Study of Efficacy and Safety of Irbesartan/Amlodipine 4 Fixed Combination Therapy in Hypertensive Patients Uncontrolled on Irbesartan or Amlodipine Monotherapy

Study Overview
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Brief Summary
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Primary Objective: - To assess the proportion of patients with controlled Office Blood Pressure Measurements (OBPM), defined as Systolic blood pressure < 140 mmHg and Diastolic blood pressure <90mmHg, at the end of the study Secondary Objectives: To examine over time the antihypertensive effect of the 4 doses of the fixed combination therapy irbesartan/amlodipine on OBPM (SBP (systolic blood pressure) and DBP (diastolic blood pressure) To examine the proportion of patients with controlled OBPM (systolic BP<140 mm Hg and diastolic BP<90 mmHg) of the different dose groups over time To determine the incidence and severity of adverse events.

Detailed Description
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16 weeks V1 (week 0): Inclusion visit. V2 (Week 4): Irbesartan/amlodipine 150/5 mg fixed combination visit V3 (Week 8): 1st dose escalation for patients in whom OBPM is not controlled (SBP ≥ 140 mmHg or DBP ≥ 90mmHg, V4 (Week 12): 2nd Dose escalation visit for patients in whom OBPM is not controlled (SBP ≥ 140 mmHg or DBP ≥ 90mmHg V5 (Week 16): End of study visit

Official Title
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A Prospective Open-label Multicentre Study of Efficacy and Safety of Irbesartan/Amlodipine 4 Fixed Combination Therapy in Hypertensive Patients Uncontrolled on Irbesartan 150 mg or Amlodipine 5 mg Monotherapy

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Irbesartan/Amlodipine (150/5mg)
* Drug: Irbesartan/Amlodipine (150/10mg)
* Drug: Irbesartan/Amlodipine (300/5mg)
* Drug: Irbesartan/Amlodipine (300/10mg)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Men and women ≥18 years old Established essential hypertension Treated with irbesartan 150 mg or amlodipine 5 mg as monotherapy for at least 2 weeks With uncontrolled systolic BP (blood pressure) defined as ≥140 mm Hg assessed by OBPM (office blood pressure measurements) Signed written informed consent obtained prior to inclusion to the study Exclusion criteria: Mean systolic BP ≥180 mm Hg and/or mean diastolic BP ≥110 mm Hg by OBPM on Visit 1 Known or suspected causes of secondary hypertension Patients with bilateral artery stenosis, renal artery stenosis in a solitary kidney, renal transplant or only has one functioning kidney Known contraindications or hypersensitivity to either amlodipine or irbesartan or to the combination History of angioedema related to the administration of an angiotensin II receptor antagonist or any combination of the drugs used Severe hepatic impairment (Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) >5 times the upper normal limit (ULN) or history of hepatic encephalopathy, esophageal varices or portocaval shunt) Severe renal impairment (glomerular filtration rate <30 ml/min) Concomitant use of any other antihypertensive treatment except of Irbesartan and Amlodipine Administration of any other investigational drug within 30 days before inclusion Presence of any other conditions that would restrict or limit the patient participation for the duration of the study Pregnant or breast feeding women Women of childbearing potential unable or unwilling to use an acceptable method to avoid pregnancy for the entire study period Patient is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Irbesartan/Amlodipine 150/5 mg fixed combination<br>1 tablet once daily in the morning for 4 weeks Patient will be first treated with irbesartan 150mg or amlodipine 5mg, 1 tablet /day for 4 weeks. If OBPM is controlled on monotherapy at week 4 (SBP <140 mmHg and DBP<90 mmHg), patient will be withdrawn from the study | Drug: Irbesartan/Amlodipine (150/5mg)<br>* Pharmaceutical form: tablet Route of administration: oral<br>|
| Experimental: Irbesartan/Amlodipine 150/10 mg fixed combination<br>1 tablet once daily in the morning for 4 weeks | Drug: Irbesartan/Amlodipine (150/10mg)<br>* Pharmaceutical form: tablet Route of administration: oral<br>|
| Experimental: Irbesartan/Amlodipine 300/5 mg fixed combination<br>1 tablet once daily in the morning for 4 weeks | Drug: Irbesartan/Amlodipine (300/5mg)<br>* Pharmaceutical form: tablet Route of administration: oral<br>|
| Experimental: Irbesartan/Amlodipine 300/10 mg fixed combination<br>1 tablet once daily in the morning for 4 weeks. If OBPM is controlled at week 12, patients will continue on the same therapy until the end of the study | Drug: Irbesartan/Amlodipine (300/10mg)<br>* Pharmaceutical form:tablet Route of administration: oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with controlled OBPM (SBP<140 mmHg and DBP<90 mmHg) at the end of the study |  | up to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with controlled OBPM by visit and treatment group | at Visit 3 (Week 8), at Visit 4 (Week 12) and at Visit 5 (Week 16) | up to 16 weeks | 
| Mean change in OBPM between 2 visits | Visit 2 (Week 4) and Visit 5 (Week 16), Visit 2 (Week 4) and Visit 4 (week 12), Visit 2 (Week 4) and Visit 5 (Week 16), Visit 3 (Week 8) and Visit 4 (Week 12), Visit 3 (Week 8) and Visit 5 (Week 16) | up to 16 weeks | 
| Number of patients with adverse events |  | up to 16 weeks | 
| Number of patients who discontinue from the study due to adverse events |  | up to 16 weeks | 
| Number of patients with abnormal liver function | As measured by AST, ALT, total bilirubin and serum creatinine | up to 16 weeks |