E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | M15 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020772 |
E.1.2 | Term | <Manually entered code. Term in E.1.1> |
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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 |
• To assess and compare the effects of aliskiren/amlodipine and amlodipine on pedal edema after 4 weeks treated as measured by ankle foot volume (AFV) (water displacement method) in patients with mild to moderate hypertension |
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E.2.2 | Secondary objectives of the trial |
• To assess the safety and tolerability of aliskiren/ amlodipine and amlodipine in patients with mild to moderate hypertension
Exploratory objective • To investigate the effect on ms SBP and ms DBP of SPA100 and amlodipine in subjects with mild to moderate hypertension.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female 18-65 yrs old (inclusive). 2. Patients with a diagnosis of hypertension and naïve to antihypertensive medication: Mild to moderate hypertension (msDBP ≥90 mmHg and <110 mmHg and/or msSBP ≥140 mmHg and <180 mmHg) at screening, and after 2 weeks of placebo run-in period. OR Patients with (a history of) mild to moderate hypertension with a controlled BP at screening lower than 180/100 mmHg (due to antihypertensive medication), and after 2 weeks of placebo run-in period their msDBP ≥90 mmHg and <110 mmHg; and/or msSBP ≥140 mmHg and <180 mmHg. 3. Amlodipine naïve or no amlodipine use in previous year from screening visit. 4. Female subjects must be of non-child bearing potential as defined as postmenopausal females with no regular menstrual bleeding for at least one (1) year prior to initial dosing. Menopause will be confirmed by a plasma FSH level of >40IU/L at screening, OR Female subjects surgically sterilized at least 6 months prior to screening (Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and noted in the Relevant Medical History/ Current Medical Conditions section of the CRF. All female subjects must have negative pregnancy results at screening and at baseline (regardless of reported reproductive status). 5. Body mass Index (BMI) must be 18-32 kg/m2 (inclusive) and subjects must weigh at least 50 kg at screening and baseline. 6. Able to communicate well with the investigator, and to understand and comply with the requirements of the study and able to provide written informed consent prior to study participation. |
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E.4 | Principal exclusion criteria |
1. Inability of the subjects to switch from all prior antihypertensive medications safely as required by the protocol and need for drugs other than study drugs at the time of baseline. 2. Severe hypertension (msSBP ≥180 mmHg and/or msDBP ≥110 mmHg) at screening and/or baseline. 3. Pregnant or nursing (lactating) women 4. History or evidence of a secondary form of hypertension 5. Any history within 12 months prior to Visit 1 of the following: hypertensive encephalopathy or cerebrovascular accident, or history of transient ischemic attack (TIA), myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI). 6. Previous or current diagnosis of heart failure (NYHA Class II-IV) 7. Confirmed serum potassium ≥5.3 mEq/L (mmol/L) at screening or baseline 8. Patients with Type 1 or Type 2 diabetes mellitus. 9. Current angina pectoris requiring pharmacological therapy 10. Second or third degree heart block without a pacemaker, or potentially life-threatening arrhythmia during the 12 months prior to screening 11. Clinically symptomatic valvular heart disease at screening visit 12. Known or suspected contraindications, including history of allergy or hypersensitivity to renin inhibitors (such as angioedema), calcium channel blockers, or to drugs with similar chemical structures 13. Participation in any clinical investigation within four (4) weeks prior to initial dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations. 14. A past medical history of clinically significant ECG abnormalities. 15. 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. 16. History or evidence of drug or alcohol abuse within the last 12 months. 17. Any subjects clinical management which necessities use of diuretic and cannot be discontinued before the start of trial. 18. Any surgical or medical condition which in the opinion of the investigator may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study. 19. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study. The Investigator should make this determination in consideration of the subject’s medical history and/or clinical or laboratory evidence of any of the following: • History of inflammatory bowel diseases, ulcers, gastrointestinal or rectal bleeding; during the last 12 months • History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection; • Currently active gastritis, duodenal or gastric ulcers, or history of gastrointestinal bleeding during the 3 months prior to screening visit. • Liver disease or liver injury as indicated by abnormal liver function tests such as SGOT (AST), SGPT (ALT), γ-GGT, alkaline phosphatase, or serum bilirubin. The Investigator should be guided by the following criteria: o Any single parameter may not exceed 3 x upper limit of normal (ULN). A single parameter elevated up to and including 3 x ULN should be re-checked once more as soon as possible, and in all cases, at least prior to enrollment/randomization, to rule out lab error. o If the total bilirubin concentration is increased above 3 X ULN, total bilirubin should be differentiated into direct and indirect reacting bilirubin. In any case serum bilirubin should not exceed the value of 27 µmol/L (1.6 mg/dl). Re-check results must be within normal limits in order for subject to qualify. • Pancreatic injury or pancreatitis • Evidence of renal impairment as determined by any one of the following: estimated glomerular filtration rate (GFR) <30 ml/min/1.73 m2 using the MDRD formula at Visit 1, a history of dialysis, or a history of nephrotic syndrome. 20. Donation or loss of 400 ml or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation.
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment on the effects of aliskiren/amlodipine and amlodipine on pedal edema measured by ankle foot volume (AFV) in patients naive to trial drugs with mild to moderate hypertension |
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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 | 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 | 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) | 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 | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 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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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 | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
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 |