A Phase 1B, Multiple Ascending Dose Trial Examining The Safety And Tolerability Of Subcutaneous MANP In Difficult To Control/Resistant Hypertensive Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 5
- 主要终点
- Blood Pressure
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 -
- •BMI within the range of 18-40 kg/m
- •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.
排除标准
- •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.
研究组 & 干预措施
Placebo Comparator
- Subjects randomized to the placebo arm, will receive a single subcutaneous injection each morning daily.
- Intervention: Placebo
干预措施: Placebo (Drug)
MANP
- Subjects randomized to the experimental arm, will receive a single subcutaneous injection each morning daily. (multiple ascending dose cohorts)
- Intervention: Drug: MANP
干预措施: MANP (Drug)
结局指标
主要结局
Blood Pressure
时间窗: From baseline to Days 1-6, Day 12, and 21.
Change in SBP and DBP
Physical Examination: Body Parts
时间窗: From baseline to Day 21
Change in investigator assessment of the condition of body parts (head, throat, abdomen, and extremities)
Chemistry: Sodium
时间窗: From baseline to Day 21
Change in Sodium concentration.
Chemistry: Chloride
时间窗: From baseline to Day 21
Change in Chloride concentration
Chemistry: Aspartate aminotransferase
时间窗: From baseline to Day 21
Change in AST (IU/L)
Chemistry: Blood urea nitrogen
时间窗: From baseline to Day 21
Change in BUN (mg/dL)
Chemistry: Alanine aminotransferase
时间窗: From baseline to Day 21
Change in ALT (IU/L)
Adverse Events
时间窗: 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
时间窗: From baseline to Day 21
Change in g/dL Hemoglobin
Hematology: Platelets
时间窗: From baseline to Day 21
Change in platelet count
Chemistry: Potassium
时间窗: From baseline to Day 21
Change in Potassium concentration.
Temperature
时间窗: From baseline to Days 1-6, Day 12, and 21.
Change in Temperature
Hematology: Mean Corpuscular Hemoglobin
时间窗: From baseline to Day 21
Change in the mean corpuscular hemoglobin.
Hematology: RBC
时间窗: From baseline to Day 21
Change in red blood cell count
Chemistry: Bicarbonate
时间窗: From baseline to Day 21
Change in Bicarbonate concentration
Chemistry: Bilirubin
时间窗: From baseline to Day 21
Change in Total bilirubin (mg/dL)
Chemistry: Creatinine
时间窗: From baseline to Day 21
Change in Creatinine (mg/dL)
ECG: QT interval
时间窗: From baseline to Days 1-6 and Day 21.
Change in 12-Lead ECG QT Interval
Chemistry: HbA1c
时间窗: From baseline to Day 21
Change in percent HbA1c
ECG: QTc interval
时间窗: From baseline to Days 1-6 and Day 21
Change in 12-Lead ECG QTc (Fridericia's) Interval
Hematology Hematocrit
时间窗: From baseline to Day 21.
Change in Percent Hematocrit
Pulse Rate
时间窗: From baseline to Days 1-6, Day 12, and 21.
Change in Pulse Rate
Hematology: RBC distribution
时间窗: From baseline to Day 21
Change in red blood cell distribution width
Hematology: WBC
时间窗: From baseline to Day 21
Change in white blood cell count
Chemistry: Alkaline phosphatase
时间窗: From baseline to Day 21
Change in Alkaline phosphatase (IU/L)
Chemistry: Glucose
时间窗: From baseline to Day 21
Change in Glucose (mg/dL)
Physical Examination: Organs
时间窗: 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
时间窗: From baseline to Day 21
Change in investigator assessment of neurological condition
次要结局
- MANP(From baseline for Day 1 & Day 5)
- Cardiac Metrics:(From Baseline for Day 1-6)
- Cardiac Metrics: Blood pressures(From Baseline for Day 1-6)
- Metabolics(From baseline for Day 1 & Day 5)
- Serum creatinine(From Baseline for Day 1-6)
- Urine flow rate(From Baseline for Day 1-6)
- Immune Response(From baseline for Day 1, Day 5, Day 12, & Day 21)
- Urinary Sodium Excretion(From Baseline for Day 1-6)
- eGFR,(From Baseline for Day 1-6)
- cGMP(from baseline for Day 1 & Day 5)
- Aldosterone(from baseline for Day 1 & Day 5)