An Open-Label Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Bempedoic Acid in Pediatric Patients (6 to 17 Years of Age) with Heterozygous Familial Hypercholesterolemia
- Conditions
- Familial HypercholesterolemiaHeterozygous Familial Hypercholesterolemia10027424
- Registration Number
- NL-OMON53717
- Lead Sponsor
- Esperion Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 15
1. The patient*s parent(s)/guardian(s) must be willing to provide written
informed consent and the patient must provide informed assent before any
study-specific procedures are performed;
2. The patient must be aged 6-17 years old;
3. The patient must weigh at least 16 kg;
4. The patient must have a diagnosis of HeFH per MEDPED criteria by meeting at
least one of the following clinical criteria*
a. Documented diagnosis of HeFH determined by positive genetic testing; or
b. Documented LDL-C or TC meeting one or more of the following criteria:
i. LDL-C >200 mg/dL (5.2 mmol/L) or total cholesterol (TC) >270 mg/dL (7.0
mmol/L), with no first- second- or third-degree relative with documented FH
diagnosis (general population); or
ii. LDL-C >155 mg/dL (4.0 mmol/L) or TC >220 mg/dL (5.7 mmol/L), and also
having a first-degree relative with documented familial hypercholesterolemia
(FH) diagnosis; or
iii. LDL-C >165 mg/dL (4.3 mmol/L) or TC >230 mg/dL (5.9 mmol/L), and also
having a second-degree relative with documented FH diagnosis; or
iv. LDL-C >170 mg/dL (4.4 mmol/L) or TC >240 mg/dL (6.2 mmol/L), and also
having a third-degree relative with documented FH diagnosis
5. Current treatment with approved stable LMTs, including optimal dose of
statin +/- other LMT(s), at stable dose for at least 4 weeks prior to screening
Visit S1 (6 weeks for fibrates; however, gemfibrozil is not allowed in patients
taking a statin as per co-administration instructions defined in the statin
label) and must remain on that stable dose throughout the duration of the
trial.
6. The patient must have a fasting LDL-C level >=130 mg/dL (3.4 mmol/L);
7. The patient may be male or female. Females must not be pregnant (or planning
to become pregnant within 30 days after the last dose of investigational
medicinal product [IMP]) breastfeeding and must be sexually inactive or willing
to use 1 acceptable method of birth control. The minimal requirement for use
of acceptable contraception is from the time the informed consent form (ICF) is
signed, during the study period, and for at least 30 days after the last dose
of IMP.
1. The patient has a diagnosis of HoFH or compound HeFH;
2. The patient has a fasting triglyceride (TG) level >=400 mg/dL (4.5 mmol/L);
3. The patient has uncontrolled hypothyroidism, including a value for
thyroid-stimulating hormone (TSH) < lower limit of normal (LLN) or >1.5 × the
upper limit of normal (ULN);
4. The patient has liver disease or dysfunction, including:
a. positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C
virus antibodies (HCV-AB), or
b. serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
value >=2 × ULN and/or serum total bilirubin (TB) value >=2 × ULN. If the serum
TB value is >=1.2 × ULN, a reflex indirect (unconjugated) bilirubin will be
obtained and, if consistent with Gilbert*s disease or if the patient has a
history of Gilbert*s disease, the patient may be enrolled in the study.
5. The patient has renal dysfunction or glomerulonephritis, including an
estimated glomerular filtration rate (eGFR) <75 mL/min/1.73 m2 (as determined
by the central laboratory using the Revised [*Bedside*] Schwartz formula);
6. The patient has Stage 2 hypertension (based on gender, age and height;
7. The patient has a gastrointestinal condition that may affect drug
absorption;
8. The patient has a history of hematologic or coagulation disorders, anemia,
or a hemoglobin (Hgb) level <11.5 g/dL;
9. The patient has type 1 or type 2 diabetes, or newly diagnosed impaired
glucose tolerance (within 3 months of Screening);
10. The patient had an active malignancy, including those requiring surgery,
chemotherapy, and/or radiation, in the past 5 years. Nonmetastatic basal or
squamous cell carcinoma of
the skin and cervical carcinoma in situ are allowed;
11. The patient has an unexplained (ie, not associated with recent trauma or
physically strenuous activity) serum creatine kinase (CK) value >3 × ULN at any
time before randomization. Patients with an explained elevation in serum CK
must have single repeat serum CK value <=3 × ULN before enrollment;
12. The patient has a history of drug or alcohol abuse within the last 2 years
or is unwilling to refrain from alcohol consumption for the duration of the
study, or uses any illicit drugs, or has a history of amphetamine or
derivatives abuse or cocaine abuse. Patients who are using amphetamine
derivatives prescribed by and who are under the care of a health care
practitioner can be enrolled after evaluation by the Investigator;
13. The patient has donated blood, undergone multiple blood draws in a clinical
study, experienced major trauma, received a blood transfusion, or undergone
surgery, with or without blood loss, within 30 days before enrollment;
14. The patient has used any experimental or investigational drugs within 30
days before screening and throughout the trial;
15. The patient has previously participated in a clinical study of bempedoic
acid;
16. The patient is taking any of the following medications or therapies, except
as indicated below:
a. Mipomersen or lomitapide (current or within 6 months of Screening).
b. PCKS9 inhibitors including evolocumab or alirocumab (current or within 3
months of Screening).
c. Lipid apheresis (current or within 8 weeks of Screening or intends to have
lipid apheresis treatments throughout the trial).
d. Systemic corticosteroid
Study & Design
- Study Type
- Observational invasive
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• Observed trough plasma concentration of ETC-1002 following 8 weeks of<br /><br>steady-state dosing of bempedoic acid<br /><br>• Model-based PK parameters including steady-state estimates of:<br /><br>* area under the plasma concentration-time curve (AUCss),<br /><br>* average plasma concentration (Cavg,ss) and<br /><br>* maximum plasma concentration (Cmax,ss)</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Endpoints<br /><br>• Observed trough plasma concentration of ESP15228 (active metabolite)<br /><br>following 8 weeks of steady-state dosing of bempedoic acid<br /><br>• Plasma concentration at 4 hours (C4hr) of ETC-1002 and ESP15228 following<br /><br>first dose<br /><br>• ETC-1002 dose and exposure/LDL-C-lowering response relationship.<br /><br>• Percent and absolute change from baseline to Weeks 8 and 16 in LDL-C, TC,<br /><br>non-HDL-C, and hsCRP.<br /><br>• Evaluation of acceptability (taste and ease of swallowing) of the<br /><br>age-appropriate formulations.<br /><br><br /><br>Safety Endpoints<br /><br>• Adverse events;<br /><br>• Clinical safety laboratories (hematology, clinical chemistry, and urinalysis);<br /><br>• Vital signs;<br /><br>• Electrocardiogram (ECG) readings;<br /><br>• Physical examinations (PEs)</p><br>