Clinical trial NCT03038022 (phase 2, status: completed)
Conditions: heterozygous familial hypercholesterolemia
ICD codes: E78.01, E78.00, Z83.42
Drugs: mgl-3196, placebo
SMILES: CC(C)C1=CC(OC2=C(Cl)C=C(C=C2Cl)N2N=C(C#N)C(=O)NC2=O)=NNC1=O, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
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 patients 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 (ie, condoms, diaphragm,
             non-hormonal intrauterine device [IUD], or sexual abstinence [only if this is in line
             with the patient's current lifestyle]) throughout the study and for at least 1 month
             after study completion; hormonal contraception (estrogens stable ≥3 months) and
             hormonal IUDs are permitted if used with a secondary birth control measure (eg,
             condoms); OR female patients of non-child bearing potential (ie, surgically [bilateral
             oophorectomy, hysterectomy, or tubal ligation] or naturally sterile [>12 consecutive
             months without menses]); male patients 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 patients 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 WHO/Dutch Lipid Network (score >8);

          -  Must have a fasting LDL-C ≥ 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 ≤ 20 mg daily, atorvastatin ≤ 80 mg daily), with or
             without ezetimibe.

        Exclusion Criteria:

          -  Homozygous familial hypercholesterolemia

          -  Low-density lipoprotein (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 (QTcF) >450 msec for males and >470 msec for females at the
             screening electrocardiogram (ECG) 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
             [HbA1c] >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 patients and >30 g/day in male patients;

          -  Thyroid replacement therapy;

          -  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). Patients with positive anti-HCV who test negative for
             HCV RNA at screening will be allowed to participate in the study;

          -  Serum alanine aminotransferase (ALT) >1.5 × ULN (one repeat allowed);

          -  Estimated glomerular filtration rate <60 mL/min;

          -  Creatine kinase >3 × 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
             patient.