BP-EASE -Effectiveness of Losartan 50 mg/Hydrochlorothiazide (HCTZ) 12.5 mg Versus Valsartan 80 mg/HCTZ 12.5 mg Titrated as Needed in Patients With Essential Hypertension Not Controlled on Monotherapy (0954A-333)

Study Overview
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Brief Summary
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To evaluate the blood pressure efficacy between losartan and valsartan at equivalent dosage during a 3 months treatment.

Official Title
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BP-EASE-A 12-Week, Multicenter, Open-Label, Randomized, Controlled Trial To Compare The Effectiveness of Losartan 50 mg/HCTZ 12.5 mg Titrated as Needed to Losartan 100 mg/HCTZ 25 mg or Valsartan 160 mg/HCTZ 25 mg, in Patients With Essential Hypertension Who Have Not Achieved Target Blood Pressure With

Conditions
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Hypertension

Intervention / Treatment
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* Drug: losartan potassium (+) hydrochlorothiazide
* Drug: Comparator: Valsartan (+) Hydrochlorothiazide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: An Adult Patient 18 to 75 Years Of Age Patient with essential hypertension receiving an antihypertensive agent in monotherapy for at least 4 weeks for whom the antihypertensive agent can (and will) be discontinued and whose blood pressure is not controlled: Either systolic or diastolic blood pressure > 140/90 mm Hg up to 180/110 mm Hg (inclusive) Either systolic or diastolic blood pressure > 130/80 mm Hg up to 160/100 mm Hg (inclusive) for diabetic patients Patient is male or a female who is highly unlikely to conceive as she falls into one of the categories listed below: Surgically sterilized female Postmenopausal female > 45 years of age with > 2 years since her last menses Non-sterilized pre-menopausal female who agrees to: (1) use 2 adequate methods of contraception to prevent pregnancy [either 2 barrier methods or a barrier method plus a hormonal method]; or (2) abstain from heterosexual activity throughout the study starting with Visit 1 and for 14 days after the last dose of study medication; or (3) only engage in heterosexual activity with surgically sterilized male partner(s) throughout the study starting with Visit 1 and for 14 days after the last dose of study medication Patient judged to be in otherwise good, stable health on the basis of medical history and physical examination Exclusion Criteria: Known secondary hypertension of any aetiology (e.g., uncorrected renal artery stenosis, malignant hypertension, or hypertensive encephalopathy) Patient Needing An Initiation Of A Lipid Lowering Agent Or A Modification Of His Lipid Therapy At Visit 1 Or During The Study Period (12 Weeks) Patient taking allopurinol Patient Previously Shown To Be Intolerant To Any Component Of Losartan Valsartan, Or HCTZ Or With A Documented History Of Angioedema/Anaphylaxis Patient With Confirmed Clinically Significant Renal Or Hepatic Dysfunction And/Or Electrolyte Imbalance Laboratory Test Within The Last 3 Months Prior To Visit 1: Serum Creatinine > 130 Umol/L Or Creatinine Clearance < 45 Ml/Min, Aspartate transaminase (AST) > 2 Times Above The Normal Range, Alanine transaminase (ALT) > 2 Times Above The Normal Range, Serum Potassium < 3.5 Or > 5.5 Meq/L Patient with osteoarthritis who has undergone hip or knee replacement within the last 4 months Patient with chronic inflammatory conditions such as rheumatoid arthritis, lupus, inflammatory bowel disease and those that need a chronic inflammatory therapy such as prednisone or other steroid agents Patient with symptomatic heart failure (classes 3 and 4) Patient with a history of stroke within the last 6 months Patient with coronary heart disease: has undergone percutaneous coronary angioplasty, has had coronary artery bypass, has had past myocardial infarction, all that occurred less than 6 months prior to visit 1 or has unstable angina Patient having participated in an investigational drug program in the last 30 days (prior to Visit 1) Unable or unwilling to comply with the protocol, therefore likely to leave the trial before its completion Patient intends to move or to vacation away from home during the course of the study which would interfere with the scheduled visits.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: 1<br>Drug Arm | Drug: losartan potassium (+) hydrochlorothiazide<br>* losartan potassium 50 mg/12.5 Hydrochlorothiazide (HCTZ) titrated as needed to losartan potassium 100 mg/25 mg Hydrochlorothiazide<br>|
| Active Comparator: 2<br>active comparator | Drug: Comparator: Valsartan (+) Hydrochlorothiazide<br>* Valsartan 80 mg/ Hydrochlorothiazide 12.5 mg/day titrated as needed to valsartan 160 mg/25 mg Hydrochlorothiazide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Systolic Blood Pressure From Baseline to Week 12 |  | Baseline and Week 12 | 
| Change in Diastolic Blood Pressure From Baseline to Week 12 |  | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Systolic Blood Pressure From Baseline to Week 6 |  | Baseline and Week 6 | 
| Change in Diastolic Blood Pressure From Baseline to Week 6 |  | Baseline and Week 6 | 
| Number of Patients Achieving Target Blood Pressure at Week 6 | Number of Patients Achieving Target Blood Pressure (<140/90 mm Hg and <130/80 mm Hg for diabetics) at week 6 | Week 6 | 
| Number of Patients Achieving Target Blood Pressure at Week 12 | Number of Patients Achieving Target Blood Pressure (<140/90 mm Hg and <130/80 mm Hg for diabetics) at week 12 | 12 Weeks | 
| Time to Achieve Target Blood Pressure | Time to achieve the target blood pressure (<140/90 mmHg and <130/80 mmHg for diabetics) | 12 weeks | 
| Change in Uric Acid From Baseline to Week 6 |  | Baseline and Week 6 | 
| Change in Uric Acid From Baseline to Week 12 |  | Baseline and Week 12 | 
| Change in Serum Highly Sensitive C-reactive Protein From Baseline to Week 6 |  | Baseline and Week 6 | 
| Change in Serum Highly Sensitive C-reactive Protein From Baseline to Week 12 |  | Baseline and Week 12 | 
| Change in Gamma-Glutamyl Transpeptidase (Gamma-GT) From Baseline to Week 6 |  | Baseline and Week 6 | 
| Change in Gamma-Glutamyl Transpeptidase (Gamma-GT) From Baseline to Week 12 |  | Baseline and Week 12 |