An 18-week, International, Multi-centre, Randomized, Parallel-group, Double-Blind, Active-Controlled Phase IIIb Study to Evaluate the Efficacy and Safety of Saxagliptin in combination with Metformin in Comparison with Sitagliptin 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: 19 March 2012
• Main ID: EUCTR2007-006095-11-SE
• Date of registration: 29/01/2008
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: An 18-week, International, Multi-centre, Randomized, Parallel-group, Double-Blind, Active-Controlled Phase IIIb Study to Evaluate the Efficacy and Safety of Saxagliptin in combination with Metformin in Comparison with Sitagliptin in combination with Metformin in Adult Patients with Type 2 Diabetes Who Have Inadequate Glycaemic Control on Metformin Therapy alone
• Scientific title: An 18-week, International, Multi-centre, Randomized, Parallel-group, Double-Blind, Active-Controlled Phase IIIb Study to Evaluate the Efficacy and Safety of Saxagliptin in combination with Metformin in Comparison with Sitagliptin in combination with Metformin in Adult Patients with Type 2 Diabetes Who Have Inadequate Glycaemic Control on Metformin Therapy alone
• Date of first enrolment: 17/03/2008
• Target sample size: 710
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-006095-11
• 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

Denmark, France, Italy, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
Provision of informed consent
Diagnosed with type 2 diabetes
Man or women equal to or above 18 years of age
Treatment with metformin alone on stable doses of 1500 mg or higher per day for at least 8 weeks
Women of childbearing potential must be using an adequate method of contraception.
HbA1c above 6.5% and below or equal to 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:
Type 1 diabetes, history of diabetic ketoacidosis or hyperosmolar non-ketonic coma.
Pregnant of breastfeeding patients
Insulin therapy within 1 year
Previous treatment with any DPP-4 inhibitor
Treatment with thiazolidinedione within 12 weeks
Treatment with systemic glucocorticoids other than replacement therapy, CYP460 3A4 inducers and/or HIV treatment/antiviral drugs
Potential allergy to metformin, saxagliptin, sitagliptin, or placebo
Contraindications to therapy as outlined in the saxagliptin IB, metformin package insert or sitagliptin package insert
Congestive heart failure defined as NYHA class III or IV and/or left ventricular ejection fraction equal to or below 40%
Significant cardiovascular history within the 6 past months
History of haemoglobinopathies, alcohol abuse or illegal drug abuse
Involvement in the planning and conduct of the study
Previous enrolment or randomization of treatment in the present study
Participation in a clinical study during the last 90 days
Donation of blood, plasma or platelets within the past 3 months
Any condition where, in the opinion of the investigator, participation in this study may pose a significant risk to the patient or could render the patient unable to successfully complete the study
Suspected or confirmed poor protocol or medication compliance as judged by the investigator
Serum creatinine equal to or above 133 micromol/L, for men and 124 micromol/L for women
Active liver disease and/or significant abnormal liver function
Creatinine kinase equal or above 3xULN
History of positive serologic evidence of current infectious liver disease
Any clinically significant abnormality identified on physical examination or laboratory tests or ECG, which in the judgement of the investigator would compromise the patient's 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
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: Januvia
Product Name: Januvia
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: sitagliptin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: Efficacy:
To compare the effects of saxagliptin 5 mg per day versus sitalgiptin 100 mg per day given as add on therapy to metformin after 18 weeks of double-blind treatment period by evaluation of markers of diabetes progression including fasting plasma glucose, insulin, C-peptide, glucagon and proinsulin.
Safety:
Safety and tolerability will be evaluated by assessment of AEs, laboratory values, ECG, pulse, blood pressure, body weight and physical examination.

Primary end point(s): The primary outcome variable is the change in HbA1c from baseline to Week 18 in the double-blind phase achieved with saxagliptin 5 mg per day versus sitagliptin 100 mg per day both added onto metformin.

Main Objective: To compare that, after 18 weeks of oral administration of double-blind treatment, the change from baseline in HbA1c achieved with saxagliptin 5 mg per day added onto metformin is non-inferior to sitagliptin 100 mg per day added onto metformin in patients with type 2 diabetes who have inadequate glycaemic control on 1500 mg or higher doses of metformin therapy alone.

Secondary ID(s)

D1680C00002