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.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Male and Female Subjects
• Intervention / Treatment: Drug: Y-4 tablet; Drug: Pregabalin capsule; Drug: Riluzole tablet

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 11
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Frank Lee; Phone Number: (201)416-7753; Email: flee@frontagelab.com

Study Locations

• United States
  • New Jersey
    • Secaucus, New Jersey, United States, 07094
      • Frontage Clinical Services,Inc.
      • Contact: Frank Lee; Phone Number: (201)416-7753; Email: flee@frontagelab.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Y-4 tables; In the morning of Day 1 ，single oral administration one Y-4 tablet in the state of fasting state.	Drug: Y-4 tablet; Participants will be admitted to research center on Day-1. Participants are required to fast for at least 10 hours prior to dosing on Day 1. In the morning of Day 1, participants will be administered with one tablet of Y-4 (pregabalin 112.5 mg and riluzole 28.125 mg), then participants will be monitored and blood samples will be collected for the following 72 hours (Day4).
Experimental: Pregabalin capsule; In the morning of Day 8 ，single oral administration one pregabalin capsule in the state of fasting state.	Drug: Pregabalin capsule; Participants are required to fast for at least 10 hours prior to dosing on Day 8. In the morning of Day 8, participants will be administered with one pregabalin capsule (75 mg pregabalin), then participants will be monitored and blood samples will be collected for the following 72 hours (Day 11).
Experimental: Riluzole tablet; In the morning of Day 15 ，single oral administration one riluzole tablet in the state of fasting state.	Drug: Riluzole tablet; Participants are required to fast for at least 10 hours prior to dosing on Day 15. In the morning of Day 15, participants will be administered with one riluzole tablet (50 mg riluzole), then participants will be monitored and blood samples will be collected for the following 72 hours (Day 18).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum observed concentration, it was obtained directly from the measured plasma concentration-time data;	On Day1-4、Day8-11、Day15-18 of observation period.
AUC0-t	Area under the concentration-time curve from time zero to the last detectable concentration	On Day1-4、Day8-11、Day15-18 of observation period.
AUC0-∞	Area under the concentration-time curve from time 0 to infinity (extrapolated).	On Day1-4、Day8-11、Day15-18 of observation period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax	Time of observed Cmax, it was obtained directly from the measured plasma concentration-time data;	On Day1-4、Day8-11、Day15-18 of observation period.
λz	Terminal-phase elimination rate constant, slope of curves terminal segment at semi-log concentration-time curve calculated by linear regression;	On Day1-4、Day8-11、Day15-18 of observation period.
t1/2	Terminal elimination half-life	On Day1-4、Day8-11、Day15-18 of observation period.
CL/F	Apparent total body clearance	On Day1-4、Day8-11、Day15-18 of observation period.
Vz/F	Apparent volume of distribution	On Day1-4、Day8-11、Day15-18 of observation period.
MRT0-t	Mean residence time within the time from time zero to the lowest testing plasma concentration	On Day1-4、Day8-11、Day15-18 of observation period.
MRT0-∞	Mean residence time extrapolated from zero to infinity	On Day1-4、Day8-11、Day15-18 of observation period.
AUC_%Extrap	The percentage of the AUC0-inf that has been extrapolated.	On Day1-4、Day8-11、Day15-18 of observation period.
The Incidence of subject getting abnormal results of clinical adverse events after treatment.	An AE is defined as any untoward medical event that occurs after receiving a drug or treatment or any deterioration of a disease or symptom that existed before receiving the investigational product or treatment (excluding the disease studied in this trial) in a subject or a clinical investigation subject, whether or not considered related to the investigational product or treatment. All AEs will be coded using the MedDRA, and summarized by SOC and PT. Number and percentage of participants with AEs,SAEs, and AEs that lead to early withdrawal will be summarized. AEs might be summarized by severity (grade) and relationship to investigational product if judged appropriate.	From the first day to the 25th± 1st day after the start of administration
The Incidence of subject getting abnormal results of laboratory tests after treatment.	Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment.Clinical laboratory examinations including hematology, serum chemistry, ,urinalysis,coagulation test (PT/APTT/FIB/TT).Normal range is provided by the site.	From the first day to the 25th± 1st day after the start of administration
The Incidence of subject getting abnormal results of 12-lead electrocardiograms after treatment.	Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment.Standard ECG parameters will be measured including RR, PR, and QTc intervals, and QRS duration .Normal range is provided by the site.	From the first day to the 25th± 1st day after the start of administration
The Incidence of subject getting abnormal results of vital signs after treatment	Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment.Vital signs, including blood pressure (sitting position), pulse rate, temperature (frontal temperature, Celsius), and respiration.Normal range is provided by the site.	From the first day to the 25th± 1st day after the start of administration
The Incidence of subject getting abnormal results of blood oxygen saturation after treatment.	Record changes of blood oxygen saturation from baseline to post-treatment, listing deviations from normal ranges post-treatment. Normal range is provided by the site	From the first day to the 25th± 1st day after the start of administration
The Incidence of subject getting abnormal results of physical examinations after treatment.	Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. The physical examinations will consist of a general assessment, dermatologic, lymph nodes, head, eyes, ears, nose, throat, chest, neck, thyroid gland, cardiac, lung, chest (included breast), abdomen, extremities, musculoskeletal, neurologic, and other physical findings of note. Normal range is provided by the site.	From the first day to the 25th± 1st day after the start of administration
The Incidence of subject getting abnormal results of C-SSRS scale evaluation after treatment.	Record changes of C-SSRS scale evaluation from baseline to post-treatment.	From the first day to the 25th± 1st day after the start of administration

Collaborators and Investigators

• Sponsor: Neurodawn Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: May 24, 2026
• First Submitted That Met QC Criteria: May 24, 2026
• First Posted (Actual): June 1, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 24, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Postherpetic Neuralgia; Phase Ⅰ; Y-4 Tablet
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neuralgia, Postherpetic; Amino Acids, Peptides, and Proteins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiazoles; Benzothiazoles; Azoles; Acids, Acyclic; Carboxylic Acids; Amino Acids; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Pregabalin; Riluzole
• Other Study ID Numbers: Y-4-LC-02 (US)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes