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

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

Study Overview

• Status: Unknown
• Conditions: Paroxysmal Atrial Fibrillation
• Intervention / Treatment: Drug: M201-A Injection; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Ibaraki
    • Koga-City, Ibaraki, Japan, 306-0041
      • Recruiting
      • Koga General Hospital
      • Contact: Koji Uchida; Phone Number: +81280471010; Email: uchida@kogahosp.jp
      • Principal Investigator: Masataka Fukue
      • Sub-Investigator: Tetsuya Ishikawa
  • Kanagawa
    • Sagamihara-city, Kanagawa, Japan, 252-0375
      • Recruiting
      • Kitasato University Hospital
      • Contact: Kimiko Yamamura; Phone Number: ＋81427788462; Email: kimiko-y@kitasato-u.ac.jp
      • Sub-Investigator: Takao Shimohama
      • Sub-Investigator: Hidehira Fukaya
      • Sub-Investigator: Jun Kishihara
      • Sub-Investigator: Jun Oikawa
      • Sub-Investigator: Naruya Ishizue
  • Miyagi
    • Sendai-city, Miyagi, Japan, 981-3133
      • Recruiting
      • Sendai Cardiovascular Center
      • Contact: Masahiro Yagi; Phone Number: +81223721111; Email: ccuami@star.gmobb.jp
      • Principal Investigator: Masahiro Yagi
      • Sub-Investigator: Tatsuro Uchida
      • Sub-Investigator: Shinya Fujii
      • Sub-Investigator: Hiroshi Kobayashi
      • Sub-Investigator: Shoko Uematsu
      • Sub-Investigator: Chikahiko Koeda
      • Sub-Investigator: Yukako Tanaka
      • Sub-Investigator: Satoshi Miyazawa
      • Sub-Investigator: Ryozo Maeda
      • Sub-Investigator: JIHAENG Im
  • Saitama
    • Koshigaya-city,, Saitama, Japan, 343-8555
      • Recruiting
      • Dokkyo Medical University Saitama Medical Center
      • Contact: Mariko Iyama; Phone Number: +81489650658; Email: m-iyama@dokkyomed.ac.jp
      • Principal Investigator: Shiro Nakahara
      • Sub-Investigator: Reiko Fukuda
      • Sub-Investigator: Naoki Nishiyama
      • Sub-Investigator: Yuri Koshikawa
      • Sub-Investigator: Tomoaki Ukaji
  • Yamanashi
    • Kofu-city, Yamanashi, Japan, 400-8506
      • Recruiting
      • Yamanashi Prefectural Central Hospital
      • Contact: Masahiko Nakamura; Phone Number: +81552537111; Email: m-nakamura@ych.pref.yamanashi.jp
      • Principal Investigator: Masahiko Nakamura
      • Sub-Investigator: Ken Umetani
      • Sub-Investigator: Keita Sano
      • Sub-Investigator: Aritaka Makino
      • Sub-Investigator: Toshiaki Yano
      • Sub-Investigator: Takuya Shimizu
      • Sub-Investigator: Serina Ono
      • Sub-Investigator: Chisa Asahina
      • Sub-Investigator: Koki Fukasawa
      • Sub-Investigator: Miu Eguchi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 84 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: M201-A Injection; Active Substance: M201-A Route of administration: continuous intravenous injection	Drug: M201-A Injection; Active Substance: M201-A Route of administration: continuous intravenous injection 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.)
PLACEBO_COMPARATOR: Placebo; Saline Placebo for M201-A Route of administration: continuous intravenous injection	Drug: Placebo; Saline Placebo: M201-A Placebo Route of administration: continuous intravenous injection 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.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Assessment	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)	throughout the study duration(up to day7)
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.)	throughout the study duration(Within 2 hours)

Collaborators and Investigators

• Sponsor: Kitasato University
• Collaborators: Aetas Pharma Co. Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 7, 2019
• Primary Completion (ACTUAL): October 1, 2019
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: September 16, 2020
• First Submitted That Met QC Criteria: October 23, 2020
• First Posted (ACTUAL): October 30, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 30, 2020
• Last Update Submitted That Met QC Criteria: October 23, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: M201-A-CT-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No