A Multicenter, Double-Blind, Randomized, Parallel-Group Study to Demonstrate the Effect of 12 Weeks Treatment with Initial Combination of Vildagliptin 100 mg qd plus Metformin 1000 mg bid as compared to Metformin 1000 mg bid in Drug-naïve Patients with Type 2 Diabetes

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-005969-18-HU
• Date of registration: 15/08/2007
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A Multicenter, Double-Blind, Randomized, Parallel-Group Study to Demonstrate the Effect of 12 Weeks Treatment with Initial Combination of Vildagliptin 100 mg qd plus Metformin 1000 mg bid as compared to Metformin 1000 mg bid in Drug-naïve Patients with Type 2 Diabetes
• Scientific title: A Multicenter, Double-Blind, Randomized, Parallel-Group Study to Demonstrate the Effect of 12 Weeks Treatment with Initial Combination of Vildagliptin 100 mg qd plus Metformin 1000 mg bid as compared to Metformin 1000 mg bid in Drug-naïve Patients with Type 2 Diabetes
• Date of first enrolment: 09/10/2007
• Target sample size: 254
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-005969-18
• 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: multi-center If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Hungary, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male, non-fertile female or female of childbearing potential using a medically approved birth control method.
• A non-fertile female is defined as: post menopausal (12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/ml); 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 method include: hormonal contraceptives, 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. Drug naïve patients with T2DM (drug naïve patients are defined as subjects who have had no treatment with oral antidiabetic agents for at least 12 weeks prior to study entry (visit 1) and no treatment with oral antidiabetic agents at any time in the past for > 3 consecutive months).
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 9 - 11% 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. Ability to comply with all study requirements and signed informed consent to participate in the study.

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. Evidence of significant diabetic complications, e.g. symptomatic autonomic neuropathy or gastroparesis.
4. Acute infections which may affect blood glucose control within 4 weeks prior to visit 1 and other concurrent medical conditions that may interfere with the interpretation of efficacy and safety data during the study.
5. A history of:
• Torsades de pointes, sustained and clinically relevant ventricular tachycardia or ventricular fibrillation.
• percutaneous coronary intervention within the past 3 months.
• 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 study at the discretion of the investigator and the sponsor); coronary artery bypass surgery; unstable angina; or stroke.
6. Congestive heart failure requiring pharmacologic treatment.
7. Any of the following ECG abnormalities:
• second degree AV block (Mobitz 1 and 2)
• third degree AV block
• prolonged QTc (> 500 ms)
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.
10. Significant renal dysfunction (see also exclusion criteria 20 laboratory abnormalities).
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 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. Treatment with growth hormone or similar drugs.
16. Chronic oral or parenteral corticosteroid treatment (> 7 consecutive days of treatment) within 8 weeks prior to visit 1.
17. Treatment with class Ia, Ib and Ic or III anti-arrhythmics.
18. Use of other investigational drugs at visit 1, or within 30 days or 5 half-lives of visit 1, whichever is longer, unless local health authority guidelines mandate a longer period.
19. Treatment with any drug with a known and frequent toxicity to a major organ system within the past 3 months (i.e. cytostatic drugs).
20. Any of the following significant laboratory abnormalities:
• ALT, AST greater than 3 times the upper limit of the normal range at visit 1.
• Direct bilirubin greater than 1.3 times the upper limit of the normal range at visit 1.
• Serum creatinine levels = 1.5 mg/dL (132 µmol/L) males, = 1.4 mg/dL (123 µmol/L) females, or a history of abnormal creatinine clearance at visit 1.
• Clinically significant TSH values outside of normal range at visit 1.
• Clinically significant laboratory abnormalities, confirmed by repeat measurement, other than hyperglycemia, hyperinsulinemia, and glycosuria at visit 1.
21. History of active substance abuse (including alcohol) within the past 2 years and potentially unreliable patients.



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

Health Condition(s) or Problem(s) studied

Diabetes Type II

Intervention(s)

Product Name: Vildagliptin
Product Code: LAF237A
Pharmaceutical Form: Tablet
INN or Proposed INN: Vildagliptin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Metformine
Product Name: metformin
Pharmaceutical Form: Tablet
INN or Proposed INN: Metformin
CAS Number: 657-24-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Secondary Objective: 1. To demonstrate the efficacy of vildagliptin in drug naïve patients with type 2 diabetes by testing the hypothesis that the FPG reduction with initial combination of vildagliptin 100 mg qd plus metformin 1000 mg bid is superior to metformin 1000 mg bid alone after 12 weeks treatment.
2. To demonstrate the safety of vildagliptin in drug naïve patients with type 2 diabetes by showing that initial combination of vildagliptin 100 mg qd plus metformin 1000 mg bid has comparable AE profiles including GI tolerability to metformin 1000 mg bid alone during 12 weeks treatment.
3. To evaluate the body weight change of vildagliptin in drug naïve patients with type 2 diabetes by testing the hypothesis that vildagliptin 100 mg qd plus metformin 1000 mg bid has a neutral effect on body weigh relative to metformin 1000 mg bid alone after 12 weeks treatment.

For detailed list of secondary objectives see full protocol

Main Objective: To demonstrate the efficacy of vildagliptin in drug naïve patients with type 2 diabetes by testing the hypothesis that the HbA1c reduction with initial combination of vildagliptin 100 mg qd plus metformin 1000 mg bid is superior to metformin 1000 mg bid alone after 12 weeks treatment.

Primary end point(s): The primary efficacy variable is change from baseline in HbA1c at Week 12 or at the final visit with HbA1c measurement for those patients who do not have a Week 12 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 -2, visit 1) if Day 1 measurement is missing.

Secondary ID(s)

CLAF237A23122

2006-005969-18-ES