The primary objective of the study is to evaluate the safety and tolerability of single ascending doses of Vasomera (PB1046) administered subcutaneously in adult subjects with Stage 1 or Stage 2 essential hypertension. The secondary objectives of the study are to characterize the pharmacokinetic profile of single ascending doses of Vasomera and the relationship between serum concentrations of Vasomera and change in systolic and diastolic blood pressure as measured by: * Mean change from baseline in 24-hour systolic and diastolic blood pressure measured by ambulatory blood pressure monitoring (ABPM) as compared to placebo. * Identification of the minimum and maximum decrease in systolic and diastolic blood pressure as measured by ABPM. * Mean change from baseline in cuff systolic and diastolic blood pressure as compared to placebo. * Effect of Vasomera on pulse pressure and heart rate. An additional secondary objective of this study will be to characterize the immunogenicity profile of Vasomera following a single subcutaneous dose.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
68
Single dose of Vasomera
Placebo injection
Pinnacle Research
Anniston, Alabama, United States
Diablo Clinical Research
Walnut Creek, California, United States
Prism Research Inc.
Saint Paul, Minnesota, United States
New Orleans Center for Clinical Research
Knoxville, Tennessee, United States
Rainier Clinical Research
Renton, Washington, United States
Safety/Tolerability
* Incidence and severity of adverse events (AEs) and their relationship to Vasomera (including AEs of interest, gastrointestinal effects, injection site reaction and hypotension) * Changes in vital signs, ECGs, and safety laboratory parameters from baseline * Discontinuations from the study due to AEs
Time frame: Day -45 to Day 28
Pharmacokinetics
Maximum peak steady state drug concentration (Cmax), Time to Cmax (Tmax), Elimination Rate Constant, t1/2, AUC(inf), Total serum clearance, and Volume of distribution of Vasomera
Time frame: Pre-dose, 1, 2, 3, 6, 8 and 12 hours post-dose, 24, 30 and 36 hours, Days 2, 3, 6, 7, 14, 21 and 28
Pharmacodynamics
* Change in mean 24-hour systolic blood pressure (SBP) and diastolic blood pressure (DBP) and mean daytime and mean nighttime SBP and DBP compared to placebo * Change in mean cuff systolic, diastolic and mean arterial blood pressure as compared to placebo * Mean change from baseline in effect of Vasomera on pulse pressure and heart rate * Proportion of subjects treated with study drug who were discontinued from treatment due to uncontrolled hypertension (i.e., SBP \>169 mmHg or DBP \>109 mmHg).
Time frame: ABPM (Day 0 and Day 6), Telemetry (Day -1, 0, 1 and Day 2 and 3 as needed), Daily home BP monitoring and Vital Signs (up to 3x times/day) during each visit (Day -35, -14, -7, -4, -1, 0, 1, 2, 3, 6, 7, 14, 21 and 28)
Immunogenicity
Presence of anti-drug antibodies and anti-VIP antibodies.
Time frame: Pre-dose, Day 14 and Day 28
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