Study to Evaluate the Efficacy and Safety of Combination Aliskiren/Amlodipine in Patients Not Adequately Responding to Aliskiren Alone

• ClinicalTrials.gov Identifier: NCT00777946
• Recruitment Status: Completed
• First Posted: October 22, 2008
• Results First Posted: June 15, 2011
• Last Update Posted: July 12, 2011
• Sponsor: Novartis
• Information provided by: Novartis

Study Description

Brief Summary:

This study will assess the safety and efficacy of combination aliskiren/amlodipine in patients not adequately controlled with aliskiren alone

Condition or disease	Intervention/treatment	Phase
Hypertension	Drug: Aliskiren 300 mg; Drug: Aliskiren/Amlodipine 300/5 mg; Drug: Aliskiren/Amlodipine 300/10 mg; Drug: Placebo to Aliskiren; Drug: Placebo to Aliskiren/Amlodipine	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 818 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Eight-week Double-blind, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of the Combination of Aliskiren / Amlodipine (300/5 mg and 300/10 mg) in Comparison With Aliskiren 300 mg in Patients With Essential Hypertension Not Adequately Responsive to Aliskiren 300 mg Monotherapy
• Study Start Date: October 2008
• Actual Primary Completion Date: May 2009
• Actual Study Completion Date: May 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Aliskiren 300 mg/Amlodipine 5 mg; Participants received 1 Aliskiren/Amlodipine 300/5mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks.	Drug: Aliskiren/Amlodipine 300/5 mg; Aliskiren/Amlodipine 300/5 mg tablet taken orally once a day with a glass of water.; Drug: Placebo to Aliskiren; Placebo to Aliskiren tablet taken orally once a day.
Experimental: Aliskiren 300 mg/Amlodipine 10 mg; Participants received 1 Aliskiren/Amlodipine 300/10 mg tablet + 1 Placebo to Aliskiren tablet orally once daily in the morning for 8 weeks.	Drug: Aliskiren/Amlodipine 300/10 mg; Aliskiren/Amlodipine 300/10 mg taken orally once a day with a glass of water.; Drug: Placebo to Aliskiren; Placebo to Aliskiren tablet taken orally once a day.
Active Comparator: Aliskiren 300 mg; Participants received 1 Aliskiren 300 mg tablet + 1 Placebo to Aliskiren/Amlodipine tablet orally once daily in the morning for 8 weeks.	Drug: Aliskiren 300 mg; Aliskiren 300 mg tablet taken orally once a day with a glass of water.; Drug: Placebo to Aliskiren/Amlodipine; Placebo to Aliskiren/Amlodipine taken orally once a day.

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline to End of Study in the Mean Sitting Diastolic Blood Pressure (msDBP) [ Time Frame: Baseline, End of Study (Week 8) ]
   After the patient had been sitting for 5 minutes, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. The difference of the msDBP at baseline from the msDBP at 8 weeks was calculated using an Analysis of Covariance (ANCOVA) model with baseline as a covariate and treatment and region as two factors.

Secondary Outcome Measures :

1. Change From Baseline to End of Study in the Mean Sitting Systolic Blood Pressure (msSBP) [ Time Frame: Baseline, End of Study (Week 8) ]
   After the patient had been sitting for 5 minutes, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. The difference of the msSBP at baseline from the msSBP at 8 weeks was calculated using an ANCOVA model with baseline as a covariate and treatment and region as two factors.
2. Number of Participants With Serious Adverse Events and Adverse Events [ Time Frame: 8 weeks ]

   The number of participants with any Serious Adverse Event and the number of participants with Adverse Events in any system organ class.

   Additional information about Adverse Events can be found in the Adverse Event Section.

3. Percentage of Participants Achieving Blood Pressure Control [ Time Frame: 8 weeks ]

   After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit.

   Blood Pressure control was defined as having a mean sitting Diastolic Blood Pressure <90 and a mean sitting Systolic Blood Pressure <140.

4. Percentage of Participants Achieving a Diastolic Blood Pressure Response [ Time Frame: 8 weeks ]

   After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit.

   A Diastolic Blood Pressure Response was defined as a mean sitting Diastolic Blood Pressure (msDBP) <90 mmHg or a ≥ 10 mmHg reduction in msDBP from baseline.

5. Percentage of Participants Achieving a Systolic Blood Pressure Response [ Time Frame: 8 weeks ]

   After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit.

   A Systolic Blood Pressure Response was defined as a mean sitting Systolic Blood Pressure (msSBP) <140 mmHg or a ≥ 20 mmHg reduction in msSBP from baseline.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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 Diastolic Blood Pressure (msDBP) ≥ 95 mmHg and < 110 mmHg at Visits 1 and 2
• Patients who have been treated for hypertension within the 4 weeks prior to - Visit 1 must have a msDBP ≥ 90 mmHg and < 110 mmHg at Visit 2
• All patients must have a msDBP ≥ 90 mmHg and < 110 mmHg at Visit 4

Exclusion Criteria:

• Severe hypertension
• Pregnant or nursing (lactating) women
• Women of child-bearing potential
• Previous or current diagnosis of heart failure New York Heart Association (NYHA Class II-IV)
• Serum potassium ≥ 5.3 mEq/L (mmol/L) at Visit 1
• Uncontrolled Type 1 or Type 2 diabetes mellitus
• Hypersensitivity to renin inhibitors, calcium channel blockers, or to drugs with Similar chemical structures
• History of hypertensive encephalopathy or cerebrovascular accident, or history of transient ischemic attack (TIA), myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

Estonia

Investigative site

Estonia, Estonia

France

Investigative site

France, France

Iceland

Investigative Site

Iceland, Iceland

India

Investigative Site

India, India

Italy

Investigative site

Italy, Italy

Korea, Republic of

Investigative Site

Republic of Korea, Korea, Republic of

Lithuania

Investigative Site

Lithuania, Lithuania

Spain

Investigative Site

Spain, Spain

Venezuela

Investigative Site

Venezuela, Venezuela

Sponsors and Collaborators

Novartis

Investigators

• Study Chair: Novartis; Novartis

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Glorioso N, Thomas M, Troffa C, Argiolas G, Patel S, Baek I, Zhang J. Antihypertensive efficacy and tolerability of aliskiren/amlodipine single- pill combinations in patients with an inadequate response to aliskiren monotherapy. Curr Vasc Pharmacol. 2012 Nov;10(6):748-55.

• Responsible Party: External Affairs, Novartis
• ClinicalTrials.gov Identifier: NCT00777946
• Other Study ID Numbers: CSPA100A2303
• First Posted: October 22, 2008
• Results First Posted: June 15, 2011
• Last Update Posted: July 12, 2011
• Last Verified: June 2011

Keywords provided by Novartis:

Aliskiren, Amlodipine, Non-responder to aliskiren

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases; Amlodipine; Antihypertensive Agents; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Vasodilator Agents