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

NCT04609059 | Unknown Phase 2

• 1 other identifier: M201-A-CT-002
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Paroxysmal Atrial Fibrillation

Outcome Measures

Primary Outcomes (2)

• 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)

Study Arms (2)

M201-A Injection

EXPERIMENTAL

Active Substance: M201-A Route of administration: continuous intravenous injection

Drug: M201-A Injection

Placebo

PLACEBO COMPARATOR

Saline Placebo for M201-A Route of administration: continuous intravenous injection

Drug: Placebo

Interventions

M201-A Injection DRUG

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.)

M201-A Injection

Placebo DRUG

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.)

Placebo

Eligibility Criteria

• Age: 20 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (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.

You may not qualify if:

• (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)
• \[0\]: 440 ms or more in standard 12-lead electrocardiogram at the time of sinus rhythm within 3 months prior to administration
• 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.
• 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.
• T-wave abnormality of electrocardiogram at the time of sinus rhythm
• Past medical history as fainting; syncope with unknown etiology or complicating illness.
• 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.

Sponsors & Collaborators

• Kitasato University: lead
• Aetas Pharma Co. Ltd.: collaborator

Study Sites (5)

Koga general Hospital

Koga, Ibaraki, 306-0041, Japan

RECRUITING

Kitasato University Hospital

Sagamihara, Kanagawa, 252-0375, Japan

RECRUITING

Sendai Cardiovascular Center

Sendai, Miyagi, 981-3133, Japan

RECRUITING

Dokkyo Medical University Saitama Medical Center

Koshigaya, Saitama, 343-8555, Japan

RECRUITING

Yamanashi Prefectural Central Hospital

Kofu, Yamanashi, 400-8506, Japan

RECRUITING

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Miwa Nonaka

CONTACT

+81357916398; m201-a@insti.kitasato-u.ac.jp

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Yuji KUMAGAI, Professor, Kitasato University

Study Record Dates

• First Submitted: September 16, 2020
• First Posted: October 30, 2020
• Study Start: May 7, 2019
• Primary Completion: October 1, 2019
• Study Completion: December 31, 2020
• Last Updated: October 30, 2020

Record last verified: 2020-10

Locations

JP (5)