INhalation of Flecainide to Convert Recent Onset SympTomatic Atrial Fibrillation to siNus rhyThm (INSTANT) (INSTANT)
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|ClinicalTrials.gov Identifier: NCT03539302|
Recruitment Status : Recruiting
First Posted : May 29, 2018
Last Update Posted : January 5, 2021
|Condition or disease||Intervention/treatment||Phase|
|Paroxysmal Atrial Fibrillation (PAF)||Drug: Flecainide Acetate||Phase 2|
Subjects eligible to participate in the study must provide written informed consent (IC) before randomization or any study- specific procedures.
The study consists of 2 parts (PART A and PART B) as described below:
PART A: was completed in March 2020 and was an open-label, randomized, multicenter design to evaluate the feasibility of administration of inhaled flecainide in two dosing regimens.
Subjects are randomized at a 1:1 ratio to a single (N = 10) or repeat (N = 10) dose regimen.
After completion of the 60 mg dose cohort and review of safety/tolerability and PK data, additional subjects were enrolled in an additional repeat dose regimen (90 mg eTLD, N= up to 30 subjects. An additional dose cohort of 120 mg was added to Part A which utilized a different concentration of flecainide (75 mg/mL) and formulation (FlecIH-103). The final dose of 120 mg was selected as the dose to continue evaluating in Part B.
PART B: is an open-label, multicenter design to confirm the safety (including tolerability) and efficacy of the optimal inhaled flecainide dose determined from Part A (120 mg, using the FlecIH-103 inhalation solution).
Randomization, for the initial 20 patients in Part A was stratified by duration of the presenting AF episode (≥ 1 h up to ≤ 24 hours; > 24h up to ≤ 48h).
Once study regimen is allocated, the subject will self-administer the study treatment and inhalation regimen.
If at 60 minutes after initiation of dosing, no conversion to SR is observed, the Investigator may offer the subject another appropriate therapy. Discharge is left up to the discretion of the treating physician but no less than 240 min after initiation of dosing. Heart rhythm will be confirmed with event recorder in follow up.
An independent Data and Safety Monitoring Board (DSMB) is responsible for monitoring safety during the study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||130 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
Part A is open-label however subjects will be randomized to either a single dose or a double dose.
Part B is an open-label, multicenter design to confirm the safety (including tolerability) and efficacy of the optimal dose from Part A.
|Official Title:||A Prospective Randomized Multicenter Study of Flecainide Acetate Oral Inhalation Solution in Single and Repeat Dose Regimens for Acute Conversion to Sinus Rhythm in Subjects With Recent Onset of Symptomatic Paroxysmal Atrial Fibrillation|
|Actual Study Start Date :||May 29, 2018|
|Estimated Primary Completion Date :||May 2021|
|Estimated Study Completion Date :||May 2021|
Experimental: Repeat dose inhaled flecainide acetate
One 120 mg dose of flecainide acetate inhalation solution will be administered via two oral inhalations of 3.5 minutes. There will be a 1 minute break between the two inhalations. A single nebulizer will be used.
Drug: Flecainide Acetate
Oral inhalation form using a nebulizer
Other Name: FlecIH
- Efficacy Objective evaluated using ECGs and telemetry to record heart rhythm [ Time Frame: 90 minutes ]To evaluate the conversion of AF to SR and symptom relief by inhaled flecainide acetate inhalation solution, under two oral inhalation dosing regimens in subjects with recent onset of paroxysmal AF. The subjects will be monitored via ECG and telemetry while in the hospital for 90 minutes.
- Safety Objectives by monitoring the patient for AEs, SAEs, AESIs and SAESIs [ Time Frame: 90 minutes, 24 hours and 5 days ]To assess the safety and tolerability of inhaled flecainide under two oral inhalation dosing regimens in subjects with recent onset of paroxysmal AF. All subjects are monitored for safety for 90 minutes while in the hospital. Two follow up telephone assessments will be completed 24 hours and 5 days post treatment. The clinical safety of inhaled flecainide is evaluated by comparing the frequency of treatment emergent SAEs between the treatment groups.
- PK Objectives by analyzing blood samples to evaluate peak plasma concentration (Cmax) [ Time Frame: 90 minutes ]To explore the population pharmacokinetics (PK) of inhaled flecainide under two oral inhalation dosing regimens in subjects with recent onset paroxysmal AF. Blood samples are collected from each subject for pharmacokinetic analysis.
- PD Objectives by performing serial 12-Lead ECG recordings [ Time Frame: 90 minutes ]To explore the electrocardiographic effects of inhaled flecainide under two oral inhalation dosing regimens in subjects with recent onset of paroxysmal AF. Serial 12-Lead ECG measurements are extracted from the Holter recording in triplicate before, after the allocated inhalation regimen and at the time of conversion to sinus rhythm for pharmacodynamic analysis.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03539302
|Contact: Meisa Propst||510-422-5522 ext email@example.com|
|United States, California|
|Memorial Long Beach Medical Center||Recruiting|
|Long Beach, California, United States, 90807|
|Contact: Elysse Ballon 562-933-2334|
|Principal Investigator: Mark Lee, MD|
|Contact: Tom Rossenbacker|
|Principal Investigator: Tom Rossenbacker|
|Contact: Pascal Vranckx|
|Principal Investigator: Pascal Vranckx|
|Contact: Giovanni Tahapary|
|Principal Investigator: Giovanni Tahapary|
|Contact: Jonas de Jong|
|Principal Investigator: Jonas de Jong|
|Contact: Ype Tuininga|
|Principal Investigator: Ype Tuininga|
|Admiraal De Ruyter Ziekenhuis||Recruiting|
|Contact: Ismail Aksoy|
|Contact: Robert Tieleman|
|Principal Investigator: Robert Tieleman|
|Contact: I.C. van Gelder|
|Principal Investigator: I.C. van Gelder|
|Contact: A.F.M. Kuijper|
|Principal Investigator: A.F.M. Kuijper|
|Maastricht University Medical Center||Recruiting|
|Contact: Harry Crijns|
|Principal Investigator: Harry Crijns|
|Contact: Jeroen van der Heijden|
|Principal Investigator: Jeroen van der Heijden|
|Contact: Nadea Al-Windy|
|Principal Investigator: Nadea Al-Windy|
|Contact: Arif Elvan|
|Principal Investigator: Arif Elvan|
|Study Director:||Luiz Belardinelli, MD||Chief Medical Officer at InCarda Therapeutics|