A 24-week Open-Label, Phase 3b Trial With a 28-week Extension to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin Compared to Insulin Glargine in Subjects withType 2 Diabetes Who Have Glycemic Control on Metformin

Phase 3

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Saxagliptin, Onglyza; Drug: Glargine insulin; Drug: Dapagliflozin, Farxiga; Drug: Metformin

• Registration Number: NCT02551874
• Lead Sponsor: AstraZeneca

Brief Summary

This research study of subjects with inadequately controlled type 2 diabetes mellitus (T2DM) will compare the glycemic control (measured by HbA1c) in subjects co-administered saxagliptin and dapagliflozin, in addition to metformin with or without sulfonylurea, to subjects receiving insulin glargine, in addition to metformin with or without sulfonylurea, over a treatment period of 52 weeks.

Detailed Description

CV181-369; A 24 Week International, Open-Label Trial With a 28 Week Extension to Evaluate the Efficacy of Saxagliptin Co-administered With Dapagliflozin Compared to Insulin Glargine in Subjects With Type 2 Diabetes on Metformin With or Without Sulfonylurea Therapy

Study Timeline

• Study First Submitted: 2015-09-15
• Study First Submitted QC: 2015-09-15
• Study First Posted: 2015-09-16
• Study Start: 2015-10-20
• Primary Completion: 2017-05-08
• Study Completion: 2017-11-10
• Results First Submitted: 2018-05-07
• Results First Submitted QC: 2018-08-20
• Results First Posted: 2018-09-18
• Status Verified: 2018-11
• Last Update Submitted: 2018-11-20
• Last Update Posted: 2018-12-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 650

Inclusion Criteria

• At least 18 years of age at screening
• HbA1c ≥ 8% and ≤ 12% at screening
• Fasting plasma glucose (FPG) ≤ 270 mg/dL (15mmol/L)
• Stable dose metformin ≥ 1500 mg per day with or without a stable dose of sulfonylurea (defined as at least 50% maximal dose per local label) for at least 8 weeks
• estimated glomerular filtration rate (eGFR) < 60 ml/ml/1.73m2
• Body Mass Index ≤ 45.0 kg/m2

Read More

Exclusion Criteria

• Clinical diagnosis of Type 1 diabetes
• History of ketoacidosis
• Renal, hepatic or pancreatic disease
• Impairment of renal function (defined as creatinine clearance [CrCl] < 60 mL/min
• Cardiovascular or vascular diseases identified within 3 months of participationImpairment of renal function (defined as creatinine clearance [CrCl] < 60 mL/min

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Saxagliptin/Dapagliflozin/Metformin	Saxagliptin, Onglyza	Oral route. Saxagliptin/Dapa adminsitered once daily for 24 weeks at a dose of 5 mg Saxagliptin and 10 mg Dapagliflozin
Saxagliptin/Dapagliflozin/Metformin	Dapagliflozin, Farxiga	Oral route. Saxagliptin/Dapa adminsitered once daily for 24 weeks at a dose of 5 mg Saxagliptin and 10 mg Dapagliflozin
Saxagliptin/Dapagliflozin/Metformin	Metformin	Oral route. Saxagliptin/Dapa adminsitered once daily for 24 weeks at a dose of 5 mg Saxagliptin and 10 mg Dapagliflozin
Insulin Glargine, Lantos/Metformin	Glargine insulin	Insulin glargine administered once a day with starting dose of 0.2 Unit per kg or 10 units.

Primary Outcome Measures

Name	Time	Method
Mean Change From Baseline in HbA1c at Week 24	Baseline and Week 24	To examine whether the mean change from baseline in HbA1c with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU is noninferior (noninferiority margin of 0.3%) to titrated insulin glargine plus metformin with or without SU after 24 weeks of open-label treatment.

Secondary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Total Body Weight at Week 24	Baseline and Week 24	To compare the mean change from baseline in total body weight with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU versus titrated insulin glargine plus metformin with or without SU after 24 weeks of open-label treatment
Percentage of Subjects With Confirmed Hypoglycaemia at Week 24	Baseline and Week 24	Hypoglycemia defined as plasma glucose ≤70 mg/dL (3.9 mmol/L)
Percentage of Subjects Achieving a Therapeutic Glycemic Response, Without Hypoglycaemia, at Week 24	Baseline and Week 24	To compare the percentage of subjects achieving a therapeutic glycemic response, defined as HbA1c \<7.0%, without any reported hypoglycemia, with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU versus titrated insulin glargine plus metformin with or without SU after 24 weeks of open-label treatment.
Percentage of Subjects Achieving a Therapeutic Glycemic Response at Week 24	Baseline and Week 24	To examine whether the percentage of subjects achieving a therapeutic glycemic response, defined as HbA1c \<7.0%, with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU is noninferior (noninferiority margin of 10%) to titrated insulin glargine plus metformin with or without SU after 24 weeks of open-label treatment.
Change From Baseline in the Mean Value of 24-hour Glucose at Week 2	Baseline and Week 2	Change from baseline in the mean value of 24-hour glucose readings measured by Continuous Glucose Monitoring with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU is noninferior to titrated insulin glargine plus metformin with or without SU after 2 weeks of open-label treatment.

Trial Locations

Locations (1)

Research Site; 🇸🇪 Uddevalla, Sweden