Hypertension
Conditions
Interventions
Trade Name: Rasilez
Product Name: Aliskiren
Product Code: SPP100
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Aliskiren
CAS Number: 173334-58-2
Current Sponsor code: SPP100
Concentrati
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patients 18 to 65 years of age included, with a diagnosis of hypertension and with abdominal obesity (elevated waist circumference, = 102 cm in men and = 88 cm in women) 2. Systolic and diastolic blood pressure and pulse rate will be assessed after the patient has rested for at least five (5) minutes. Vital signs should be within the following ranges: Patients with history of treated hypertension: msSBP/msDBP =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Hypertension Grade 2 (msSBP = 160 and/or msDBP = 100 mmHg). 2. Current treatment with three or more antihypertensive treatments. 3. Moderate to heavy smokers (use of tobacco products equivalent to >10 normal strength cigarettes per day in the previous 3 months). Non-smokers and light smokers (use of tobacco products equivalent to =10 normal strength cigarettes per day) are permitted. Each patient will be tested for urine cotinine levels. Patients with levels greater than 500 ng/mL will be considered moderate to heavy smokers. 4. Type 2 and Type 1 diabetes. 5. 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). • Postmenopausal women using hormone replacement therapy. • 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 a plasma 17ß- estradiol concentration of 40 IU/L 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. • 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. 6. ASA treatment >1g/day or regular use of NSAIDs 7. Current of planned treatment with potent P-gp inhibitors, e.g. cyclosporin or anti-fungal itraconazole. 8. Use of any prescription drugs within four (4) weeks prior dosing, or over-the- counter (OTC) medication (vitamins, herbal supplements, dietary supplements) within two (2) weeks prior to dosing. Paracetamol is acceptable, but must be documented in the Concomitant medications / Significant non-drug therapies page of the CRF. 9. Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations. 10. Donation or loss of 500 ml or more of blood within 8 weeks prior to first dosing, or longer if required by local regulation. 11. Significant illness within two weeks prior to dosing. 12. A past medical history of clinically significant ECG abnormalities or a family history grandparents, parents and siblings) of a prolonged QT-interval syndrome. 13. History of autonomic dysfunction (e.g. history of recurrent fainting in the recent past, orthostatic hypotension, sinus arrhythmia). 14. History of hypertensive encephalopathy or cerebrovascular accident at any time prior to Visit 1. 15. History of past cardiovascular events (e.g. myocardial infarction, unstable Angina pectoris etc...) during at least the 6 months prior to Visit 1. 16. Second or third degree heart block without a pacemaker. 17. Concurrent potenti
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 - Quantify the concentration of aliskiren, amlodipine and angiotensin II (Ang II) in interstitial fluid (microdialysis), and quantify the concentration of aliskiren, angiotensin II and renin concentration and activity in the plasma and in the tissue (biopsy) of subcutaneous fat and skeletal muscle in hypertensive patients with abdominal obesity. Part 2 (depending on the successful results of part 1): Compare the effects of aliskiren and amlodipine on Ang II in interstitial fluid of subcutaneous fat and skeletal muscle and on RAS biomarkers in the plasma from hypertensive patients with abdominal obesity.;Secondary Objective: Compare the effects of aliskiren and amlodipine on lipid and carbohydrate metabolism in the interstitial fluid of subcutaneous fat and skeletal muscle before and during an intravenous glucose tolerance test with insulin bolus (FSIGT). Explore the effects of aliskiren and amlodipine on peripheral insulin sensitivity using FSGIT test in hypertensive patients with abdominal obesity. Explore the effects of aliskiren and amlodipine on mitochondrial mass and function in subcutaneous fat and skeletal muscle (tissue biopsies) in hypertensive patients with abdominal obesity. Explore the relationship between changes in blood pressure and in RAS biomarkers measures in plasma and in fat and skeletal muscle interstitial fluid in hypertensive patients with abdominal obesity. Assess the safety and tolerability of aliskiren and amlodipine in hypertensive patients with abdominal obesity.;Primary end point(s): Pharmacodynamic assessment of concentration of aliskiren, amlodipine and RAS biomarkers in hypertensive patients with abdominal obesity. | — |
Countries
Germany
Outcome results
None listed