Safety And Tolerability Of Subcutaneous MANP In Difficult To Control/Resistant Hypertensive Subjects

E-Star BioTech, LLC37 enrolled

Overview

A randomized, double-blind, placebo-controlled multiple ascending dose study in hypertensive subjects on stable doses of at least three hypertensive drugs for at least 6 weeks prior to Screening. The study will consist of screening, PK-unit admittance, and safety follow up periods. Subjects will be randomized at a 6:2 ratio of either MANP or placebo and will be stratified by race in each dosage cohort. The entire first Cohort will be given the lowest dosage with subsequent cohorts progressing sequentially to the higher doses depending on safety and tolerability of the previous cohort. Endpoints not related to the safety reviews will be analyzed after the last patient last visit (LPLV).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Resistant Hypertension Difficult to Control Hypertension

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * DTC/RH diagnosed with clinic SBP ≥140 mmHg or DBP ≥ 90 mmHg (or SBP ≥ 130 mmHg or DBP ≥ 80 mmHg for diabetics) while on at least three standard-of-care antihypertensive medications (which must include a diuretic). * MDRD eGFR ≥ 30 mL/min. * Men and women between the ages of 18 - 80. * BMI within the range of 18-40 kg/m2. * Women of childbearing potential must not be pregnant and agree to avoid becoming pregnant while receiving study treatment and for 14 days after the last study visit. Exclusion Criteria: * HbA1c ≥ 8% at Screening. * Use of other investigational drugs within 30 days of screening or foreseen use during the study. * Inability to comply with study requirements as judged by the Investigator. * Pregnant and/or breastfeeding. * Any disease or condition (medical or surgical) which, in the opinion of the investigator, might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism or excretion of study drug, or would place the subject at increased risk.

Locations (5)

USA Clinical Site 03

Anniston, Alabama, United States

USA Clinical Site 01

Tustin, California, United States

USA Clinical Site 02

DeLand, Florida, United States

USA Clinical Site 04

Decatur, Georgia, United States

USA Clinical Site 05

Owensboro, Kentucky, United States

Outcomes

Primary Outcomes

Adverse Events

Number and percent of participants with one or more Treatment Emergent Adverse Events (TEAEs) or any serious adverse events (SAEs).

Time frame: through study completion, an average of 2 months.

Blood Pressure

Change in SBP and DBP

Time frame: From baseline to Days 1-6, Day 12, and 21.

Hematology Hematocrit

Change in Percent Hematocrit

Time frame: From baseline to Day 21.

Physical Examination: Body Parts

Change in investigator assessment of the condition of body parts (head, throat, abdomen, and extremities)

Time frame: From baseline to Day 21

ECG: QT interval

Change in 12-Lead ECG QT Interval

Time frame: From baseline to Days 1-6 and Day 21.

Temperature

Change in Temperature

Time frame: From baseline to Days 1-6, Day 12, and 21.

Pulse Rate

Change in Pulse Rate

Time frame: From baseline to Days 1-6, Day 12, and 21.

Hematology: Hemoglobin

Change in g/dL Hemoglobin

Time frame: From baseline to Day 21

Hematology: Mean Corpuscular Hemoglobin

Change in the mean corpuscular hemoglobin.

Time frame: From baseline to Day 21

Hematology: Platelets

Change in platelet count

Time frame: From baseline to Day 21

Hematology: RBC distribution

Change in red blood cell distribution width

Time frame: From baseline to Day 21

Hematology: RBC

Change in red blood cell count

Time frame: From baseline to Day 21

Hematology: WBC

Change in white blood cell count

Time frame: From baseline to Day 21

Chemistry: Sodium

Change in Sodium concentration.

Time frame: From baseline to Day 21

Chemistry: Potassium

Change in Potassium concentration.

Time frame: From baseline to Day 21

Chemistry: Chloride

Change in Chloride concentration

Time frame: From baseline to Day 21

Chemistry: Bicarbonate

Change in Bicarbonate concentration

Time frame: From baseline to Day 21

Chemistry: Alanine aminotransferase

Change in ALT (IU/L)

Time frame: From baseline to Day 21

Chemistry: Aspartate aminotransferase

Change in AST (IU/L)

Time frame: From baseline to Day 21

Chemistry: Alkaline phosphatase

Change in Alkaline phosphatase (IU/L)

Time frame: From baseline to Day 21

Chemistry: Bilirubin

Change in Total bilirubin (mg/dL)

Time frame: From baseline to Day 21

Chemistry: Blood urea nitrogen

Change in BUN (mg/dL)

Time frame: From baseline to Day 21

Chemistry: Creatinine

Change in Creatinine (mg/dL)

Time frame: From baseline to Day 21

Chemistry: Glucose

Change in Glucose (mg/dL)

Time frame: From baseline to Day 21

Chemistry: HbA1c

Change in percent HbA1c

Time frame: From baseline to Day 21

Physical Examination: Organs

Change in investigator assessment of the condition of organs (skin, eyes, ears, nose, thyroid, lungs, liver, spleen, and lymph nodes)

Time frame: From baseline to Day 21

Abbreviated Neurological Examination

Change in investigator assessment of neurological condition

Time frame: From baseline to Day 21

ECG: QTc interval

Change in 12-Lead ECG QTc (Fridericia's) Interval

Time frame: From baseline to Days 1-6 and Day 21

Secondary Outcomes

Cardiac Metrics: Blood pressures

Change in SBP and DBP

Time frame: From Baseline for Day 1-6

Serum creatinine

Change in Serum creatinine

Time frame: From Baseline for Day 1-6

MANP

Change in amount of Plasma MANP both in plasma.

Time frame: From baseline for Day 1 & Day 5

Immune Response

Change in amount of anti-MANP and anti-ANP

Time frame: From baseline for Day 1, Day 5, Day 12, & Day 21

Metabolics

Change in amount of non-esterified insulin and glucose.

Time frame: From baseline for Day 1 & Day 5

eGFR,

Change in eGFR,

Time frame: From Baseline for Day 1-6

Urine flow rate

Change in urine flow rate

Time frame: From Baseline for Day 1-6

Urinary Sodium Excretion

Change in amount of urinary sodium excretion

Time frame: From Baseline for Day 1-6

cGMP

Change in amount of cGMP both in plasma and urine

Time frame: from baseline for Day 1 & Day 5

Aldosterone

Change in amount of aldosterone both in plasma and urine

Time frame: from baseline for Day 1 & Day 5