A Study To Evaluate The Dose-Related Efficacy and Safety of PS433540 in Subjects With Hypertension

Study Overview
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Brief Summary
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The purpose of this study is to learn which doses of PS433540 should be given to patients with high blood pressure to lower their blood pressure. This study will also examine how safe PS433540 is when taken by patients with high blood pressure. Approximately 720 patients will be evaluated so that about 375 patients will be entered into the treatment phase of the study and be given PS433540.

Official Title
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A Randomized, Double-Blind, Placebo And Active-Controlled, Parallel Group Study To Evaluate The Dose-Related Efficacy And Safety Of PS433540 In Subjects With Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: irbesartan
* Drug: placebo
* Drug: PS433540
* Drug: PS433540
* Drug: PS433540


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females 18 - 70 years Mean seated Systolic Blood Pressure (SBP) ≥ 140 mmHg and < 180 mmHg and mean seated Diastolic Blood Pressure (DBP) > 90 and < 109 mmHg at two consecutive qualifying visits (Visits 3/3.5 and Visit 4). The mean difference in DBP between the two consecutive qualifying visits must be ≤ 10 mmHg. Women of child-bearing potential (WOCBP) must use two reliable forms of contraception if sexually active. Alternatively, female subjects must be postmenopausal (for at least 1 year). Exclusion Criteria: Subjects with serious disorders which may limit the ability to evaluate the efficacy or safety of PS433540, including cardiovascular (includes subjects who are known to have coronary artery disease), renal (including the absence of one kidney), pulmonary, hepatic, gastrointestinal (including clinically significant malabsorption), endocrine/metabolic, hematologic, neurologic and psychiatric diseases. History of malignancy other than adequately treated basal cell or squamous cell skin cancer. Subjects with a history of myocardial infarction or New York Heart Association (NYHA) class II-IV heart failure. Subjects with a history of cerebrovascular accident or transient ischemic attack. Subjects with clinically significant cardiac conduction defects, including second or third degree Atrioventricular Block (AV block), left bundle branch block, sick sinus syndrome, atrial fibrillation, atrial flutter, an accessory bypass tract, or any arrhythmia requiring medication. Subjects with hemodynamically significant valvular disease. Subjects with history of type 1 diabetes mellitus and subjects with a history of type 2 diabetes mellitus using antihyperglycemic medication (oral medication, insulin, or exenatide) are excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Irbesartan 300mg<br>Irbesartan 300 mg once daily | Drug: irbesartan<br>* 300 mg (2 x 150 mg capsules) once daily for 12 weeks<br>* Other names: Avapro;|
| Placebo Comparator: Placebo<br>Blinded Placebo Treatment | Drug: placebo<br>* placebo capsules once daily for 12 weeks<br>|
| Experimental: PS433540 200mg<br>PS433540 200mg once daily | Drug: PS433540<br>* 200 mg (2 x 100 mg capsules) once daily for 12 weeks<br>|
| Experimental: PS433540 400mg<br>PS433540 400mg once daily | Drug: PS433540<br>* 400 mg (4 x 100 mg capsules) once daily for 12 weeks<br>|
| Experimental: PS433540 800mg<br>PS433540 800mg once daily | Drug: PS433540<br>* 800 mg (8 x 100 mg capsules) once daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Seated Systolic Blood Pressure (SBP) Following 12 Weeks of Treatment With PS433540 200 mg, 400 mg, 800 mg and Placebo. |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Seated Diastolic Blood Pressure (DBP) Following 12 Weeks of Treatment With PS433540 200 mg, 400 mg, 800 mg and Placebo. |  | 12 weeks | 
| The Percentage of Patients Treated With Each Dose of PS433540 Who Achieved Blood Pressure Control, Defined as <140/90 mmHg, After 12 Weeks of Treatment. |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, High Blood Pressure