Efficacy and Safety of Dapagliflozin and Dapagliflozin plus Saxagliptinin in Combination with Metformin in Type 2 Diabetes Patients compared with Sulphonylurea.

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2015-002376-24-DE
• Date of registration: 02/07/2015
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: Efficacy and Safety of Dapagliflozin and Dapagliflozin plus Saxagliptinin in Combination with Metformin in Type 2 Diabetes Patients compared with Sulphonylurea.
• Scientific title: A 52-Week, Multi-Centre, Randomised, Parallel-Group, Double-Blind, Active Controlled, Phase IV Study to Evaluate the Safety and Efficacy of Dapagliflozin or Dapagliflozin plus Saxagliptin compared with Sulphonylurea all given as Add-on Therapy to Metformin in Adult Patients with Type 2 Diabetes Who Have Inadequate Glycaemic Control on Metformin Monotherapy
• Date of first enrolment: 06/10/2015
• Target sample size: 930
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002376-24
• 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 Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Czech Republic, Germany, Hungary, Poland, Slovakia

Contacts

• Name: Clinical Trial Transparency
• Affiliation: AstraZeneca AB

• Name: Clinical Trial Transparency
• Affiliation: AstraZeneca AB

Key inclusion & exclusion criteria

Inclusion criteria:
Main Inclusion Criteria:
1. Is male or female and =18 and <75 years old at time of informed consent.
2. Has a HbA1c of =7.5% and =10.5% based on central laboratory results from Visit 1, with individual need for therapy escalation.
3. Currently treated with a stable maximum tolarated dose (MTD) (=1500 mg/day) of metformin therapy for at least 8 weeks prior to Enrolment visit.
4. Has a BMI of =45 kg/m2 at Enrolment visit.
5. Has a C-peptide laboratory value of =1.0 ng/mL (0.33 nmol/L; 331 pmol/L) based on central laboratory results from Visit 1.



Main
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 700
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 230

Exclusion criteria:
1.Clinically diagnosed with Type I diabetes, known diagnosis of maturity onset diabetes of the young (MODY), or secondary diabetes mellitus or known presence of glutamate decarboxylase 65 (GAD65) antibodies.
2. Patients who, in the judgment of the Investigator, may be at risk for dehydration or volume depletion that may affect the patient’s safety and/or the interpretation of efficacy or safety data.
3. Clinically significant cardiovascular disease or procedure within 3 months prior to Enrolment or expected to require coronary revascularization procedure during the course of the study.
4. Concomitant treatment with loop diuretics


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

Health Condition(s) or Problem(s) studied

Type 2 diabetes mellitus, inadequate glycaemic control
MedDRA version: 19.1 Level: HLT Classification code 10012602 Term: Diabetes mellitus (incl subtypes) System Organ Class: 100000004860

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Trade Name: Forxiga
Product Name: Dapagliflozin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: DAPAGLIFLOZIN PROPANEDIOL
CAS Number: 960404-48-2
Other descriptive name: DAPAGLIFLOZIN PROPANEDIOL MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Onglyza
Product Name: Saxagliptin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SAXAGLIPTIN
CAS Number: 361442-04-8
Other descriptive name: SAXAGLIPTIN
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: Glimepiride
Product Name: Glimepiride
Pharmaceutical Form: Capsule
CAS Number: 93479-97-1
Other descriptive name: GLIMEPIRIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Trade Name: Glimepiride
Product Name: Glimepiride
Pharmaceutical Form: Capsule
CAS Number: 93479-97-1
Other descriptive name: GLIMEPIRIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Trade Name: Glimepiride
Product Name: Glimepiride
Pharmaceutical Form: Capsule
CAS Number: 93479-97-1
Other descriptive name: GLIMEPIRIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: - To compare the proportion of patients reporting hypoglycaemia episodes during the 52-week treatment period between dapagliflozin plus metformin and dapagliflozin plus saxagliptin plus metformin with glimepiride plus metformin
- To compare the change from baseline in total body weight at Week 52 between dapagliflozin plus metformin and dapagliflozin plus saxagliptin plus metformin with glimepiride plus metformin
- To compare the change from baseline in FPG at Week 52 between dapagliflozin plus metformin and dapagliflozin plus saxagliptin plus metformin with glimepiride plus metformin
- To compare the time to rescue among the treatment groups during the 52 week treatment period between dapagliflozin plus metformin and dapagliflozin plus saxagliptin plus metformin with glimepiride plus metformin

Primary end point(s): Change in HbA1c from baseline to Week 52.

Main Objective: To compare the absolute change from baseline in HbA1c at Week 52 between dapagliflozin plus metformin and dapagliflozin plus saxagliptin plus metformin with glimepiride plus metformin

Timepoint(s) of evaluation of this end point: at 52 week

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: at 52 week

Secondary end point(s): • Proportion of patients reporting at least 1 episode of hypoglycaemia during the double-blind treatment period.
•Change in total body weight from baseline at Week 52.
•Change in FPG from baseline at Week 52.
•Time to rescue (start of insulin or discontinuation due to lack of glycaemic control) during the 52-week double-blind treatment period.

Secondary ID(s)

D1689C00014

Source(s) of Monetary Support

AstraZeneca AB