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This study is an exploratory Phase 1 randomized, double-blind (Investigator and study subject and 2-D echo endpoint assessor), placebo-controlled single IV infusion dose escalation study that will enroll up to approximately 32 subjects with stage 1 or 2 essential hypertension.
The study will be conducted in two parts.
Part 1: For the initial evaluation of safety, pharmacokinetic exposure and pharmacodynamic response, subjects will be tapered off antihypertensive background therapy.The initial starting dose will be a sub-therapeutic dose. Dose escalation will continue with a maximum of a doubling of the previous dose until either 1) a maximum tolerated dose (MTD) is identified or 2) modeling of the pharmacokinetic (PK) data indicate that maximum exposure (Cmax) at the next planned dose level would exceed a maximum drug concentration (Cmax) which was the maximum observed drug concentration following a single subcutaneous administration in Study PB1046-PT-CL-0001.
Part 2: The dose group which is capable of providing a Cmax exposure which is capable of eliciting a clinically relevant hemodynamic response, will be expanded to enroll an additional 12 subjects (6 active and 6 placebo).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: Single IV Infusion Vasomera (PB1046) or Placebo | Experimental | Cohort 1 - Single 30 minute infusion Vasomera (PB1046) at 0.01 mg/kg diluted in 0.9% Sodium Chloride or Placebo (0.9% Sodium Chloride) |
|
| Cohort 2: Single IV Infusion Vasomera (PB1046) or Placebo | Experimental | Cohort 2 - Single 30 minute infusion Vasomera (PB1046) at 0.005mg/kg in 0.9% Sodium Chloride or Placebo (0.9% Sodium Chloride) |
|
| Cohort 3: Single IV Infusion Vasomera (PB1046) or Placebo | Experimental | Cohort 3 - Single 30 minute infusion Vasomera (PB1046) at 0.02mg/kg 0.9% Sodium Chloride or Placebo (0.9% Sodium Chloride) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo Single IV (Intravenous) Infusion | Drug | 0.9% Sodium Chloride - 30 minute IV infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Tolerability | To evaluate the safety and tolerability of single ascending doses of Vasomera administered as a 30 minute intravenous (IV) infusion to subjects with stage 1 or stage 2 essential hypertension.
| Days -45 to 28: Vital signs (Days -45, -14, -1, 0, 1, 2, 3, 4, 7, 14 and 28), ECGs (Days -45, -1, 0, 1 and 2), Safety Labs (Days -45, -1, 1, 7 and 28), and Telemetry (Days -1, 0 and 1) |
| Pharmacokinetic Profile | To evaluate the pharmacokinetic profile of single ascending doses of Vasomera administered as a 30 minute intravenous (IV) infusion to subjects with stage 1 or stage 2 essential hypertension.
| Days 0, 1, 2, 3, and 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Hemodynamic Parameters | Compare changes in hemodynamic parameters as measured by serial systolic and diastolic blood pressure (BP) measurements and echocardiography compared to placebo. Change from baseline in systolic and diastolic BP and heart rate (HR). Change from baseline in two-dimensional echocardiography parameters which may include:
|
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| William B. Smith, MD | New Orleans Center for Clinical Research- Knoxville | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| New Orleans Center for Clinical Research - Knoxville | Knoxville | Tennessee | 37920 | United States |
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| Experimental: Single IV Infusion Vasomera (PB1046) | Drug |
|
| Days -14, 0, 1, 2, 3, 4, 7, 14 and 28 |
| Immunogenicity Assessment | Evaluate if subjects elicit an immune response to study drug and if that response cross reacts with related endogenous compounds following a single 30 minute IV infusion. | Days 0, 14 and 28 |
| ID | Term |
|---|---|
| D000075222 | Essential Hypertension |
| ID | Term |
|---|---|
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C000706508 | VIP-ELP fusion molecule PB1046 |
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