A Trial to Evaluate the Safety and Efficacy of PS433540 to Treat Hypertension

• PS433540 (Drug): 200mg capsule, once daily for 28 days
• placebo (Drug): placebo capsule, once daily for 28 days
• PS433540 (Drug): 500mg capsule, once daily for 28 days

Primary outcomes

• Change From Baseline in Mean 24-hour Ambulatory Systolic Blood Pressure [4 weeks of treatment with PS43540]

Secondary outcomes

• Change From Baseline in Mean 24-hour Ambulatory Diastolic Blood Pressure [4 weeks of treatment with PS43540]
• Change From Baseline in Mean Seated Systolic and Diastolic Blood Pressure [4 weeks of treatment with PS43540]

Sex: All, ages: 30 Years to 80 Years

Inclusion Criteria:

* Males or females 30 - 80 years
* Mean seated Systolic Blood Pressure (SBP) ≥ 150 - ≤ 179 mmHg and mean seated DBP < 110 mmHg at two consecutive qualifying visits. The mean difference in SBP between the two consecutive qualifying visits must be ≤ 10 mmHg.
* Mean daytime (8AM - 4PM) ambulatory SBP must be between ≥ 140 - ≤ 179 mmHg and mean daytime (8AM - 4PM) Diastolic Blood Pressure (DBP) ≤ 110 mmHg
* Subjects must have a usual daytime schedule. Night shift workers are excluded from participation.
* Women of child-bearing potential (WOCBP) and male subjects 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, renal (including the absence of one kidney), pulmonary, hepatic, gastrointestinal (including clinically significant malabsorption), endocrine/metabolic, hematologic/oncologic (including an active malignancy other than basal cell carcinoma), neurologic and psychiatric diseases.
* Subjects with a history of myocardial infarction, angina, coronary angioplasty, bypass surgery or New York Heart Association (NYHA) class II-IV heart failure within the last 6 months.
* Subjects with a history of cerebrovascular accident or transient ischemic attack within the last 1 year.
* Subjects with diabetes mellitus (type I and type II).

Participant flow

Outcome results

• Change From Baseline in Mean 24-hour Ambulatory Systolic Blood Pressure (Primary), Mean, mmHg: 1- Placebo -0.3 (-4.8 to 4.2); 2- PS433540 200mg -11.9 (-15.3 to -8.6); 3- PS433540 500mg -15.3 (-18.8 to -11.8)
• Change From Baseline in Mean 24-hour Ambulatory Diastolic Blood Pressure (Secondary)
• Change From Baseline in Mean Seated Systolic and Diastolic Blood Pressure (Secondary)

Adverse events

Serious adverse events by term

Other adverse events by term

• Joel M Neutel, MD, Principal investigator, Integrium