First-in-Patient Study for Sing le Dose of M201-A Hydrochloride Injection in Japanese Patients With Paroxysmal Atrial Fibrillation

Phase 2

• Conditions: Paroxysmal Atrial Fibrillation
• Interventions: Drug: M201-A Injection; Drug: Placebo

• Registration Number: NCT04609059
• Lead Sponsor: Kitasato University

Brief Summary

First-in-Patient Study for sing le dose of M201-A hydrochloride injection in Japanese patients with paroxysmal atrial fibrillation.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-05-07
• Primary Completion: 2019-10-01
• Study First Submitted: 2020-09-16
• Status Verified: 2020-10
• Study First Submitted QC: 2020-10-23
• Last Update Submitted: 2020-10-23
• Study First Posted: 2020-10-30
• Last Update Posted: 2020-10-30
• Study Completion: 2020-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 42

Inclusion 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 (8) Excluded administration of amiodarone: It should be confirmed that amiodarone hydrochloride is not unadministered within one (1) year before the screening.

Exclusion 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)

  1. [0]: 440 ms or more in standard 12-lead electrocardiogram at the time of sinus rhythm within 3 months prior to administration

  2. 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 [1]/L or less.

  3. 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.

  4. T-wave abnormality of electrocardiogram at the time of sinus rhythm

  5. Past medical history as fainting; syncope with unknown etiology or complicating illness.

  6. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
M201-A Injection	M201-A Injection	Active Substance: M201-A Route of administration: continuous intravenous injection
Placebo	Placebo	Saline Placebo for M201-A Route of administration: continuous intravenous injection

Primary Outcome Measures

Name	Time	Method
Arrest of atrial fibrillation (AF)	throughout the study duration(Within 2 hours)	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.)
Safety Assessment	throughout the study duration(up to day7)	Safety investigation based on combined Investigator examination, Adverse Events (particulary, incidence of abnormal laboratory tests,abnormal vital sings,abnormal 12-lead ECG, abnormal 24-hour Holter ECG)

Trial Locations

Locations (5)

Koga general Hospital; 🇯🇵 Koga-City, Ibaraki, Japan

Sendai Cardiovascular Center; 🇯🇵 Sendai-city, Miyagi, Japan

Dokkyo Medical University Saitama Medical Center; 🇯🇵 Koshigaya-city,, Saitama, Japan

Yamanashi Prefectural Central Hospital; 🇯🇵 Kofu-city, Yamanashi, Japan

Kitasato University Hospital; 🇯🇵 Sagamihara-city, Kanagawa, Japan