E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 compare the effects of multiple dose administration of aliskiren and irbesartan on systemic biomarkers of inflammation and other markers associated with cardiovascular and/or metabolic disease. |
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E.2.2 | Secondary objectives of the trial |
• To perform exploratory pharmacogenetic assessments to examine whether individual variation in genes relating to drug metabolism, hypertension, metabolic syndrome, and the renin-angiotensin pathway predict response to aliskiren or irbesartan. . • To conduct exploratory genomic, proteomic and metabonomic studies to identify proteins and metabolites in blood and urine that are associated with treatment response to aliskiren or irbesartan, or that may correlate with baseline disease status.
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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, 40-75 years of age at screening. 2. Patients with a history of essential hypertension, either drug naïve or under a maximum of two current antihypertensive treatments. 3. Raised blood pressure (MSSBP ≥ 130 mmHg and/or MSDBP ≥ 85 mmHg) at screening and baseline. 4. Central obesity (defined as waist circumference ≥ 102 cm for men and ≥ 88 cm for women). 5. Patients should have either or both of the following: i) Triglyceride levels of ≥ 1.7 mmol/L (150 mg/dL). ii) Fasting plasma glucose (FPG) ≥ 5.6 mmol/L (100.8 mg/dL) < 7.0 mmol/L (126 mg/dL). 6. Patients who are eligible and able to participate in the study, and who consent to do so after the purpose and nature of the investigation has been clearly explained to them (written informed consent).
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E.4 | Principal exclusion criteria |
1. Severe hypertension (MSSBP of ≥ 180 mmHg and/or MSDBP of ≥ 110 mmHg). 2. Previous treatment in an aliskiren study and who qualified to be randomized or enrolled into the active drug treatment period. 3. Current treatment with three or more antihypertensive treatments. 4. Current treatment with hormone replacement therapy (HRT). 5. Smokers. Urine cotinine levels will be measured during screening for all subjects and a smoker will be defined as any subject who has a urine cotinine level > 500 ng/mL. 6. History or evidence of a secondary form of hypertension. 7. Known Keith-Wagener grade III or IV hypertensive retinopathy. 8. History of hypertensive encephalopathy or cerebrovascular accident. 9. Current diagnosis of heart failure (NYHA Class II-IV). 10. History of transient ischemic cerebral attack within the last 12 months. 11. History of myocardial infarction. 12. History of coronary bypass surgery, or any percutaneous coronary intervention (PCI). 13. Serum sodium less than lower limit of normal, serum potassium < 3.5 mEq/L or ≥ 5.3 mEq/L or dehydration at screening. 14. History of Type 1 or Type 2 diabetes. 15. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL). • Women of child-bearing potential (WOCBP), 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), hormonal contraception (implantable, patch, oral), and double-barrier methods. • Acceptable methods of contraception may include total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the patient ensures compliance. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Reliable contraception should be maintained throughout the study and for 7 days after study drug discontinuation. • Women using hormonal contraception that has not been at a consistent dose for at least 3 months and is not expected to remain at this dose throughout the study . 16. Current angina pectoris requiring pharmacological therapy. 17. Second or third degree heart block without a pacemaker. 18. Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia. 19. Clinically significant valvular heart disease. 20. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs including, but not limited to, any of the following: • History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection. • Currently active or previously active inflammatory bowel disease during the 12 months prior to screening. • Currently active gastritis, duodenal or gastric ulcers, or gastrointestinal/rectal bleeding during the 3 months prior to screening. • Any history of pancreatic injury, pancreatitis, or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase. • Evidence of hepatic disease as determined by any one of the following: SGOT or SGPT values exceeding 3 x ULN at screening, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt. • Evidence of renal impairment as determined by any one of the following: serum creatinine > 1.5 x ULN at screening, a history of dialysis, or a history of nephrotic syndrome. • Current treatment with cholestyramine or colestipol resins. 21. History of hypersensitivity to any of the study drugs or to drugs belonging to the same therapeutic class (ARB’s or renin inhibitors) as the study drugs. 22. History of angioedema due to usage of an ARB or ACE, or dry cough due to usage of an ACE 23. 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. 24. History or evidence of drug or alcohol abuse within the last 12 months.
etc.... For entire list of 31 exclusion criteria see full protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacodynamic assessment of the effects of multiple dose administration of aliskiren and irbesartan on systemic biomarkers of inflammation and other markers associated with cardiovascular and/or metabolic disease |
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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 | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 |
double-dummy, multiple dose |
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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 | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 11 |