Long Term Study of Valsartan and Amlodipine in Patients With Essential Hypertension (Extension to Study CVAA489A1301)

A 54-week Extension to the Multi-center, Randomized, Double-blind, Parallel-group, Placebo-controlled, Factorial Study to Evaluate the Efficacy and Safety of VAA489 (Valsartan and Amlodipine Combined) and Alone in Essential Hypertensive Patients - Long Term Study of VAA489 in Patients With Essential Hypertension (Extension From A1301 Study)

The purpose of this study is to evaluate long-term safety and tolerability of once daily administration of the combination of Valsartan and Amlodipine 80/5 mg for 52 weeks in patients with essential hypertension.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Valsartan + Amlodipine besilate

• Study Type: Interventional
• Enrollment (Actual): 403
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who successfully complete the core study (Study CVAA489A1301.
• Patients whose blood pressure at Visit 7 of the Study CVAA489A1301 had to be well controlled defined as MSDBP < 90 mmHg and MSSBP < 140 mmHg. At the investigator's or sub-investigator's discretion, those patients who were not well controlled (MSDBP ≥ 90 mmHg or MSSBP ≥ 140 mmHg), and whose MSDBP was < 100 mmHg and MSSBP was < 160 mmHg might participate in the extension if this was considered an acceptable level of blood pressure control for the patient.
• Male or female outpatients.
• Patients who have written informed consent to participate in this study.

Exclusion Criteria:

• Presence of major protocol violation in Study CVAA489A1301.
• Patients who experienced any adverse events considered serious and drug related in Study CVAA489A1301.
• Patients who experienced any adverse events considered serious and drug related in Study CVAA489A1301.
• Patients who are considered unlikely to comply with the requirements specified in the protocol by the investigator or sub-investigator.
• Patients who have gout or gouty arthritis.
• Patients hypersensitive to diuretics (except for potassium sparing diuretics).

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Valsartan + Amlodipine 80/5 mg; Valsartan 80 mg or Amlodipine 5 mg ---> Valsartan + Amlodipine 80 / 5 mg	Drug: Valsartan + Amlodipine besilate; During the run-in period, either Valsartan 80 mg or Amlodipine 5 mg tablet was given once daily. Throughout the Valsartan + Amlodipine treatment period, a Valsartan + Amlodipine tablet 80/5 mg was given once daily at around 8:00 AM in the morning.; Other Names: Valsartan, Amlodipine besilate, VAL, AML
Experimental: Valsartan + Amlodipine 80/5 mg + Diuretic; Valsartan + Amlodipine 80 / 5 mg + Diuretic	Drug: Valsartan + Amlodipine besilate; During the run-in period, either Valsartan 80 mg or Amlodipine 5 mg tablet was given once daily. Throughout the Valsartan + Amlodipine treatment period, a Valsartan + Amlodipine tablet 80/5 mg was given once daily at around 8:00 AM in the morning.; Other Names: Valsartan, Amlodipine besilate, VAL, AML

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety assessed by serious and non-serious adverse events	No new unexpected AE's were observed in long-term treatment with VAA 80/5 mg. There were no deaths during the study. The SAEs were rare, with 9 patients (2.5%) reporting 10 events (1 patient experienced 2 SAEs). These events were not clustered to any particular primary system organ class and only 2 events the investigators could not excluded a relationship to study drug. The events that occurred were expected in this study population and/or were known to be associated with either valsartan or amlodipine. AEs leading to discontinuation occurred in 14 patients (3.8%).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy assessed by the changes-from baseline measurements in mean sitting diastolic blood pressure, mean sitting systolic blood pressure, standing diastolic blood pressure, and standing systolic blood pressure	Clinically meaningful reductions in MSDBP and MSSBP were observed after 2 weeks of VAA 80/5 mg treatment and were maintained until the end of the 52-week VAA treatment period. The MSDBP and MSSBP were controlled below 85 mmHg and 130 mmHg, respectively for the entire 52-week VAA treatment period. At endpoint the MSDBP was controlled below 80 mmHg.	12 months
Laboratory tests	Laboratory changes observed with the long-term administration of VAA 80/5 mg were consistent with the known effects of each monotherapy agent.	12 months
Vital signs	Mean changes from baseline at endpoint were small and clinically unremarkable in extension population for weight, sitting/standing pulse values. AEs related to abnormal vital signs were rare during the VAA treatment period. No patient reported orthostatic hypotension as an AE. Only one patient (PID 0045/00007) was discontinued from the study due to blood pressure decreased and dizziness.	12 months
Electrocardiogram (ECG)	None of the patients reported shifting from clinically non-significant to clinically significant ECG abnormality. However, three patients experienced clinically significant ECG abnormalities and were reported as AEs during the VAA treatment period.	12 months

Collaborators and Investigators

• Sponsor: Novartis

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: March 9, 2007
• First Submitted That Met QC Criteria: March 9, 2007
• First Posted (Estimate): March 13, 2007

Study Record Updates

• Last Update Posted (Actual): March 28, 2017
• Last Update Submitted That Met QC Criteria: March 24, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Hypertension, Valsartan, Amlodipine, high blood pressure
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Amlodipine; Valsartan
• Other Study ID Numbers: CVAA489A1302