M201-A

JRCT ID: jRCT2031190069

Registered date:07/08/2019

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Symptomatic Paroxysmal atrial fibrillation
• Date of first enrollment: 01/10/2019
• Target sample size: 42
• Study type: Interventional

Intervention(s)

Step 1: Continuous Intravenous Injection administered with single dose of M201-A hydrochloride or placebo 0.4 mg/kg in 50 mL, controlled with a syringe driver at a rate of 2.5 mL/min for 20 minutes
Step 2: Continuous Intravenous Injection administered with single dose of M201-A hydrochloride or placebo 0.6 mg/kg in 50 mL, controlled with a syringe driver at a rate of 2.5 mL/min for 20 minutes
(Based on recommendations of an independent data monitoring committee; data and safety monitoring board, it will be decided that dosage is 0.20 mg/kg or 0.40 mg/kg. If appropriate, Step 2 will not be conducted.)

Outcome(s)

Primary Outcome

I. Safety Assessment
Safety investigation based on combined Investigator examination, Adverse Events (particulary, Side Effects and safety assessments of clinical examinations, vital sings, 12-lead ECGs and 24-hour-Holter ECGs at pre- and post-administration.
II. Arrest of atrial fibrillation (AF)
Ratio of arrested AF* in administered subjects within 2 hours after administration
(*Restoration of sinus rhythm should be kept at least one (1) minute or more.)

Secondary Outcome

I. Arrest of atrial fibrillation (AF)
1) Ratio of arrested AF* in administered subjects within 4 hours after administration
(*Restoration to sinus rhythm should be kept at least one (1) minute or more.)
II. Restoration of sinus rhythm
1) Ratio of restored sinus rhythm at 2 hours after administration
2) Ratio of restored sinus rhythm at 8 hours after administration
3) Ratio of restored sinus rhythm at 24 hours after administration
III. Duration of sinus rhythm
Duration of restored sinus rhythm on arrested AF subject(s) after administration
IV. Prevention of Recurrent AF up to 24 hours after administration
1) Ratio of non-recurrent AF on subjects with restored sinus rhythm up to 24hours after administration
V. Causality between two events a) duration of AF onset to the administration of investigational product and b) arrested AF
1) Ratio of arrested AF as duration of AF onset to the administration is 24 hours or less.
2) Ratio of arrested AF as duration of AF onset to the administration is 72 hours or less. of arrested AF as duration of AF onset to the administration is 24 hours or less.Percentage of stop atrial fibrillation, and time from onset of atrial fibrillation to administration (Within 24 hours / 72 hours)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 85age old
• Gender: Both

Include criteria

(1) Japanese (male, female) adult with symptomatic paroxysmal atrial fibrillation (AF)
- Written informed consent must be obtained on a voluntary basis before any assessment is performed.
(2) Age: 20 to less than 85 years of age
(3) Weight: 40 kilograms(kg) or more
BMI: 18.5 to less than 28.0 on screening examination(screening)
(4) Past AF History: Event(s) as symptomatic AF with (at least) 2 hours or more AF lasting has (have) occurred at least once or more a half year (6 months) prior to the screening.
(5) Occurrence time of the latest AF: Record(s) of the patient portable electrocardiograph shows evidence to support that the latest AF has occurred within 3 hours to less than 3 days (72 hours) prior to an administration of the investigational product.
(6) The AF lasting prior to the administration: 12 lead electrocardiogram just prior to the administration shows that AF has not stopped.
(7) Excluded medication: Based on propositions of a principal investigator or a co-investigator(s), a patient can consent for discontinuation of below antiarrhythmic agents (the Vaughan-Williams classification) for at least 7 days after administration since an advanced registration. Nonetheless, if a period between the advanced registration and the administration is less than 7 days, it should be confirmed those agent has unadministered during 7 days prior to the administration.
[Vaughan-Williams classification]
Antiarrhythmic drug group I
Antiarrhythmic drug group III
Antiarrhythmic drug group IV Bepridil (Bepricol)
(8) Excluded administration of amiodarone: It should be confirmed that amiodarone hydrochloride is not unadministered within one (1) year before the screening.

Exclude criteria

(1) Heart failure (NYHA II, III, IV). Excluding palpitations induced by atrial fibrillation (AF)
(2) Any atrioventricular block of first, second or third degree at the time of sinus rhythm
(3) Any risk factor leads to Torsades de Pointes (TdP)
a) QTcF: 440 ms or more in standard 12-lead electrocardiogram at the time of sinus rhythm within 3 months prior to administration
b) Hypokalemia or suspected to be hypokalemia:
One or more of serum potassium levels, obtained at any time during 6 months in advance of administration including pre-administration examination, has been 3.6 mEq/L or less.
c) Hypomagnesemia or suspected be hypomagnesemia: One or more of serum magnesium levels, obtained at any time during 6 months in advance of administration including pre-administration examination, has been 1.8 mg/dL or less.
d) T-wave abnormality of electrocardiogram at the time of sinus rhythm
e) Past medical history as fainting; syncope with unknown etiology or complicating illness.
f) Past own medical history or family medical history as long QT syndrome
(4) Severe heart hypertrophy; Cardiomegaly: Septal Thickness of cardiac ultrasound has been exceeded over 15 mm.
(5) Left atrial dimension (parasternal long-axis view) of cardiac ultrasound has been exceeded over 45 mm.

Related Information

• Primary Sponsor: Kumagai Yuji
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development
• Secondary ID(s): NCT04609059