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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Valsartan + Amlodipine besilate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valsartan + Amlodipine 80/5 mg<br>Valsartan 80 mg or Amlodipine 5 mg ---> Valsartan + Amlodipine 80 / 5 mg | Drug: Valsartan + Amlodipine besilate<br>* 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.<br>* Other names: Valsartan, Amlodipine besilate, VAL, AML;|
| Experimental: Valsartan + Amlodipine 80/5 mg + Diuretic<br>Valsartan + Amlodipine 80 / 5 mg + Diuretic | Drug: Valsartan + Amlodipine besilate<br>* 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.<br>* Other names: Valsartan, Amlodipine besilate, VAL, AML;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Valsartan, Amlodipine, high blood pressure