Bioequivalence of Sitagliptin Phosphate/Metformin Hydrochloride Tablets in Healthy Chinese Subjects

Study Overview
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Brief Summary
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An open-label, randomized, single-dose, two-period, two-group, crossover study was conducted in 48 healthy Chinese volunteers under fasted or fed conditions (24 volunteers for each condition) to assess the bioequivalence between two formulations of Sitagliptin Phosphate/metformin Hydrochloride Tablets.

Detailed Description
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The single-dose randomized, open-label, two-period crossover study was executed in the Phase I Clinical Research Center of the Affiliated Hospital of Qingdao University. This study was conducted to assess the bioequivalence of Sitagliptin Phosphate/metformin Hydrochloride Tablets in healthy Chinese subjects and estimate the pharmacokinetics profiles of Sitagliptin Phosphate/metformin Hydrochloride Tablets. An open-label, randomized, single-dose, two-period, crossover study was conducted in 48 healthy Chinese volunteers under fasted or fed conditions (24 subjects for each condition) to assess the bioequivalence between two formulations of Sitagliptin Phosphate/metformin Hydrochloride Tablets. Blood samples were collected at specified time intervals, and the plasma concentrations of sitagliptin and metformin were determined by a validated liquid chromatography mass spectrum/ mass spectrum method. Pharmacokinetic and bioavailability parameters were estimated via non-compartmental methods. Adverse events were also recorded. If the 90% confidence intervals of the ratios of geometrical mean of test and reference formulations for Cmax, AUC0-t and AUC0-∞ are all within the predefined bioequivalence criteria range of 80%-125% for sitagliptin and metformin, the two formulations can be considered bioequivalent.

Official Title
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Bioequivalence of Sitagliptin Phosphate/Metformin Hydrochloride Tablets in Healthy Chinese Subjects: A Single-dose and Two-period Crossover Study

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Sitagliptin Phosphate/metformin Hydrochloride Tablets(JANUMET®,50mg/850mg)
* Drug: Sitagliptin Phosphate/metformin Hydrochloride Tablets (50mg/850mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female aged between 18 and 45 years old (including the critical value). The body mass index is in the range of 19-28 kg/m2 (including the critical value). The weight of male is not less than 50 kg, and that of female is not less than 45 kg (including the critical value). Subjects who had not any medical history of cardiovascular, digestive, respiratory, nervous or hepatic/renal impairment. The following examination show that the indicators are normal or abnormal without clinical significance. The examination including: physical examination, 12-lead ECG, vital sign measurements, and laboratory safety tests. The subjects have no family planning within 6 months and could select contraceptive method. Before the study, all subjects have been informed of the study's purpose, protocol, benefits, and risks, and signed the informed consent voluntarily. The subjects could complete the study according to the protocol. Exclusion Criteria: Being allergy to the study medications, smoking, alcohol abuse. Participation in another clinical trial within 3 months. Any history of hypersensitivity, needlesickness or idiosyncratic reactions to any food or drug; Any use of other prescription drugs (including contraceptive) 14 days prior to medication for this study; Any use of prescription or over-the-counter drugs, functional vitamin, herbal/ alcohol products, grapefruit-containing or caffeine/xanthine-rich food and beverages 48 h prior to medication for this study; dysphagia or having special dietary requirements; occurring acute disease in the screening period or before the medication lactating or pregnant women;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Sitagliptin Phosphate/metformin Hydrochloride Tablets (JANUMET®)<br>JANUMET®, 50mg/850mg, batch no. M047893, manufactured by MSD Pharma (Singapore) Pte.Ltd | Drug: Sitagliptin Phosphate/metformin Hydrochloride Tablets(JANUMET®,50mg/850mg)<br>* The subjects randomly received single oral administration of Sitagliptin Phosphate/metformin Hydrochloride Tablets (JANUMET®, 50mg/850mg)<br>|
| Experimental: Sitagliptin Phosphate/metformin Hydrochloride Tablets<br>50mg/850mg, batch no. 161006, manufactured by Tonghua Dongbao Pharmaceutical Co., Ltd. | Drug: Sitagliptin Phosphate/metformin Hydrochloride Tablets (50mg/850mg)<br>* The subjects randomly received single oral administration of Sitagliptin Phosphate/metformin Hydrochloride Tablets (50mg/850mg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The ratios of geometrical mean | The two preparations were considered bioequivalent if the 90% CIs of the ratios of the primary pharmacokinetics parameters were within the predefined acceptance range of 80%-125%. | 80 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The occurrence rate of adverse events | Adverse events were recorded to evaluate the safety of the studied drugs. | 80 days |