M201-A-CT-004

JRCT ID: jRCT2031240034

Registered date:16/04/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Patients with heart failure who are admitted or hospitalized due to worsening of heart failure desp
• Date of first enrollment: 16/04/2024
• Target sample size: 112
• Study type: Interventional
• Intervention(s): M201-A hydrochloride injection once or twice a day for heart failure patients who are hospitalized or hospitalized due to exacerbation of heart failure despite the use of existing oral heart failure treatments (including diuretics). The safety, tolerability, and efficacy of repeated intravenous 20-minute administration for 7 days will be investigated in a placebo-controlled, double-blind study.

Outcome(s)

Primary Outcome

Safety evaluation items
Adverse events and side effects
Vital signs (body temperature, blood pressure/pulse rate)
Laboratory test values (general blood/biochemical tests, blood renal function tests, urinalysis (qualitative/biochemistry), urinalysis (kidney function)
Standard 12-lead ECG and Holter ECG
Effectiveness evaluation items
Urine volume
Urinary Na, Cl, K excretion
Water balance (difference between the amount of water consumed, amount of water in meals, amount of transfusion, etc., and urine amount)
Change in weight
NYHA classification
Evaluate pulmonary congestion with chest X-ray
Assessment of congestion (edema, pulmonary crackles)
Renal function indicators (serum Cre, serum BUN, serum Cystatine C, eGFRcystatine, eGFRcre, CCr, urinary NAG, urinary beta2 microglobulin, urinary L-FABP, urinary albumin, etc.)
Change in blood BNP
Inferior vena cava diameter (during inspiration and expiration)
Cardiac function measured by cardiac ultrasound: cardiac chamber inner diameter size, ventricular wall motion, left ventricular shortening (FS), left ventricular ejection fraction (EF), tricuspid regurgitation pressure gradient, left ventricular inflow Fast waveform (early diastolic wave/atrial systolic wave: E/A), E wave deceleration time (DT), left ventricular early diastolic wave/mitral valve annulus movement speed
E/E', Presence of pericardial effusion, aortic diameter (AoD), left atrial diameter (LAD), left ventricular end-diastolic diameter (LVDd), left ventricular end-systolic diameter (LVDs), left ventricular wall thickness [ventricular septal thickness (IVSth)], posterior wall thickness (PWth)], left ventricular outflow tract waveform (LVOF VTI), left atrial volume index (LAVI)
Percentage of subjects who received additional/emergency drug therapy for heart failure between Day 1 and Day 8 and discontinued it
Percentage of subjects who received a bolus of loop diuretic injection between Day 1 and Day 8
The period from the start of the study drug administration (Day 1) to discharge
Percentage of subjects who died from the start of study drug administration (Day 1) to Day 39
Percentage of subjects who were readmitted to the hospital by Day 39 after discharge
The following items are for reference data
Changes in physical activity before and after administration of study drug (at admission, Day 9, and post-test (Day 16, Day 39)) Physical activity questionnaire completed by a physician
Pharmacokinetic endpoints
Plasma drug concentration
Pharmacokinetic parameters
Urinary drug concentration (urinary excretion amount, urinary excretion rate)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 86age old
• Gender: Both

Include criteria

Subjects who meet all of the following criteria will be eligible for this clinical trial.
(1) Japanese adult, male or female
(2) Persons who are hospitalized or currently hospitalized due to worsening of heart failure* despite using oral heart failure medications (including oral diuretics)
*: Exacerbation of heart failure is a condition in which one or more of the following is observed: dyspnea, pulmonary congestion, pulmonary rales, onset or progression of edema, and short-term weight gain.
(3) Persons who are 20 years or older and less than 86 years old on Day -2 before the start of the study drug administration
(4) Persons with heart failure determined to be grade II or III according to NYHA classification (HFrEF, HFmrEF, or HFpEF)
(5) Persons with eGFR less than 60 mL/min/1.73 m2 and more than 30 mL/min/1.73 m2
(6) Those whose weight is 40 kg or more for women and 45 kg or more for men, and whose BMI* is 18.0 or more and less than 30.0.
*: BMI = Weight (kg) / [Height (m)2] (rounded down to the second decimal place)
(7) Subjects who are able to measure urine storage and water intake, and measure body weight after urinating every morning before administering the study drug.
(8) Subjects who have given written consent to participate in this clinical trial based on their own free will.

Exclude criteria

In this clinical trial, subjects who fall under any of the following exclusion criteria will not be included in this clinical trial, considering the impact on subject safety and efficacy.
(1) Persons hospitalized for acute myocardial infarction and less than 30 days after onset of symptoms
(2) Persons with cardiogenic shock
(3) Subjects who received emergency infusion treatment with catecholamines, carperitide (hANP), tolvaptan sodium phosphate (Samutas), or vasodilators, which are injectable treatments for heart failure, within 30 days before the start of study drug administration.
(4) Loop diuresis must be completed within 32 hours before the scheduled morning administration time on Day 1 (if administration starts at 9 a.m. on Day 1, from 1 a.m. on Day -1 until before the start of study drug administration on Day 1). Those who received a bolus dose of drug injections
If a bolus of the above loop diuretic injection is administered on Day -1, Day -1 shall be reset and the necessary tests shall be conducted. For handling when using loop diuretic injections, see "7.9 Emergency Measures/Treatment."
(5) Subjects who used antiarrhythmic drugs for the period specified below before starting study drug administration.
Amiodarone: within 1 year
Group IV (bepridil): within 14 days
Group Ia, Group Ic, Group III: within 7 days
For details on drugs applicable to Group Ia, Group Ic, and Group III, see Table 7.8-1 in "7.8.1 Drugs prohibited for concomitant use."
(6) Those whose creatinine value exceeds 2.5 mg/dL
(7) Subjects who have newly administered, changed the dose, or discontinued an SGLT2 inhibitor within 120 days before starting study drug administration.
(8) Subjects with QTcF of 440 ms or more in standard 12-lead electrocardiogram measurement. However, this standard does not apply to patients with atrial fibrillation.
(9) Persons with risk factors for torsade de pointes (TdP) (e.g., hypokalemia, hypomagnesemia, history or complications of unexplained syncope, long QT syndrome or a family history thereof) etc)
(10) Persons with BNP less than 100 pg/mL or NT-proBNP less than 400 pg/mL
(11) Tests from 6 months before administration of the study drug to Day -1
and whose serum potassium level has ever been less than 3.6 mEq/L or more than 5.5 mEq/L
(12)
Subjects whose serum magnesium level has been found to be 1.8 mg/dL or less at least once during a test between 6 months before administration of the study drug and Day -1.
(13) Persons with blood hemoglobin levels less than 9 g/dL
(14) Persons with bradycardia with heart rate below 50 or sinus arrest for 2 seconds or more
(15) Persons with grade II Mobitz type atrioventricular block or grade III atrioventricular block
(16) Persons with systolic blood pressure less than 90 mmHg
(17) Persons with sustained ventricular tachycardia
(18) Persons who have a cardiac assist circulation device or a biventricular pacemaker implanted.
(19) Those who have undergone cardiac surgery within 60 days before administration of the study drug
(20) Persons undergoing endotracheal intubation
(21) Persons undergoing artificial dialysis
(22) Persons with treatment-resistant, refractory, or end-stage heart failure who are considered for special treatment including ventricular assist device or heart transplantation.
(23) Persons with severe aortic valve stenosis, severe left ventricular hypertrophy, serious gastrointestinal (gastrointestinal, liver, gallbladder, bile duct, pancreas, etc.) diseases, severe thyroid dysfunction, or those who are undergoing treatment with serious respiratory disease, blood disease, or anti-cancer drugs.
(24) Do not use drugs, herbs, drinks, etc. that may inhibit or induce QT prolongation and cytochrome P450 3A (see Tables 7.8-2 and 7.8-3 in "7.8.1 Drugs prohibited for concomitant use"). person who is
(25) Persons with a history of epileptic seizures or organic brain disorders that may induce epileptic seizures.
(26) Persons with a history of anaphylaxis
(27) Subjects who have received a blood transfusion of 200 mL or more or blood component transfusion within 3 months before administration of the study drug.
(28) Those who do not agree to quit smoking during this study period
(29) Persons who have tested positive for any of the drug of abuse test items
(30) Persons with alcoholism or a history of alcoholism
(31) Persons who cannot agree not to consume coffee, oolong tea, green tea, or black tea during hospitalization.
(32) Persons who have participated in clinical trials of other drugs, medical devices, regenerative medicine products, etc. within 3 months before administration of the investigational drug.
(33) Those who cannot consent to contraception* for 90 days after administration of the study drug
*: Use medically appropriate methods of contraception (condoms, contraceptive pills, etc.)
(34) Pregnant women, lactating women, and those who may be pregnant*
*: For subjects who may be pregnant, the presence or absence of pregnancy will be confirmed using a pregnancy test (such as one based on the beta-subunit of HCG) at screening, Day -1, and Day 39 post-tests.
(35) Persons who have received M201-A hydrochloride in the past
(36) Others who are judged by the principal investigator (co-investigator) to be unsuitable subjects for this study.

Related Information

• Primary Sponsor: Shimamoto Ken
• Secondary Sponsor: Aetas Pharma Inc.