To Evaluate the Effect of Food on the Pharmacokinetics of Y-4 Tablets in Healthy Subjects

Официальное название

A Randomized, Open-label, Single-dose, Two-period, Crossover Phase I Clinical Trial With Two Parallel Arms Evaluating the Impact of Food on the Pharmacokinetics of Y-4 Tablets in Healthy Subjects

Обзор

Y-4 is a new fixed-dose combination drug product containing two active ingredients of pregabalin and riluzole. The objective is to assess the effect of food on the pharmacokinetics (PK) of pregabalin and riluzole in healthy adult subjects after a single oral dose of Y-4 tablets.

Подробное описание

This study will be a single-center, open-label, single-dose, randomized, two period, two-way crossover study in which the effect of a high-fat breakfast on the pharmacokinetics of Y-4 tablets will be assessed. A total of 20 subjects will be enrolled in this trial.

The enrolled subjects will be randomly divided into group AB and group BA, with a total of 10 subjects in each group, all subjects will take one Y-4 tablet (pregabalin 112.5 mg, riluzole 28.125 mg) at each period. Subjects of group AB will take Y-4 tablet under fasted condition in period 1, and take Y-4 tablet under fed condition in period 2. In contrast, subjects of group BA will take Y-4 tablet under fed condition in period 1, and take Y-4 tablet under fasted condition in period 2. There will be 7 days of wash-out between the two periods.

Subjects will be admitted to the clinical phase 1 research center the day before taking the drug, and fasted for at least 10 hours (overnight fast). Water will be forbidden from 1 hour pre-dose to 2 hours post-dose of investigational drug.

Вмешательства

• Препарат Y-4 tablet
  The enrolled subjects will be randomly divided into group AB and group BA, with a total of 10 subjects in each group, all subjects will take one Y-4 tablet (pregabalin 112.5 mg, riluzole 28.125 mg) at each period. Subjects of group AB will take Y-4 tablet under fasted condition in period 1, and take Y-4 tablet under fed condition in period 2. In contrast, subjects of group BA will take Y-4 tablet under fed condition in period 1, and take Y-4 tablet under fasted condition in period 2. There will

Первичные конечные точки

• adverse events [Срок оценки: From the first day to the 19th± 1st day after the start of administration]
• Incidence of subject getting abnormal results of laboratory tests after treatment [Срок оценки: From the first day to the 19th± 1st day after the start of administration]
• Incidence of subject getting abnormal results of 12-lead ECG after treatment [Срок оценки: From the first day to the 19th± 1st day after the start of administration]
• Incidence of subject getting abnormal results of vital signs after treatment. [Срок оценки: From the first day to the 19th± 1st day after the start of administration]
• Incidence of subject getting abnormal results of physical examinations after treatment. [Срок оценки: From the first day to the 19th± 1st day after the start of administration]
• Incidence of subject getting abnormal results of blood oxygen saturation after treatment [Срок оценки: rom the first day to the 19th± 1st day after the start of administration]
• Incidence of subject getting abnormal results of C-SSSRS scale evaluation after treatment after treatment [Срок оценки: From the first day to the 19th± 1st day after the start of administration]

Вторичные конечные точки (11)

• Cmax [Срок оценки: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration]
• AUC0-t [Срок оценки: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration]
• AUC0-∞ [Срок оценки: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration]
• Tmax [Срок оценки: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration]
• t1/2 [Срок оценки: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration]
• λz [Срок оценки: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration]
• AUC_%Extrap [Срок оценки: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration]
• Vz/F [Срок оценки: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration]
• CL/F [Срок оценки: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration]
• MRT0-t [Срок оценки: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration]
• MRT0-∞ [Срок оценки: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration]

Критерии участия

Критерии включения

• Healthy adult male and female subjects, 18-45 years of age (including both ends).
• Body weight ≥ 50 kg for male and ≥ 45 kg for female, body mass index (BMI) within the range of 19 - 28 kg/m2 (including both ends).
• During the screening period, serum creatinine is within the normal range, or the standard creatinine clearance (CLcr) estimated by Cockcroft-Gault formula is ≥ 80 mL/min (for female subject, according to the calculation result × 0.85）.
• Subjects who are able to understand and give their signed informed consent before any trial related procedures are performed.

Критерии исключения

• Subjects who are known to be allergic to pregabalin, riluzole or any excipients of Y-4 tablets (microcrystalline cellulose, Copovidone, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate and Opadry amb Ⅱ), have allergic diseases or allergic constitution;
• Subjects who have special requirements for diet and cannot follow the unified diet;
• Physical examinations, vital signs, 12-lead electrocardiograms (ECG), chest X-ray (front position), laboratory tests (hematology, serum chemistry, coagulation test, urinalysis, etc.) and other screening tests found abnormalities that the researchers judged to be of clinical significance;
• Subjects who have experienced angioedema in the past (such as swelling of the face, mouth (tongue, lips, and gums), and neck (pharynx and throat));
• History of dizziness or vertigo with clinical significance, or disease of inner ear known to cause dizziness or vertigo;
• QTcF > 450 msec at the screening stage;
• Diagnosed with insomnia, anxiety disorder, depression, epilepsy, or other serious mental disorders, and principal investigator determines that the subject is not suitable to participate in this trial;
• Presence or history of hepatic or renal disease or any other condition known to interfere with the absorption, distribution, metabolism or excretion of medicines;
• Subjects who drink too much tea, coffee and/or caffeine-containing beverages (more than 8 cups, 1 cup = 250 mL) every day within 3 months prior to screening, or disagree that any caffeine-containing beverages are prohibited during the trial;
• Subjects who have consume any diet (food or beverage) rich in grapefruit, pitaya, mango and cranberry within 14 days prior to screening;
• Subjects have disease history or current disease that may affect the safety evaluation of the subject or the internal process of the study drug, including the central nervous system, cardiovascular system, digestive system, respiratory system, urinary system, hematological system, immunology, psychiatry, metabolic abnormalities, gastrointestinal surgery (excluding appendicitis surgery), etc. In particular, there is a history of dysphagia or any gastrointestinal disease affecting drug absorption (including frequent nausea or vomiting caused by any cause) and eye diseases;
• Donation or loss of blood equal to or in excess of 400 mL, or blood transfusion within 3 months prior to screening; or donation or loss of blood equal to or in excess of 200 mL within 1 month prior to screening;
• Subjects who have taken any drugs known to be strong inhibitors or inducers of cytochrome P450 enzymes within 2 months prior to screening (such as inducers - barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole; inhibitors - serotonin reuptake inhibitors (SSRI) antidepressants, cimetidine, diltiazem, macrolides, nitroimidazoles, sedative hypnotics, verapamil, fluoroquinolones, antihistamines); or subjects who have taken any prescription drugs, over-the-counter drugs and Chinese herbal medicine other than the above drugs within 14 days prior to screening;
• Subjects who have taken central nervous system (CNS) depressants including opioids (pethidine hydrochloride, morphine, dihydromorphine hydrochloride, fentanyl, tramadol, etc), benzodiazepines (diazepam, flurazepam, clonazepam, oxazepam, chlordiazepine and triazolam etc), antiepileptic drugs (carbamazepine, sodium valproate, phenobarbital drugs etc) within 2 months prior to screening;
• Subject with sleep apnea, or subjects with severe sleep snoring and daytime drowsiness;
• Subjects with suicidal thoughts and behavior;
• Subject participated in any other clinical trials within 3 months prior to screening;
• Current or former drug users, or positive urine screen for drugs of abuse at screening (screening items include: dimethylenedioxyamphetamine, methamphetamine, ketamine, morphine, tetrahydrocannabinoid acid, cocaine);
• Alcoholics or regular drinkers within 3 months prior to screening, that is, those who drink more than 14 units of alcohol per week (1 unit = 360 mL of beer or 45 mL of alcohol with 40% alcohol content or 150 mL of wine), or whose alcohol breath test results are greater than 0.0 mg/100 mL, or who cannot abstain from alcohol during the trial;
• Smokers or those who cannot comply with the prohibition of smoking during the trial, or positive for cotinine screening;
• Subjects who is positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, syphilis antibody or human immunodeficiency virus (HIV) antibody;
• Male subjects (or their partners) or female subjects have baby plans during the whole trial period and within 3 months after the end of the trial, or subjects are unwilling to take one or more non-drug contraceptive measures (such as complete abstinence, condoms, ligation, etc.) during the trial period;
• Female subjects who have unprotected intercourse within 14 days prior to screening, or pregnant or lactating women;
• Subjects with poor compliance or other factors unsuitable for participation in this trial.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Beijing Tiantan Hospital, Capital Medical University Beijing — Пекин

Идентификаторы

NCT: NCT07013773 · Y-4-LC-03

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗