Phase 3 Study to Compare the Efficacy and Safety of Gemigliptin and Vildagliptin as Add-on Therapy to Metformin in People With Type 2 Diabetes Inadequately Controlled With Metformin

A Multicentre, National, Randomized, Parallel-group, Phase 3 Study to Compare the Efficacy and Safety of Gemigliptin and Vildagliptin as Add-on Therapy to Metformin in People With Type 2 Diabetes Inadequately Controlled With Metformin

Primary Objective:

To compare the clinical efficacy of gemigliptin and vildagliptin as add-on therapy to metformin in terms of change in Hemoglobin A1c (HbA1c) reduction.

Secondary Objectives:

To compare the safety and tolerability of gemigliptin and vildagliptin:

• Number of patients who experience at least one episode of hypoglycemia.
• Number of patients experiencing adverse event (AE), serious adverse event (SAE).
• Assessment of patients compliance defined as number tablets returned by patients.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: GEMIGLIPTIN LS15-0444; Drug: metformin; Drug: vildagliptin

Detailed Description

The study consists of 2 weeks screening and 24 weeks of treatment (a total of 26 weeks).

The protocol includes a screening period of two weeks, after which they will be randomized to receive gemigliptin or vildagliptin.

Patients will be evaluated through 4 mandatory visits during the study. Visit 1: Week -2 (screening) Visit 2: Week 0 (randomization) Visit 3: Week 12 (efficacy and safety evaluation) Visit 4: Week 24 (efficacy and safety evaluation)

• Study Type: Interventional
• Enrollment (Actual): 443
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Vladimirskaya Oblast
    • Vladimir, Vladimirskaya Oblast, Russian Federation, 600023
      • Investigational site 03

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Patients with Type 2 diabetes mellitus.
• Patients inadequately controlled with metformin at the maximal effective and tolerated dose of metformin for at least 12 weeks or who are on a stable dose of ≥1500 mg daily for a minimum of ≥4 weeks prior to study entry.
• Signed informed consent obtained prior to any study procedures.

Exclusion criteria:

• Patients with type 1 diabetes mellitus, gestational diabetes, or diabetes secondary to pancreatic disorders, drug or chemical agent intake.
• Male and female younger than 18 and older than 75 years old.
• Patients with HbA1c ≤7% and ≥9.5%.
• Patients with 20 kg/m^2 > body mass index (BMI) >40 kg/m^2.
• Patients with history of hypersensitivity to metformin.
• Patients with history of hypersensitivity to vildagliptin.
• Lactose intolerance, lactase deficit, glucose-galactose malabsorption.
• Patients who have a history of acute metabolic complications such as lactic acidosis, diabetic pre-coma, diabetic ketoacidosis or hyperosmolar hyperglycemic state within 3 months before study entry.
• Patients who were treated with insulin or glucagon-like peptide-1 (GLP-1) analogue.
• Patients who have been treated by thiazolidinediones (pioglitazone) in the last 6 months.
• Use of systemic glucocorticosteroids (excluding topical application or inhaled forms) for 7 consecutive days or within more than 3 months prior to study entry.
• Patients with impaired hepatic function (alanine transaminase [ALT], aspartate transaminase [AST] activity >1.5 times the upper limit of normal [ULN]).
• Patients with impaired renal function (serum creatinine concentration >135ɥmol/l in men and >110ɥmol/l in female).
• Patients who had experienced myocardial infarction, stroke, unstable angina or coronary artery bypass surgery within 6 months prior to screening, or patients with arrhythmia requiring treatment.
• Patients with chronic heart failure II-IV functional class according to the classification of NYHA (New York Heart Association).
• Patients taking medicines of thyroid hormones, warfarin, dicoumarin or digoxin.
• Patients who took sodium channel blockers and SGLT2 inhibitors (or inhibitors sodium glucose transporters 2) in the last 6 weeks prior to study entry.
• Known history of alcohol or drug abuse within 6 months prior to screening.
• Pregnant or woman during breast feeding period.
• Women of childbearing potential not protected by effective contraceptive method of birth control.
• Men whose partners are planning pregnancy.
• History of hypersensitivity to the study drug or to a drug with a similar chemical structure.
• Use of any investigational drug within 3 months prior to study entry.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gemigliptin; GEMIGLIPTIN LS15-0444 administered once a day for 24 weeks as add-on therapy to metformin	Drug: GEMIGLIPTIN LS15-0444; Pharmaceutical form:tablet Route of administration: oral; Other Names: Zemiglo; Drug: metformin; Pharmaceutical form:tablet Route of administration: oral
Active Comparator: Vildagliptin; Vildagliptin administered twice a day for 24 weeks as add-on therapy to metformin	Drug: metformin; Pharmaceutical form:tablet Route of administration: oral; Drug: vildagliptin; Pharmaceutical form:tablet Route of administration: oral; Other Names: Galvus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in HbA1c	Up to Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in fasting plasma glucose	Up to Week 24
Change from baseline in postprandial glucose	Up to Week 24
Percentage of patients achieving HbA1c <7% and <6.5%	Up to Week 24
Percentage of patients with at least one episode of hypoglycemia	Up to Week 24
Number of episode of hypoglycemia (symptomatic, asymptomatic, severe hypoglycemia)	Up to Week 24
Change from baseline in body weight	Up to Week 24
Number of adverse events	Up to Week 24
Number of serious adverse events	Up to Week 24

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: January 16, 2015
• First Submitted That Met QC Criteria: January 16, 2015
• First Posted (Estimate): January 22, 2015

Study Record Updates

• Last Update Posted (Estimate): May 18, 2016
• Last Update Submitted That Met QC Criteria: May 17, 2016
• Last Verified: May 1, 2016

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; Protease Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Vildagliptin
• Other Study ID Numbers: GEMIGL07185; U1111-1165-9138 (Other Identifier: UTN)