E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Essential hypertension and hypercholesterolemia |
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MedDRA Classification |
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 |
To demonstrate that the combination of valsartan 160mg/simvastatin 40mg has superior efficacy compared to the combination of valsartan 160mg/simvastatin 20mg in the percentage change from baseline to week 6 in LDL-C |
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E.2.2 | Secondary objectives of the trial |
•To compare the effects of valsartan 160mg/simvastatin 20mg versus valsartan 160mg/simvastatin 40mg in reducing total cholesterol (TC), triglycerides (TG), non-high density lipoprotein cholesterol (non-HDL-C) and in increasing high density lipoprotein cholesterol (HDL-C) from baseline to week 6 •To compare the effects of valsartan 320mg/simvastatin 20mg titrated treatment versus valsartan 320mg/simvastatin 40mg titrated treatment in reducing LDL-C, TC, TG, non-HDL-C and in increasing HDL-C from baseline to week 12 •To estimate the percentage of patients who reach BP (BP <140/90 mmHg non-diabetic patients and < 130/80 mmHg diabetic patients) and/or LDL-C control at week 6 and 12 in each treatment group
For detailed list see full protocol |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Male or female outpatients ≥ 18 years of age, at Visit 1 2. Elevated LDL-C ≥ 3.4mmol/l (130mg/dl) [or ≥ 2.6mmol/l (100mg/dl) for diabetic patients] and < 4.9 mmol/l (190 mg/dl) and TG ≤ 4mmol/l (350mg/dl) based on lab results of lipid profile drawn at Visit 3 for previously treated patients and at Visit 1 and 3 for previously untreated patients. 3. MSSBP ≥ 140 mmHg (or ≥ 130 mmHg for diabetic patients) and < 180 and/or MSDBP ≥ 90 mmHg (or > 80 mmHg for diabetic patients) and < 110 mmHg at Visit 4 for previously treated patients and at Visit 1, 2, 3, and 4 for previously untreated patients. 4. Written informed consent to participate in this study prior to any study procedures
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E.4 | Principal exclusion criteria |
1. MSSBP ≥ 180 mmHg and/or MSDBP ≥ 110 mmHg at any time between Visit 1 and Visit 4 2. Inability to discontinue all prior lipid lowering and antihypertensive medications safely for a period of six and four weeks respectively prior to randomization 3. History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures 4. Prior or known muscular or neuromuscular disease of any type 5. A history of cardiovascular disease, including angina, myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, transient ischemic attack, stroke, and peripheral artery disease 6. Known Keith-Wagener grade III or IV hypertensive retinopathy 7. Second or third degree heart block without a pacemaker, concurrent potentially life threatening arrhythmia or symptomatic arrhythmia, clinically significant valvular heart disease 8. Heart failure requiring treatment 9. Evidence of a secondary form of hypertension, to include coarctation of the aorta, hyperaldosteronism, Cushing’s disease, unilateral or bilateral renal artery stenosis, pheochromocytoma, polycystic kidney disease 10. Evidence of hypercholesterolemia secondary to other causes. This includes, but is not restricted to: alcoholism, auto-immune disease, nephrotic syndrome, any viral or non-viral hepatitis clinically active within 12 months prior to Visit 1, obstructive hepatic or biliary disease, dys- or macroglobulinemia, multiple myeloma, glycogen storage disease, uncontrolled hypothyroidism or hyperthyroidism, chronic pancreatitis and porphyria 11. Uncontrolled diabetes mellitus type 2, as defined by glycosylated hemoglobin HbA1c > 8% at Visit 1 12. Diabetic patients requiring insulin treatment 13. Evidence of hepatic disease as determined by AST (SGOT) or ALT (SGPT) values > 2 x ULN at Visit 1 14. A history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt 15. Evidence of renal impairment as determined by one of the followings: serum creatinine > 1.5 x ULN at Visit 1, a history of dialysis, or a history of nephrotic syndrome. If creatinine is found to be between 1.5 and 2 x UNL, a retest can be performed prior to randomization 16. Serum creatine kinase (CK) levels > 2 x ULN at Visit 1. In case of doubt the test should be redone at the discretion of the investigator 17. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. 18. Any severe, life-threatening disease within the past five years 19. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of any drug including but not limited to any of the following: • History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection, gastric bypass, gastric stapling, or gastric banding • Currently active or active inflammatory bowel disease during the 12 months prior to Visit 1 • Currently active gastritis, ulcers, or gastrointestinal/rectal bleeding or urinary tract obstruction regarded as clinically meaningful by the investigator 20. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy OR are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation, hysterectomy), or double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap) 21. Pregnant or nursing (lactating) women at Visit 1 22. Any surgical or medical condition which, at the discretion of the investigator, place the patient at higher risk from his/her participation in the study, or are likely to prevent the patient from complying with the requirements of the study or completing the trial period 23. History of drug or alcohol abuse within the last 2 years 24. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer 25. History of noncompliance to medical regimens, or patients unwilling to comply with the study protocol 26. Persons directly involved in the execution of this protocol/study 27. Inability to communicate and comply with all study requirements
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is the percentage change from baseline in LDL-C to week 6. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |