An 8 week, double-blind, randomized, parallel group, active-controlled study to evaluate the efficacy and safety of the combination of Aliskiren /Amlodipine / HCTZ in patients with moderate to severe hypertension.

• Register: EUCTR
• Last refreshed on: 11 September 2012
• Main ID: EUCTR2008-003199-23-LV
• Date of registration: 19/08/2008
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: An 8 week, double-blind, randomized, parallel group, active-controlled study to evaluate the efficacy and safety of the combination of Aliskiren /Amlodipine / HCTZ in patients with moderate to severe hypertension.
• Scientific title: An 8 week, double-blind, randomized, parallel group, active-controlled study to evaluate the efficacy and safety of the combination of Aliskiren /Amlodipine / HCTZ in patients with moderate to severe hypertension.
• Date of first enrolment: 20/10/2008
• Target sample size: 1160
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-003199-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: yes Other:

Countries of recruitment

Denmark, Germany, Italy, Latvia, Lithuania, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
1. Outpatients 18 years of age or older
2. Male or female patients are eligible.
3. msDBP & msSBP Requirements:
3A:
• Diagnosis of moderate to severe hypertension (msSBP = 160 mmHg and < 200 mmHg, and/or msDBP = 100 mmHg and < 120 mmHg) at Visits 4, 5 or 6 (Qualifying BP visit)
• In addition, at the visit immediately prior to the above qualifying visit, patients must also have msSBP = 145 mmHg and < 200 mmHg and msDBP = 95 mmHg and < 120 mmHg) at Visits 3, 4 or 5
• Patients must meet the above two sets of requirements at subsequent adjacent visits, i.e., either Visits 3 and 4, Visits 4 and 5, or Visits 5 and 6
OR
3B:
• msSBP = 180 mmHg and < 200 mmHg with msDBP = 95 mmHg and < 120 mmHg, or msDBP = 110 mmHg and < 120 mmHg with msSBP = 150 mmHg and < 200 mmHg after at least one week of treatment with placebo (Visit 3 and on)
4. For patients requiring tapering off their previous antihypertensive medication, they must meet the above criteria and completely discontinue all antihypertensive treatment prior to entering the treatment phase (placebo period) of the study.
5. 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).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
For full list, please refer to the protocol.

1. Inability to discontinue all prior antihypertensive medications at Visit 2 (start of placebo) or complete the taper within 4 weeks after Visit 1.
2. Patients with an msSBP = 200 mmHg or msDBP = 120 mmHg at any time during the placebo run-in period must be discontinued from the study.
3. Patients on four or more antihypertensive drugs at Visit 1.
4. Pregnant or nursing (lactating) women, where pregnancy is defined as a state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (= 10 mIU/ml).
5. 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/ml or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy OR are using one or more of the following acceptable methods of contraception such as surgical sterilization (e.g., bilateral tubal ligation) or hormonal contraception (implantable, patch, oral), or double-barrier methods (if accepted by the local Health Authority and Ethics Committee) Reliable contraception should be maintained throughout the study and for 7 days after study medication discontinuation.
6. History or evidence of a secondary form of hypertension.
7. Any history of hypertensive encephalopathy or cerebrovascular accident, or history of transient ischemic attack (TIA), myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI).
8. Previous or current diagnosis of heart failure (NYHA Class II-IV).
9. Serum potassium = 5.5 mEq/L (mmol/L) at Visit 1.
10. Patients with Type 1 or Type 2 diabetes mellitus who are not well controlled based on the investigator's clinical judgment. Patients with diabetes mellitus enrolled in this study should be well controlled. It is recommended that patients currently being treated for diabetes mellitus be on a stable dose of antidiabetic medication for at least 4 weeks prior Visit 1.
11. Current angina pectoris requiring pharmacological therapy except for nitrates.
12. Second or third degree heart block with or without a pacemaker, atrial fibrillation or atrial flutter at Visit 1, or potentially life-threatening arrhythmia during the 12 months prior to Visit 1.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

hypertension
MedDRA version: 9.1 Level: LLT Classification code 10015488 Term: Essential hypertension

Intervention(s)

Trade Name: Rasilez
Product Name: Aliskiren
Product Code: SAH100
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: aliskiren
Current Sponsor code: SAH100
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Rasilez
Product Name: Aliskiren
Product Code: SAH100
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: aliskiren
Current Sponsor code: SAH100
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Norvasc
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: amlodipine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Norvasc
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: amlodipine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Pharmaceutical Form: Capsule, hard
INN or Proposed INN: hydrochlorothiazide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12.5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Pharmaceutical Form: Capsule, hard
INN or Proposed INN: hydrochlorothiazide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of the study is to demonstrate that a once daily dosing regimen of the triple combination of aliskiren/amlodipine/HCTZ is superior to the double combinations of aliskiren/amlodipine, aliskiren/HCTZ and amlodipine/HCTZ in lowering mean sitting systolic blood pressure (msSBP) in patients with moderate to severe hypertension.

Primary end point(s): The primary efficacy variable is change from baseline in msSBP. msSBP is the average of available readings of sitting systolic blood pressure for a given visit.
The primary analysis time point will be the Week 8 endpoint. For each patient, the last post-baseline measurement during the double-blind treatment period will be carried forward to Week 8 as the Week 8 endpoint measurement.

Secondary Objective: Key secondary objectives are listed below. For full list, please refer to the protocol.
• To demonstrate that a once daily dosing regimen of the triple combination of aliskiren/amlodipine/HCTZ is superior to the double combinations of aliskiren/amlodipine, aliskiren/HCTZ and amlodipine/HCTZ in lowering mean sitting diastolic blood pressure (msDBP) in patients with moderate to severe hypertension.
• To evaluate the decrease in 24-hour mean ambulatory diastolic and systolic blood pressures produced by the triple combination of aliskiren/HCTZ/amlodipine in comparison to the double combinations of aliskiren/HCTZ, aliskiren/amlodipine, or HCTZ/amlodipine in patients with moderate to severe hypertension.
• To evaluate the safety and tolerability of the triple combination of aliskiren/HCTZ/amlodipine in comparison to the double combinations of aliskiren/HCTZ, aliskiren/amlodipine and HCTZ/amlodipine in patients with moderate to severe hypertension.

Secondary ID(s)

CSAH100A2302

2008-003199-23-DK