Efficacy and Safety of Dapagliflozin and Dapagliflozin Plus Saxagliptin in Combination With Metformin in Type 2 Diabetes Patients Compared With Sulphonylurea

Phase 4

Completed

• Conditions: Type 2 Diabetes Mellitus; Inadequate Glycaemic Control
• Interventions: Drug: Dapagliflozin; Drug: Glimepiride; Drug: Placebo for saxagliptin; Drug: Saxagliptin; Drug: Placebo for dapagliflozin; Drug: Placebo for glimepiride

• Registration Number: NCT02471404
• Lead Sponsor: AstraZeneca

Brief Summary

This study is being carried out to see if dapagliflozin and dapagliflozin plus saxagliptin as an addition to metformin is effective and safe in treating patients with type 2 diabetes when compared to glimepiride (sulphonylurea) as an addition to metformin treatment.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-06-11
• Study First Submitted QC: 2015-06-11
• Study First Posted: 2015-06-15
• Study Start: 2015-09-21
• Primary Completion: 2017-03-13
• Study Completion: 2017-03-13
• Results First Submitted: 2018-03-13
• Status Verified: 2019-03
• Results First Submitted QC: 2019-03-22
• Last Update Submitted: 2019-03-22
• Results First Posted: 2019-03-26
• Last Update Posted: 2019-03-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 939

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; 333.3 pmol/L) based on central laboratory results from Visit 1.

Main,

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dapagliflozin+metformin	Placebo for saxagliptin	Dapagliflozin + saxagliptin placebo + glimepiride placebo + metformin
Dapagliflozin+metformin	Dapagliflozin	Dapagliflozin + saxagliptin placebo + glimepiride placebo + metformin
Dapagliflozin+metformin	Placebo for glimepiride	Dapagliflozin + saxagliptin placebo + glimepiride placebo + metformin
Dapagliflozin+saxagliptin+metformin	Dapagliflozin	Dapagliflozin + saxagliptin + glimepiride placebo+ metformin
Dapagliflozin+saxagliptin+metformin	Saxagliptin	Dapagliflozin + saxagliptin + glimepiride placebo+ metformin
Dapagliflozin+saxagliptin+metformin	Placebo for glimepiride	Dapagliflozin + saxagliptin + glimepiride placebo+ metformin
Glimepiride+metformin	Glimepiride	Glimepiride + dapagliflozin placebo + saxagliptin placebo + metformin
Glimepiride+metformin	Placebo for dapagliflozin	Glimepiride + dapagliflozin placebo + saxagliptin placebo + metformin
Glimepiride+metformin	Placebo for saxagliptin	Glimepiride + dapagliflozin placebo + saxagliptin placebo + metformin

Primary Outcome Measures

Name	Time	Method
Change in Haemoglobin A1c (HbA1c) From Baseline to Week 52	Baseline, week 52. Values recorded after rescue treatment or collected more than 8 days after the last dose date were excluded from the analysis	Change in HbA1c from baseline (week 0) to week 52.

Secondary Outcome Measures

Name	Time	Method
Patients With at Least One Episode of Confirmed Hypoglycaemia	Up to Week 52. Values recorded after rescue treatment or collected more than 8 days after the last dose date were excluded from the analysis	Percentage of patients reporting at least 1 episode of hypoglycaemia (symptomatic + blood glucose \<=50 mg/dL) during the double-blind treatment period
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 52	Baseline, week 52. Values recorded after rescue treatment or collected more than 8 days after the last dose date were excluded from the analysis	Change in FPG from baseline (week 0) to week 52
Time to Rescue	Over the 52 week treatment period	The time to rescue (from first dose date after randomisation to start of rescue medication or discontinuation due to lack of glycaemic control) during the 52 week double blind treatment period
Change in Total Body Weight From Baseline at Week 52	Baseline, week 52. Values recorded after rescue treatment or collected more than 8 days after the last dose date were excluded from the analysis	Change in body weight from baseline (week 0) to week 52
Number of Patients Rescued	Over the 52 week treatment period	Number (%) of patients rescued.

Trial Locations

Locations (1)

Research Site; 🇸🇰 Vrutky, Slovakia