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

Primary Purpose

Type 2 Diabetes Mellitus

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Dapagliflozin 10 mg

Dapagliflozin 5 mg

Dapagliflozin 10 mg placebo to match

Dapagliflozin 5 mg placebo to match

Saxagliptin 5 mg

Metformin

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring DPP-4 inhibitor, HbA1c, Incretin, Dapagliflozin

Eligibility Criteria

18 Years - 130 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Provision of informed consent before participating in the study
Diagnosed with type 2 diabetes mellitus
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
Body mass index ≤ 40.0 kg/m^2

Exclusion Criteria:

Women of childbearing potential unable or unwilling to use acceptable birth control, or women who are pregnant or breastfeeding
History of diabetes insipidus and type 1 diabetes
History of diabetic ketoacidosis requiring medical intervention within 1 month prior to screening
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
History of unstable or rapidly progressing renal disease
Subjects with significant hepatic disease or severe hepatic impairment, or positive serologic evidence of current infectious liver disease
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
Malignancy within 5 years of the screening
History of hemoglobinopathy
Hematuria (by microscopy) positive at screening visit
FPG > 270 mg/dL obtained at open-label period
An abnormal TSH value at screening will be further evaluated for free T4. Subjects with abnormal free T4 values will be excluded

Sites / Locations

Research Site
Research Site
Research Site
Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Dapagliflozin 10 mg

Dapagliflozin 5 mg

Placebo

Arm Description

Dapagliflozin 10 mg and dapagliflozin 5 mg placebo to match added to saxagliptin 5 mg and metformin

Dapagliflozin 5 mg and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin

Dapagliflozin 5 mg placebo to match and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin

Outcomes

Primary Outcome Measures

Mean change from baseline in HbA1c at 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

Mean change from baseline in fasting plasma glucose (FPG) at 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

Mean change in 2-hour postprandial glucose during a meal tolerance test (2-hour MTT) at 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

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

Percent of subjects achieving a therapeutic glycaemic response of HbA1c <7.0% 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

Full Information

NCT ID

NCT03608358

First Posted

July 11, 2018

Last Updated

May 25, 2022

Sponsor

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT03608358

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Terminated

Why Stopped

Sponsor decided to stop commercialization of QTERNMet/Qtrilmet and to stop all related ongoing activities/studies for business reasons.

Study Start Date

February 27, 2019 (Actual)

Primary Completion Date

August 4, 2020 (Actual)

Study Completion Date

August 4, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes Mellitus

Keywords

DPP-4 inhibitor, HbA1c, Incretin, Dapagliflozin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

41 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dapagliflozin 10 mg

Arm Type

Experimental

Arm Description

Dapagliflozin 10 mg and dapagliflozin 5 mg placebo to match added to saxagliptin 5 mg and metformin

Arm Title

Dapagliflozin 5 mg

Arm Type

Experimental

Arm Description

Dapagliflozin 5 mg and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Dapagliflozin 5 mg placebo to match and dapagliflozin 10 mg placebo to match added to saxagliptin 5 mg and metformin

Intervention Type

Drug

Intervention Name(s)

Dapagliflozin 10 mg

Intervention Description

10 mg, oral tablet, once daily for 24 weeks of double-blind treatment period

Intervention Type

Drug

Intervention Name(s)

Dapagliflozin 5 mg

Intervention Description

5 mg, oral tablet, once daily for 24 weeks of double-blind treatment period

Intervention Type

Drug

Intervention Name(s)

Dapagliflozin 10 mg placebo to match

Intervention Description

10 mg, oral tablet, once daily for 24 weeks of double-blind treatment period

Intervention Type

Drug

Intervention Name(s)

Dapagliflozin 5 mg placebo to match

Intervention Description

5 mg, oral tablet, once daily for 24 weeks of double-blind treatment period

Intervention Type

Drug

Intervention Name(s)

Saxagliptin 5 mg

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Metformin

Intervention Description

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

Primary Outcome Measure Information:

Title

Mean change from baseline in HbA1c at Week 24

Description

Time Frame

Baseline to Week 24

Secondary Outcome Measure Information:

Title

Mean change from baseline in fasting plasma glucose (FPG) at Week 24

Description

Time Frame

Baseline to Week 24

Title

Mean change in 2-hour postprandial glucose during a meal tolerance test (2-hour MTT) at Week 24

Description

Time Frame

Baseline to Week 24

Title

Mean change from baseline in total body weight at Week 24

Description

Time Frame

Baseline to Week 24

Title

Percent of subjects achieving a therapeutic glycaemic response of HbA1c <7.0% at Week 24

Description

Time Frame

At week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

130 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Provision of informed consent before participating in the study Diagnosed with type 2 diabetes mellitus 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 Body mass index ≤ 40.0 kg/m^2 Exclusion Criteria: Women of childbearing potential unable or unwilling to use acceptable birth control, or women who are pregnant or breastfeeding History of diabetes insipidus and type 1 diabetes History of diabetic ketoacidosis requiring medical intervention within 1 month prior to screening 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 History of unstable or rapidly progressing renal disease Subjects with significant hepatic disease or severe hepatic impairment, or positive serologic evidence of current infectious liver disease 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 Malignancy within 5 years of the screening History of hemoglobinopathy Hematuria (by microscopy) positive at screening visit FPG > 270 mg/dL obtained at open-label period An abnormal TSH value at screening will be further evaluated for free T4. Subjects with abnormal free T4 values will be excluded

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Linong Ji, Professor

Organizational Affiliation

People's Hospital of Peking Universty

Official's Role

Principal Investigator

Facility Information:

Facility Name

Research Site

City

Bangkok

ZIP/Postal Code

10330

Country

Thailand

Facility Name

Research Site

City

Bangkok

ZIP/Postal Code

10400

Country

Thailand

Facility Name

Research Site

City

Ho Chi Minh

ZIP/Postal Code

10000

Country

Vietnam

Facility Name

Research Site

City

Ho Chi Minh

ZIP/Postal Code

700000

Country

Vietnam

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing URL

https://astrazenecagroup-dt.pharmacm.com/DT/Home

Links:

URL

https://www.trialsummaries.com/Study/StudyDetails?id=3235&tenant=MT_MED_9011

Description

Clinical Study Results on trialsummaries.com

Learn more about this trial

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

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