received MGL-3196 60 mg between Weeks 2 and 4 visits. At Week 2 visit, a 4 hour post-dose PK sample was added and based on the results of that PK sample, at the Week 4 visit, participants randomized to MGL-3196 either continued on 60 mg or received 100 mg per day for the duration of the study. - Participants were instructed to take statins every evening starting 2 weeks before randomization and during the study, participants were to record the exact timing of statin intake the evening before the study visit. - Participants were to fast at least 10 hours before the study visits. - Language regarding a DSMB meeting was changed. - Drug Inducted Liver Injury Monitoring was added. - Additional secondary objectives were added. - Instructions on when participants should take their bile acid sequestrants were added.
    30 Dec 2016
    Amendment 2 (The Netherlands) -Removal of requirement for 30 min rest at Week 4 electrocardiogram (ECG) (Section 6.4.3) -Corrected the QTc assessment to QTcB assessment (Section 9.10)
    05 Jan 2017
    Amendment 2 (Norway) - Removal of requirement for 30 minutes rest at Week 4 ECG (Section 6.4.3) - Corrected QTc assessment to QTcB (Section 9.10)
    18 May 2017
    Amendment 3 (The Netherlands) - Update of inclusion criteria to allow for inclusion of participants with documented history of cardiovascular disease with a fasting LDL-C of >/= 1.8 mmol/L (70 mg/dL)
    18 May 2017
    Amendment 3 (Norway) - Update of inclusion criteria to allow for inclusion of participants with documented history of cardiovascular disease with a fasting LDL-C of >/= 1.8 mmol/L (70 mg/dL)
    18 May 2017
    Amendment 2 (Denmark) - Update of inclusion criteria to allow for inclusion of participants with documented history of cardiovascular disease with a fasting LDL-C of >/= 1.8 mmol/L (70 mg/dL)
    04 Jul 2017
    Amendment 3 (Denmark) -Change to allow rosuvastatin doses up to 40 mg. (Synopsis, Sections 1.2.1, 4.1, and 6.2). - Change to Inclusion Criteria #4 to allow up to 10% of study participants with probable HeFH based on a score of >=6, <=8 using World Health Organization (WHO)/Dutch criteria. (Synopsis and Section 4.1). - Update to Protocol Section 5.6.1 Excluded Medications and/or Procedures to allow up to 10% of study participants to be on stably dosed PCSK9 inhibitors (at least 3 months). - Added that for participants undergoing PCSK9 inhibitor treatment that the baseline and Week 12 visits occur within 5 days of the next scheduled PCSK9 inhibitor dose (Sections 6.4.1 and 6.4.5).
    04 Jul 2017
    Amendment 4 (The Netherlands) - Change to allow rosuvastatin doses up to 40 mg. (Synopsis, Sections 1.2.1, 4.1, and 6.2). - Change to Inclusion Criteria #4 to allow up to 10% of study participants with probable HeFH based on a score of >=6, <=8 using WHO/Dutch criteria. (Synopsis and Section 4.1). - Update to Protocol Section 5.6.1 Excluded Medications and/or Procedures to allow up to 10% of study participants to be on stably dosed PCSK9 inhibitors (at least 3 months). - Added that for participants undergoing PCSK9 inhibitor treatment that the baseline and week 12 visits occur within 5 days of the next scheduled PCSK9 inhibitor dose (Sections 6.4.1 and 6.4.5).
    04 Jul 2017
    Amendment 4 (Norway) - Change to allow rosuvastatin doses up to 40 mg. (Synopsis, Sections 1.2.1, 4.1, and 6.2). - Change to Inclusion Criteria #4 to allow up to 10% of study participants with probable HeFH based on a score of >=6, <=8 using WHO/Dutch criteria. (Synopsis and Section 4.1). - Update to Protocol Section 5.6.1 Excluded Medications and/or Procedures to allow up to 10% of study participants to be on stably dosed PCSK9 inhibitors (at least 3 months). - Added that for participants undergoing PCSK9 inhibitor treatment that the baseline and week 12 visits occur within 5 days of the next scheduled PCSK9 inhibitor dose (Sections 6.4.1 and 6.4.5).
    02 Aug 2017
    Amendment 4.1 (The Netherlands) - Restored Inclusion Criteria #4 to diagnosis of HeFH only. Removed possible inclusion of 10% of study participants with probable HeFH (Synopsis and Section 4.1).

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun Apr 28 18:06:51 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA