Bioequivalence Study of Dronedarone Hydrochloride Tablets

This is a single-center, randomized, open-label, single-dose, two-formulation, two-sequence crossover study designed to evaluate the bioequivalence and safety of a generic formulation versus the reference formulation of Dronedarone Hydrochloride Tablets (400 mg) in healthy Chinese male subjects under fed conditions. A planned total of 48 eligible subjects will be enrolled.

Venous blood samples are collected for the determination of plasma concentrations of dronedarone and its metabolite N-desbutyl dronedarone. In each study period, samples are taken at pre-dose (0 h) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 24, 48, and 72 h post-dose.

Inclusion criteria

• Healthy male subjects who voluntarily participate and provide written informed consent in accordance with Good Clinical Practice (GCP) guidelines.
• Age ≥ 18 years.
• Body weight ≥ 50.0 kg and body mass index (BMI) between 19.0 and 26.0 kg/m² (inclusive).
• In good health as determined by comprehensive medical history, physical examination, and laboratory tests.
• Able to comply with the study protocol and scheduled visits.

Exclusion criteria

• Any clinically significant abnormalities in physical examination, vital signs, 12-lead ECG, cardiac ultrasound, or laboratory tests (including hematology, blood biochemistry, urinalysis, virology serology, and coagulation function).
• History or presence of severe cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immune, dermatological, neurological, or psychiatric diseases. Specific exclusions include: renal insufficiency, heart failure, stroke, permanent atrial fibrillation, second- or third-degree atrioventricular block or sick sinus syndrome, bradycardia (heart rate < 50 bpm), prior amiodarone-associated hepatotoxicity or pulmonary toxicity, hypokalemia, hypomagnesemia, or family history of long QT syndrome.
• History of specific allergies (e.g., asthma, urticaria, eczema), allergic constitution (allergy to two or more drugs or substances like milk/pollen), or known hypersensitivity to dronedarone, its components, or related compounds.
• Major trauma or significant blood loss within 3 months prior to screening.
• History of drug abuse within the past 5 years or positive urine drug screen.
• Difficulty with blood sampling, needle phobia, or intolerance to venipuncture.
• Positive alcohol breath test at screening.
• Excessive alcohol consumption (>14 units per week; 1 unit = 285 mL beer, 25 mL spirits, or 100 mL wine) within 3 months prior to screening, or unwillingness to abstain from alcohol during the study.
• Excessive consumption of tea, coffee, or caffeine-containing beverages (>8 cups per day; 1 cup = 250 mL) within 3 months prior to screening, or consumption of any alcohol, caffeine, or xanthine-rich products (e.g., coffee, strong tea, chocolate, cola, grapefruit) within 48 hours prior to dosing.
• Inability to comply with a standardized diet, including food intolerance (e.g., to the standard meal), lactose intolerance, or dysphagia.
• Smoking ≥5 cigarettes per day within 3 months prior to screening or unwillingness to refrain from smoking during the study.
• Use of any medication (prescription, over-the-counter, herbal, or supplements) within 14 days prior to screening.
• Use of any medication known to interact with dronedarone within 1 month prior to screening, including: QT-prolonging drugs, digoxin, calcium channel blockers, CYP2D6 substrates, potent CYP3A inhibitors, CYP3A inducers, statins, and narrow therapeutic index CYP3A substrates (e.g., dabigatran etexilate, warfarin).
• Vaccination within 1 month prior to screening or planned vaccination during the study.
• Participation in any other clinical trial within 3 months prior to screening.
• Blood donation or significant blood loss (≥400 mL in total) within 3 months prior to screening.
• Male subjects (or their partners) planning pregnancy from 2 weeks prior to screening until 3 months after study completion, or unwilling to use a medically acceptable non-pharmacological contraceptive method during the study.
• Any other condition considered by the investigator as unsuitable for participation or voluntary withdrawal.