Vildagliptin/Metformin in T2DM Patients Starting Basal Insulin (ADDONIS)

Randomized, Open-label, SU-controlled Study of 24-week Duration to Compare Metformin/Vildagliptin + Basal Insulin Versus Metformin/SU + Basal Insulin in T2DM Patients Starting Basal Insulin After Failing Metformin/SU

To compare a therapeutic strategy combining vildagliptin+metformin + Basal Insulin versus SU+metformin + Basal Insulin on the incidence of hypoglycemic events over 24 weeks.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus (T2DM)
• Intervention / Treatment: Drug: Metformin; Drug: sulfonylurea (SU); Drug: Basal Insulin; Drug: Vildagliptin

Detailed Description

This study, conducted in T2DM patients failing a dual therapy with metformin/SU in whom the decision to start basal insulin has been taken, will compare vildagliptin+metformin versus the previously used SU+met combination (regimen kept unchanged) in association with basal insulin, up-titrated as per usual algorithms primarily based on FPG to obtain a similar improvement in glycemic control in both arms, on the incidence of hypoglycemic episodes over 24 weeks.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Antibes, France, 06600
    • Novartis Investigative Site
  • Auxerre, France, 89000
    • Novartis Investigative Site
  • Bar le Duc, France, 55012
    • Novartis Investigative Site
  • Bondy, France, 93143
    • Novartis Investigative Site
  • Brest, France, 29200
    • Novartis Investigative Site
  • Caen, France, 14000
    • Novartis Investigative Site
  • Corbeil Essonnes, France, 91100
    • Novartis Investigative Site
  • Fleury sur Orne, France, 14123
    • Novartis Investigative Site
  • Maisons Laffitte, France, 78600
    • Novartis Investigative Site
  • Menton, France, 06500
    • Novartis Investigative Site
  • Montpellier, France, 34090
    • Novartis Investigative Site
  • Paris, France, 75010
    • Novartis Investigative Site
  • Rennes, France, 35203
    • Novartis Investigative Site
  • Saint Nazaire, France, 44600
    • Novartis Investigative Site
  • Sanary Sur Mer, France, 83110
    • Novartis Investigative Site
  • Strsbourg, France, 67000
    • Novartis Investigative Site
  • Toulouse, France, 31300
    • Novartis Investigative Site
  • Valence, France, 26000
    • Novartis Investigative Site
  • Valenciennes, France, 59300
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• T2DM patients inadequately controlled with metformin+ SU combination therapy at max tolerated doses and in whom the decision to start basal insulin has been taken
• with stable metformin+ SU combination therapy for at least 12 weeks prior to randomization
• with a glycemic target of HbA1c <= 7%
• with HbA1c at inclusion >7% and <=9%
• Patients willing and able to start basal insulin and perform appropriate self monitoring of blood glucose (SMBG)

Exclusion Criteria:

• contraindication for either SUs, metformin or insulin and history of hypersensitivity to vildagliptin
• acute or chronic diseases that interfere with efficacy/safety results of this trial or put patient at risk

Other protocol defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: SU+metformin + Basal Insulin; Randomized patient will remain on their previous dual therapy by SU+metformin, which will be kept unchanged, + start of Basal Insulin up-titrated as per usual algorithms primarily based on FPG	Drug: Metformin; metformin is to be kept unchanged; Drug: sulfonylurea (SU); Drug: Basal Insulin
EXPERIMENTAL: Metformin/vildagliptin + Basal Insulin; Randomized patient will receive Vildagliptin 50 mg twice daily (b.i.d) + continued therapy with Metformin, + start of Basal Insulin up-titrated as per usual algorithms primarily based on FPG	Drug: Metformin; metformin is to be kept unchanged; Drug: Basal Insulin; Drug: Vildagliptin; 50 mg b.i.d; Other Names: Galvus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Patients Who Reported at Least One Symptomatic Hypoglycemic Event During the 24 Week Randomized Period in Both Treatment Arms	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Reaching Their Glycemic Target Without Hypoglycemic Events	Glycemic target is defined as Glycated hemoglobin(HbA1c) ≤ 7%	24 weeks
Change From Baseline in HbA1c to Week 24 in Both Treatment Arms		Baseline, Week 24
Change From Baseline in Body Weight in Both Treatment Arms		Baseline, Week 24
Mean Daily Insulin Dose at Week 24		Week 24
Percentage of Patients With Severe and Confirmed Hypoglycemic Events	Severe hypoglycemic events (and number of events) , defined as events requiring assistance of a third party, and with confirmed hypoglycemic events (and number of events) defined as events with concomitant self monitoring of blood glucose (SMBG) < 70 mg/dL	24 weeks
Percent of Participants That Reach Therapeutic Goal (HbA1c ≤ 7%) at Week 24 Without Any Hypoglycaemic Episode (Symptomatic or Not) and Without Any Weight Gain (Variation ≥3% Compared to Baseline)	HbA1c <= 7% without any hypoglycaemic episode (symptomatic or not) and without any weight gain	week 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (ACTUAL): February 1, 2015
• Study Completion (ACTUAL): February 1, 2015

Study Registration Dates

• First Submitted: June 4, 2013
• First Submitted That Met QC Criteria: June 4, 2013
• First Posted (ESTIMATE): June 6, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): April 21, 2016
• Last Update Submitted That Met QC Criteria: March 22, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: type 2 diabetes; vildagliptin; basal insulin
• 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: CLAF237AFR07