Safety and Efficacy of Dapagliflozin in Triple Therapy to Treat Subjects With Type 2 Diabetes

NCT01646320 | Completed Phase 3 Results

• 2 other identifiers: MB102-1292011-006324-20
• Study Type: interventional
• Target: 320
• Locations: 8 countries
• Sites: 66

Brief Summary

The purpose of this study is to learn if BMS-512148 (Dapagliflozin) as part of a triple combination therapy can improve (decrease) hemoglobin A1c in patients with type 2 diabetes after 24 weeks of treatment compared to a 2 drug oral antidiabetic therapy. The safety of this treatment will also be studied.

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24

  HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 6, 12, 18, and 24 in the double-blind period.

  From Baseline to Week 24

Secondary Outcomes (4)

• Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24

  From Baseline to Week 24

• Adjusted Mean Change From Baseline in 120-minute Postprandial Glucose (PPG) at Week 24

  From Baseline to Week 24

• Adjusted Mean Change From Baseline in Body Weight at Week 24

  From baseline to Week 24

• Percentage of Subjects Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF])

  From baseline to week 24

Study Arms (2)

Arm1: Dapagliflozin (10 mg) + Saxagliptin + Metformin IR

EXPERIMENTAL

Drug: Dapagliflozin; Drug: Saxagliptin; Drug: Metformin immediate release (IR)

Arm 2: Placebo + Saxagliptin + Metformin IR

EXPERIMENTAL

Drug: Placebo matching with Dapagliflozin; Drug: Saxagliptin; Drug: Metformin immediate release (IR)

Interventions

Dapagliflozin DRUG

Tablets, Oral, 10 mg, Once daily, Up to 52 weeks

Arm1: Dapagliflozin (10 mg) + Saxagliptin + Metformin IR

Placebo matching with Dapagliflozin DRUG

Tablets, Oral, 0 mg, Once daily, Up to 52 weeks

Arm 2: Placebo + Saxagliptin + Metformin IR

Saxagliptin DRUG

Tablets, Oral, 5 mg, Once daily, Up to 52 weeks

Also known as: Onglyza

Arm 2: Placebo + Saxagliptin + Metformin IR; Arm1: Dapagliflozin (10 mg) + Saxagliptin + Metformin IR

Metformin immediate release (IR) DRUG

Tablets, Oral, ≥ 1500 mg, Twice daily, Up to 52 weeks

Arm 2: Placebo + Saxagliptin + Metformin IR; Arm1: Dapagliflozin (10 mg) + Saxagliptin + Metformin IR

Eligibility Criteria

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

You may qualify if:

• Signed Written Informed Consent
• Subjects must be willing and able to give signed and dated written informed consent.
• Target Population
• i) Subjects with T2DM with inadequate glycemic control, defined as central laboratory HbA1c ≥ 8.0 and ≤ 11.5% obtained at the screening visit (ie Week -18 visit), on stable metformin therapy alone for at least 8 weeks prior to screening visit at a dose ≥ 1500 mg per day
• ii) Subjects with T2DM with inadequate glycemic control, and HbA1c ≥ 7.5 and ≤ 10.5% obtained at the screening visit and on stable metformin therapy at a dose ≥ 1500 mg per day AND a DPP4 inhibitor at the maximum approved dose for at least 8 weeks prior to screening visit.
• b) C-peptide ≥ 1.0 ng/mL (0.34 nmol/L) at screening visit. c) BMI ≤ 45.0 kg/m2 at the screening visit.
• Age and Reproductive Status
• Men and women, aged ≥ 18 years old at time of screening visit.
• Women of childbearing potential (WOCBP) must be using an acceptable method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized.
• WOCBP must have a negative serum or urine pregnancy test within 24 hours prior to the start of investigational product.
• Women must not be breastfeeding
• Sexually active fertile men must use highly effective birth control if their partners are WOCBP.

You may not qualify if:

• Target Disease Exceptions
• History of diabetes insipidus
• Symptoms of poorly controlled diabetes that would preclude participation in this trial including but not limited to marked polyuria and polydipsia with greater than 10% weight loss during the three months prior to screening, or other signs and symptoms.
• History of diabetic ketoacidosis or hyperosmolar nonketotic coma.
• Medical History and Concurrent Diseases
• History of bariatric surgery or lap-band procedure within 12 months prior to screening.
• Any unstable endocrine, psychiatric or rheumatic disorders as judged by the Investigator.
• Subject who, in the judgment of the investigator, may be at risk for dehydration or volume depletion that may affect the interpretation of efficacy or safety data and concomitant use of loop diuretics in countries where this is not recognized in the Dapagliflozin label.
• Subject is currently abusing alcohol or other drugs or has done so within the last 6 months.
• Acute Vascular Event:
• Uncontrolled hypertension defined as systolic blood pressure (SBP) ≥ 160 mmHg and/or diastolic blood pressure (DBP) ≥ 100 mmHg.
• Cardiovascular Disease within 3 months of the screening visit \[ie myocardial infarction, cardiac surgery or revascularization (CABG/PTCA), unstable angina, stroke or transient ischemic attack (TIA)\].
• Congestive heart failure as New York Association (NYHA) class IV, unstable or acute congestive heart failure.
• Renal Diseases:
• Moderate or severe impairment of renal function \[defined as eGFR \< 60 mL/min/1.73m2 (estimated by MDRD) or serum creatinine (Scr) ≥ 1.5 mg/dL in males or ≥ 1.4 mg/dL in females.\]

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (66)

University Of Alabama At Birmingham

Birmingham, Alabama, 35294, United States

Location

Clinical Research Advantage Inc/Desert Clinical Research Llc

Mesa, Arizona, 85213, United States

Location

Clinical Research Advantage, Inc.

Phoenix, Arizona, 85018, United States

Location

Elite Clinical Studies, Llc

Phoenix, Arizona, 85018, United States

Location

Arkansas Clinical Research

Little Rock, Arkansas, 72205, United States

Location

Torrance Clinical Research Institute Inc.

Lomita, California, 90717, United States

Location

Randall G. Shue, Do, Inc.

Los Angeles, California, 90023, United States

Location

National Research Institute

Los Angeles, California, 90057, United States

Location

Diabetes Medical Center Of California

Northridge, California, 91325, United States

Location

Cassidy Medical Group/Clinical Research Advantage

Vista, California, 92083, United States

Location

Palm Springs Research Institute

Hialeah, Florida, 33012, United States

Location

Fpa Clinical Research

Kissimmee, Florida, 34741, United States

Location

International Research Associates, Llc

Miami, Florida, 33183, United States

Location

Omega Research Consultants, Llc

Orlando, Florida, 32804, United States

Location

Compass Research East, Llc

Oviedo, Florida, 32765, United States

Location

Palm Harbor Medical Associates

Palm Harbor, Florida, 34684, United States

Location

Cedar Crosse Research Center

Chicago, Illinois, 60607, United States

Location

Clinical Research Advantage

Evansville, Indiana, 47714, United States

Location

Associated Internal Medicine Specialists

Battle Creek, Michigan, 49015, United States

Location

Jackson Clinic

Rolling Fork, Mississippi, 39159, United States

Location

Premier Research

Trenton, New Jersey, 08611, United States

Location

Metrolina Internal Medicine

Charlotte, North Carolina, 28204, United States

Location

Sterling Research Grp, Ltd.

Cincinnati, Ohio, 45246, United States

Location

Endocrine Associates

Houston, Texas, 77004, United States

Location

Sam Clinical Research Center

San Antonio, Texas, 78229, United States

Location

Tidewater Integrated Medical Research

Virginia Beach, Virginia, 23454, United States

Location

Local Institution

Broumov, 550 01, Czechia

Location

Local Institution

Pardubice, 530 02, Czechia

Location

Local Institution

Prague, 100 00, Czechia

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Prague, 149 00, Czechia

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Pribram V, 261 95, Czechia

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Aguascalientes, Aguascalientes, 20127, Mexico

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Guadalajara, Jalisco, 44670, Mexico

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Zapopan, Jalisco, 45116, Mexico

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Zapopan, Jalisco, 45200, Mexico

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Monterrey, Nuevo León, 64060, Mexico

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Monterrey, Nuevo León, 64460, Mexico

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Bialystok, 15-435, Poland

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Krakow, 30-015, Poland

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Ruda Śląska, 41-709, Poland

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Warsaw, 00-465, Poland

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Warsaw, 01-868, Poland

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Warsaw, 03-003, Poland

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Żory, 44-240, Poland

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Clinical Research Puerto Rico

San Juan, 00909, Puerto Rico

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Bucharest, Bucharest, 070208, Romania

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Bucharest, 010825, Romania

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Constanța, 900591, Romania

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Craiova, 200349, Romania

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Galati, 800098, Romania

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Ploieşti, 100097, Romania

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Kursk, 305035, Russia

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Moscow, 119034, Russia

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Saint Petersburg, 194044, Russia

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Saint Petersburg, 194156, Russia

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Saint Petersburg, 195112, Russia

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Saint Petersburg, 195257, Russia

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Saint Petersburg, 197022, Russia

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Saint Petersburg, 197136, Russia

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Yaroslaval, 150062, Russia

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Portsmouth, Hants, PO3 6LY, United Kingdom

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Newport, Isle of Wight, PO30 5TG, United Kingdom

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Liverpool, Merseyside, L7 8XP, United Kingdom

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Chippenham, Wiltshire, SN15 1HP, United Kingdom

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Bedfordshire, SG19 3JR, United Kingdom

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Local Institution

London, W6 7HY, United Kingdom

Location

Related Publications (3)

• Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.

  PMID: 38770818 DERIVED

• Mathieu C, Catrinoiu D, Ranetti AE, Johnsson E, Hansen L, Chen H, Garcia-Sanchez R, Iqbal N, Celinski A. Characterization of the Open-Label Lead-In Period of Two Randomized Controlled Phase 3 Trials Evaluating Dapagliflozin, Saxagliptin, and Metformin in Type 2 Diabetes. Diabetes Ther. 2018 Aug;9(4):1703-1711. doi: 10.1007/s13300-018-0445-x. Epub 2018 May 25.

  PMID: 29802530 DERIVED

• Mathieu C, Ranetti AE, Li D, Ekholm E, Cook W, Hirshberg B, Chen H, Hansen L, Iqbal N. Randomized, Double-Blind, Phase 3 Trial of Triple Therapy With Dapagliflozin Add-on to Saxagliptin Plus Metformin in Type 2 Diabetes. Diabetes Care. 2015 Nov;38(11):2009-17. doi: 10.2337/dc15-0779. Epub 2015 Aug 5.

  PMID: 26246458 DERIVED

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

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

Results Point of Contact

• Title: Eva Johnsson, Clinical Science Lead
• Organization: AstraZeneca Pharmaceuticals

Eva.Johnsson@astrazeneca.com

+46 31 7762484

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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 18, 2012
• First Posted: July 20, 2012
• Study Start: September 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: February 1, 2015
• Last Updated: June 22, 2016
• Results First Posted: April 11, 2016

Record last verified: 2016-05

Locations

PL (7); US (26); PR (1); RO (6); RU (9); ME (6); CZ (5); GB (6)