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A Multicenter, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, and Efficacy of Budiodarone in Subjects with Non-permanent Atrial Fibrillation

Trial ID
2025-523860-19-00
Protocol
CLN-209
Sponsor
Xyra LLC

Trial statistics

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1
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13
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1
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13
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3
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Diseases & Conditions

Atrial fibrillation

Objectives

The primary objectives are to evaluate the safety and tolerability of budiodarone, specifically monitoring the occurrence of treatment emergent adverse events, serious adverse events, and adverse events of special interest, including major adverse cardiac events. Additionally, the study aims to assess the efficacy of the pharmacological intervention to prevent left atrial enlargement and fibrosis in subjects with non-permanent atrial fibrillation. Secondary objectives include:

  • Evaluation of efficacy in reducing the Atrial Fibrillation Symptom Score.
  • Assessment of efficacy regarding improvement in the Patient Global Impression of Change.
  • Evaluation of efficacy in reducing atrial fibrillation burden.
Trial scope: 4, 5.

Participants

This study involves 500 adult participants, aged 18 to 80 years, including both males and females. The study population consists of patients diagnosed with non-permanent atrial fibrillation, encompassing those with paroxysmal atrial fibrillation or persistent atrial fibrillation. Eligible individuals may include those with a cardiac implantable electronic device, such as a pacemaker or an implantable loop recorder, as well as those utilizing wearable patches for rhythm monitoring. Inclusion requires a history of long episodes of atrial fibrillation lasting more than 5 hours and a failure of at least one prior therapy, such as antiarrhythmic drugs, rate control medications, or catheter ablation. Additionally, participants must have an Atrial Fibrillation Symptom Score greater than 3 and a specific CHA₂DS₂-VASc score. The population includes individuals with NYHA Class I or II heart failure. Participants must be on stable direct oral anticoagulants for at least 3 weeks prior to treatment. Women must be postmenopausal or utilize approved contraception, and men must also adhere to contraceptive requirements throughout the 12-week period. The study objectives are:

  • To evaluate the safety and tolerability of budiodarone.
  • To evaluate the occurrence of treatment emergent adverse events, serious adverse events, and adverse events of special interest, including major adverse cardiac events.
  • To evaluate the efficacy of budiodarone to prevent long episodes of atrial fibrillation.

Plans and Procedures

This multicenter, open-label, dose escalation study is designed to evaluate the safety, tolerability, and efficacy of budiodarone in subjects diagnosed with non-permanent atrial fibrillation. The research methodology focuses on monitoring treatment-emergent adverse events, serious adverse events, and adverse events of special interest, including major adverse cardiac events. The primary efficacy endpoint is the proportion of participants experiencing no long episodes of atrial fibrillation during the final month of treatment. The study involves an initial screening period, which includes a 28-day baseline period to assess atrial fibrillation burden and qualifying episodes. Participants will undergo a 12-week treatment period involving the oral administration of budiodarone tartrate in capsule form. Clinical assessments will include monitoring of vital signs, physical examinations, and clinical laboratory parameters such as thyroid function. Study participation involves multiple visits to assess efficacy and safety through the end-of-study period.

Treatment

The investigational product is budiodarone tartrate, administered in the form of a capsule. The oral dosage is 1600 mg.

Efficacy

The primary efficacy assessment is defined as the proportion of participants experiencing no LEAF, which is characterized as an uninterrupted episode of atrial fibrillation lasting 5 hours or longer, or a cumulative duration of the arrhythmia in any rolling 24-hour period exceeding 5 hours, during the final month of treatment. An exploratory endpoint evaluates the proportion of participants with no LEAF episodes lasting one hour or longer in the final month of budiodarone treatment.

Secondary efficacy parameters include:

  • Change in percent AFSS from baseline during the final month of treatment.
  • PGI-C during the final month of treatment.
  • Percent change in AFB from baseline during the final month of treatment.

Inclusion and Exclusion Criteria

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Inclusion Criteria

  • CIED (Pacemaker or implantable loop recorder) Population o Participants with a history of paroxysmal AF with LEAF lasting more than 5 hours recorded in their pacemaker within the 3 months before screening. o The CIED data will be used to assess baseline AF eligibility criteria
  • Elective Cardioversion Population (Persistent AF) o Participants undergoing first-time elective cardioversion for persistent AF, or second-time cardioversion and no antiarrhythmic concomitant drugs (or who wash out) and who are on stable DOAC for at least 3 weeks and who do not require a TEE to rule out thrombus.
  • PAF Population Without Pacemakers or ILR where AF is quantified with wearable bands / patches o 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 and are on oral anticoagulant for at least 3 weeks prior to receiving the study medication. o The patch data will be used to assess baseline AF eligibility criteria
  • Age: Adults between 18 and 80 years old.
  • Informed Consent: Must be capable and willing to provide written IC.
  • Women: Either postmenopausal for at least one year or surgically sterile; if premenopausal, must agree to use an approved method of contraception
  • Men: Must agree to use an approved method of contraception, such as condoms with spermicide, or have a sterile partner, throughout the 12-week treatment period
  • Proven paroxysmal atrial fibrillation (ECG, Holter monitor, cardiac patch, wearable or pacemaker diagnosis obtained by the clinical site or patient’s prior medical record documenting clear evidence of a diagnosis of PAF) or undergoing first-time elective cardioversion for persistent atrial fibrillation, or second-time cardioversion and no antiarrhythmic concomitant drugs (or who wash out) and who are on stable DOAC for at least 3 weeks and who do not require a TEE to rule out thrombus.
  • 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: • 2 continuous AF episodes (LEAF) of 5 hours or longer • 2 rolling 24-hour periods in which cumulative AF duration is 5 hours or longer • 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
  • Prior Therapy: Must have failed at least one prior therapy for AF including: • Prior AAD based upon physician judgement • Prior rate control drugs based upon physician judgement and continued symptoms • AF catheter ablation
  • AFSS: 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.
  • NYHA Class I or II heart failure. However, those with NYHA Class II heart failure or a documented ejection fraction (EF) below 45% within the past two years must complete additional assessments
  • Able to understand study requirements and willing to follow instructions, attend all required study visits, and undergo all planned tests.
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Exclusion Criteria

  • Pregnancy/Contraception: Pregnant women, women intending to become pregnant, or women not practicing effective contraception (pharmacological or barrier methods).
  • Lactating Women: Breastfeeding women are excluded.
  • Concomitant Risks: Participants with conditions or treatments that could: a. Interfere with the study's conduct. b. Pose an unacceptable risk to safety, or compromise study data interpretation, such as: i. Life expectancy less than 2 years. ii. Active/suspected malignancy (except history of malignancy treated ≥2 years ago without evidence of recurrence). iii. Substance abuse (alcohol/illicit drugs) in the last 12 months. iv. Any known or suspicion for relevant infectious diseases associated with clinical signs (e.g., TSE/Cruetzfield Jacobs disease, Viral Hepatitis, HIV/AIDS, Ebola, West Nile virus, Zika virus). v. The participant is receiving analgesia via a continuous pain pump.
  • Investigational Drug Use: Recent treatment with investigational drugs within 30 days or 5 half-lives, whichever is longer.
  • Protocol Compliance: Subjects unable/unwilling to follow the study protocol.
  • 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 (>500 ms with QRS ≤120 ms).
  • Presence or history of congenital or primary cardiac channelopathies. This includes, but is not limited to: a. Congenital Long QT Syndrome (LQTS), including: i. Romano–Ward syndrome (autosomal dominant LQTS) ii. Jervell and Lange–Nielsen syndrome (autosomal recessive LQTS with sensorineural deafness) iii. Andersen–Tawil syndrome (LQT7; KCNJ2 mutation) iv. Timothy syndrome (LQT8; CACNA1C mutation) b. Brugada syndrome (SCN5A-related sodium channelopathy) c. Short QT syndrome d. Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT; RyR2 or CASQ2 mutations) e. Long–Ganong–Levine syndrome f. Wolff–Parkinson–White syndrome or any form of pre-excitation due to an accessory pathway
  • Third-degree Atrioventricular Block without a functioning pacemaker.
  • Advanced His-Purkinje system disease or bifascicular block associated with syncope or presyncope without a functioning pacemaker.
  • Prior history of sustained ventricular tachycardia without an AICD or Torsades de Pointes.
  • Reversible causes of AF (e.g., hyperthyroidism, recent open- heart surgery, metabolic or electrolyte shift, or ongoing active ischemia).
  • 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 and no antiarrhythmic concomitant drugs (or who wash out) and who are on stable DOAC for at least 3 weeks and who do not require a TEE to rule out thrombus.
  • 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: a. Estimated glomerular filtration rate (eGFR) <30 mL/min at screening. b. Advanced hepatic disease. c. Advanced pulmonary disease. d. Severe psychiatric disorders, e.g., advanced dementia.
  • Known allergy or hypersensitivity to amiodarone or iodine.
  • Termination of previous amiodarone treatment for severe toxicity.
  • Ongoing alcohol or substance abuse.
  • Anemia [hemoglobin <10 g/deciliter (dL) at screening].
  • Thrombocytopenia (platelet count <90,000/μL at screening).
  • Active/uncontrolled thyroid disease, unexplained thyroid function test abnormalities under investigation, history of thyroid malignancy/nodules, or conditions/medications affecting thyroid function, unless stable for ≥3 months with normal thyroid function tests (stable hypo/hyperthyroid patients on consistent therapy are eligible).
  • Any illness or condition judged by the investigator to compromise the participant’s safety during study drug administration.

Trial Status by Country

Country Status Start of Recruitment Planned Patients
Poland PolandRecruiting01 May 2026100

Sites & Investigators

Investigational Products

Details about the medicinal products being studied in this clinical trial.

Product Name Role in Trial Formulation Administration Max Daily Dose Treatment Duration EU MP Number
BUDIODARONE
TestCAPSULEORAL USE160048PRD13227500

Conditions Studied in This Trial