Safety and Efficacy of Dapagliflozin in Asian T2DM Subjects With Inadequate Glycemic Control on Metformin/Saxagliptin

Phase 3

Terminated

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Dapagliflozin 5 mg; Drug: Dapagliflozin 10 mg; Drug: Dapagliflozin 5 mg placebo to match; Drug: Dapagliflozin 10 mg placebo to match; Drug: Saxagliptin 5 mg; Drug: Metformin

• Registration Number: NCT03608358
• Lead Sponsor: AstraZeneca

Brief Summary

This is a 24-week, multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group, phase 3 study designed to evaluate if the safety and efficacy of dapagliflozin 5 mg or 10 mg added to saxagliptin 5 mg plus metformin is superior to placebo added to saxagliptin 5 mg plus metformin in reducing hemoglobin A1c (HbA1c).

Detailed Description

This study will be conducted in approximately 36 sites in Asian countries. Approximately 1004 subjects will be screened and 342 randomized. Prior to the screening, subjects of Stratum A should have a stable dose of metformin (≥1500 mg/day or a maximal tolerated dose) for at least 8 weeks. And subjects of Stratum B should have a stable dose of metformin (≥1500 mg/day or a maximal tolerated dose) AND a dipeptidyl peptidase-4 inhibitor at maximum approved dose for at least 8 weeks prior to the screening. Eligible subjects who complete the screening visit will enter the lead-in period, which includes open-label saxagliptin 5 mg and metformin treatment for 16 weeks in Stratum A or 8 weeks in Stratum B. At randomization visit, eligible subjects will be randomized into 1 of 3 treatment groups in a 1:1:1 ratio, receiving blinded dapagliflozin 5 mg, 10 mg or placebo plus metformin and saxagliptin 5 mg treatment for 24 weeks.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-07-11
• Study First Submitted QC: 2018-07-24
• Study First Posted: 2018-07-31
• Study Start: 2019-02-27
• Primary Completion: 2020-08-04
• Study Completion: 2020-08-04
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-25
• Last Update Posted: 2022-05-31

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 41

Inclusion Criteria

1. Provision of informed consent before participating in the study

2. Diagnosed with type 2 diabetes mellitus

3. Inadequate glycemic control defined as below:

   • HbA1c ≥ 8.0% and ≤ 11.5% for Stratum A and HbA1c ≥ 7.5% and ≤ 10.5% for Stratum B at screening visit
   • HbA1c ≥ 7.0 and ≤ 10.5% for both strata at Week -2 visit

4. Body mass index ≤ 40.0 kg/m^2

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Exclusion Criteria

1. Women of childbearing potential unable or unwilling to use acceptable birth control, or women who are pregnant or breastfeeding

2. History of diabetes insipidus and type 1 diabetes

3. History of diabetic ketoacidosis requiring medical intervention within 1 month prior to screening

4. Subjects with moderate to severe renal impairment (defined as estimate glomerular filtration rate calculated by the MDRD Formula < 60mL/min/1.73 m^2 or serum creatinine ≥ 1.5 mg/dL in males or ≥ 1.4 mg/dL in females) or end-stage renal disease

5. History of unstable or rapidly progressing renal disease

6. Subjects with significant hepatic disease or severe hepatic impairment, or positive serologic evidence of current infectious liver disease

7. Prohibited Treatment and Therapies

   • Administration of any anti-hyperglycemic therapy [other than metformin, or Dipeptidyl peptidase-4 (DPP-4) inhibitors] for more than 14 days (consecutive or not) during the 8 weeks prior to screening
   • Any use of Sodium glucose cotransporter 2 (SGLT2) inhibitor within 8 weeks prior to screening
   • Prescription and over-the-counter weight loss medications within 3 months prior to screening
   • Current treatment with potent cytochrome P450 3A4/5 inhibitors

8. Malignancy within 5 years of the screening

9. History of hemoglobinopathy

10. Hematuria (by microscopy) positive at screening visit

11. FPG > 270 mg/dL obtained at open-label period

12. An abnormal TSH value at screening will be further evaluated for free T4. Subjects with abnormal free T4 values will be excluded

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dapagliflozin 10 mg	Saxagliptin 5 mg	Dapagliflozin 10 mg and dapagliflozin 5 mg placebo to match added to saxagliptin 5 mg and metformin
Dapagliflozin 10 mg	Metformin	Dapagliflozin 10 mg and dapagliflozin 5 mg placebo to match added to saxagliptin 5 mg and metformin
Dapagliflozin 5 mg	Dapagliflozin 5 mg	Dapagliflozin 5 mg and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin
Placebo	Dapagliflozin 5 mg placebo to match	Dapagliflozin 5 mg placebo to match and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin
Placebo	Saxagliptin 5 mg	Dapagliflozin 5 mg placebo to match and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin
Placebo	Metformin	Dapagliflozin 5 mg placebo to match and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin
Dapagliflozin 5 mg	Saxagliptin 5 mg	Dapagliflozin 5 mg and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin
Dapagliflozin 10 mg	Dapagliflozin 10 mg	Dapagliflozin 10 mg and dapagliflozin 5 mg placebo to match added to saxagliptin 5 mg and metformin
Dapagliflozin 10 mg	Dapagliflozin 5 mg placebo to match	Dapagliflozin 10 mg and dapagliflozin 5 mg placebo to match added to saxagliptin 5 mg and metformin
Dapagliflozin 5 mg	Dapagliflozin 10 mg placebo to match	Dapagliflozin 5 mg and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin
Placebo	Dapagliflozin 10 mg placebo to match	Dapagliflozin 5 mg placebo to match and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin
Dapagliflozin 5 mg	Metformin	Dapagliflozin 5 mg and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin

Primary Outcome Measures

Name	Time	Method
Mean change from baseline in HbA1c at Week 24	Baseline to Week 24	To compare the mean change from baseline in HbA1c achieved with dapagliflozin 5 mg or dapagliflozin 10 mg added to saxagliptin 5 mg plus metformin versus placebo added to saxagliptin 5 mg plus metformin after 24 weeks of oral administration of double-blind treatment

Secondary Outcome Measures

Name	Time	Method
Mean change from baseline in fasting plasma glucose (FPG) at Week 24	Baseline to Week 24	To compare the mean change from baseline in FPG achieved with dapagliflozin 5 mg or dapagliflozin 10 mg added to saxagliptin 5 mg plus metformin versus placebo added to saxagliptin 5 mg plus metformin after 24 weeks of oral administration of double-blind treatment
Percent of subjects achieving a therapeutic glycaemic response of HbA1c <7.0% at Week 24	At week 24	To compare the proportion of subjects achieving a therapeutic glycaemic response of HbA1c \< 7.0% with dapagliflozin 5 mg or dapagliflozin 10 mg added to saxagliptin 5 mg plus metformin vs. placebo added to saxagliptin 5 mg plus metformin after 24 weeks of oral administration of double-blind treatment
Mean change in 2-hour postprandial glucose during a meal tolerance test (2-hour MTT) at Week 24	Baseline to Week 24	To compare the mean change from baseline in 2-hour postprandial glucose from a meal tolerance test (2-hour MTT) achieved with dapagliflozin 5 mg or dapagliflozin 10 mg added to saxagliptin 5 mg plus metformin versus placebo added to saxagliptin 5 mg plus metformin after 24 weeks of oral administration of double-blind treatment
Mean change from baseline in total body weight at Week 24	Baseline to Week 24	To compare the mean change from baseline in total body weight achieved with dapagliflozin 5 mg or dapagliflozin 10 mg added to saxagliptin 5 mg plus metformin versus placebo added to saxagliptin 5 mg plus metformin after 24 weeks of oral administration of double-blind treatment

Trial Locations

Locations (1)

Research Site; 🇻🇳 Ho Chi Minh, Vietnam