A 24-week, Multicentre, Randomised, Double-Blind, Placebo-Controlled Phase IIIb tudy to Evaluate the Efficacy and Safety of Saxagliptin in Combination with Metformin and Sulfonylurea in Subjects with Type 2 Diabetes who have Inadequate Glycaemic control with the Combination of Metformin and Sulfonylurea

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2010-019428-30-GB
• Date of registration: 25/06/2010
• Prospective Registration: No
• Primary sponsor: AstraZeneca Singapore Pte Ltd
• Public title: A 24-week, Multicentre, Randomised, Double-Blind, Placebo-Controlled Phase IIIb tudy to Evaluate the Efficacy and Safety of Saxagliptin in Combination with Metformin and Sulfonylurea in Subjects with Type 2 Diabetes who have Inadequate Glycaemic control with the Combination of Metformin and Sulfonylurea
• Scientific title: A 24-week, Multicentre, Randomised, Double-Blind, Placebo-Controlled Phase IIIb tudy to Evaluate the Efficacy and Safety of Saxagliptin in Combination with Metformin and Sulfonylurea in Subjects with Type 2 Diabetes who have Inadequate Glycaemic control with the Combination of Metformin and Sulfonylurea
• Date of first enrolment: 14/05/2010
• Target sample size: 275
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019428-30
• 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: no Placebo: yes Other: no

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provision of written informed consent prior to the performance of any study-related procedures.

2.Males and females who are =18 years of age at the time of obtaining consent at Visit 1.

3.Clinical diagnosis of type 2 diabetes with uncontrolled glycaemia in spite of being on the combination of metformin IR or XR (MTD, minimum dose for enrolment being 1500 mg) plus sulfonylurea (at MTD, with minimum dose for enrolment being =50% of the maximum recommended dose) daily, for at least 8 weeks prior to Visit 1.

4. HbA1c =7% and =10% obtained at Visit 1 as confirmed by the central laboratory.

5.BMI =40 kg/m2.

6.Females of childbearing potential 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 minimised and have a negative urine preganancy test at Visit 2 and each scheduled study visit thereafter.
Definitions: - Females of Child Bearing Potential - women who have experienced menarche but who have not been permanently or surgically sterilised, are not postmenopausal and are capable of procreation. - Females NOT of Child Bearing Potential - women who have undergone successful surgical sterilisation (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or who are postmenopausal. - Postmenopausal Women - women will be considered postmenopausal if they have had amenorrhea > or = 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level >35 mIU/ml.


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.Pregnant or breastfeeding females.

3.Symptoms of poorly controlled diabetes including but not limited to marked polyuria and polydipsia with more than 10% weight loss in the 3 months before Visit 1 or other signs and symptoms.

4.History of diabetic ketoacidosis or hyperosmolar non-ketotic coma.

5.Current or prior use within 3 months of Visit 1, of insulin, DPP4 inhibitor, GLP-1 analogues (exenatide or liraglutide), and/or other oral anti-diabetic agents (other than metformin and sulfonylurea).

6.Estimated CrCl <60 ml/min at Visit 2.

7.Congestive heart failure defined as New York Heart association (NYHA) class III or IV (see Appendix D) and/or left ventricular ejection fraction of <40%.

8.Active liver disease and/or significant abnormal liver function define as aspartate aminotransferase (AST) >3 x the upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3 x ULN and/or bilirubin >2.0 mg/dL (> 34 µmol) at Visit 2.

9.Creatine kinase =10 x ULN at Visit 2.

10.Treatment with systemic glucocorticoids other than replacement therapy. Inhaled, local injected and topical use of glucocorticoids is allowed.

11.Treatment with CYP3A4 inducers, such as carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin and St. John’s Wort, and/or potent CYP3A4/5 inhibitors, such as delavirdine, indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole (topical use is allowed), nefazodone, saquinavir and telithromycin.

12.Patients who could have a potential allergy to the investigational product or any of its formulation excipients.

13.Contraindications to therapy as outlined in the metformin and/or sulfonylurea package insert including conditions leading to an increased risk of hypoxemia and lactic acidosis.

14.History of haemoglobinopathies (sickle cell anaemia or thalassemias, sideroblastic anaemia).

15.History of alcohol abuse or illegal drug abuse within the past 12 months prior to Visit 1.

16.Involvement in the planning and conduct of the study (applies to both AstraZeneca and Bristol-Myers Squibb personnel or personnel at the study centre).

17.Participation in an interventional clinical study during the 30 days prior to Visit 1.

18.Donation of blood, plasma or platelets within the 3 months prior to Visit 1.

19.Individuals, in the opinion of the investigator, whose 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.

21.Previous enrolment or randomisation in the present study.



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

Health Condition(s) or Problem(s) studied

Type 2 diabetes mellitus
MedDRA version: 12.1 Level: LLT Classification code 10067585 Term: Type 2 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

Primary Outcome(s)

Main Objective: The primary efficacy analysis is to compare the difference between saxagliptin 5 mg od plus metformin plus sulfonylurea versus placebo plus metformin plus sulfonylurea, in patients with type 2 diabetes, as determined by the change in HbA1c levels from Baseline to Week 24/Endpoint.

Primary end point(s): Primary endpoint is change in HbA1c from Baseline to Week 24/Endpoint.

Secondary endpoints are Change in FPG from Baseline to Week 24/Endpoint, change in PPG (measured 2 hours after breakfast) from Baseline to Week 24/Endpoint and proportion of patients achieving a therapeutic glycaemic response at Week 24/Endpoint defined as HbA1c <7%

Secondary Objective: Compare change in fasting plasma glucose (FPG) from Baseline to Week 24/Endpoint between the treatment groups.
Compare change in postprandial glucose (PPG) (measured 2 hours after breakfast) from Baseline to Week 24/Endpoint between the treatment groups;
Compare proportion of patients achieving a therapeutic glycaemic response at Week 24/Endpoint defined as HbA1c <7% between the treatment groups.

Secondary ID(s)

D1680L00006