A 52-Week International, Multi-centre, Randomised, Parallel-group, Double-blind, Active-controlled, Phase III study with a 52-Week Extension Period to Evaluate the Safety and Efficacy of Saxagliptin in Combination with Metformin compared with Sulphonylurea in Combination with Metformin in Adult Patients with Type 2 Diabetes who have Inadequate Glycaemic Control on Metformin Therapy Alone.

• Register: EUCTR
• Last refreshed on: 17 July 2012
• Main ID: EUCTR2007-003998-55-FI
• Date of registration: 05/10/2007
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A 52-Week International, Multi-centre, Randomised, Parallel-group, Double-blind, Active-controlled, Phase III study with a 52-Week Extension Period to Evaluate the Safety and Efficacy of Saxagliptin in Combination with Metformin compared with Sulphonylurea in Combination with Metformin in Adult Patients with Type 2 Diabetes who have Inadequate Glycaemic Control on Metformin Therapy Alone.
• Scientific title: A 52-Week International, Multi-centre, Randomised, Parallel-group, Double-blind, Active-controlled, Phase III study with a 52-Week Extension Period to Evaluate the Safety and Efficacy of Saxagliptin in Combination with Metformin compared with Sulphonylurea in Combination with Metformin in Adult Patients with Type 2 Diabetes who have Inadequate Glycaemic Control on Metformin Therapy Alone.
• Date of first enrolment: 27/11/2007
• Target sample size: 2200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-003998-55
• 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: yes Placebo: no Other: no

Countries of recruitment

Finland, Germany, Hungary, Netherlands, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provision of informed consent
2. Diagnosed with type 2 diabetes
3. Men or women above or equal to 18 years
4. Women of childbearing potential must be using an adequate method of contraception
5. Treatment with metformin alone on a stable dose of 1500 mg or higher per day for at least 8 weeks prior to visit 1
6. HbA1c higher than 6.5% and less than or equal to 10.0% at lead in visit
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. Type 1 diabetes, history of diabetic ketoacidosis or hyperosmolar non-ketonic coma
2. Pregnant or breastfeeding patients
3. Insulin therapy within 1 year of enrolment
4. Previous treatment with any DPP-4 inhibitor
5. Treatment with thiazolidindione within 12 weeks prior to visit 1
6. Treatment with systemic glucocorticoids other than replacement therapy
7. Treatment with Cytochrome P450 3A4 inducers
8. Treatment with human immunodeficiency virus (HIV) treatment
9. Potential allergy to metformin, saxagliptin, glipizide, or placebo or excipients
10. Congestive heart failure
11. Significant cardiovascular history
12. History of haemoglobinopathies
13. History of alcohol abuse or illegal drug abuse within the past 12 months
14. Involvement in the planning and conduct of the study
15. Previous enrolment or randomization of treatment in the present study
16. Participation in a clinical study during the last 90 days prior to visit 1
17. Donation of blood, plasma or platelets within the past 3 months prior to visit 1
18. Individuals who could render the patient unable to complete the study
19. Suspected or confimed poor protocol or medication compliance



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

Health Condition(s) or Problem(s) studied

Type 2 diabetes
MedDRA version: 9.1 Level: LLT Classification code 10029505 Term: Non-insulin-dependent diabetes mellitus

Intervention(s)

Product Name: Saxagliptin
Product Code: BMS-477118-11
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Saxagliptin
CAS Number: 361442-04-8
Current Sponsor code: BMS-477118-11
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Glipizide BP 5 mg
Product Name: Glipizide
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: glipizide
CAS Number: 29094-61-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To compare that after 52-week oral administration of double-blind treatment, the absolute change from baseline in glycosylated haemoglobin A1c (HBA1c) level with saxagliptin plus metformin is non-inferior to glipizide (sulphonylurea) plus metformin in patients with type 2 diabetes who have inadequate glycaemic control on 1500 mg or higher doses of metformin alone.

Primary end point(s): The primary outcome variable is the change from baseline in HbA1c at 52 weeks of treatment

Secondary Objective: Three secondary objectives among all secondary objectives, are identified a priori for special attention to compare the effects of saxagliptin versus glipizide given as add-on therapy to metformin after a 52-week double-blind treatment period by evaluation of:
- Proportion of patients reporting at least one episode of hypoglycaemic event at week 52.
- Change from baseline in body weight at week 52.
- Durability of HbA1c effect based on week 24 over the 52 weeks as an efficacy objective

Secondary ID(s)

D1680C00001