Bioequivalence Study of Nalfurafine Hydrochloride Orally Disintegrating Tablets on Fasting and Fed in Humans

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 Nalfurafine Hydrochloride Orally Disintegrating Tablets (2.5 μg) in healthy Chinese male and female subjects under fed conditions. A planned total of 72 eligible subjects will be enrolled. Venous blood samples are collected for the determination of plasma concentrations of nalfurafine. In each study period, samples are taken at pre-dose (0#h) and at 0.25, 0.5, 1, 1.5, 2, 2.5,3, 3.5,4, 4.5, 5, 6, 8, 10, 12, 24, and 36 #h post-dose.

Inclusion criteria

• Voluntarily participate and sign the informed consent form, with the informed consent process complying with GCP requirements;
• Healthy male or female;
• Aged 18 years or older;
• Female body weight ≥45.0 kg, male body weight ≥50.0 kg, with body mass index (BMI) = weight (kg) / height² (m²), and BMI within the range of 19.0-26.0 kg/m², inclusive.

Exclusion criteria

• A history or current presence of abnormalities in the motor system, nervous system, mental system, endocrine system, blood circulation system, respiratory system, digestive system, urinary system, or reproductive system, which is deemed clinically significant by the investigator;
• Undergone surgery within 3 months prior to screening or during the screening period, or undergone surgery that affects drug absorption, distribution, metabolism, or excretion, or planned surgery during the study period;
• A history of habitual constipation;
• Chronic insomnia or a habit of taking sleeping pills;
• Blood donation or significant blood loss (≥400 mL) within 3 months prior to screening or during the screening period (excluding physiological blood loss in women);
• A history of drug abuse within the past 5 years or a positive result in drug screening;
• A specific allergy history (asthma, urticaria, eczema, etc.), or allergies to drugs, environments, foods, or known allergy to the components or analogs of this drug;
• Excessive consumption of tea, coffee, or caffeinated beverages within 3 months prior to screening (more than 8 cups per day, 1 cup = 250 mL), or intake of any food or beverage containing alcohol, caffeine, or xanthine-rich substances (such as coffee, strong tea, chocolate, cola, grapefruit, etc.) within 48 hours before taking the investigational drug;
• Alcohol abuse within 3 months prior to screening (consuming more than 14 units of alcohol per week: 1 unit ≈ 285 mL of beer, 25 mL of spirits, or 100 mL of wine), unwillingness to abstain from alcohol during the study, or an alcohol breath test result > 0 mg/100 mL;
• Smoking ≥5 cigarettes per day within 3 months prior to screening or unwillingness to quit smoking during the study;
• Inability to adhere to a uniform diet or difficulty swallowing;
• Intolerance to standard meals or lactose intolerance (e.g., diarrhea after consuming milk);
• Use of any prescription drugs, over-the-counter medications, herbal medicines, or health supplements within 14 days prior to screening;
• Use of any drugs that inhibit or induce liver metabolism of drugs within 28 days prior to screening;
• Vaccination within 28 days prior to screening or planned vaccination during the study period;
• Participation in another clinical trial and use of investigational drugs or devices within 3 months prior to screening, or planned participation in other clinical trials during this study, or participation in clinical trials not conducted in person;
• Pregnant or breastfeeding women, or male subjects (or their partners) or female subjects with pregnancy plans within 2 weeks prior to screening to 3 months after the study, or unwillingness to adopt a medically recognized non-drug contraceptive method (such as intrauterine devices or condoms) during the study;
• Difficulty in blood collection, a history of needle phobia or blood phobia, or inability to tolerate venous puncture;
• Abnormalities in physical examination, blood routine, blood biochemistry, urine routine, 12-lead electrocardiogram, coagulation function, infectious disease screening, or pregnancy test (applicable to female subjects) that are clinically significant;
• Abnormal vital signs that remain abnormal after re-examination;
• Subjects deemed unsuitable for enrollment by the investigator or those who withdraw for personal reasons.