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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
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.
Beijing Tiantan Hospital, Capital Medical University Beijing
Beijing, Beijing Municipality, China
RECRUITINGadverse events
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. Therefore, an AE can be a discomfort sign (including an abnormal laboratory finding), symptom, or transient disease beyond any indication, whether or not related to the investigational product or treatment. The investigator will name each AE reported during the study by MedDRA PT and evaluate their severity using the criteria of "mild", "moderate" and "severe". The relevance evaluation is divided into 5 grades: 1-certainly related; 2- probably/likely related; 3-possibly related; 4-unlikely related; 5 not related.
Time frame: 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
Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. Laboratory tests are composed of hematology, urinalysis, serum chemistry, coagulation test. Normal range is provided by the site.
Time frame: 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
Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. 12-lead ECG will be analyzed by single RR Heart Rate, aggregate PR Interval, aggregate QRS Duration, aggregate RR Interval, aggregate QT Interval, aggregate QTC Interval. Normal range is provided by the site.
Time frame: 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.
Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. Vital signs(body temperature, respiration, blood pressure, and pulse) will be assessed by according equipment.(electronic sphygmomanometer, thermometer).
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Time frame: 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.
Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. Physical examinations will be conduct by the investigator through observation.
Time frame: 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
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
Time frame: 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
Record changes of C-SSSRS scale evaluation from baseline to post-treatment
Time frame: From the first day to the 19th± 1st day after the start of administration
Cmax
peak plasma concentration after single dose
Time frame: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration
AUC0-t
Area under the plasma concentration versus time curve from time 0 to the time of the last quantifiable concentration after single dose
Time frame: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration
AUC0-∞
Area under the plasma concentration-time curve from time 0 to infinity (extrapolated) after single dose
Time frame: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration
Tmax
Time to reach maximum observed plasma concentration after single dose
Time frame: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration
t1/2
Terminal elimination half-life after single dose
Time frame: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration
λz
Terminal-phase elimination rate constant, slope of curves terminal segment at semi-log concentration-time curve calculated by linear regression.
Time frame: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration
AUC_%Extrap
The percentage of the AUC0-inf that has been extrapolated. AUC\_%Extrap = \[(AUC0-∞-AUC0-t)/AUC0-∞\] × 100%
Time frame: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration
Vz/F
apparent volume of distribution after single dose. Vz/F = Dose/AUC0-∞/λz
Time frame: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration
CL/F
Total body clearance after single dose. CL/F = Dose/AUC0-inf
Time frame: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration
MRT0-t
Mean residence time within the time from time zero to the lowest testing plasma concentration after single dose. MRT0-t = AUMC0-t/AUC0-t
Time frame: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration
MRT0-∞
Mean residence time extrapolated from zero to infinity after single dose. MRT 0-∞ = AUMC 0-∞/AUC 0-∞.
Time frame: From day 1 to day 4 and day 8 to day 11 in each period after the start of administration