A 24-Week, Randomised, Double-Blind, Active-Controlled, Multi-Centre Phase IIIb/IV Study to Evaluate the Efficacy and Tolerability of Saxagliptin Add-on Compared to Uptitration of Metformin in Patients with Type 2 Diabetes Mellitus With Inadequate Glycaemic Control on Sub-Maximal Doses of Metformin - Prompt

• Register: EUCTR
• Last refreshed on: 1 April 2013
• Main ID: EUCTR2009-012775-10-DE
• Date of registration: 13/07/2009
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A 24-Week, Randomised, Double-Blind, Active-Controlled, Multi-Centre Phase IIIb/IV Study to Evaluate the Efficacy and Tolerability of Saxagliptin Add-on Compared to Uptitration of Metformin in Patients with Type 2 Diabetes Mellitus With Inadequate Glycaemic Control on Sub-Maximal Doses of Metformin - Prompt
• Scientific title: A 24-Week, Randomised, Double-Blind, Active-Controlled, Multi-Centre Phase IIIb/IV Study to Evaluate the Efficacy and Tolerability of Saxagliptin Add-on Compared to Uptitration of Metformin in Patients with Type 2 Diabetes Mellitus With Inadequate Glycaemic Control on Sub-Maximal Doses of Metformin - Prompt
• Date of first enrolment: 28/09/2009
• Target sample size: 268
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012775-10
• 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: yes Other: no

Countries of recruitment

Belgium, France, Germany, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provision of informed consent.
2. Men or women who are =18 years of age at time of consenting upon Visit 1.
3. Clinical diagnosis of type 2 diabetes.
4. Treatment with metformin alone (any formulation) on stable doses of 1500 to 1700 mg per day for at least 8 weeks prior to Visit 1.
5. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the study in such a manner that the risk of pregnancy is minimized.
- WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea =12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level >35 mIU/mL).
- Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (eg, vasectomy), should be considered to be of childbearing potential.
6. HbA1c =7.0% and =10.0%.
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. Any clinically significant abnormality identified on physical examination or
laboratory tests that would compromise patient’s safety or successful
participation in the study as judged by the investigator.
2. Patients who have previously been intolerant to or non-compliant with a total
daily dose of metformin higher than 1500 to 1700 mg.
3. Type 1 diabetes, history of diabetic ketoacidosis or hyperosmolar non-ketonic
coma.
4. Pregnant or breastfeeding patients.
5. Prior use of insulin or injectable GLP-1 analogue (exenatide or liraglutide) within 3
months of the study start.
6. Treatment with systemic glucocorticoids other than replacement therapy. Inhaled,
local injected and topical use of glucocorticoids are allowed.
7. Treatment with cytochrome P450 3A4 (CYP450 3A4) inducers, eg, carbamazepine,
dexamethasone, phenobarbital, phenytoin, rifampin and St. John’s Worth.
8. Potential allergy to saxagliptin, placebo or formulation excipients.
9. Past hypersensitivity reaction to a DPP-4 inhibitor.
10. Contraindications to therapy as outlined in the saxagliptin Investigator’s
Brochure.



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

Health Condition(s) or Problem(s) studied

Non-insulin dependent type 2 diabetes mellitus
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: 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

Product Name: metformin hydrochloride
Product Code: BMS-207150-01
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: metformin (free base)
CAS Number: 1115-70-4
Current Sponsor code: BMS-207150-01
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To show the superiority of saxagliptin 5 mg once daily added on to metformin 1500 mg daily, compared to metformin up-titrated to a maximum of 2500 mg daily, in improving glycaemic control as determined by the absolute change in HbA1c levels from baseline to Week 24, in patients with type 2 diabetes who have inadequate glycaemic control on a submaximal total daily dose of 1500 mg of metformin.

Primary end point(s): Absolute change from baseline in HbA1c at Week 24.

Secondary Objective: To compare the effects of saxagliptin 5 mg once daily added on to metformin 1500 mg daily, compared to metformin up-titrated to a maximum of 2500 mg daily, after 24 weeks of treatment, by evaluation of the secondary efficacy and safety endpoints described below:

Efficacy:
- Change from baseline to Week 24 in fasting plasma glucose (FPG) and fasting insulin and ß-cell function as measured by Homeostasis Model Assessment-ß (HOMA-ß)
- Proportion of patients achieving a therapeutic glycaemic response at Week 24 defined as HbA1c <7.0% or <6.5%

Safety:
- Safety and tolerability will be evaluated by assessment of adverse events, laboratory values, electrocardiogram (ECG), pulse, blood pressure, body weight, height and physical examination
- Rates of hypoglycaemic events (number of confirmed hypoglycemic episodes per unit of time, eg, week or month)

Secondary ID(s)

D1680L00003