Back to resultsSafety And Tolerability Of Subcutaneous MANP In Difficult To Control/Resistant Hypertensive Subjects (DTC/RHS)
Primary Purpose
Resistant Hypertension, Difficult to Control Hypertension
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MANP
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Resistant Hypertension
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.
Sites / Locations
- USA Clinical Site 03
- USA Clinical Site 01
- USA Clinical Site 02
- USA Clinical Site 04
- USA Clinical Site 05
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo Comparator
MANP
Arm Description
Subjects randomized to the placebo arm, will receive a single subcutaneous injection each morning daily. Intervention: Placebo
Subjects randomized to the experimental arm, will receive a single subcutaneous injection each morning daily. (multiple ascending dose cohorts) Intervention: Drug: MANP
Outcomes
Primary Outcome Measures
Adverse Events
Number and percent of participants with one or more Treatment Emergent Adverse Events (TEAEs) or any serious adverse events (SAEs).
Blood Pressure
Change in SBP and DBP
Hematology Hematocrit
Change in Percent Hematocrit
Physical Examination: Body Parts
Change in investigator assessment of the condition of body parts (head, throat, abdomen, and extremities)
ECG: QT interval
Change in 12-Lead ECG QT Interval
Temperature
Change in Temperature
Pulse Rate
Change in Pulse Rate
Hematology: Hemoglobin
Change in g/dL Hemoglobin
Hematology: Mean Corpuscular Hemoglobin
Change in the mean corpuscular hemoglobin.
Hematology: Platelets
Change in platelet count
Hematology: RBC distribution
Change in red blood cell distribution width
Hematology: RBC
Change in red blood cell count
Hematology: WBC
Change in white blood cell count
Chemistry: Sodium
Change in Sodium concentration.
Chemistry: Potassium
Change in Potassium concentration.
Chemistry: Chloride
Change in Chloride concentration
Chemistry: Bicarbonate
Change in Bicarbonate concentration
Chemistry: Alanine aminotransferase
Change in ALT (IU/L)
Chemistry: Aspartate aminotransferase
Change in AST (IU/L)
Chemistry: Alkaline phosphatase
Change in Alkaline phosphatase (IU/L)
Chemistry: Bilirubin
Change in Total bilirubin (mg/dL)
Chemistry: Blood urea nitrogen
Change in BUN (mg/dL)
Chemistry: Creatinine
Change in Creatinine (mg/dL)
Chemistry: Glucose
Change in Glucose (mg/dL)
Chemistry: HbA1c
Change in percent HbA1c
Physical Examination: Organs
Change in investigator assessment of the condition of organs (skin, eyes, ears, nose, thyroid, lungs, liver, spleen, and lymph nodes)
Abbreviated Neurological Examination
Change in investigator assessment of neurological condition
ECG: QTc interval
Change in 12-Lead ECG QTc (Fridericia's) Interval
Secondary Outcome Measures
Cardiac Metrics: Blood pressures
Change in SBP and DBP
Serum creatinine
Change in Serum creatinine
MANP
Change in amount of Plasma MANP both in plasma.
Immune Response
Change in amount of anti-MANP and anti-ANP
Metabolics
Change in amount of non-esterified insulin and glucose.
eGFR,
Change in eGFR,
Urine flow rate
Change in urine flow rate
Urinary Sodium Excretion
Change in amount of urinary sodium excretion
cGMP
Change in amount of cGMP both in plasma and urine
Aldosterone
Change in amount of aldosterone both in plasma and urine
Cardiac Metrics:
Heart Rate
Full Information
NCT ID
NCT05247528
First Posted
December 22, 2021
Last Updated
November 22, 2022
Sponsor
E-Star BioTech, LLC
Collaborators
Mayo Clinic, Integrium
1. Study Identification
Unique Protocol Identification Number
NCT05247528
Brief Title
Safety And Tolerability Of Subcutaneous MANP In Difficult To Control/Resistant Hypertensive Subjects
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
December 20, 2021 (Actual)
Primary Completion Date
October 31, 2022 (Actual)
Study Completion Date
October 31, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
E-Star BioTech, LLC
Collaborators
Mayo Clinic, Integrium
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Resistant Hypertension, Difficult to Control Hypertension
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo Comparator
Arm Type
Placebo Comparator
Arm Description
Subjects randomized to the placebo arm, will receive a single subcutaneous injection each morning daily.
Intervention: Placebo
Arm Title
MANP
Arm Type
Experimental
Arm Description
Subjects randomized to the experimental arm, will receive a single subcutaneous injection each morning daily. (multiple ascending dose cohorts)
Intervention: Drug: MANP
Intervention Type
Drug
Intervention Name(s)
MANP
Intervention Description
Novel designer peptide to represent a pGC-A/cGMP therapeutic
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo Comparator
Primary Outcome Measure Information:
Title
Adverse Events
Description
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.
Title
Blood Pressure
Description
Change in SBP and DBP
Time Frame
From baseline to Days 1-6, Day 12, and 21.
Title
Hematology Hematocrit
Description
Change in Percent Hematocrit
Time Frame
From baseline to Day 21.
Title
Physical Examination: Body Parts
Description
Change in investigator assessment of the condition of body parts (head, throat, abdomen, and extremities)
Time Frame
From baseline to Day 21
Title
ECG: QT interval
Description
Change in 12-Lead ECG QT Interval
Time Frame
From baseline to Days 1-6 and Day 21.
Title
Temperature
Description
Change in Temperature
Time Frame
From baseline to Days 1-6, Day 12, and 21.
Title
Pulse Rate
Description
Change in Pulse Rate
Time Frame
From baseline to Days 1-6, Day 12, and 21.
Title
Hematology: Hemoglobin
Description
Change in g/dL Hemoglobin
Time Frame
From baseline to Day 21
Title
Hematology: Mean Corpuscular Hemoglobin
Description
Change in the mean corpuscular hemoglobin.
Time Frame
From baseline to Day 21
Title
Hematology: Platelets
Description
Change in platelet count
Time Frame
From baseline to Day 21
Title
Hematology: RBC distribution
Description
Change in red blood cell distribution width
Time Frame
From baseline to Day 21
Title
Hematology: RBC
Description
Change in red blood cell count
Time Frame
From baseline to Day 21
Title
Hematology: WBC
Description
Change in white blood cell count
Time Frame
From baseline to Day 21
Title
Chemistry: Sodium
Description
Change in Sodium concentration.
Time Frame
From baseline to Day 21
Title
Chemistry: Potassium
Description
Change in Potassium concentration.
Time Frame
From baseline to Day 21
Title
Chemistry: Chloride
Description
Change in Chloride concentration
Time Frame
From baseline to Day 21
Title
Chemistry: Bicarbonate
Description
Change in Bicarbonate concentration
Time Frame
From baseline to Day 21
Title
Chemistry: Alanine aminotransferase
Description
Change in ALT (IU/L)
Time Frame
From baseline to Day 21
Title
Chemistry: Aspartate aminotransferase
Description
Change in AST (IU/L)
Time Frame
From baseline to Day 21
Title
Chemistry: Alkaline phosphatase
Description
Change in Alkaline phosphatase (IU/L)
Time Frame
From baseline to Day 21
Title
Chemistry: Bilirubin
Description
Change in Total bilirubin (mg/dL)
Time Frame
From baseline to Day 21
Title
Chemistry: Blood urea nitrogen
Description
Change in BUN (mg/dL)
Time Frame
From baseline to Day 21
Title
Chemistry: Creatinine
Description
Change in Creatinine (mg/dL)
Time Frame
From baseline to Day 21
Title
Chemistry: Glucose
Description
Change in Glucose (mg/dL)
Time Frame
From baseline to Day 21
Title
Chemistry: HbA1c
Description
Change in percent HbA1c
Time Frame
From baseline to Day 21
Title
Physical Examination: Organs
Description
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
Title
Abbreviated Neurological Examination
Description
Change in investigator assessment of neurological condition
Time Frame
From baseline to Day 21
Title
ECG: QTc interval
Description
Change in 12-Lead ECG QTc (Fridericia's) Interval
Time Frame
From baseline to Days 1-6 and Day 21
Secondary Outcome Measure Information:
Title
Cardiac Metrics: Blood pressures
Description
Change in SBP and DBP
Time Frame
From Baseline for Day 1-6
Title
Serum creatinine
Description
Change in Serum creatinine
Time Frame
From Baseline for Day 1-6
Title
MANP
Description
Change in amount of Plasma MANP both in plasma.
Time Frame
From baseline for Day 1 & Day 5
Title
Immune Response
Description
Change in amount of anti-MANP and anti-ANP
Time Frame
From baseline for Day 1, Day 5, Day 12, & Day 21
Title
Metabolics
Description
Change in amount of non-esterified insulin and glucose.
Time Frame
From baseline for Day 1 & Day 5
Title
eGFR,
Description
Change in eGFR,
Time Frame
From Baseline for Day 1-6
Title
Urine flow rate
Description
Change in urine flow rate
Time Frame
From Baseline for Day 1-6
Title
Urinary Sodium Excretion
Description
Change in amount of urinary sodium excretion
Time Frame
From Baseline for Day 1-6
Title
cGMP
Description
Change in amount of cGMP both in plasma and urine
Time Frame
from baseline for Day 1 & Day 5
Title
Aldosterone
Description
Change in amount of aldosterone both in plasma and urine
Time Frame
from baseline for Day 1 & Day 5
Title
Cardiac Metrics:
Description
Heart Rate
Time Frame
From Baseline for Day 1-6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lucia Gonzalez
Organizational Affiliation
E-Star
Official's Role
Study Director
Facility Information:
Facility Name
USA Clinical Site 03
City
Anniston
State/Province
Alabama
ZIP/Postal Code
36207
Country
United States
Facility Name
USA Clinical Site 01
City
Tustin
State/Province
California
ZIP/Postal Code
92780
Country
United States
Facility Name
USA Clinical Site 02
City
DeLand
State/Province
Florida
ZIP/Postal Code
32738
Country
United States
Facility Name
USA Clinical Site 04
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30030
Country
United States
Facility Name
USA Clinical Site 05
City
Owensboro
State/Province
Kentucky
ZIP/Postal Code
42303
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
All IPD that underlie results in a publication
Learn more about this trial
Safety And Tolerability Of Subcutaneous MANP In Difficult To Control/Resistant Hypertensive Subjects
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