A 52-Week, Randomised, Double-Blind, Active-Controlled, Multi-Centre Phase IIIb/IV Study to Evaluate the Efficacy and Tolerability of Saxagliptin Compared to Glimepiride in Elderly Patients with Type 2 Diabetes Mellitus Who Have Inadequate Glycaemic Control on Metformin Monotherapy - Generation

• Register: EUCTR
• Last refreshed on: 14 January 2013
• Main ID: EUCTR2009-012816-41-SE
• Date of registration: 15/07/2009
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A 52-Week, Randomised, Double-Blind, Active-Controlled, Multi-Centre Phase IIIb/IV Study to Evaluate the Efficacy and Tolerability of Saxagliptin Compared to Glimepiride in Elderly Patients with Type 2 Diabetes Mellitus Who Have Inadequate Glycaemic Control on Metformin Monotherapy - Generation
• Scientific title: A 52-Week, Randomised, Double-Blind, Active-Controlled, Multi-Centre Phase IIIb/IV Study to Evaluate the Efficacy and Tolerability of Saxagliptin Compared to Glimepiride in Elderly Patients with Type 2 Diabetes Mellitus Who Have Inadequate Glycaemic Control on Metformin Monotherapy - Generation
• Date of first enrolment: 12/08/2009
• Target sample size: 698
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012816-41
• 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

Austria, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Norway, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provision of informed consent prior to any study specific procedures.
2. Established clinical diagnosis of type 2 diabetes.
3. Men or women who are =65 years of age at time of consenting upon Visit 1.
NB: The cohorts will be approximately 60% of the patients for age group 65 to
75 years and 40% for age-group =75 years. The enrolment to the cohorts will
be stopped when the number of patients is reached.
4. Treatment with a stable metformin monotherapy, at any dose, for at least 8
weeks prior to Visit 1.
5. HbA1c =7.0% and =9.0%.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
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. Any clinically significant abnormality identified on physical examination, ECG or
laboratory tests that would compromise patient’s safety or successful
participation in the study as judged by the investigator.
2. Type 1 diabetes, history of diabetic ketoacidosis or hyperosmolar non-ketonic
coma.
3. Current use of any injectable or oral antihyperglycaemic agent excluding
metformin.
4. Treatment with any additional oral or injectable antihyperglycaemic agent within
8 weeks prior to Visit 1.
5. Renal impairment as defined by a creatinine clearance <60 mL/min (using the
Modification of Diet in Renal Disease [MDRD] equation), as well as patients with
End Stage Renal Disease (ESRD) on haemodialysis
6. Treatment with systemic glucocorticoids other than replacement therapy.
Inhaled, local injected and topical use of glucocorticoids is allowed.
7. Treatment with cytochrome P450 3A4 (CYP450 3A4) inducers, eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin and St. John’s Worth.
8. Past history of intolerance, allergy or hypersensitivity to glimepiride, other
sulphonylureas or sulphonamides.
9. Past hypersensitivity reaction to a DPP-4 inhibitor.
10. Contraindications to therapy as outlined in the saxagliptin IB.
11. Contraindications to therapy as outlined in the glimepiride package insert.
12. Contraindications to therapy as outlined in the metformin package insert,
including conditions leading to an increased risk of hypoxaemia and lactic
acidosis.
13. History of haemoglobinopathies (sickle cell anaemia or thalassemias,
sideroblastic anaemia).
14. History of alcohol abuse or illegal drug abuse within the past 12 months.
15. Involvement in the planning and conduct of the study (applies to AstraZeneca
and Bristol-Myers Squibb personnel and study centre personnel).
16. Participation in a clinical study testing a medication during the last 3 months prior to Visit 1.
17. Donation of blood, plasma or platelets within 3 months prior to Visit 1.
18. Important cognitive function problems.
19. Individuals who, in the opinion of the investigator, in which participation in this
study may pose a significant risk to the patient and could render the patient
unable to successfully complete the study.
20. Suspected or confirmed poor protocol or medication compliance as judged by
the investigator.

Additional exclusion criteria at Visit 2:
21. Active liver disease and/or significant abnormal liver function
22. Creatine kinase (CK) >10xULN
23. Any clinically significant abnormality identified on physical examination or
laboratory tests, which in the judgement of the investigator would compromise
the patient’s safety or successful participation in the clinical study.

Additional exclusion criteria at Visit 3:
24. Any clinically significant abnormality identified on brief physical examination,
which in the judgement of the investigator would compromise the patient safety
or successful participation in the clinical study.



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

Health Condition(s) or Problem(s) studied

Non-insulin dependent type 2 diabetes mellitus in elderly patients (= 65 years)
MedDRA version: 14.0 Level: LLT Classification code 10029505 Term: Non-insulin-dependent diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders

Intervention(s)

Product Name: Saxagliptin
Product Code: BMS-477118-11
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Saxagliptin
CAS Number: 945667-22-1
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: Amaryl
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Glimepiride
CAS Number: 93479971
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Amaryl
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Glimepiride
CAS Number: 93479971
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Amaryl
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Glimepiride
CAS Number: 93479971
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of this study will be to show the superiority of saxagliptin compared to glimepiride in bringing elderly patients (=65 years) with type 2 diabetes to HbA1c target <7% without hypoglycaemia (confirmed or severe) over a 52-week treatment period. Saxagliptin or glimepiride will be administered as an add-on therapy to a background therapy with metformin.

Primary end point(s): The primary endpoint is the proportion of patients reaching HbA1c target <7% without hypoglycaemia (confirmed or severe) over a 52-week treatment period.

Secondary Objective: To compare the effects of saxagliptin versus glimepiride given as add-on to a metformin therapy after 52 weeks of a double-blind treatment period by evaluation of secondary efficacy and safety endpoints described below:
Key secondary (safety analysis)
- Proportion of patients having experienced at least one hypoglycaemic event (confirmed or severe) over the 52-week double-blind treatment period

Efficacy
- Change from baseline to Week 52 in HbA1c
- Proportion of patients achieving a therapeutic glycaemic response at Week 52 defined as HbA1c <7.0% or <6.5%
- Change from baseline to Week 52 in fasting plasma glucose (FPG) and insulin
- Change from baseline to Week 52 in ß-cell function (as measured by Homeostasis Model Assessment-ß [HOMA-ß]

Secondary ID(s)

D1680L00002