E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Homozygous Familial Hypercholesterolemia (HoFH) |
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E.1.1.1 | Medical condition in easily understood language |
patients with extremely high LDL-C levels due to genetic mutations affecting ability to remove cholesterol from their blood |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
In adults with HoFH on a stable dose regimen of statin ± other lipid-lowering
medications, evaluate the effects of adding anacetrapib 100 mg for 12 weeks relative to placebo on
plasma concentrations of LDL-C and summarize the safety and tolerability of 12 weeks of treatment |
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E.2.2 | Secondary objectives of the trial |
In adults with HoFH on a stable dose regimen of statin ± other lipid-lowering
medications, evaluate the effects of anacetrapib 100 mg on HDL-C and ApoA-1 relative to placebo after 12 weeks of treatment and summarize the safety and tolerability of up to 64 weeks of treatment with anacetrapib100 mg.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Patient is male or female and 18 years of age on day of signing informed consent.
-Patient is diagnosed with HoFH by genotyping as defined by documented mutations causing familial hypercholesterolemia in both alleles of LDLR including, but not limited to a LDLR null mutation.
-A patient who is of reproductive potential agrees to remain abstinent* or use (or have their partner use) 2 acceptable methods of birth control for the duration of the study.
-Patients have been stabilized on statin monotherapy or statin therapy coadministered with other lipid medications for at least 6 weeks prior to randomization along with adequate stabilization of LDL apheresis regimen. A new lipid-modifying therapy or apheresis regimen should not be initiated during the first 12 weeks after randomization, but can be initiated at any time during the open-label extension.
-Patient provides written informed consent/assent for the trial.
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E.4 | Principal exclusion criteria |
Patient has a triglyceride value >400 mg/dL (6.78 mmol/L), creatine kinase (CK) >2x upper limit of normal (ULN), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2x upper limit of normal (ULN) [per central laboratory reference ranges].
-Patient has severe chronic heart failure defined by New York Heart Association (NYHA) Classes III or IV or uncontrolled cardiac arrhythmias, MI, PCI, CABG, unstable angina or stroke within 3 months prior to Visit 1 or has planned procedures scheduled within the first 12-weeks of the study.
-Patient has uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins, thyroid stimulating hormone (TSH) values outside the central laboratory normal ranges or chronic hepatobiliary or gall bladder disease.
-Patient has eGFR <30 mL/min/1.73m2 based on 4-variable MDRD equation, nephrotic syndrome or other clinically significant renal disease.
-Patient is pregnant or breast-feeding or plans to become pregnant during the study or
within 2 years of stopping study medication.
-Patient has history of ileal bypass, gastric bypass, or other significant condition associated with malabsorption.
-Patient is human immunodeficiency virus (HIV) positive.
- Patient has donated blood products or has had phlebotomy of >300 mL within 8 weeks of signing informed consent (excluding apheresis), or intends to donate 250 mL of blood products or receive blood products within the projected duration of the study.
- Patient has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might confound the results of the study, or interfere with the patient’s participation for the full duration of the study, such that it is not in the best interest of the patient to participate.
-Patient is currently taking medications that are potent inhibitors or inducers of CYP3A4 or has discontinued treatment <3 weeks prior to Visit 1. Consumption of >1 liter of grapefruit juice per day is also prohibited.
-Patient is currently participating or has participated in a study with an investigational compound or device within 3 months of signing informed consent.
-Patient consumes more than 2 alcoholic drinks per day.
- Patient is receiving treatment with systemic corticosteroids or systemic anabolic agents.
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E.5 End points |
E.5.1 | Primary end point(s) |
Effects of adding anacetrapib 100 mg to ongoing lipid therapy relative to placebo on plasma concentrations of LDL-C
Summary of safety and tolerability
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Effects of adding anacetrapib 100 mg to ongoing lipid therapy relative to placebo on plasma concentrations of HDL-C and apoA-1 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
12 (HDL-C and apoA-1) & 64 (safety)weeks |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 12 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Israel |
Malaysia |
South Africa |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |