Pharmacokinetics of Y-4 Tablets With Pregabalin Capsules and Riluzole Tablets in U.S. Healthy Participants

An Open-label, Single-dose, Three-period Phase Ⅰ Study to Compare the Pharmacokinetics of Y-4 Tablets With Pregabalin Capsules and Riluzole Tablets in U.S. Healthy Participants

The primary goal of this clinical trial is to compare pharmacokinetic characteristics of Y-4 tablets with pregabalin capsules and riluzole tablets in the US healthy adult participants after single oral administration under fasted condition.

The secondary goal of the trial is to evaluate the safety and tolerability of Y-4 tablets, pregabalin capsules and riluzole tablets in the US healthy adult participants.

This study will be an open-label, single-dose, three-period study in healthy adult participants. A total of at least 10 participants (about half men and half women) will be will be enrolled and needed to complete in the study. Participants enrolled in this study wil be administered with Y-4 tablets, pregabalin capsules and riluzole tablets at three periods with a 7-day washout.

Periods and corresponding treatments are planned as following:

Period 1: Y-4 tablet, one tablet, 112.5 mg/28.125 mg (pregabalin/riluzole) Period 2: pregabalin capsule, one capsule, 75 mg/capsule Period 3: riluzole tablet, one tablet, 50 mg/tablet

Inclusion Criteria:

1. Healthy adult male and female participants, 18-45 years of age (including both ends).
2. 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).
3. 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 participant, according to the calculation result × 0.85）
4. Participants who are able to understand and give their signed informed consent before any trial related procedures are performed.

Exclusion Criteria:

1. Participants 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, Opadry amb Ⅱ), have allergic diseases or allergic constitution;
2. Participants who have special requirements for diet and cannot follow the unified diet;
3. Physical examinations, vital signs, 12-lead electrocardiograms (ECG), laboratory tests (Hematology, serum chemistry, coagulation test, urinalysis, etc.) and other screening tests found abnormalities that the researchers judged to be of clinical significance;
4. Participants who have experienced angioedema in the past (such as swelling of the face, mouth (tongue, lips, and gums), and neck (pharynx and throat));
5. History of dizziness or vertigo with clinical significance, or disease of inner ear known to cause dizziness or vertigo;
6. QTcF > 450 msec at the screening stage (Corrected using Fridericia's formula: QTcF = QT /(RR^0.33), where RR = 60 / heart rate);
7. Diagnosed with insomnia, anxiety disorder, depression, epilepsy, or other serious mental disorders, and principal investigator determines that the participant is not suitable to participate in this trial;
8. Presence or history of hepatic or renal disease or any other condition known to interfere with the absorption, distribution, metabolism or excretion of medicines, participants who have impaired hepatic function at the time of screening: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 ULN; or total bilirubin (TBIL) > 1.0 ULN;
9. Participants 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;
10. Participants who have consume any diet (food or beverage) rich in grapefruit, pitaya, mango and cranberry within 14 days prior to screening;
11. Participants have disease history or current disease that may affect the safety evaluation of the participant or the internal process of the study drug, including the central nervous system, cardiovascular system, digestive system, endocrine 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;
12. 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;
13. Participants 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 participants who have taken any prescription drugs, over-the-counter drugs and traditional Chinese medicine or herbal medicine other than the above drugs within 14 days prior to screening;
14. Participants 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;
15. Participant with sleep apnea, or participants with severe sleep snoring and daytime drowsiness;
16. Participants with history of neuropsychiatric disorders, including current or past history of mental illness, suicidal ideation based on the C-SSRS score of 1 or higher;
17. Participant participated in any other clinical trials within 3 months prior to screening;
18. Current or former drug users, or positive urine screen for drugs of abuse at screening (screening items include: Opiates, Amphetamines, Cocaine, Cannabinoids, Barbiturates, Benzodiazepines);
19. 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;
20. Smokers or those who cannot comply with the prohibition of smoking during the trial, or positive for cotinine screening;
21. Participants who is positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, syphilis antibody or human immunodeficiency virus (HIV) antibody;
22. Male participants (or their partners) or female participants have baby plans during the whole trial period and within 3 months after the end of the trail, or participants are unwilling to take one or more non-drug contraceptive measures (such as complete abstinence, condoms, ligation, etc.) during the trial period.
23. Female participants who have unprotected intercourse within 14 days prior to screening, or pregnant or lactating women;
24. Participants with poor compliance or other factors unsuitable for participation in this trial.