E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment with AMR101 as an adjunct to diet to reduce triglyceride (TG) levels in patients with high (≥200 mg/dL) TG levels not controlled by diet and statin therapy. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10014486 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020870 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to determine the efficacy of AMR101 2 g daily and 4 g daily, compared to placebo, in lowering fasting TG levels in patients with high risk for cardiovascular disease (CVD) and with fasting TG levels >/= 200 mg/dL and </= 500 mg/dL, despite treatment to LDL-C goal on statin therapy. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are the following: 1. To determine the safety and tolerability of AMR101 2 g daily and 4 g daily; 2. To determine the effect of AMR101 on lipid and apolipoprotein profiles; 3. To determine the effect of AMR101 on (Lp-PLA2)from baseline to Week 12; 4. To determine the effect of AMR101 on LDL number and size; 5. To determine the effect of AMR101 on oxidized LDL; 6. To determine the effect of AMR101 on fasting plasma glucose (FPG) and HbA1c; 7. To determine the effect of AMR101 on insulin resistance; 8. To determine the effect of AMR101 on hsCRP; 9. To determine the effects of AMR1 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Understanding of the study procedures, willing to adhere to the study schedule, and agreement to participate in the study by giving written informed consent prior to screening (Visit 1 [Week -8 or Week -6]); 2. Men or women >18 years of age; Women may be enrolled if all 3 of the following criteria are met: − They are not pregnant, − They are not breastfeeding, and − They do not plan on becoming pregnant during the study; 3. At high risk for cardiovascular disease, i.e., patients with clinical coronary heart disease (CHD) or clinical CHD risk equivalents (10-year risk >20%) as defined in the NCEP ATP III Guidelines 4. On a stable dose of statin therapy (with or without ezetimibe) 5. Triglyceride levels ≥200 mg/dL and <500 mg/dL (based on an average [arithmetic mean] of Visit 2 [Week -2] and Visit 3 [Week -1]). 6. Low-density lipoprotein cholesterol levels ≥40 mg/dL and <100 mg/dL (based on an average [arithmetic mean] of Visit 2 [Week -2] and Visit 3 [Week -1]). 7. Willingness to maintain stable diet and physical activity level throughout the study. |
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E.4 | Principal exclusion criteria |
1. BMI >45 kg/m2; 2. Participation in another clinical trial within 30 days prior to screening 3. Weight change >3 kg between screening 4.Mean Non-HDL-C levels <100 mg/dL from the last 2 visits before randomization. 5. Hemoglobin A1c >9.0% at screening 6. Use after Visit 1 and during the study of any non-study drug related, non-statin, lipid-altering medications or supplements 7. Use after Visit 1 and during the study of any statin other than atorvastatin, rosuvastatin or simvastatin. 8. PCI within 4 weeks prior to screening 9. Hospitalization for acute coronary syndrome and discharge within 4 weeks prior to screening 10. Known nephrotic range (>3 g/day) proteinuria 11.History or evidence of major and clinically significant, hepatic, pulmonary, renal, hematologic, gastrointestinal (including clinically significant malabsorption), endocrine (other than type 1 or type 2 diabetes), immunologic, dermatologic, neurologic, psychiatric, oncologic, or allergic (including drug allergies, but excluding untreated or treated seasonal allergies at the time of dosing) disease that would interfere with the conduct of the study or interpretation of the data; 12. Known lipoprotein lipase impairment or deficiency (Fredrickson Type I), apolipoprotein C-II deficiency, or familial dysbetalipoproteinemia (Fredrickson Type III); 13. Requirement for peritoneal dialysis or hemodialysis 14. History of malignancy, except patients who have been disease-free for >5 years, or whose only malignancy has been basal or squamous cell skin carcinoma; 15. History of bariatric surgery; 16. Uncontrolled hypertension 17. Known to be infected with human immunodeficiency virus (HIV); 18. Positive test for hepatitis B surface antigen or hepatitis C antibody at screening 19. Anticipation of major surgery during the screening or double-blind periods of the study; 20. Treatment with chronic prescription pharmacotherapy for metabolic or cardiovascular disease management or risk factor modification that has not been stable for ≥4 weeks prior to screening; 21. Ongoing treatment with weight loss drugs; 22. Ongoing treatment with HIV-protease inhibitors, cyclophosphamide, or isotretinoin; 23. Treatment with tamoxifen, estrogens, or progestins that has not been stable for ≥4 weeks prior to screening; 24. Routine or anticipated use of all systemic corticosteroids. 25. TSH) >1.5 � upper limit of normal (ULN),clinical evidence of hypothyroidism, or thyroid hormone therapy that has not been stable for ≥6 weeks prior to screening; 26. ALT or AST >2 � ULN; 27. Unexplained creatine kinase concentration >3 � ULN or creatine kinase elevation due to known muscle disease 28. Blood donation of ≥1 pint (0.5 L) within 30 days prior to screening, or plasma donation within 7 days prior to screening ; 29. Consumption of >2 alcoholic beverages per day following screening; 30. History of illicit drug use within 1 year of screening; 31. Any condition or therapy which, in the opinion of the investigator, might pose a risk to the patient or make participation in the study not in the patient s best interest; or 32. Poor mental function or any other reason to expect patient difficulty in complying with the requirements of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable for the double-blind treatment period is percent change in TG from baseline to Week 12 endpoint. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
12 settimane in doppio cieco seguite da 40 settimane in aperto |
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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.8.2.3.1 | Comparator description |
- same IMP used at different dosage |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | Information not present in EudraCT |
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 |
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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 | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |