Difficult to Control Hypertension, Resistant Hypertension
Conditions
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).
Interventions
DRUGMANP
Novel designer peptide to represent a pGC-A/cGMP therapeutic
DRUGPlacebo
Placebo Comparator
Sponsors
Mayo Clinic
Integrium
E-Star BioTech, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ECG: QTc interval | From baseline to Days 1-6 and Day 21 | Change in 12-Lead ECG QTc (Fridericia's) Interval |
| Chemistry: Bicarbonate | From baseline to Day 21 | Change in Bicarbonate concentration |
| Chemistry: Alanine aminotransferase | From baseline to Day 21 | Change in ALT (IU/L) |
| Chemistry: Aspartate aminotransferase | From baseline to Day 21 | Change in AST (IU/L) |
| Chemistry: Alkaline phosphatase | From baseline to Day 21 | Change in Alkaline phosphatase (IU/L) |
| Chemistry: Bilirubin | From baseline to Day 21 | Change in Total bilirubin (mg/dL) |
| Chemistry: Blood urea nitrogen | From baseline to Day 21 | Change in BUN (mg/dL) |
| Chemistry: Creatinine | From baseline to Day 21 | Change in Creatinine (mg/dL) |
| Chemistry: Glucose | From baseline to Day 21 | Change in Glucose (mg/dL) |
| Chemistry: HbA1c | From baseline to Day 21 | Change in percent HbA1c |
| 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 |
| 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). |
| Blood Pressure | From baseline to Days 1-6, Day 12, and 21. | Change in SBP and DBP |
| Hematology Hematocrit | From baseline to Day 21. | Change in Percent Hematocrit |
| Physical Examination: Body Parts | From baseline to Day 21 | Change in investigator assessment of the condition of body parts (head, throat, abdomen, and extremities) |
| ECG: QT interval | From baseline to Days 1-6 and Day 21. | Change in 12-Lead ECG QT Interval |
| Temperature | From baseline to Days 1-6, Day 12, and 21. | Change in Temperature |
| Pulse Rate | From baseline to Days 1-6, Day 12, and 21. | Change in Pulse Rate |
| Hematology: Hemoglobin | From baseline to Day 21 | Change in g/dL Hemoglobin |
| Hematology: Mean Corpuscular Hemoglobin | From baseline to Day 21 | Change in the mean corpuscular hemoglobin. |
| Hematology: Platelets | From baseline to Day 21 | Change in platelet count |
| Hematology: RBC distribution | From baseline to Day 21 | Change in red blood cell distribution width |
| Hematology: RBC | From baseline to Day 21 | Change in red blood cell count |
| Hematology: WBC | From baseline to Day 21 | Change in white blood cell count |
| Chemistry: Sodium | From baseline to Day 21 | Change in Sodium concentration. |
| Chemistry: Potassium | From baseline to Day 21 | Change in Potassium concentration. |
| Chemistry: Chloride | From baseline to Day 21 | Change in Chloride concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Aldosterone | from baseline for Day 1 & Day 5 | Change in amount of aldosterone both in plasma and urine |
| 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 |
| Serum creatinine | From Baseline for Day 1-6 | Change in Serum creatinine |
| MANP | From baseline for Day 1 & Day 5 | Change in amount of Plasma MANP both in plasma. |
| Immune Response | From baseline for Day 1, Day 5, Day 12, & Day 21 | Change in amount of anti-MANP and anti-ANP |
| Metabolics | From baseline for Day 1 & Day 5 | Change in amount of non-esterified insulin and glucose. |
| eGFR, | From Baseline for Day 1-6 | Change in eGFR, |
| Urine flow rate | From Baseline for Day 1-6 | Change in urine flow rate |
| Urinary Sodium Excretion | From Baseline for Day 1-6 | Change in amount of urinary sodium excretion |
| cGMP | from baseline for Day 1 & Day 5 | Change in amount of cGMP both in plasma and urine |
Countries
United States
Outcome results
None listed