Hypertension
Conditions
Keywords
Hypertension, High Blood Pressure
Brief summary
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.
Interventions
DRUGirbesartan
300 mg (2 x 150 mg capsules) once daily for 12 weeks
DRUGplacebo
placebo capsules once daily for 12 weeks
DRUGPS433540
200 mg (2 x 100 mg capsules) once daily for 12 weeks
Sponsors
Ligand Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
United States
Participant flow
Pre-assignment details
All subjects were weaned off all antihypertensive medication prior to be entered into a 4-week single-blind placebo run-in period. Subjects had to have eligible Seated systolic and diastolic BP measurements during the single-blind placebo run-in phase to be eligible for the double blind portion of the study.
Participants by arm
| Arm | Count |
|---|---|
| Irbesartan 300mg Irbesartan 300 mg once daily | 58 |
| Placebo Blinded Placebo Treatment | 59 |
| PS433540 200mg PS433540 200mg once daily | 58 |
| PS433540 400mg PS433540 400mg once daily | 58 |
| PS433540 800mg PS433540 800mg once daily | 28 |
| Total | 261 |
Baseline characteristics
| Characteristic | Placebo | PS433540 200mg | PS433540 400mg | Irbesartan 300mg | PS433540 800mg | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 8 Participants | 10 Participants | 5 Participants | 0 Participants | 30 Participants |
| Age, Categorical Between 18 and 65 years | 52 Participants | 50 Participants | 48 Participants | 53 Participants | 28 Participants | 231 Participants |
| Age Continuous | 54.2 years STANDARD_DEVIATION 8.12 | 53.2 years STANDARD_DEVIATION 10.58 | 53.4 years STANDARD_DEVIATION 10.71 | 51.5 years STANDARD_DEVIATION 8.97 | 51.4 years STANDARD_DEVIATION 9.92 | 52.9 years STANDARD_DEVIATION 9.66 |
| Region of Enrollment United States | 59 participants | 58 participants | 58 participants | 58 participants | 28 participants | 261 participants |
| Sex: Female, Male Female | 30 Participants | 27 Participants | 26 Participants | 23 Participants | 17 Participants | 123 Participants |
| Sex: Female, Male Male | 29 Participants | 31 Participants | 32 Participants | 35 Participants | 11 Participants | 138 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 19 / 58 | 20 / 59 | 10 / 58 | 25 / 58 | 17 / 28 |
| serious Total, serious adverse events | 0 / 58 | 0 / 59 | 0 / 58 | 1 / 58 | 0 / 28 |
Outcome results
Primary
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.
Time frame: 12 weeks
Population: The primary efficacy population was the Full Analysys Set (FAS) population= all randomized subjects who took at least one dose of the assigned study drug and had both baseline and post-baseline mean seated SBP. Both LOCF and observed-data set approach were performed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Irbesartan 300mg | 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. | -10.7 mm Hg | Standard Deviation 14.32 |
| Placebo | 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. | 1.8 mm Hg | Standard Deviation 14.16 |
| PS433540 200mg | 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. | -13.2 mm Hg | Standard Deviation 13.61 |
| PS433540 400mg | 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. | -14.2 mm Hg | Standard Deviation 11.9 |
| PS433540 800mg | 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. | -23.4 mm Hg | Standard Deviation 18.7 |
Secondary
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.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Irbesartan 300mg | 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. | -7.1 mm Hg | Standard Deviation 9.19 |
| Placebo | 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. | 0.2 mm Hg | Standard Deviation 9.68 |
| PS433540 200mg | 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. | -7.2 mm Hg | Standard Deviation 8.34 |
| PS433540 400mg | 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. | -9.2 mm Hg | Standard Deviation 9.1 |
| PS433540 800mg | 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. | -14.3 mm Hg | Standard Deviation 10.53 |
Secondary
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.
Time frame: 12 weeks
Population: Full analysis set (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Irbesartan 300mg | 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. | 17 participants |
| Placebo | 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. | 5 participants |
| PS433540 200mg | 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. | 21 participants |
| PS433540 400mg | 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. | 28 participants |
| PS433540 800mg | 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. | 16 participants |