A multicenter, double-blind, randomized study to compare the efficacy of 24 weeks treatment with fixed combination therapy of vildagliptin and metformin (25/1000 mg bid) versus metformin monotherapy (1000 mg bid) in patients with type 2 diabetes inadequately controlled with metformin monotherapy

• Register: EUCTR
• Last refreshed on: 4 February 2013
• Main ID: EUCTR2008-001246-21-DE
• Date of registration: 06/08/2008
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A multicenter, double-blind, randomized study to compare the efficacy of 24 weeks treatment with fixed combination therapy of vildagliptin and metformin (25/1000 mg bid) versus metformin monotherapy (1000 mg bid) in patients with type 2 diabetes inadequately controlled with metformin monotherapy
• Scientific title: A multicenter, double-blind, randomized study to compare the efficacy of 24 weeks treatment with fixed combination therapy of vildagliptin and metformin (25/1000 mg bid) versus metformin monotherapy (1000 mg bid) in patients with type 2 diabetes inadequately controlled with metformin monotherapy
• Date of first enrolment: 04/11/2008
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-001246-21
• 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: yes Other trial design description: Double dummy If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

France, Germany, Hungary, Poland

Key inclusion & exclusion criteria

Inclusion criteria:
Patients eligible for inclusion in this study have to fulfill all of the following criteria:
1.Male, non-fertile female or female of childbearing potential using a medically approved birth control method by the country health authorities:
•A non-fertile female is defined as: post menopausal (12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 mIU/m); 6 weeks post bilateral oophorectomy with or without hysterectomy; post hysterectomy; or sterilized by tubal ligation
•A female of childbearing potential is defined as any woman physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means
•Medically approved birth control methods may include: hormonal contraceptives, intrauterine contraceptive device (IUD), and double-barrier contraception. Acceptable methods of contraception may include total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the subject ensures compliance. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
•Reliable contraception should be maintained throughout the study
2.Patients with T2DM who have received metformin for at least three months and have been on a stable dose of at least 1500 mg daily for a minimum of 4 weeks prior to visit 1. If patients are currently treated with their maximum tolerated dose of metformin but it is < 2000 mg daily, the patients are not eligible for screening. Patients treated with < 2000 mg who have not been previously titrated to a higher dose will start metformin 2000 mg daily at visit 1; if the higher dose is not tolerated, the patients will not be eligible for randomization. Patients receiving a daily dose of metformin > 2000 mg at visit 1 are not eligible.
3.Age in the range of 18-78 years inclusive.
4.Body mass index (BMI) in the range of 22-40 kg/m2 inclusive at visit 1.
5.HbA1c in the range of 7 to 10% inclusive at visit 1.
6.FPG < 270 mg/dL (15 mmol/L) at visit 1.
7.Agreement to maintain prior diet and exercise habits during the full course of the study.
8.Written informed consent to participate in the study and ability to comply with all study requirements.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.Pregnant or lactating female.
2.A history of:
•type 1 diabetes, diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g., Cushing’s syndrome and acromegaly.
•acute metabolic diabetic complications such as ketoacidosis or hyperosmolar state (coma) within the past 6 months.
3.Patients that have been enrolled in a vildagliptin clinical trial or other DPP-4 inhibitor, GLP-1 mimetics (e.g. exenatide), GLP-1 analogues (e.g. liraglutide) studies within six months prior to visit 1
4.Acute infections which may affect blood glucose control within 4 weeks prior to visit 1 and other concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study.
5.Any of the following within the past 6 months:
•myocardial infarction (MI) (if the visit 1 ECG reveals patterns consistent with a MI and the date of the event cannot be determined, then the patient can enter the clinical trial at the discretion of the investigator and/or local medical monitor);
•unstable angina
•coronary artery bypass surgery or percutaneous coronary intervention;
•stroke
6.Congestive heart failure requiring pharmacologic treatment.
7.Any of the following ECG abnormalities:
•Uncontrolled second (Mobitz 1 and 2) or third degree AV block (patients with pacemakers that control the AV blocks are eligible)
•prolonged QTc (> 500 ms)
•Torsades de pointes, sustained and clinically relevant ventricular tachycardia or ventricular fibrillation
8.Malignancy including leukemia and lymphoma (not including basal cell skin cancer) within the last 5 years.
9.Liver disease such as cirrhosis or chronic active hepatitis B and C.
10.Acromegaly or treatment with growth hormone or similar drugs.
11.Donation of one unit (500 mL) or more of blood, significant blood loss equaling to at least one unit of blood within the past 2 weeks or a blood transfusion within the past 8 weeks.
12.Contraindications and warnings according to the country specific label for metformin not listed in the other exclusion criteria.
13.Treatment with any oral anti-diabetic other than metformin within 3 months prior to visit 1
14.Chronic insulin treatment (> 4 weeks of treatment in the absence of an intercurrent illness) within the past 6 months.
15.Chronic oral or parenteral corticosteroid treatment (> 7 consecutive days of treatment) within 8 weeks prior to visit 1.

For detailed list see full protocol


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

Health Condition(s) or Problem(s) studied

Type II Diabetes

Intervention(s)

Product Name: Vildagliptin/Metformin
Product Code: LMF237
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: vildagliptin/metformin
Current Sponsor code: LMF237
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25/1000-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Metformin Sandoz® 500 mg Filmtabletten
Product Name: metformin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: metformin
CAS Number: 1115-70-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: 1. To demonstrate that the FPG reduction with fixed dose combination therapy of vildagliptin and metformin (25/1000 mg bid) is superior to that with metformin monotherapy (1000 mg bid) after 24 weeks of treatment in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy.
2. To evaluate the safety and tolerability of the fixed dose combination therapy of vildagliptin and metformin (25/1000 mg bid) compared to metformin monotherapy (1000 mg bid) over 24 weeks of treatment in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy.
3. To evaluate the body weight change from baseline with the fixed dose combination therapy of vildagliptin and metformin (25/1000 mg bid) compared to metformin monotherapy (1000 mg bid) after 24 weeks of treatment in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy.

For detailed list of the secondary objectives see full protocol.

Main Objective: To demonstrate that the HbA1c reduction with fixed dose combination therapy of vildagliptin and metformin (25/1000 mg bid) is superior to that with metformin monotherapy (1000 mg bid) after 24 weeks of treatment in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy.

Primary end point(s): The primary efficacy variable is change from baseline in HbA1c at Week 24 or at the final visit with HbA1c measurement for those patients who do not have a Week 24 HbA1c measurement (the last observation carried forward (LOCF) approach). Baseline is the measurement obtained on the day of randomization (Day 1, Visit 2), or the screening measurement (Week -4, Visit 1) if Day 1 measurement is missing.

Secondary ID(s)

CLMF237A2309

not applicable