Comparative Bioavailability Study of Sitagliptin/Metformin 50 mg/1000 mg Tablets in Healthy Male and Female Volunteers

Study Overview
=================
Brief Summary
-----------------
The objective of this study was to determine the bioequivalence of two different formulations of sitagliptin/ metformin after a single oral dose administration under fed conditions.

Official Title
-----------------
Single Dose Crossover Comparative Bioavailability Study of Sitagliptin/Metformin 50 mg/1000 mg Film-coated Tablets in Healthy Male and Female Volunteers / Fed State

Conditions
-----------------
Bioequivalence, Type 2 Diabetes

Intervention / Treatment
-----------------
* Drug: Sitagliptin/metformin hydrochloride (HCl) 50/1000 mg film-coated tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
The main Inclusion Criteria were: non- or ex-smokers body mass index within 18.5 kg/m2 to 30.0 kg/m2, inclusively no clinically significant abnormality found in the 12-lead electrocardiogram (ECG) performed at screening negative pregnancy test for female subjects healthy according to medical history, complete physical examination (including Exclusion Criteria: Females who were lactating at screening Females who were pregnant according to the pregnancy test at screening or prior to the first study drug administration History of significant hypersensitivity to sitagliptin, metformin or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs Presence of significant gastrointestinal, liver or kidney disease, or any other condition known to interfere with drug absorption, distribution, metabolism or excretion, or known to potentiate or predispose to undesired effects History of significant gastrointestinal, liver or kidney disease that may have affected drug bioavailability History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease Presence of out-of-range cardiac interval (PR <110 msec, PR >200 msec, QRS<60 msec, QRS >110 msec and QTc >440 msec) on the ECG at screening or other clinically significant ECG abnormalities, unless deemed non-significant by the investigator Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (>3 units of alcohol per day, intake of excessive alcohol, acute or chronic) Any clinically significant illness in the 28 days prior to the first study drug administration Use of any prescription drugs (with the exception of hormonal contraceptives or hormone replacement therapy) in the 28 days prior to the first study drug administration, that in the opinion of the investigator would have put into question the status of the volunteer as healthy Any history of tuberculosis or proven contact with tuberculosis Positive test result for alcohol and/or drugs of abuse at screening or prior to the first drug administration Positive screening results to HIV Ag/Ab Combo, Hepatitis B surface Antigen (HBsAG [B] [hepatitis B]) or Hepatitis C Virus (HCV [C]) tests Volunteers who had already been included in a previous group for this clinical study Volunteers who took sitagliptin and/or metformin in the 28 days prior to the first study drug administration Volunteers who took an Investigational Product in the 28 days prior to the first study drug administration Volunteers who donated 50 mL or more of blood in the 28 days prior to the first study drug administration Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the 56 days prior to the first study drug administration

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reference group<br>Thirty minutes after the start of the breakfast, a single dose of the Reference formulation was administered with approximately 240 mL of water at ambient temperature | Drug: Sitagliptin/metformin hydrochloride (HCl) 50/1000 mg film-coated tablet<br>* The subjects randomly received single oral dose of Sitagliptin/metformin hydrochloride (HCl) 50/1000 mg film-coated tablet<br>|
| Experimental: Test group<br>Thirty minutes after the start of the breakfast, a single dose of the Test formulation was administered with approximately 240 mL of water at ambient temperature | Drug: Sitagliptin/metformin hydrochloride (HCl) 50/1000 mg film-coated tablet<br>* The subjects randomly received single oral dose of Sitagliptin/metformin hydrochloride (HCl) 50/1000 mg film-coated tablet<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) | Evaluation of Peak Plasma Concentration (Cmax) | 48 hours | 
| Area under the plasma concentration versus time curve (AUC) 0-t | Evaluation of plasma concentration-time curve from zero to the time of the last measurable time point t | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs), abnormal clinical laboratory test results, physical examination findings and glycemia. | Adverse events were classified by System Organ Class (SOC) and Preferred Term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA), version 20.1 (Medrio database) and graded as mild, moderate, or severe. The principal investigator or qualified designee determined the relationship of any AE to the investigational product. | 1 week |