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

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ClinicalTrials.gov Identifier: NCT03608358
Recruitment Status : Recruiting
First Posted : July 31, 2018
Last Update Posted : November 7, 2019
Sponsor:
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Dapagliflozin 10 mg Drug: Dapagliflozin 5 mg Drug: Dapagliflozin 10 mg placebo to match Drug: Dapagliflozin 5 mg placebo to match Drug: Saxagliptin 5 mg Drug: Metformin Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 342 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin in Asian Subjects With T2DM and Inadequate Glycemic Control on Metformin and Saxagliptin (DS Navigation)
Actual Study Start Date : February 27, 2019
Estimated Primary Completion Date : November 1, 2021
Estimated Study Completion Date : November 1, 2021


Arm Intervention/treatment
Experimental: Dapagliflozin 10 mg
Dapagliflozin 10 mg and dapagliflozin 5 mg placebo to match added to saxagliptin 5 mg and metformin
Drug: Dapagliflozin 10 mg
10 mg, oral tablet, once daily for 24 weeks of double-blind treatment period

Drug: Dapagliflozin 5 mg placebo to match
5 mg, oral tablet, once daily for 24 weeks of double-blind treatment period

Drug: Saxagliptin 5 mg
5 mg, oral tablet, once daily for 24 weeks of double-blinded treatment period, and for 16 weeks of open-label treatment period in Stratum A or 8 weeks of open-label treatment period in Stratum B

Drug: Metformin
Stable dose of metformin immediate release/extended release (≥ 1500 mg/day or at a maximal tolerated dose) throughout the whole study period

Experimental: Dapagliflozin 5 mg
Dapagliflozin 5 mg and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin
Drug: Dapagliflozin 5 mg
5 mg, oral tablet, once daily for 24 weeks of double-blind treatment period

Drug: Dapagliflozin 10 mg placebo to match
10 mg, oral tablet, once daily for 24 weeks of double-blind treatment period

Drug: Saxagliptin 5 mg
5 mg, oral tablet, once daily for 24 weeks of double-blinded treatment period, and for 16 weeks of open-label treatment period in Stratum A or 8 weeks of open-label treatment period in Stratum B

Drug: Metformin
Stable dose of metformin immediate release/extended release (≥ 1500 mg/day or at a maximal tolerated dose) throughout the whole study period

Placebo Comparator: Placebo
Dapagliflozin 5 mg placebo to match and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin
Drug: Dapagliflozin 10 mg placebo to match
10 mg, oral tablet, once daily for 24 weeks of double-blind treatment period

Drug: Dapagliflozin 5 mg placebo to match
5 mg, oral tablet, once daily for 24 weeks of double-blind treatment period

Drug: Saxagliptin 5 mg
5 mg, oral tablet, once daily for 24 weeks of double-blinded treatment period, and for 16 weeks of open-label treatment period in Stratum A or 8 weeks of open-label treatment period in Stratum B

Drug: Metformin
Stable dose of metformin immediate release/extended release (≥ 1500 mg/day or at a maximal tolerated dose) throughout the whole study period




Primary Outcome Measures :
  1. Mean change from baseline in HbA1c at Week 24 [ Time Frame: 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 :
  1. Mean change from baseline in fasting plasma glucose (FPG) at Week 24 [ Time Frame: 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

  2. Mean change in 2-hour postprandial glucose during a meal tolerance test (2-hour MTT) at Week 24 [ Time Frame: 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

  3. Mean change from baseline in total body weight at Week 24 [ Time Frame: 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

  4. Percent of subjects achieving a therapeutic glycaemic response of HbA1c <7.0% at Week 24 [ Time Frame: 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03608358


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

  Show 53 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Linong Ji, Professor People's Hospital of Peking Universty

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03608358     History of Changes
Other Study ID Numbers: D1683C00008
First Posted: July 31, 2018    Key Record Dates
Last Update Posted: November 7, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
DPP-4 inhibitor
HbA1c
Incretin
Dapagliflozin
Additional relevant MeSH terms:
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Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Saxagliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors