Dose Escalation Study to Assess Safety, Tolerability, and Efficacy of Budiodarone Treatment With Non-permanent Atrial Fibrillation

Phase 2RecruitingNCT07792239

Xyra, LLC100 enrolled

Overview

This multicenter, open-label study aims to assess the safety, tolerability and efficacy of budiodarone in treating participants with non-permanent AF, in particular paroxysmal atrial fibrillation (PAF). The trial will serve as a 6-month safety and a proof-of-concept study for a dose escalation strategy using AF monitoring, enrolling approximately 100 participants who will undergo 24 weeks of treatment. The study aims to evaluate the feasibility of dose escalation through AF monitoring of long episodes atrial fibrillation last 5 hours or longer.

The study will allow AF participants from three specific populations: 1) Participants with a pre-implanted Cardiac Implantable Electrical Device (CIED), which includes implantable pacemakers or implantable loop recorders (ILR) and who have a history of paroxysmal AF with LEAF lasting 5 hours or longer recorded in their pacemaker within the 3 months before screening; 2) Participants undergoing first-time elective electrical (direct current) cardioversion for persistent AF, or second-time elective electrical (direct current) cardioversion; and 3) Participants with paroxysmal AF who do not have a pacemaker or ILR and who have a history of frequent AF and LEAF, with a minimum CHA2DS2-VASc score of 1 or more for males and 2 or more for females. AF monitoring will be conducted via a pre-implanted Cardiac Implantable Electrical Device (CIED), which includes implantable pacemakers or implantable loop recorders (ILR), for those who have one. Participants without a CIED will undergo AF monitoring using a cardiac patch and/or a wearable device on the wrist. All participants who meet the study entry criteria will be started on 200 mg budiodarone BID. The participants will return to the study site every 4 weeks and dose adjustments will follow the following algorithm. If no AF episode lasting 5 hours or longer is recorded and no rolling 24-hour period shows a cumulative AF burden of 5 hours or longer, the participant is classified as a monthly responder, and the budiodarone dose remains unchanged. If at least one AF episode of 5 hours or longer is observed, or if any rolling 24-hour period indicates a cumulative AF burden of 5 hours or longer, the participant is designated as a monthly non-responder, and the budiodarone dose is increased by 200 mg BID up to a maximum of 800 mg BID.

Study Type

INTERVENTIONAL

Allocation

Interventions

Budiodarone 200 mg BIDDRUG

Budiodarone is formulated as 200 mg capsules, to be administered as 1 capsule (200mg) twice a day (BID).

Budiodarone 400 mg BIDDRUG

Budiodarone is formulated as 200 mg capsules, to be administered as 2 capsules (400 mg) BID.

Budiodarone 600 mg BIDDRUG

Budiodarone is formulated as 200 mg capsules, to be administered as 3 capsules (600 mg) BID.

Budiodarone 800 mg BIDDRUG

Budiodarone is formulated as 200 mg capsules, to be administered as 4 capsules (800 mg) BID.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Proven paroxysmal atrial fibrillation or undergoing first-time elective electrical (direct current) cardioversion for persistent atrial fibrillation, or second-time elective electrical (direct current) cardioversion. * Baseline AF Criteria: To qualify for treatment, each participant must have during the 28-day baseline period an AFB greater than 5% and one of the following qualifying events: 1) 2 continuous AF episodes (LEAF) of 5 hours or longer; or 2) 2 rolling 24-hour periods in which cumulative AF duration is 5 hours or longer; or 3) 1 continuous AF episode (LEAF) of 5 hours or longer plus 1 rolling 24-hour period in which cumulative AF duration is 5 hours or longer * Must have failed at least one prior therapy for AF * Must have an AFSS greater than 3. * CHA₂DS₂-VASc score of 1 or more for males and 2 or more for females and be on oral anticoagulant for at least 3 weeks prior to receiving the study medication. * For participants with heart failure: NYHA Class I or II heart failure. Key Exclusion Criteria: * NYHA Class 3 or 4 heart failure. * MI, ischemic stroke, or any clinically relevant venous thromboembolism within 3 months of screening. * Unstable angina, percutaneous transluminal coronary angioplasty (PTCA), or CABG within 3 months of screening. * Prolonged QTcF Interval with a normal QRS duration (\>500 ms with QRS ≤120 ms). * Persistent AF (≥7 consecutive days or episodes \>23 hours). Those presenting with persistent AF at screening are eligible if they are scheduled to undergo first-time elective cardioversion, or second-time cardioversion * Recent treatment with rhythm control medications (Class I or III Singh-Vaughan Williams) within five half-lives before screening (rate control drugs permitted) and amiodarone within 3 months prior to screening. * Cardiac ablation procedures within 30 days of screening or participants who have scheduled an ablation procedure * Severe end-organ disease

Locations (4)

Oddział Kardiologiczny, Szpital Miejski Św. Wincentego a Paulo w Gdyni

Gdynia, Poland

RECRUITING

Klinika Kardiologii

Krakow, Poland

RECRUITING

EMED Centrum Usług Medycznych Ewa Śmiałek

Rzeszów, Poland

RECRUITING

Klinika Kardiologii i Chorób Wewnętrznych Wojskowy Instytut Medyczny, Państwowy Instytut Badawczy

Warsaw, Poland

RECRUITING

Outcomes

Primary Outcomes

Proportion of participants that have no long episodes of atrial fibrillation (LEAF) in the final month of treatment

Proportion of participants that have no LEAF (uninterrupted episode of AF of 5 hours or longer in duration or cumulative duration of AF in any rolling 24-hour period that is 5 hours or longer) in the final month of treatment.

Time frame: 24 weeks

Secondary Outcomes

Percent Change in Atrial Fibrillation Burden (AFB)

Percent change in AFB during final month of treatment compared to baseline.

Time frame: 24 weeks

Change in percent of Atrial Fibrillation Severity Scale (AFSS) during final month of treatment.

The University of Toronto Atrial Fibrillation Severity Scale (AFSS) is a patient-reported outcome instrument developed to quantify atrial fibrillation (AF). In this study, Part C of the scale will be used. In Part C, participants are asked to asses how AF symptoms affect daily activities, physical functioning, and overall quality of life. The minimum score is 0 and the maximum score is 35. Higher scores reflect greater impairment from AF-related symptoms. AFSS score during final month of treatment will be compared to baseline for multiple doses of budiodarone.

Time frame: 24 weeks

Patient Global Impression of Change (PGI-C) during the final month of treatment

The Patient Global Impression of Change (PGI-C) is a two-question instrument that employs a Likert scale to assess participants' perceived changes in AF symptom control and overall satisfaction. Response options for symptom control include: Made them worse, No change, Slight improvement, Moderate improvement, A lot of improvement, and Complete relief. For overall satisfaction, participants choose from: Not at all, A little bit, Somewhat, A lot, and Completely.

Time frame: 24 weeks

Dose Escalation Study to Assess Safety, Tolerability, and Efficacy of Budiodarone Treatment With Non-permanent Atrial Fibrillation

Overview

Conditions

Interventions

Eligibility

Locations (4)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts