Safety, Tolerability, and Efficacy of Once Daily Amlodipine/Valsartan 5/80 as Compared to Amlodipine/Valsartan 5/40 or to Amlodipine 5 mg Monotherapy in Patients 65 Years of Age and Older With Essential Hypertension

NCT00699192 | Completed Phase 3 Results

• 1 other identifier: CVAA489A2318
• Study Type: interventional
• Target: 965
• Locations: 10 countries
• Sites: 18

Brief Summary

To characterize the safety, tolerability, and efficacy profile of amlodipine/valsartan 5/80 mg as compared to amlodipine/valsartan 5/40 mg (with optional titration to 5/80 mg) and amlodipine 5 mg monotherapy in elderly patients (≥ 65 years of age) with essential hypertension. All three regimens are expected to be well tolerated.

Conditions

Hypertension

Keywords

Blood pressure; hypertension; elderly

Outcome Measures

Primary Outcomes (1)

• Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (Week 8)

  At study entry, blood pressure (BP) was measured in both arms with an automatic BP monitor. The arm with the higher systolic BP reading was used for all measurements throughout the study. At each study visit, 3 separate sitting BPs were obtained 23-26 hours post-dose with at least 2 minutes between measurements and with the cuff fully deflated. Mean BP was automatically calculated from the 3 readings. A negative change from baseline indicates lowered BP.

  Baseline to end of study (Week 8)

Secondary Outcomes (4)

• Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8)

  Baseline to end of study (Week 8)

• Percentage of Patients Achieving a Systolic Blood Pressure Response at Week 8

  Baseline to end of study (Week 8)

• Percentage of Patients Achieving Systolic Blood Pressure Control at the End of the Study (Week 8)

  End of study (Week 8)

• Percentage of Patients Achieving Overall Blood Pressure Control at the End of the Study (Week 8)

  End of study (Week 8)

Study Arms (3)

Amlodipine/Valsartan 5/80 mg

EXPERIMENTAL

1 capsule amlodipine 5 mg, 1 capsule valsartan 80 mg once daily

Drug: Amlodipine 5 mg; Drug: Valsartan 80 mg

Amlodipine/Valsartan 5/40 mg

ACTIVE COMPARATOR

1 capsule amlodipine 5 mg, 1 capsule valsartan 40 mg once daily

Drug: Amlodipine 5 mg; Drug: Valsartan 40 mg

Amlodipine 5 mg

ACTIVE COMPARATOR

1 capsule amlodipine 5 mg, 1 capsule placebo to match valsartan once daily

Drug: Amlodipine 5 mg; Drug: Placebo

Interventions

Amlodipine 5 mg DRUG

1 capsule amlodipine 5 mg orally once daily

Amlodipine 5 mg; Amlodipine/Valsartan 5/40 mg; Amlodipine/Valsartan 5/80 mg

Valsartan 80 mg DRUG

1 capsule valsartan 80 mg orally once daily

Amlodipine/Valsartan 5/80 mg

Valsartan 40 mg DRUG

1 capsule valsartan 40 mg orally once daily

Amlodipine/Valsartan 5/40 mg

Placebo DRUG

1 capsule placebo to match valsartan orally once daily

Amlodipine 5 mg

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Provide written informed consent before any assessment was performed.
• Male or female at least 65 years of age.
• Diagnosed as having hypertension:
• At Visit 1/Screening, treatment naïve patients had to have a mean seated SBP ≥ 155 mmHg and \< 180 mmHg; patients undergoing washout from their previous antihypertension medication had to have a mean seated SBP \<180 mmHg.
• At Visit 2/Single-blind run-in entry, all patients had to have a mean seated SBP ≥ 155 mmHg and \< 180 mmHg.
• At Visit 3/Core double-blind treatment period entry, all patients had to have a mean seated SBP ≥ 145 mmHg and \< 180 mmHg.
• Ability to communicate and comply with all study requirements including measuring their blood pressure at home, daily as instructed, using the home blood pressure monitor provided by the Sponsor.
• Female patients had to be post-menopausal for at least one year.

You may not qualify if:

• Severe hypertension (mean seated SBP ≥ 180 mmHg and/or a mean seated DBP ≥ 110 mmHg).
• History of secondary hypertension (including primary aldosteronism, renovascular hypertension, pheochromocytoma, etc.).
• Use of three or more antihypertensive drugs. Dual fixed dose combination therapy was considered as two antihypertensive drugs.
• Administration of any agent indicated for the treatment of hypertension after Visit 1, with the permitted exception of those antihypertensive medications requiring tapering down (e.g. beta-blocker and/or clonidine) commencing with Visit 1.
• Known moderate or malignant retinopathy. Moderate was defined as retinal signs of hemorrhage, microaneurysm, cotton-wool spot, hard exudates, or a combination thereof; malignant defined as signs of moderate retinopathy plus swelling of the optic disk.
• Known or suspected contraindications, including history of allergy or hypersensitivity to angiotensin receptor blockers (ARB), calcium channel blockers (CCB), or to drugs with similar chemical structures.
• History of cerebrovascular accident, thrombotic stroke, or transient ischemic attack.
• Significant history of coronary artery disease (CAD) such as any history of myocardial infarction (MI), angina pectoris, and all types of revascularization procedures.
• History of or diagnosis of congestive heart failure Grade II-IV according to the New York Heart Association (NYHA) classification.
• Clinically significant valvular heart disease.
• All patients with Type 1 diabetes mellitus and those patients with Type 2 diabetes mellitus who, in the opinion of the investigator, were not well controlled. Patients who needed oral anti-diabetic medication to adequately control their Type 2 diabetes had to be on a stable dose of oral anti-diabetic medication for at least 4 weeks prior to Visit 1.
• Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia.
• Second or third degree heart block with or without a pacemaker.
• Significant hepatic disease, as demonstrated by any one of the following: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values greater than two times the upper limit of normal at Visit 1, a history of hepatic encephalopathy, a history of esophageal varices, or a history of a portocaval shunt.
• Evidence of renal impairment as determined by any one of the following: glomerular filtration rate (GFR) \< 50 ml/min/1.73m2 as measured by the Modification of Diet in Renal Disease (MDRD) formula at Visit 1, a history of dialysis, or a history of nephrotic syndrome.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (18)

Novartis Investigative site

Brno, Czechia

Location

Investigative site Czech Republic

Chrudim, Czechia

Location

Investigative sites Czech Repbulic

Hodonín, Czechia

Location

Investigative site Czech Repbulic

Jičín, Czechia

Location

Sites in Czech Republic

Náchod, Czechia

Location

Investigative sites Czech Republic

Prague, Czechia

Location

Investigative site Finland

Helsinki, Finland

Location

Investigative site Finland

Joensuu, Finland

Location

Investigative site Finland

Kerava, Finland

Location

Investigative site Finland

Tampere, Finland

Location

Investigative site France

Paris, France

Location

Investigative site Germany

Berlin, Germany

Location

Investigative site Hungary

Budapest, Hungary

Location

Investigative site Italy

Rome, Italy

Location

Investigative site Poland

Warsaw, Poland

Location

Investigative site Slovakia

Bratislava, Slovakia

Location

Investigative site Spain

Valencia, Spain

Location

Investigative site Sweden

Malmo, Sweden

Location

MeSH Terms

Conditions

Hypertension

Interventions

Amlodipine; Valsartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles; Azoles; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 9, 2008
• First Posted: June 17, 2008
• Study Start: May 1, 2008
• Primary Completion: May 1, 2009
• Study Completion: May 1, 2009
• Last Updated: June 6, 2011
• Results First Posted: June 6, 2011

Record last verified: 2011-05

Locations

DE (1); FR (1); SL (1); ES (1); CZ (6); PL (1); FI (4); HU (1); IT (1); SE (1)