Bioequivalence Study for Acarbose/Metformin FDC

Study Overview
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Brief Summary
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The purpose of this study is to establish the bioequivalence (i.e. similar pharmacokinetics and pharmacodynamics characteristics) between acarbose/metformin FDC (50 mg/500 mg) and loose combination of acarbose (50 mg) and metformin (500 mg)

Official Title
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Randomized, Non-blinded Crossover Study to Establish the Bioequivalence Between Fixed Dose Combination (FDC) and the Loose Combination of Acarbose and Metformin Following Single Oral Dosing in Chinese Healthy Adult Male and Female Subjects

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Acarbose/Metformin FDC(BAY81-9783)
* Drug: Glucobay
* Drug: Glucophage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chinese healthy male or non-pregnant, non-lactating female subject, age ≥ 18 years at the first screening examination / visit. Body Mass Index (BMI): ≥ 19 to <28 kg / m*2 , with body weight ≥ 50 kg. Results of HbA1c value are within the normal range (4.0-6.0%, inclusive). Plasma glucose after 75g oral glucose loading show: FPG (Fast Plasma Glucose) < 6.1 mmol / dL. 2-h PG (Plasma Glucose 2 hours after glucose loading) < 7.8 mmol/dL Women and men of reproductive potential must agree to use adequate contraception when sexually active. This applies for the time phase between signing of the informed consent form and the last visit. The acceptable methods of contraception available to men include, for example (e.g.) condoms with or without a spermicidal agent; the acceptable methods of contraception available to women include e.g. (a) diaphragm or cervical cap with spermicide; (b) intra-uterine device; (c) hormone-based contraception (only for the female partners of male subjects) One method has to be used by the man and one method by the female partner. No need to use two methods at the same time if subject or his female partner has been surgically sterilized , Subjects who are able to understand and follow instructions and who are able to participate in the study for the entire period Subjects must give their written informed consent to participate in the study after receiving adequate previous information and prior to any study specific procedures Exclusion Criteria: Screening test results likely to show inappropriateness for participation in this study: Any clinically relevant abnormality identified on the screening medical examination Systolic blood pressure < 90 or ≥ 140 mmHg (after at least 5 min in supine position) Diastolic blood pressure < 60 or ≥ 90 mmHg (after at least 5 min in supine position) Pulse rate < 50 or > 100 beats/min (after at least 5 min in supine position) Clinically relevant findings in the electrocardiogram (ECG) such as a second- or third-degree AV block, prolongation of the QRS complex over 120 msec or of the QTcB-interval over 450 msec Positive results for hepatitis B virus surface antigen (hepatitis B surface antigene (HBsAg)), hepatitis C virus antibodies (anti-HCV) and human immune deficiency virus antibodies (human immunodeficiency virus antibodies (anti-HIV)) and treponema pallidum specific antibody. Positive urine drug screening Hemoglobin level lower than Lower limit of normal value Clinical laboratory results evaluated by the investigators to be clinically abnormal values A history of relevant diseases of internal organs (diabetes mellitus, Ileus, Ileus-like symptoms, diseases that may significantly jeopardize body systems, such as malabsorption or maldigestion from gastrointestinal tract, liver cirrhosis, renal dysfunction, congestive heart failure, ischemic heart disease, malignant neoplasm), of the central nervous system (e.g. epilepsy), or other organs which are likely to show inappropriateness for participation in this study States which may deteriorate as a result of increased gas formation in the intestine (e.g. Roemheld's syndrome, major hernias, intestinal obstructions, and intestinal ulcers). Acute conditions with the potential to alter renal function such as: dehydration, severe infection, shock. Any type of acute metabolic acidosis. Family history of diabetes (within the second degree of relationship) Known drug hypersensitivity or idiosyncrasy Known severe allergies, non-allergic drug reactions, or multiple drug allergies Special diets or known hypersensitivity preventing the subjects from eating the standard meals during the study. Habitual medication including Chinese herbal drugs within 3 months before the screening Participation in another clinical trial within 3 months before the screening examination

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A-washout-treatment B<br>Subject will receive a single oral dose of acarbose/metformin FDC (Treatment A, 50 mg acarbose/500 mg metformin) in period 1, followed by a single oral dose of 50mg acarbose and 500mg metformin as loose combination (Treatment B) in period 2. Washout interval between 2 treatment periods was at least 7 days. | Drug: Acarbose/Metformin FDC(BAY81-9783)<br>* Single dose: 50 mg acarbose/500 mg metformin tablet, oral<br>Drug: Glucobay<br>* Single dose: 50 mg tablet, oral<br>Drug: Glucophage<br>* Single dose: 500 mg tablet, oral<br>|
| Experimental: Treatment B-washout-treatment A<br>Subject will receive a single oral dose of 50 mg acarbose and 500 mg metformin as loose combination (Treatment B) in period 1, followed by a single oral dose of acarbose/metformin FDC (Treatment A, 50mg acarbose/500 mg metformin) in period 2. Washout interval between 2 treatment periods was at least 7 days. | Drug: Acarbose/Metformin FDC(BAY81-9783)<br>* Single dose: 50 mg acarbose/500 mg metformin tablet, oral<br>Drug: Glucobay<br>* Single dose: 50 mg tablet, oral<br>Drug: Glucophage<br>* Single dose: 500 mg tablet, oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RatioCmax (serum glucose) | RatioCmax=Cmax,day1/ Cmax,day-1 Cmax,day-1: Maximum serum glucose after 75g sucrose loading on Day -1 Cmax,day1: Maximum serum glucose after 75g sucrose loading and single dose administration of study drug on Day 1 | Treatment period 1 and 2, Day-1 and Day 1: 10 minutes, 25 minutes, 40 minutes, 55 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 10 minutes, 3 hours 10 minutes, 4 hours 10 minutes | 
| RatioAUC(0-4) (serum glucose) | RatioAUC(0-4)=AUC(0-4),day1/AUC(0-4),day-1 AUC (0-4),day1: AUC of serum glucose from time 0 to 4 hours on Day 1 AUC(0-4),day-1: AUC of serum glucose from time 0 to 4 hours on Day -1 | Treatment period 1 and 2, Day-1 and Day 1: 10 minutes, 25 minutes, 40 minutes, 55 minutes, 1 hour 10 minutes, 1 hour 40 minutes, 2 hours 10 minutes, 3 hours 10 minutes, 4 hours 10 minutes | 
| Cmax (plasma metformin) | Cmax: Maximum observed drug concentration in measured matrix after single dose administration / maximum drug concentration in plasma after single dose administration | Treatment period 1 and 2: Pre-dose, 0.5 hour, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 15 hours, 24 hours | 
| AUC (0-tlast) (plasma metformin) | AUC (0-tlast): AUC from time 0 to the last data point > LLOQ (lower limit of quantification) | Treatment period 1 and 2: Pre-dose, 0.5 hour, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 15 hours, 24 hours | 
| AUC (plasma metformin) | AUC: Area under the concentration vs. time curve from zero to infinity after single (first) dose | Treatment period 1 and 2: Pre-dose, 0.5 hour, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 10 hours, 12 hours, 15 hours, 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of TEAE (treatment-emergent adverse event） |  | Approximate 20 days |