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

NCT03608358 | Terminated Phase 3

• 1 other identifier: D1683C00008
• Study Type: interventional
• Target: 41
• Locations: 2 countries
• Sites: 4

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).

Conditions

Type 2 Diabetes Mellitus

Keywords

DPP-4 inhibitor; HbA1c; Incretin; Dapagliflozin

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline to Week 24

Secondary Outcomes (4)

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

  Baseline to Week 24

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

  Baseline to Week 24

• Mean change from baseline in total body weight at Week 24

  Baseline to Week 24

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

  At week 24

Study Arms (3)

Dapagliflozin 10 mg

EXPERIMENTAL

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

Drug: Dapagliflozin 10 mg; Drug: Dapagliflozin 5 mg placebo to match; Drug: Saxagliptin 5 mg; Drug: Metformin

Dapagliflozin 5 mg

EXPERIMENTAL

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

Drug: Dapagliflozin 5 mg; Drug: Dapagliflozin 10 mg placebo to match; Drug: Saxagliptin 5 mg; Drug: Metformin

Placebo

PLACEBO COMPARATOR

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; Drug: Dapagliflozin 5 mg placebo to match; Drug: Saxagliptin 5 mg; Drug: Metformin

Interventions

Dapagliflozin 10 mg DRUG

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

Dapagliflozin 10 mg

Dapagliflozin 5 mg DRUG

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

Dapagliflozin 5 mg

Dapagliflozin 10 mg placebo to match DRUG

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

Dapagliflozin 5 mg; Placebo

Dapagliflozin 5 mg placebo to match DRUG

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

Dapagliflozin 10 mg; Placebo

Saxagliptin 5 mg DRUG

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

Dapagliflozin 10 mg; Dapagliflozin 5 mg; Placebo

Metformin DRUG

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

Dapagliflozin 10 mg; Dapagliflozin 5 mg; Placebo

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (4)

Research Site

Bangkok, 10330, Thailand

Location

Research Site

Bangkok, 10400, Thailand

Location

Research Site

Ho Chi Minh City, 10000, Vietnam

Location

Research Site

Ho Chi Minh City, 700000, Vietnam

Location

Related Links

• Clinical Study Results on trialsummaries.com

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dapagliflozin; saxagliptin; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Linong Ji, Professor

  People's Hospital of Peking Universty

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2018
• First Posted: July 31, 2018
• Study Start: February 27, 2019
• Primary Completion: August 4, 2020
• Study Completion: August 4, 2020
• Last Updated: May 31, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

TH (2); VN (2)