Safety And Tolerability Of Subcutaneous MANP In Difficult To Control/Resistant Hypertensive Subjects
- Conditions
- Resistant HypertensionDifficult to Control Hypertension
- Interventions
- Drug: Placebo
- Registration Number
- NCT05247528
- Lead Sponsor
- E-Star BioTech, LLC
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 37
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MANP MANP * Subjects randomized to the experimental arm, will receive a single subcutaneous injection each morning daily. (multiple ascending dose cohorts) * Intervention: Drug: MANP Placebo Comparator Placebo * Subjects randomized to the placebo arm, will receive a single subcutaneous injection each morning daily. * Intervention: Placebo
- Primary Outcome Measures
Name Time Method Chemistry: Bilirubin From baseline to Day 21 Change in Total bilirubin (mg/dL)
Chemistry: Glucose From baseline to Day 21 Change in Glucose (mg/dL)
Chemistry: Creatinine From baseline to Day 21 Change in Creatinine (mg/dL)
Blood Pressure From baseline to Days 1-6, Day 12, and 21. Change in SBP and DBP
Physical Examination: Body Parts From baseline to Day 21 Change in investigator assessment of the condition of body parts (head, throat, abdomen, and extremities)
Chemistry: Sodium From baseline to Day 21 Change in Sodium concentration.
Chemistry: Chloride From baseline to Day 21 Change in Chloride concentration
Chemistry: Aspartate aminotransferase From baseline to Day 21 Change in AST (IU/L)
Chemistry: Blood urea nitrogen From baseline to Day 21 Change in BUN (mg/dL)
Adverse Events through study completion, an average of 2 months. Number and percent of participants with one or more Treatment Emergent Adverse Events (TEAEs) or any serious adverse events (SAEs).
Hematology: Hemoglobin From baseline to Day 21 Change in g/dL Hemoglobin
Hematology: Platelets From baseline to Day 21 Change in platelet count
Chemistry: Potassium From baseline to Day 21 Change in Potassium concentration.
Chemistry: Alanine aminotransferase From baseline to Day 21 Change in ALT (IU/L)
Temperature From baseline to Days 1-6, Day 12, and 21. Change in Temperature
Hematology: Mean Corpuscular Hemoglobin From baseline to Day 21 Change in the mean corpuscular hemoglobin.
Hematology: RBC From baseline to Day 21 Change in red blood cell count
ECG: QT interval From baseline to Days 1-6 and Day 21. Change in 12-Lead ECG QT Interval
Chemistry: Bicarbonate From baseline to Day 21 Change in Bicarbonate concentration
Chemistry: HbA1c From baseline to Day 21 Change in percent HbA1c
ECG: QTc interval From baseline to Days 1-6 and Day 21 Change in 12-Lead ECG QTc (Fridericia's) Interval
Hematology Hematocrit From baseline to Day 21. Change in Percent Hematocrit
Pulse Rate From baseline to Days 1-6, Day 12, and 21. Change in Pulse Rate
Hematology: RBC distribution From baseline to Day 21 Change in red blood cell distribution width
Hematology: WBC From baseline to Day 21 Change in white blood cell count
Chemistry: Alkaline phosphatase From baseline to Day 21 Change in Alkaline phosphatase (IU/L)
Physical Examination: Organs From baseline to Day 21 Change in investigator assessment of the condition of organs (skin, eyes, ears, nose, thyroid, lungs, liver, spleen, and lymph nodes)
Abbreviated Neurological Examination From baseline to Day 21 Change in investigator assessment of neurological condition
- Secondary Outcome Measures
Name Time Method MANP From baseline for Day 1 & Day 5 Change in amount of Plasma MANP both in plasma.
Cardiac Metrics: From Baseline for Day 1-6 Heart Rate
Cardiac Metrics: Blood pressures From Baseline for Day 1-6 Change in SBP and DBP
Metabolics From baseline for Day 1 & Day 5 Change in amount of non-esterified insulin and glucose.
Serum creatinine From Baseline for Day 1-6 Change in Serum creatinine
Urine flow rate From Baseline for Day 1-6 Change in urine flow rate
Immune Response From baseline for Day 1, Day 5, Day 12, & Day 21 Change in amount of anti-MANP and anti-ANP
Urinary Sodium Excretion From Baseline for Day 1-6 Change in amount of urinary sodium excretion
eGFR, From Baseline for Day 1-6 Change in eGFR,
cGMP from baseline for Day 1 & Day 5 Change in amount of cGMP both in plasma and urine
Aldosterone from baseline for Day 1 & Day 5 Change in amount of aldosterone both in plasma and urine
Trial Locations
- Locations (5)
USA Clinical Site 01
🇺🇸Tustin, California, United States
USA Clinical Site 04
🇺🇸Decatur, Georgia, United States
USA Clinical Site 05
🇺🇸Owensboro, Kentucky, United States
USA Clinical Site 03
🇺🇸Anniston, Alabama, United States
USA Clinical Site 02
🇺🇸DeLand, Florida, United States