Safety Study of Subcutaneously Administered PL-3994 in Subjects With Controlled Hypertension

Study Overview
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Brief Summary
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The objective of this study is to evaluate the safety, tolerability, and pharmacokinetics of subcutaneous (SC) PL-3994, relative to placebo in subjects with controlled hypertension. Including in this evaluation is the effect PL3994 has on blood pressure.

Detailed Description
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Uncontrolled hypertension, including both hypertensive urgency and hypertensive emergency, is commonly seen in emergency rooms and other urgent care settings. Current standards of care include intravenously administered drugs, which can be difficult to titrate and require ongoing monitoring. This study examines the effect of PL-3994 on patients with controlled hypertension who are receiving antihypertensive medications.

Official Title
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A Single-Center, Single-Dose, Placebo-Controlled, Randomized, Double-Blind, Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics and Pharmacodynamics of Subcutaneously Administered PL-3994 in Subjects With Controlled Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: PL3994
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have had a diagnosis of essential hypertension for at least 1 year, per subject verbal history Subject must be on a stable dose of at least one, but not more than 3 antihypertensive medications for at least 3 months, per subject verbal history. Subject must have a systolic blood pressure at screening between 100 and 150 mmHg, and diastolic blood pressure must not exceed 105 mmHg. Exclusion Criteria: Subject weight greater than 100 kg or less than 50 kg. Any significant medical condition or abnormal safety laboratory results which, in the judgement of the Investigator would place the subject at significant risk.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Experimental: PL3994 Dose A<br>PL3994 Dose A | Drug: PL3994<br>* Study drug<br>|
| Experimental: PL3994 Dose B<br>PL3994 Dose B | Drug: PL3994<br>* Study drug<br>|
| Experimental: PL3994 Dose C<br>PL3994 Dose C | Drug: PL3994<br>* Study drug<br>|
| Experimental: PL3994 Dose D<br>PL3994 Dose D | Drug: PL3994<br>* Study drug<br>|
| Experimental: PL3994 Dose E<br>PL3994 Dose E | Drug: PL3994<br>* Study drug<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of Subcutaneous (SC) PL-3994 Relative to Placebo in Subjects With Controlled Hypertension. | The pharmacokinetic profile parameters for PL-3994 were calculated using a non compartmental approach. •Maximum concentration (Cmax) The subject numbers below are the evaluable subjects only. The Evaluable Subjects population consisted of subjects who received study drug and who had no major protocol deviations that would have excluded the subject from analysis, and for whom calculations of PK parameters were possible. | 24 hours | 
| Pharmacodynamics as Measured by cGMP Levels. | Pharmacodynamic parameters were calculated from the baseline-adjusted plasma cGMP level-time data using WinNonlin® 5.0.1. Actual sample times were used in the calculations. Baseline was the pre-dose levels of plasma cGMP at Visit 2 (Day 1): Emax The patient numbers below represent the evaluable subjects only. The Evaluable Subjects population consisted of subjects who received study drug and who had no major protocol deviations that would have excluded the subject from analysis, and for whom calculations of PD parameters were possible. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypertension, controlled hypertension, hypertensives