Efficacy and Safety of Vildagliptin 50mg Bid as an add-on Therapy to Insulin With or Without Metformin, in Patients With Type 2 Diabetes Mellitus

A 24-week, Multi-center, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Assess the Efficacy and Safety of Vildagliptin 50mg Bid as an add-on Therapy to Insulin, With or Without Metformin, in Patients With Type 2 Diabetes Mellitus

The purpose of this study is to assess the efficacy and safety of vildagliptin 50mg bid add-on therapy to improve overall glycemic control in patients with type 2 diabetes mellitus inadequately controlled on insulin with or without metformin treatment.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Vildagliptin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 293
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Novartis Investigative Site
  • Shanghai, China, 200025
    • Novartis Investigative Site
  • Tianjin, China, 300052
    • Novartis Investigative Site
  • Beijing
    • Beijing, Beijing, China, 100730
      • Novartis Investigative Site
  • Hunan
    • Changsha, Hunan, China, 410003
      • Novartis Investigative Site
    • Changsha City, Hunan, China, 410011
      • Novartis Investigative Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210006
      • Novartis Investigative Site
    • Wu Xi, Jiangsu, China, 214023
      • Novartis Investigative Site
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Novartis Investigative Site
  • Liaoning
    • Shenyang, Liaoning, China, 110003
      • Novartis Investigative Site
  • Shandong
    • Jinan, Shandong, China, 250031
      • Novartis Investigative Site
  • Shanxi
    • Xi'an, Shanxi, China, 710032
      • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610072
      • Novartis Investigative Site
• Philippines
  • Metro Manila, Philippines, 1500
    • Novartis Investigative Site
  • Pasay City, Philippines, 1300
    • Novartis Investigative Site
  • Quezon City, Philippines, 1102
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 169608
    • Novartis Investigative Site
  • Singapore, Singapore, 768825
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10330
    • Novartis Investigative Site
  • Bangkok, Thailand, 10400
    • Novartis Investigative Site
  • Khon Kaen, Thailand, 40002
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with confirmed diagnosis of Type2 diabetes mellitus (T2DM) by standard criteria
• C-peptide >0.6 ng/ml (>0.20 nmol/L).
• HbA1c ≥7.5 to ≤11% at Visit 1
• Treatment with stable, once or twice daily doses (maximum dose of < 1 unit/kg/day) of basal (long-acting, intermediate-acting) insulin alone or pre-mixed insulin for at least 12 weeks prior to Visit 1. Stable is defined as ±10% of the Visit 1 dose during the previous 12 weeks
• Patients receiving metformin must be on a stable dose of metformin (at least 1500 mg daily or a maximally tolerated dose) for at least 12 weeks prior to Visit 1
• Body Mass Index (BMI) ≥20 to ≤40 kg/m2 at Visit

Exclusion Criteria:

Patients fulfilling any of the following criteria are not eligible for participation in the study

• Fasting plasma glucose (FPG) ≥240 mg/dl (13.3 mmol/L) at Visit 1
• Pregnant or lactating women
• Acute metabolic diabetes complications such as ketoacidosis or hyperosmolar state (coma) within the past 6 months
• Current diagnosis of congestive heart failure (NYHA III or IV).
• Myocardial infarction (MI) within the past 6 months
• Liver disease such as cirrhosis or chronic active hepatitis

Other protocol defined inclusion/excusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vildagliptin; Eligible patients will receive vildagliptin 50 mg in addition to their stable dose of insulin with or without metformin. One tablet should be taken twice daily as one tablet before breakfast meal and one tablet before the evening meal for 24 weeks.	Drug: Vildagliptin; Patient will receive vildagliptin 50mg twice daily (bid) in addition to their stable dose of insulin with or without metformin for 24 weeks; Other Names: Galvus, LAF237
Placebo Comparator: Placebo; Eligible patients will receive matching placebo in addition to their stable dose of insulin with or without metformin. One tablet should be taken twice daily as one tablet before breakfast meal and one tablet before the evening meal for 24 weeks.	Drug: Placebo; Patient will receive matching placebo to vildagliptin in addition to their stable dose of insulin with or without metformin for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in glycosylated hemoglobin (HbA1c) at study endpoint, assessed in overall study population	HbA1c analysis will be performed on a blood sample obtained by study personnel at every visit and measured by ion exchange HPLC. Study endpoint is defined as final available post- randomization assessment obtained at any visit prior to or at the start of major change in insulin use, up to final scheduled study visit (week 24 visit) inclusive.	Baseline and every study visit up to 24 weeks
Change from baseline in glycosylated hemoglobin (HbA1c) at study endpoint, assessed in Chinese study population	HbA1c analysis will be performed on a blood sample obtained by study personnel at every visit and measured by ion exchange HPLC. Study endpoint is defined as final available post- randomization assessment obtained at any visit prior to or at the start of major change in insulin use, up to final scheduled study visit (week 24 visit) inclusive.	Baseline and every study visit up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with adverse events, serious adverse events and death on over all population	Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.	24 weeks
Change from baseline after 24 weeks of treatment in fasting plasma glucose (FPG)on overall population	FPG will be performed on the blood samples collected at all every study visits from baseline to week 24.	Baseline, week 24
Percentage of patients meeting responder criteria after 24 weeks treatment on overall population	Responder rate will be analyzed in the following categories: Endpoint HbA1c ≤ 6.5%; Endpoint HbA1c < 7%; Endpoint HbA1c <7% in patients with baseline HbA1c ≤ 8% The percentage of patients meeting each of the responder criteria as described, as well as the percentage of patients meeting any of these criteria in each treatment group will be computed	After 24 weeks
Number of patients with adverse events, serious adverse events and death on Chinese population	Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.	24 weeks
Change from baseline after 24 weeks of treatment in fasting plasma glucose (FPG) on Chinese population	FPG will be performed on the blood samples collected at all every study visits from baseline to week 24.	Baseline, week 24
Percentage of patients meeting responder criteria after 24 weeks treatment on Chinese population	Responder rate will be analyzed in the following categories: • Endpoint HbA1c ≤ 6.5% • Endpoint HbA1c < 7% • Endpoint HbA1c <7% in patients with baseline HbA1c ≤ 8% The percentage of patients meeting each of the responder criteria as described, as well as the percentage of patients meeting any of these criteria in each treatment group will be computed	After 24 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Ning G, Wang W, Li L, Ma J, Lv X, Yang M, Wang W, Woloschak M, Lukashevich V, Kothny W. Vildagliptin as add-on therapy to insulin improves glycemic control without increasing risk of hypoglycemia in Asian, predominantly Chinese, patients with type 2 diabetes mellitus. J Diabetes. 2016 May;8(3):345-53. doi: 10.1111/1753-0407.12303.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: April 18, 2012
• First Submitted That Met QC Criteria: April 19, 2012
• First Posted (Estimate): April 20, 2012

Study Record Updates

• Last Update Posted (Estimate): August 30, 2013
• Last Update Submitted That Met QC Criteria: August 29, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Type 2 diabetes mellitus; Vildagliptin
• 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; Vildagliptin
• Other Study ID Numbers: CLAF237A23155