Efficacy and Safety of Aliskiren/Ramipril/Amlodipine Compared With Ramipril/Amlodipine and Aliskiren/Amlodipine in Patients With Metabolic Syndrome - Full Text View

Sponsor:	Novartis
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00542269

Purpose

This proof of concept study is designed to evaluate the efficacy and safety of the combination therapy of aliskiren and ramipril as add-on to amlodipine in the treatment of patients with essential hypertension and metabolic syndrome who do not respond adequately to amlodipine monotherapy.

Condition	Intervention	Phase
Hypertension With Metabolic Syndrome	Drug: Amlodipine Drug: Aliskiren Drug: Ramipril	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	A Twelve Week, Randomized, Double-blind, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of the Combination of Aliskiren/Ramipril/Amlodipine (300/10/5-10 mg) Compared to the Combinations of Ramipril/Amlodipine (10/5-10 mg) and Aliskiren/Amlodipine (300/5-10 mg) in Patients With Essential Hypertension and Metabolic Syndrome Not Adequately Responsive to Amlodipine 5-10 mg

Resource links provided by NLM:

MedlinePlus related topics: High Blood Pressure Metabolic Syndrome

Drug Information available for: Ramipril Amlodipine Amlodipine besylate Aliskiren

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study - Aliskiren/Ramipril/Amlodipine vs Ramipril/Amlodipine) [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
Automated blood pressure determinations were made with the Omron HEM-705CP blood pressure monitor at trough (24 hours ± 3 hours post-dose) and recorded at all study visits following detailed directions specified in the study protocol. Three readings were made and msSBP was calculated as the average of the 3 readings. In the event of aberrant readings, ie, the lowest reading was ≥ 10 mmHg systolic or ≥ 5 mmHg diastolic lower than the highest of the 3 readings, 3 additional readings were obtained. A negative change indicates improvement.
Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study - Aliskiren/Amlodipine vs Ramipril/Amlodipine [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
Automated blood pressure determinations were made with the Omron HEM-705CP blood pressure monitor at trough (24 hours ± 3 hours post-dose) and recorded at all study visits following detailed directions specified in the study protocol. Three readings were made and msSBP was calculated as the average of the 3 readings. In the event of aberrant readings, ie, the lowest reading was ≥ 10 mmHg systolic or ≥ 5 mmHg diastolic lower than the highest of the 3 readings, 3 additional readings were obtained. A negative change indicates improvement.

Secondary Outcome Measures:

Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study - Aliskiren/Ramipril/Amlodipine vs Ramipril/Amlodipine [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
Automated blood pressure determinations were made with the Omron HEM-705CP blood pressure monitor at trough (24 hours ± 3 hours post-dose) and recorded at all study visits following detailed directions specified in the study protocol. Three readings were made and msDBP was calculated as the average of the 3 readings. In the event of aberrant readings, ie, the lowest reading was ≥ 10 mmHg systolic or ≥ 5 mmHg diastolic lower than the highest of the 3 readings, 3 additional readings were obtained. A negative change indicates improvement.
Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study - Aliskiren/Amlodipine vs Ramipril/Amlodipine [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
Automated blood pressure determinations were made with the Omron HEM-705CP blood pressure monitor at trough (24 hours ± 3 hours post-dose) and recorded at all study visits following detailed directions specified in the study protocol. Three readings were made and msDBP was calculated as the average of the 3 readings. In the event of aberrant readings, ie, the lowest reading was ≥ 10 mmHg systolic or ≥ 5 mmHg diastolic lower than the highest of the 3 readings, 3 additional readings were obtained. A negative change indicates improvement.
Percentage of Patients Who Achieved Normalized Blood Pressure at End of Study [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Normalized was defined as a msSBP < 140 mmHg and/or a msDBP < 90 mmHg.
Change in HOMA-IR From Baseline to End of Study [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
Homeostasis model assessment-insulin resistance (HOMA-IR) was defined as (fasting insulin [μU/mL] x fasting glucose [mmol/L]) / 22.5.
Change in HOMA-β From Baseline to End of Study [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
Homeostasis model assessment-β (HOMA-β) was defined as fasting insulin (μU/mL) x 20 / (fasting glucose (mmol/L) - 3.5).
Change in HbA1c (Glycated Hemoglobin) From Baseline to End of Study - Aliskiren/Ramipril/Amlodipine vs Ramipril/Amlodipine [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
Change in HbA1c (Glycated Hemoglobin) From Baseline to End of Study - Aliskiren/Amlodipine vs Ramipril/Amlodipine) [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
Percentage of Patients Who Developed Diabetes at End of Study [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
A patient had diabetes if fasting plasma glucose > 7 mmol/L.

Enrollment:	178
Study Start Date:	March 2008
Study Completion Date:	July 2009
Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Aliskiren / ramipril / amlodipine 6 weeks treatment with aliskiren 150 mg tablets, ramipril 5 mg capsules, and amlodipine 5-10 mg tablets followed by an additional 6 weeks treatment with aliskiren 300 mg tablets, ramipril 10 mg capsules, and amlodipine 5-10 mg tablets. Patients received amlodipine 5 mg (or 10 mg if they were receiving 10 mg prior to study start). Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.	Drug: Amlodipine amlodipine 5-10 mg tablets. Patients received amlodipine 5 mg (or 10 mg if they were receiving 10 mg prior to study start). Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed. Drug: Aliskiren aliskiren 150-300 mg tablets. Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed. Drug: Ramipril ramipril 5-10 mg capsules. Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.
Experimental: Aliskiren / amlodipine 6 weeks treatment with aliskiren 150 mg tablets, ramipril 5 mg placebo capsules, and amlodipine 5-10 mg tablets followed by an additional 6 weeks treatment with aliskiren 300 mg tablets, ramipril 10 mg placebo capsules, and amlodipine 5-10 mg tablets. Patients received amlodipine 5 mg (or 10 mg if they were receiving 10 mg prior to study start). Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.	Drug: Amlodipine amlodipine 5-10 mg tablets. Patients received amlodipine 5 mg (or 10 mg if they were receiving 10 mg prior to study start). Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed. Drug: Aliskiren aliskiren 150-300 mg tablets. Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.
Active Comparator: Ramipril / amlodipine 6 weeks treatment with aliskiren 150 mg placebo tablets, ramipril 5 mg capsules, and amlodipine 5-10 mg tablets followed by an additional 6 weeks treatment with aliskiren 300 mg placebo tablets, ramipril 10 mg capsules, and amlodipine 5-10 mg tablets. Patients received amlodipine 5 mg (or 10 mg if they were receiving 10 mg prior to study start). Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.	Drug: Amlodipine amlodipine 5-10 mg tablets. Patients received amlodipine 5 mg (or 10 mg if they were receiving 10 mg prior to study start). Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed. Drug: Ramipril ramipril 5-10 mg capsules. Each dose was to be taken orally with water once daily at approximately 8:00 A.M. with or without food, except on the morning of an office/clinic visit, when the study drug was to be taken at the site after the visit procedures had been completed.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Outpatients 18-75 years of age.
Male or female patients are eligible.
Patients with a diagnosis of hypertension:
Newly diagnosed patients or patients who have not been treated for hypertension within the 4 weeks prior to Visit 1 must have a mean sitting systolic blood pressure (MSSBP) > 150 mmHg and < 180 mmHg at Visit 1.
Patients treated with antihypertensive monotherapy must have a MSSBP ≥ 140 mmHg and <180 mmHg at Visit 1.
Patients taking amlodipine monotherapy MSSBP > 140 mmHg and < 180 mmHg at visit 1.
All patients must have a MSSBP ≥ 140 mmHg and < 180 mmHg at Visit 3, the end of the amlodipine run-in period.
Metabolic syndrome.
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 inform consent form).

Exclusion Criteria:

Severe hypertension (office cuff MSDBP ≥ 115 mmHg and/or MSSBP ≥ 180 mmHg).
History or evidence of a secondary form of hypertension.
History of hypertensive encephalopathy or cerebrovascular accident, transient ischemic cerebral attack (TIA), myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI).
Serum sodium < 135 mmol/L at Visit 1 if confirmed on repeat sample.
Serum potassium < 3.5 mmol/L or ≥ 5.3 mmol/L at Visit 1, if confirmed on repeat sample.
Type 1 diabetes mellitus.
Type 2 diabetes if oral hypoglycaemic therapy changed (dose change or medication change) in previous 3 months.
Pregnant or nursing (lactating) women.

Other protocol-defined inclusion/exclusion criteria applied to the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00542269

Locations

United Kingdom
Addenbrookes Hospital
Cambridge, United Kingdom

Sponsors and Collaborators

Novartis

Investigators

Study Chair:

Novartis

Novartis Great Britian

More Information

No publications provided

Responsible Party:	External Affairs, Novartis
ClinicalTrials.gov Identifier:	NCT00542269 History of Changes
Other Study ID Numbers:	CSPP100AGB01
Study First Received:	October 9, 2007
Results First Received:	January 6, 2011
Last Updated:	April 26, 2011
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:

Hypertension
Metabolic Syndrome
Dual combination therapy

Triple combination therapy
Aliskiren
Direct Renin inhibitor

Additional relevant MeSH terms:

Hypertension
Metabolic Syndrome X
Vascular Diseases
Cardiovascular Diseases
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Amlodipine
Ramipril
Calcium Channel Blockers

Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Vasodilator Agents
Antihypertensive Agents
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012