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

Resistant Hypertension Clinical Trial

— DTC/RHS  

Official title:

A Phase 1B, Multiple Ascending Dose Trial Examining The Safety And Tolerability Of Subcutaneous MANP In Difficult To Control/Resistant Hypertensive Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05247528
• Other study ID #: ES_MANP_21-01
• Status: Completed
• Phase: Phase 1
• Start date: December 20, 2021
• Est. completion date: October 31, 2022

Study information

• Verified date: November 2022
• Source: E-Star BioTech, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: October 31, 2022
• Est. primary completion date: October 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypertension
• Resistant Hypertension

Intervention

Drug:
• MANP
Novel designer peptide to represent a pGC-A/cGMP therapeutic
• Placebo
Placebo Comparator

Locations

Country	Name	City	State
United States	USA Clinical Site 03	Anniston	Alabama
United States	USA Clinical Site 04	Decatur	Georgia
United States	USA Clinical Site 02	DeLand	Florida
United States	USA Clinical Site 05	Owensboro	Kentucky
United States	USA Clinical Site 01	Tustin	California

Sponsors (3)

Lead Sponsor	Collaborator
E-Star BioTech, LLC	Integrium, Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events	Number and percent of participants with one or more Treatment Emergent Adverse Events (TEAEs) or any serious adverse events (SAEs).	through study completion, an average of 2 months.
Primary	Blood Pressure	Change in SBP and DBP	From baseline to Days 1-6, Day 12, and 21.
Primary	Hematology Hematocrit	Change in Percent Hematocrit	From baseline to Day 21.
Primary	Physical Examination: Body Parts	Change in investigator assessment of the condition of body parts (head, throat, abdomen, and extremities)	From baseline to Day 21
Primary	ECG: QT interval	Change in 12-Lead ECG QT Interval	From baseline to Days 1-6 and Day 21.
Primary	Temperature	Change in Temperature	From baseline to Days 1-6, Day 12, and 21.
Primary	Pulse Rate	Change in Pulse Rate	From baseline to Days 1-6, Day 12, and 21.
Primary	Hematology: Hemoglobin	Change in g/dL Hemoglobin	From baseline to Day 21
Primary	Hematology: Mean Corpuscular Hemoglobin	Change in the mean corpuscular hemoglobin.	From baseline to Day 21
Primary	Hematology: Platelets	Change in platelet count	From baseline to Day 21
Primary	Hematology: RBC distribution	Change in red blood cell distribution width	From baseline to Day 21
Primary	Hematology: RBC	Change in red blood cell count	From baseline to Day 21
Primary	Hematology: WBC	Change in white blood cell count	From baseline to Day 21
Primary	Chemistry: Sodium	Change in Sodium concentration.	From baseline to Day 21
Primary	Chemistry: Potassium	Change in Potassium concentration.	From baseline to Day 21
Primary	Chemistry: Chloride	Change in Chloride concentration	From baseline to Day 21
Primary	Chemistry: Bicarbonate	Change in Bicarbonate concentration	From baseline to Day 21
Primary	Chemistry: Alanine aminotransferase	Change in ALT (IU/L)	From baseline to Day 21
Primary	Chemistry: Aspartate aminotransferase	Change in AST (IU/L)	From baseline to Day 21
Primary	Chemistry: Alkaline phosphatase	Change in Alkaline phosphatase (IU/L)	From baseline to Day 21
Primary	Chemistry: Bilirubin	Change in Total bilirubin (mg/dL)	From baseline to Day 21
Primary	Chemistry: Blood urea nitrogen	Change in BUN (mg/dL)	From baseline to Day 21
Primary	Chemistry: Creatinine	Change in Creatinine (mg/dL)	From baseline to Day 21
Primary	Chemistry: Glucose	Change in Glucose (mg/dL)	From baseline to Day 21
Primary	Chemistry: HbA1c	Change in percent HbA1c	From baseline to Day 21
Primary	Physical Examination: Organs	Change in investigator assessment of the condition of organs (skin, eyes, ears, nose, thyroid, lungs, liver, spleen, and lymph nodes)	From baseline to Day 21
Primary	Abbreviated Neurological Examination	Change in investigator assessment of neurological condition	From baseline to Day 21
Primary	ECG: QTc interval	Change in 12-Lead ECG QTc (Fridericia's) Interval	From baseline to Days 1-6 and Day 21
Secondary	Cardiac Metrics: Blood pressures	Change in SBP and DBP	From Baseline for Day 1-6
Secondary	Serum creatinine	Change in Serum creatinine	From Baseline for Day 1-6
Secondary	MANP	Change in amount of Plasma MANP both in plasma.	From baseline for Day 1 & Day 5
Secondary	Immune Response	Change in amount of anti-MANP and anti-ANP	From baseline for Day 1, Day 5, Day 12, & Day 21
Secondary	Metabolics	Change in amount of non-esterified insulin and glucose.	From baseline for Day 1 & Day 5
Secondary	eGFR,	Change in eGFR,	From Baseline for Day 1-6
Secondary	Urine flow rate	Change in urine flow rate	From Baseline for Day 1-6
Secondary	Urinary Sodium Excretion	Change in amount of urinary sodium excretion	From Baseline for Day 1-6
Secondary	cGMP	Change in amount of cGMP both in plasma and urine	from baseline for Day 1 & Day 5
Secondary	Aldosterone	Change in amount of aldosterone both in plasma and urine	from baseline for Day 1 & Day 5
Secondary	Cardiac Metrics:	Heart Rate	From Baseline for Day 1-6