A 5-year study to compare the durability of glycemic control of a combination regimen with vildagliptin & metformin versus standard-of-care monotherapy with metformin, initiated in treatment-naive patients with type 2 diabetes mellitus

• Register: EUCTR
• Last refreshed on: 21 December 2021
• Main ID: EUCTR2011-003712-23-IT
• Date of registration: 17/01/2012
• Prospective Registration: Yes
• Primary sponsor: NOVARTIS FARMA
• Public title: A 5-year study to compare the durability of glycemic control of a combination regimen with vildagliptin & metformin versus standard-of-care monotherapy with metformin, initiated in treatment-naive patients with type 2 diabetes mellitus
• Scientific title: A 5-year study to compare the durability of glycemic control of a combination regimen with vildagliptin & metformin versus standard-of-care monotherapy with metformin, initiated in treatment-naive patients with type 2 diabetes mellitus
• Date of first enrolment: 07/02/2012
• Target sample size: 2000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-003712-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Argentina, Austria, Brazil, Bulgaria, Canada, China, Colombia, Costa Rica, Czech Republic, Dominican Republic, Estonia, Finland, Germany, Guatemala, Hong Kong, Hungary, India, Italy, Latvia, Lithuania, Malaysia, Mexico, Norway, Panama, Peru, Philippines, Poland, Russian Federation, Slovakia, Spain, Switzerland, Taiwan, Turkey, Venezuela, Bolivarian Republic of

Contacts

• Name: Drug Regulatory Affairs
• Affiliation: NOVARTIS FARMA

• Name: Drug Regulatory Affairs
• Affiliation: NOVARTIS FARMA

Key inclusion & exclusion criteria

Inclusion criteria:
1.Written informed consent must be obtained before any assessment is performed;2.Confirmed diagnosis of T2DM by standard criteria;3.T2DM diagnosed = 24 months ago;4.HbA1c =6.5% and =7.5% at Visit 1;5.Patients who are treatment-naïve, defined in this protocol as:-Patients not having ever received any anti-diabetic medication;-Patients who, after the diagnosis of T2DM =24 months ago, have received anti-diabetic medication cumulatively for not more than 3 months, and have not received any antidiabetic treatment within 3 months prior to Visit 1;-Patients who initiated metformin within 1 month prior to Visit 1 and take a total daily dose of maximum 2000mg metformin at Visit 1; 6. Age =18 and =70 years old at Visit 1;7.Body mass index (BMI) =22 and =40 kg/m2 at Visit 1;8.Women of child-bearing potential must use effective methods of contraception during dosing of study treatment;9.Agreement to take the study medication as required by the study procedures;10.Agreement to continue current diet and exercise regime throughout the duration of the study, unless otherwise instructed by the investigator;11.Ability to comply with all study requirements and willingness to participate in a 5-year study.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1000
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1000

Exclusion criteria:
1.Pregnant or nursing (lactating) women;2.Use of any of the following medications as assessed at Visit 1:•Any anti-diabetic treatment within 3 months prior to visit 1 and any antidiabetic treatment for more than 3 consecutive months or adding up to a total of more than 3 months in the last 2 years;•Use of weight control products including weight-loss medications in the previous 3 months;•Chronic oral, parenteral or intra-articular corticosteroid treatment within 8 weeks prior to Visit 1;•Treatment with growth hormone within the previous 6 months;•Treatment with any drug or use of herbal medicine of known and frequent toxicity to a major organ, or that may interfere with the interpretation of the efficacy and safety data during the study;3.A history or evidence of any of the following:•Acute metabolic conditions such a ketoacidosis, lactic acidosis or hyperosmolar state (including coma) within the past 6 months;•Current diagnosis of congestive heart failure (NYHA III or IV);•Myocardial infarction within the past 6 months;•Coronary artery bypass surgery or percutaneous coronary intervention within the past 6 months;•Stroke or transient ischemic attack (TIA) within the past 6 months;•Unstable angina within the past 3 months;•Sustained and clinically relevant ventricular arrhythmia;•Active substance abuse, alcohol abuse (as defined by consumption of more than 24 alcohol units per week) and alcohol related history of disease within the past 2 years;•Type 1 diabetes, monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes;•Malignancy of an organ system treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases;•Hepatic disorder defined as:•acute or chronic liver disease, evidence of hepatitis, cirrhosis or portal hypertension;•history of imaging abnormalities that suggest liver disease (except hepatic steatosis), such as portal hypertension, capsule scalloping, cirrhosis;4.Any of the following significant laboratory abnormalities as assessed at Visit 1:•Clinically significant thyroid stimulating hormone (TSH) outside of the normal range;•Renal dysfunction defined as calculated creatinine clearance <60ml/min/1.73m2 via modified diet in renal disease (MDRD) formula;•Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN) at Visit 1, confirmed by repeat measure within 3 working days;•Total bilirubin > 2 x ULN and/or direct bilirubin > 1 x ULN confirmed by repeat measure within 3 working days;•Positive Hepatitis B surface antigen (HbsAg);•Positive Hepatitis C antibody test;•Elevated fasting triglycerides (TGs) >500mg/dL;•Clinically significant laboratory abnormalities which, in the opinion of the investigator,cause the patient to be considered inappropriate for inclusion in the study;5.Any of the following electrocardiogram (ECG) abnormalities at Visit 1:•Second or third degree atrio-ventricular block without a pacemaker;•Long QT syndrome or corrected QT >500ms;6.Previous or current participation in any vildagliptin clinical study;7.History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes;8.Concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study. For more details see Sections 4.1 and 4.2 of the protocol.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Type 2 Diabetes Mellitus
MedDRA version: 14.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Trade Name: GALVUS*112CPR 50MG
Pharmaceutical Form: Tablet
INN or Proposed INN: VILDAGLIPTIN
CAS Number: 274901-16-5
Current Sponsor code: LAF237
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: METFORMINA HEX.AG*60CPR RIV500
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: METFORMIN HYDROCHLORIDE
CAS Number: 1115-70-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Main Objective: - Demonstrate the superiority of combination of vildagliptin 50mg bid and metformin over metformin monotherapy in treatment-naive patients with T2DM by testing the hypothesis that the risk of initial treatment failure (defined as HbA1c = 7.0%) is lower with the combination of vildagliptin and metformin compared to that with metformin monotherapy; - Demonstrate the long-term efficacy of combination of Vildagliptin 50mg bid and metformin over metformin monotherapy in treatmentnaive patients with T2DM by testing the hypothesis that the rate of loss in glycemic control over time (estimated annualized slope of HbA1c over time using a random coefficient model) is lower with the combination vildagliptin plus metformin compared to that with metformin monotherapy

Secondary Objective: Evaluate the effect of initiation of combination regimen with Vildagliptin plus metformin compared with metformin monotherapy in treatment naive patients within up to 5years of treatment,with regards to:-Progression of HbA1c from 26 weeks after the start of Period2 to the end of Period2 assessed by rate of losss in glycemic control over time -Progression of FPG assessed by rate of loss in glycemic control over time assessed by estimated annualized slope of FPG over time for periods defined - Change in HbA1C as defined - Safety and tolerability In a subgroup of patients,to evaluate the effect of initiation of combination regimen compared with metformin monotherapy,with regards to:-beta cell function assessed by ISR/glucose area under the curve during a standard meal-test at timepoints indicated -insulin resistance assessed byOGIS during a standard meal-test at timepoints indicated

Primary end point(s): HbA1c measurement

Timepoint(s) of evaluation of this end point: 5 years

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 5 years

Secondary end point(s): - FPG reduction - beta cell function - evaluate the safety and tolerability of vildagliptin in drug-naive T2DM patients

Secondary ID(s)

2011-003712-23-LT

CLAF237A23156

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 12/01/2012
Contact:

Results

• Results available: Yes
• Date Posted: 15/04/2020
• Date Completed: 04/04/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-003712-23/results