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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Xyra LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2026-04-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

• To evaluate the safety and tolerability of budiodarone
• To evaluate the occurrence of treatment emergent adverse
events (TEAE), serious adverse events (SAE) and adverse
events of special interest (AESI) which includes the
examples of major adverse cardiac events (MACE)
• To evaluate the efficacy of Budiodarone to prevent LEAF in
subjects with non-permanent AF.

Secondary objectives 3

1. To evaluate the efficacy of budiodarone in reducing the AFSS.
2. To evaluate the efficacy of budiodarone in improving the PGI-C.
3. To evaluate the efficacy of Budiodarone to reduce AFB in subjects with non-permanent AF.

Conditions and MedDRA coding

Non-permanent Atrial Fibrillation

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

IPD plan description

Individual participant data (IPD) will not be shared due to the nature of the study and data protection considerations. The study results will be published in aggregated form only, ensuring transparency while maintaining participant confidentiality. No requests for IPD sharing are anticipated, and no infrastructure for secure data sharing is in place.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. 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
2. 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.
3. 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
4. Age: Adults between 18 and 80 years old.
5. Informed Consent: Must be capable and willing to provide written IC.
6. Women: Either postmenopausal for at least one year or surgically sterile; if premenopausal, must agree to use an approved method of contraception
7. 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
8. 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.
9. 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
10. 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
11. AFSS: Must have an AFSS greater than 3.
12. 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.
13. 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
14. Able to understand study requirements and willing to follow instructions, attend all required study visits, and undergo all planned tests.

Exclusion criteria 25

1. Pregnancy/Contraception: Pregnant women, women intending to become pregnant, or women not practicing effective contraception (pharmacological or barrier methods).
2. Lactating Women: Breastfeeding women are excluded.
3. 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.
4. Investigational Drug Use: Recent treatment with investigational drugs within 30 days or 5 half-lives, whichever is longer.
5. Protocol Compliance: Subjects unable/unwilling to follow the study protocol.
6. NYHA Class 3 or 4 heart failure.
7. MI, ischemic stroke, or any clinically relevant venous thromboembolism within 3 months of screening.
8. Unstable angina, percutaneous transluminal coronary angioplasty (PTCA), or CABG within 3 months of screening.
9. Prolonged QTcF Interval (>500 ms with QRS ≤120 ms).
10. 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
11. Third-degree Atrioventricular Block without a functioning pacemaker.
12. Advanced His-Purkinje system disease or bifascicular block associated with syncope or presyncope without a functioning pacemaker.
13. Prior history of sustained ventricular tachycardia without an AICD or Torsades de Pointes.
14. Reversible causes of AF (e.g., hyperthyroidism, recent open- heart surgery, metabolic or electrolyte shift, or ongoing active ischemia).
15. 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.
16. 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.
17. Cardiac ablation procedures within 30 days of screening or participants who have scheduled an ablation procedure
18. 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.
19. Known allergy or hypersensitivity to amiodarone or iodine.
20. Termination of previous amiodarone treatment for severe toxicity.
21. Ongoing alcohol or substance abuse.
22. Anemia [hemoglobin <10 g/deciliter (dL) at screening].
23. Thrombocytopenia (platelet count <90,000/μL at screening).
24. 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).
25. Any illness or condition judged by the investigator to compromise the participant’s safety during study drug administration.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Safety: • Incidence of TEAE and treatment-emergent serious adverse events (TESAE). • Incidence of AESI • Mortality and Clinical Morbidity Events: o Death o Resuscitated sudden cardiac death (SCD) including appropriate implanted cardiac defibrillator (ICD) discharge o Cardiovascular hospitalization o Stroke or another thromboembolic event • Physical Exam assessments and abnormalities. • Vital sign assessments and abnormalities. • Clinical laboratory assessment and abnormalities. o Thyroid functio
2. Primary Efficacy: • Proportion of participants that have no LEAF (uninterrupted episode of AF that is 5 hours or longer in duration or cumulative duration of AF in any rolling 24-hour period that is greater than 5 hours) in the final month of treatment.
3. Exploratory Endpoint: • The proportion of participants with no LEAF episodes lasting one hour or longer in the final month of budiodarone treatment

Secondary endpoints 1

1. Secondary Efficacy: • Change in percent AFSS during final month of treatment compared to baseline for multiple doses of budiodarone. • PGI-C during the final month of treatment. • Percent change in AFB during final month of treatment compared to baseline.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Xyra LLC

Sponsor organisation

Xyra LLC

Address

Corporation Trust Center, 1209 North Orange Street 1209 North Orange Street

City

Wilmington

Postcode

19801-1120

Country

United States

Scientific contact point

Organisation

Xyra LLC

Contact name

Marek Sawicki

Public contact point

Organisation

Xyra LLC

Contact name

Global Medical Services Polska Sp. z o.o.

Third parties 3

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications