Comparative Bioavailability Study of Metformin/Sitagliptin 850 mg/50 mg Tablets in Healthy Male and Female Volunteers

Single Dose Crossover Comparative Bioavailability Study of Metformin/Sitagliptin 850 mg/50 mg Film-coated Tablets in Healthy Male and Female Volunteers.

The objective of this study was to evaluate and compare the bioavailability and therefore to assess the bioequivalence of two different formulations of metformin/sitagliptin after a single oral dose administration under fed conditions.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Bioequivalence
• Intervention / Treatment: Drug: Sitagliptin/Metformin HCl 50/850 mg film-coated tablet

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Mount Royal, Quebec, Canada, H3P 3P1
      • Algorithme Pharma

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

The main Inclusion Criteria were:

• non- or ex-smokers
• body mass index (BMI) within 18.5 to 30.0 kg/m2, inclusively
• no clinically significant abnormality found in the 12-lead electrocardiogram (ECG) performed at study entry
• negative pregnancy test for female subjects
• healthy according to medical history, complete physical examination (including vital signs) and laboratory tests (general biochemistry, hematology and urinalysis)

Exclusion Criteria:

• Females who were pregnant or were lactating
• History of significant hypersensitivity to metformin, sitagliptin 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 conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects
• History of significant gastrointestinal, liver or kidney disease that may have affected drug bioavailability
• Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
• History of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases
• Presence of out-of-range cardiac interval (PR < 110 msec, PR > 200 msec, QRS < 60 msec, QRS >119 msec and QTc > 450 msec for males and QTc > 460 for females) on the screening ECG or other clinically significant ECG abnormalities
• 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 previous 28 days before day 1 of this study
• Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and St John's Wort), in the previous 28 days before day 1 of this study
• Any history of tuberculosis and/or prophylaxis for tuberculosis
• Positive screening of alcohol and/or drugs of abuse
• Positive results to HIV Ag/Ab Combo, Hepatitis B surface Antigen (HBsAG (B) (hepatitis B)) or Hepatitis C Virus (HCV (C)) tests
• Females who were pregnant according to a positive pregnancy test
• Volunteers who took metformin and/or sitagliptin in the previous 28 days before day 1 of this study
• Volunteers who took an Investigational Product (in another clinical trial) in the previous 28 days before day 1 of this study
• Volunteers who had already participated in this clinical study
• Volunteers who donated 50 mL or more of blood in the previous 28 days before day 1 of this study
• Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the previous 56 days before day 1 of this study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reference group; 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 HCl 50/850 mg film-coated tablet; The subjects randomly received single oral dose of Sitagliptin/Metformin HCl 50/850 mg film-coated tablet
Experimental: Test group; 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 HCl 50/850 mg film-coated tablet; The subjects randomly received single oral dose of Sitagliptin/Metformin HCl 50/850 mg film-coated tablet

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

Collaborators and Investigators

• Sponsor: Galenicum Health
• Investigators: Principal Investigator: Eric Sicard, Algorithme Pharma Inc

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2017
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: September 16, 2022
• First Submitted That Met QC Criteria: September 20, 2022
• First Posted (Actual): September 22, 2022

Study Record Updates

• Last Update Posted (Actual): September 22, 2022
• Last Update Submitted That Met QC Criteria: September 20, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sitagliptin Phosphate
• Other Study ID Numbers: GLU-P6-810

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No