A 52-week International, Multicenter Trial With a Long -Term Extension to Evaluate Saxagliptin With Dapagliflozin in Combination With Metformin Compared to Glimepiride in Combination With Metformin in Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone

A 52-week International, Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel Group, Phase 3bTrial With a Blinded 104-week Long -Term Extension Period to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin in Combination With Metformin Compared to Glimepiride in Combination With Metformin ≥1500 mg in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Therapy Alone

This clincial trial is evaluating if the co-administration of saxagliptin and dapagliflozin, in addition to metformin, results in better glycemic control, as measured by HbA1c, over a treatment period of 52 weeks, compared to the addition of glimepiride to metformin in subjects with Type 2 Diabetes Mellitus who have inadequate glycemic control on Metformin Alone. We will compare the change from baseline in HbA1c achieved with saxagliptin, in co-administration with dapagliflozin, added to current background therapy with metformin compared to glimepiride added to current background therapy with metformin ≥1500 mg at Week 52.

Study Overview

• Status: Completed
• Conditions: Diabetes
• Intervention / Treatment: Other: Placebo; Drug: Dapagliflozin; Drug: Saxagliptin; Drug: Glimepiride

• Study Type: Interventional
• Enrollment (Actual): 444
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Cheb, Czechia, 350 02
    • Research Site
  • Hradec Kralove, Czechia, 503 41
    • Research Site
  • Krnov, Czechia, 794 01
    • Research Site
  • Kromeriz, Czechia, 767 01
    • Research Site
  • Nachod, Czechia, 54701
    • Research Site
  • Praha 4, Czechia, 140 00
    • Research Site
  • Praha 4, Czechia, 149 00
    • Research Site
• Germany
  • Dresden, Germany, 01307
    • Research Site
  • Leipzig, Germany, 04249
    • Research Site
• Hungary
  • Ajka, Hungary, 8400
    • Research Site
  • Balatonfüred, Hungary, 8230
    • Research Site
  • Budapest, Hungary
    • Research Site
  • Budapest, Hungary, 1033
    • Research Site
  • Budapest, Hungary, 1089
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
  • Eger, Hungary, 3300
    • Research Site
  • Gyula, Hungary, 5700
    • Research Site
  • Kaposvár, Hungary, 7400
    • Research Site
  • Kecskemét, Hungary, 6000
    • Research Site
  • Nyíregyháza, Hungary, 4405
    • Research Site
  • Zalaegerszeg, Hungary, 8900
    • Research Site
• Mexico
  • Aguascalientes, Mexico, 20230
    • Research Site
  • Chihuahua, Mexico, 31237
    • Research Site
  • Cuautla, Mexico, 62746
    • Research Site
  • Guadalajara, Mexico, 44600
    • Research Site
  • Guanajuato, Mexico, 38000
    • Research Site
  • Monterrey, Mexico, 64460
    • Research Site
  • Veracruz, Mexico, 91910
    • Research Site
• Poland
  • Białystok, Poland, 15-351
    • Research Site
  • Katowice, Poland, 40-648
    • Research Site
  • Kraków, Poland, 31-156
    • Research Site
  • Kraków, Poland, 31-261
    • Research Site
  • Opole, Poland, 45-367
    • Research Site
  • Oswiecim, Poland, 32-600
    • Research Site
  • Poznań, Poland, 61-655
    • Research Site
  • Warszawa, Poland, 02-507
    • Research Site
  • Warszawa, Poland, 00-465
    • Research Site
  • Wroclaw, Poland, 50-349
    • Research Site
  • Łódź, Poland, 90-242
    • Research Site
• Romania
  • Brasov, Romania, 500269
    • Research Site
  • Bucuresti, Romania, 020359
    • Research Site
  • Bucuresti, Romania, 020045
    • Research Site
  • Buzau, Romania, 120203
    • Research Site
  • Galati, Romania, 800291
    • Research Site
  • Oradea, Romania, 410169
    • Research Site
  • Oradea, Romania, 410032
    • Research Site
  • Ploiesti, Romania, 100342
    • Research Site
  • Ploiesti, Romania, 100163
    • Research Site
  • Satu-Mare, Romania, 440055
    • Research Site
  • Targu, Romania, 540142
    • Research Site
  • Timisoara, Romania, 300736
    • Research Site
• Russian Federation
  • Novosibirsk, Russian Federation, 630087
    • Research Site
  • Saint Petersburg, Russian Federation, 195257
    • Research Site
  • Smolensk, Russian Federation, 214018
    • Research Site
  • St. Petersburg, Russian Federation, 194354
    • Research Site
  • St. Petersburg, Russian Federation, 196084
    • Research Site
  • St. Petersburg, Russian Federation, 190013
    • Research Site
  • St.-Petersburg, Russian Federation, 195176
    • Research Site
• Sweden
  • Göteborg, Sweden, 413 45
    • Research Site
  • Helsingborg, Sweden, 25220
    • Research Site
  • Rättvik, Sweden, 79530
    • Research Site
• United Kingdom
  • Dundee, United Kingdom, DD1 9SY
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Research Site
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Research Site
    • Tempe, Arizona, United States, 85283
      • Research Site
  • California
    • Huntington Park, California, United States, 90255
      • Research Site
    • Los Angeles, California, United States, 90057
      • Research Site
    • Sacramento, California, United States, 95823
      • Research Site
    • Tarzana, California, United States, 91356
      • Research Site
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Research Site
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Research Site
    • Jacksonville, Florida, United States, 32277
      • Research Site
    • Kissimmee, Florida, United States, 34744
      • Research Site
    • Miami, Florida, United States, 33126
      • Research Site
    • Miami, Florida, United States, 33174
      • Research Site
    • New Port Richey, Florida, United States, 34652
      • Research Site
    • Palm Harbor, Florida, United States, 34684
      • Research Site
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Research Site
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Research Site
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Research Site
    • Knoxville, Tennessee, United States, 37912
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75230
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Subjects must be willing and able to give signed and dated written informed consent
• Patients with Type 2 diabetes mellitus (T2DM) with inadequate glycemic control
• Subjects should have been taking the same daily dose of metformin ≥ 1500 mg
• Fasting Plasma Glucose ≤ 270 mg/dL (≤15 mmol/L)
• Males and females, aged ≥18 years old at time of screening visit
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test
• WOCBP and males must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug

Exclusion Criteria:

• Clinical diagnosis of type I diabetes
• History of diabetic ketoacidosis
• Cardiovascular/vascular diseases within 3 months of the enrollment
• Renal disease
• Hepatic diseases
• History of, or currently, acute or chronic pancreatitis
• Hematological and oncological disease/conditions
• Patients who have contraindications to therapy being studied
• Patients on weight loss program(s)
• Replacement or chronic systemic corticosteroid therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Saxagliptin 5 mg/ dapagliflozin 10mg or Placebo; Saxagliptin 5 mg /dapagliflozin 10 mg Placebo once a day orally	Other: Placebo; Drug: Dapagliflozin; Drug: Saxagliptin
Experimental: Glimepiride or Placebo; Glimepiride or placebo 1mg or 2mg or 3mg or 4mg or 6mg once a day orally	Other: Placebo; Drug: Glimepiride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 52	To examine whether the mean change from baseline in HbA1c with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin is superior to titrated glimepiride plus metformin after 52 weeks of double-blind treatment.	Baseline and Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Total Body Weight at Week 52	To examine whether the mean change from baseline in total body weight with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin is superior to titrated glimepiride plus metformin after 52 weeks of double-blind treatment.	Baseline and Week 52
Percentage of Subjects Achieving a Therapeutic Glycemic Response, Defined as HbA1c < 7.0%, at Week 52	Therapeutic glycemic response was defined as HbA1c <7.0%. Subjects rescued or discontinued prior to, and subjects with missing measurements at Week 52 were treated as non-responders. The percentage of subjects with a therapeutic glycemic response is based on the logistic regression method with adjustment for baseline HbA1c.	At Week 52
Change From Baseline in Systolic Blood Pressure (SBP) at Week 52	To examine whether the change from baseline in SBP with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin is superior to titrated glimepiride plus metformin after 52 weeks of double-blind treatment.	Baseline and Week 52
Percentage of Subjects With Treatment Intensification During the 52-week Short-term Treatment Period	Treatment intensification was defined as the addition of insulin or other glucose-lowering agent for rescue therapy or discontinuation for lack of glycemic control. Time to treatment intensification was censored after the 52-week treatment period if treatment intensification had not occurred by then. Subjects rescued at Week 52 were counted as having an event for the analysis. The values presented are the percentage of subjects requiring the addition of insulin or other glucose-lowering agent for rescue therapy or discontinuation for lack of glycemic control during the 52-week short -term treatment period.	Up to Week 52
Percentage of Subjects With Treatment Intensification During the 156-Week Short-term Plus Long-Term Treatment Period.	Treatment intensification was defined as the addition of insulin or other glucose-lowering agent for rescue therapy or discontinuation for lack of glycemic control. Time to treatment intensification was censored after 156-week treatment period if treatment intensification had not occurred by then. Subjects rescued at Week 156 were counted as having an event for the analysis. The values presented are the percentage of subjects requiring the addition of insulin or other glucose-lowering agent for rescue therapy or discontinuation for lack of glycemic control during the 156-week treatment period.	Up to Week 156
Percentage of Subjects Achieving a Therapeutic Glycemic Response, Defined as HbA1c < 7.0%, at Week 156	Therapeutic glycemic response was defined as HbA1c <7.0%. Subjects rescued or discontinued prior to, and subjects with missing measurements at Week 156 were treated as non-responders. The percentage of subjects with a therapeutic glycemic response is based on the logistic regression method with adjustment for baseline HbA1c.	At Week 156
Time to Treatment Intensification During the 156-Week Short-term Plus Long-Term Treatment Period.	Treatment intensification was defined as the addition of insulin or other glucose-lowering agent for rescue therapy or discontinuation for lack of glycemic control. Time to treatment intensification was censored after 156-week treatment period if treatment intensification had not occurred by then. Subjects rescued at Week 156 were counted as having an event for the analysis. Time to treatment intensification curves were generated using Kaplan-Meier estimates and compared using a Cox proportional hazards model.	Up to Week 156

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Frias JP, Gonzalez-Galvez G, Johnsson E, Maaske J, Testa MA, Simonson DC, Dronamraju N, Garcia-Sanchez R, Peters AL. Efficacy and safety of dual add-on therapy with dapagliflozin plus saxagliptin versus glimepiride in patients with poorly controlled type 2 diabetes on a stable dose of metformin: Results from a 52-week, randomized, active-controlled trial. Diabetes Obes Metab. 2020 Jul;22(7):1083-1093. doi: 10.1111/dom.13997. Epub 2020 Mar 9.

Helpful Links

• CV181365_CSP_redacted

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2015
• Primary Completion (Actual): August 29, 2017
• Study Completion (Actual): September 18, 2019

Study Registration Dates

• First Submitted: April 14, 2015
• First Submitted That Met QC Criteria: April 16, 2015
• First Posted (Estimate): April 17, 2015

Study Record Updates

• Last Update Posted (Actual): June 23, 2020
• Last Update Submitted That Met QC Criteria: June 22, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Dapagliflozin; Glimepiride; Saxagliptin
• Other Study ID Numbers: CV181-365

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP