Clinical trial NCT05247528: Safety And Tolerability Of Subcutaneous MANP In Difficult To Control/Resistant Hypertensive Subjects
Official title: A Phase 1B, Multiple Ascending Dose Trial Examining The Safety And Tolerability Of Subcutaneous MANP In Difficult To Control/Resistant Hypertensive Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Resistant Hypertension
Difficult to Control Hypertension
Lead sponsor: E-Star BioTech, LLC
Sponsor class: INDUSTRY
Collaborators: name: Mayo Clinic
name: Integrium
First posted: 2022-02-21
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Adverse Events
timeFrame: through study completion, an average of 2 months.
measure: Blood Pressure
timeFrame: From baseline to Days 1-6, Day 12, and 21.
measure: Hematology Hematocrit
timeFrame: From baseline to Day 21.
measure: Physical Examination: Body Parts
timeFrame: From baseline to Day 21
measure: ECG: QT interval
timeFrame: From baseline to Days 1-6 and Day 21.
measure: Temperature
timeFrame: From baseline to Days 1-6, Day 12, and 21.
measure: Pulse Rate
timeFrame: From baseline to Days 1-6, Day 12, and 21.
measure: Hematology: Hemoglobin
timeFrame: From baseline to Day 21
measure: Hematology: Mean Corpuscular Hemoglobin
timeFrame: From baseline to Day 21
measure: Hematology: Platelets
timeFrame: From baseline to Day 21
measure: Hematology: RBC distribution
timeFrame: From baseline to Day 21
measure: Hematology: RBC
timeFrame: From baseline to Day 21
measure: Hematology: WBC
timeFrame: From baseline to Day 21
measure: Chemistry: Sodium
timeFrame: From baseline to Day 21
measure: Chemistry: Potassium
timeFrame: From baseline to Day 21
measure: Chemistry: Chloride
timeFrame: From baseline to Day 21
measure: Chemistry: Bicarbonate
timeFrame: From baseline to Day 21
measure: Chemistry: Alanine aminotransferase
timeFrame: From baseline to Day 21
measure: Chemistry: Aspartate aminotransferase
timeFrame: From baseline to Day 21
measure: Chemistry: Alkaline phosphatase
timeFrame: From baseline to Day 21
measure: Chemistry: Bilirubin
timeFrame: From baseline to Day 21
measure: Chemistry: Blood urea nitrogen
timeFrame: From baseline to Day 21
measure: Chemistry: Creatinine
timeFrame: From baseline to Day 21
measure: Chemistry: Glucose
timeFrame: From baseline to Day 21
measure: Chemistry: HbA1c
timeFrame: From baseline to Day 21
measure: Physical Examination: Organs
timeFrame: From baseline to Day 21
measure: Abbreviated Neurological Examination
timeFrame: From baseline to Day 21
measure: ECG: QTc interval
timeFrame: From baseline to Days 1-6 and Day 21
Secondary outcomes:
measure: Cardiac Metrics: Blood pressures
timeFrame: From Baseline for Day 1-6
measure: Serum creatinine
timeFrame: From Baseline for Day 1-6
measure: MANP
timeFrame: From baseline for Day 1 & Day 5
measure: Immune Response
timeFrame: From baseline for Day 1, Day 5, Day 12, & Day 21
measure: Metabolics
timeFrame: From baseline for Day 1 & Day 5
measure: eGFR,
timeFrame: From Baseline for Day 1-6
measure: Urine flow rate
timeFrame: From Baseline for Day 1-6
measure: Urinary Sodium Excretion
timeFrame: From Baseline for Day 1-6
measure: cGMP
timeFrame: from baseline for Day 1 & Day 5
measure: Aldosterone
timeFrame: from baseline for Day 1 & Day 5
measure: Cardiac Metrics:
timeFrame: From Baseline for Day 1-6
Other outcomes:
Locations:
city: Anniston
country: United States
facility: USA Clinical Site 03
state: Alabama
city: Tustin
country: United States
facility: USA Clinical Site 01
state: California
city: DeLand
country: United States
facility: USA Clinical Site 02
state: Florida
city: Decatur
country: United States
facility: USA Clinical Site 04
state: Georgia
city: Owensboro
country: United States
facility: USA Clinical Site 05
state: Kentucky
Study officials:
affiliation: E-Star
name: Lucia Gonzalez
role: STUDY_DIRECTOR
References: