Food-effect Bioavailability of Fixed Dose Combination Zemimet® SR Tab. 50/1000 mg Under Fed and Fasting Conditions

Study Overview
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Brief Summary
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A randomized, open-label, single oral dose, one-treatment, two-period, two-sequence, crossover bioavailability study under fed and fasting conditions in healthy Thai volunteers with at least 7 days washout period between the administrations of investigational products of two consecutive periods. A: Fixed dose combination Zemimet® SR Tab. 50/1000 mg orally administered once without food (fasting conditions) B: Fixed dose combination Zemimet® SR Tab. 50/1000 mg orally administered once with food (fed conditions)

Detailed Description
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[Objectives] Primary: To investigate the food-effect bioavailability of absorption of gemigliptin/metformin hydrochloride sustained release 50/1000 mg FDC tablet (Zemimet® SR Tab. 50/1000 mg) in healthy subjects under fed and fasting conditions Secondary: To evaluate safety of investigational product under fed and fasting conditions [Admission and Confinement] Fed conditions: Subjects will be admitted the night before investigational product administration, supervised for at least 8 hours overnight fasting prior to consume standard HFHC breakfast and in-house stay until 24 hours post-dose. Fasting conditions: Subjects will be admitted a night before investigational product administration, supervised for at least 8 hours overnight fasting prior to dosing and in-house stay until 24 hours post-dose.

Official Title
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A Randomized, Open-label, Single-dose, Two-way Crossover Study to Investigate Food-effect Bioavailability of Fixed Dose Combination Zemimet® SR Tab. 50/1000 mg (Gemigliptin/Metformin Hydrochloride Sustained Release 50/1000 mg) Under Fed and Fasting Conditions in Healthy Volunteers

Conditions
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Type2 Diabetes

Intervention / Treatment
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* Drug: Gemigliptin/Metformin Hydrochloride Sustained Release 50/1000 mg(Fasting)
* Drug: Gemigliptin/Metformin Hydrochloride Sustained Release 50/1000 mg(Fed)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index between 18.0 to 30.0 kg/m2. Normal laboratory values, including vital signs and physical examination, for all parameters in clinical laboratory tests at screening. Non-pregnant woman (negative pregnancy test) and not currently breast feeding. Female subjects abstain from either hormonal methods of contraception Male subjects who are willing or able to use effective contraceptive Have voluntarily given written informed consent (signed and dated) by the subject prior to participating in this study Exclusion Criteria: History serious hypersensitivity reactions History or evidence of clinically significant diseases or any significant ongoing chronic medical illness History or evidence of family diabetes History or evidence of type 1 diabetes mellitus, diabetic ketoacidosis, diabetic pre-coma History or evidence of shock or severe dehydrate or severe infection such as respiratory tract infection, urinary tract infection within 14 days prior to admission in each period History or evidence of preceding diarrhea or vomiting within 24 hours prior to admission in each period History or evidence of drug addict or investigation with urine sample shows a positive test for drug of abuse History of problems with swallowing tablet or capsule Difficulty fasting or consuming standardized meals History of sensitivity to heparin or heparin-induced thrombocytopenia Any condition possibly affecting drug absorption Have renal creatinine clearance (Clcr) < 45 mL/min based on serum creatinine results at the screening laboratory test 12-lead ECG demonstrating QTc >450 msec, a QRS interval >120 msec or with an abnormality considered clinically significant at screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: FDC Zemimet® SR Tab. 50/1000(Fasting)<br>Gemigliptin/Metformin Fixed Dose Combination Zemimet® SR Tab. 50/1000 mg (Gemigliptin/Metformin Hydrochloride Sustained Release 50/1000 mg) under fasting condition | Drug: Gemigliptin/Metformin Hydrochloride Sustained Release 50/1000 mg(Fasting)<br>* Fasting conditions: Each subject will receive a single dose of fixed dose combination Zemimet® SR Tab. 50/1000 mg with 240±2 mL of 20% glucose solution in drinking water after an overnight fasting for at least 8 hours.<br>|
| Active Comparator: FDC Zemimet® SR Tab. 50/1000(Fed)<br>Gemigliptin/Metformin Fixed Dose Combination Zemimet® SR Tab. 50/1000 mg (Gemigliptin/Metformin Hydrochloride Sustained Release 50/1000 mg) under fed condition | Drug: Gemigliptin/Metformin Hydrochloride Sustained Release 50/1000 mg(Fed)<br>* Fed conditions: Each subject will receive a single dose of fixed dose combination Zemimet® SR Tab. 50/1000 mg with 240±2 mL of 20% glucose solution in drinking water at 30 minutes after the start of standardized HFHC breakfast.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) of gemigliptin, LC 15-0636 and metformin | The observed maximum or peak concentration after administration of the drug | Blood samples (10 mL each) will be collected at time 0.00 (pre-dose; 2x10 mL in duplicate tubes) and at 0.25, 0.50, 1.00, 1.50, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 10.00, 12.00, 14.00, 24.00 and 48.00 hours post-dose. | 
| AUC0-tlast of gemigliptin, LC 15-0636 and metformin | Area under the concentration-time curve from time zero to the last time where plasma concentration can be measured | Blood samples (10 mL each) will be collected at time 0.00 (pre-dose; 2x10 mL in duplicate tubes) and at 0.25, 0.50, 1.00, 1.50, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 10.00, 12.00, 14.00, 24.00 and 48.00 hours post-dose. | 
| AUC0-∞ of gemigliptin, LC 15-0636 and metformin | Area under the concentration-time curve from time zero to infinity by the extrapolation of the rest of AUC from last time where plasma concentration can be measured to time infinity | Blood samples (10 mL each) will be collected at time 0.00 (pre-dose; 2x10 mL in duplicate tubes) and at 0.25, 0.50, 1.00, 1.50, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 10.00, 12.00, 14.00, 24.00 and 48.00 hours post-dose. |