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Type 2 DiabetesPhase 3NCT01646320

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

A Phase 3 study testing Dapagliflozin, Saxagliptin and Metformin immediate release (IR) in people with Type 2 Diabetes, run by AstraZeneca at 66 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Type 2 Diabetes
What is being tested?
Dapagliflozin, Saxagliptin and Metformin immediate release (IR)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
320 participants
Where
66 sitesin 8 countries
Study dates
Sep 2012to Feb 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed Written Informed Consent
  • Subjects must be willing and able to give signed and dated written informed consent.
  • Target Population
  • For inclusion into Stratum A:
  • 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
  • For inclusion into Stratum B:
Show all 16Show fewer
  • 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.
  • 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.
  • For Stratum A AND Stratum B:
  • Subjects with T2DM with inadequate glycemic control, defined as central laboratory HbA1c ≥ 7.0 and ≤ 10.5% obtained at the Week -2 visit of the open-label treatment period.

Who cannot join

  • 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.
Show all 55Show fewer
  • 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.]
  • Conditions of congenital renal glucosuria
  • Hepatic Diseases:
  • Significant hepatic disease, including, but not limited to, chronic active hepatitis and/or severe hepatic insufficiency, including subjects with ALT and/or AST > 3x ULN and or Total Bilirubin > 2.5 x ULN.
  • Hematological and Oncological Disease/Conditions:
  • History of hemoglobinopathy, with the exception of sickle cell trait (SA) or thalassemia minor; or chronic or recurrent hemolysis.
  • Malignancy within 5 years of the screening visit (with the exception of treated basal cell or treated squamous cell carcinoma)
  • Known immunocompromised status, including but not limited to, individuals who have undergone organ transplantation or who are positive for the human immunodeficiency virus.
  • Donation of blood or blood products to a blood bank, blood transfusion, or participation in a clinical study requiring withdrawal of > 400 mL of blood during the 6 months prior to the screening visit.
  • Prohibited treatment and therapies:
  • Administration of any antihyperglycemic therapy, other than metformin and DPP4's, for more than 14 days (consecutive or not) during the 12 weeks prior to screening, as well as previous exposure to DPP4 or SGLT-2 inhibitor in any DPP4 or SGLT-2 inhibitor trial is an exclusion criterion.
  • Current treatment with potent cytochrome P450 3A4/5 inhibitors (in countries where dose adjustment would be required by the dapagliflozin label).
  • Administration of any other investigational drug or participation in any interventional clinical studies within 30 days of planned screening to this study. Subjects who failed to satisfy all eligibility criteria at screening and did not enter the lead-in or open-label period in CV181-168 or CV181-169 studies specifically, do not need to wait 30 days.
  • Physical and Laboratory Test Findings
  • Hemoglobin ≤ 11.0 g/dL (110 g/L) for men; hemoglobin ≤ 10.0 g/dL (100 g/L) for women
  • Presence of hematuria:
  • For male subjects being considered for Stratum A: microscopic hematuria present at Week -18 or Week -16 AND no common cause that can be confirmed is exclusionary. Male subjects with a confirmed common cause can be entered into the open-label phase with a documented negative result for hematuria microscopic urinalysis performed by the central laboratory.
  • For male subjects being considered for Stratum B: microscopic hematuria present at Week -10 or Week -8 AND no common cause that can be confirmed is exclusionary. Male subjects with a confirmed common cause can be entered into the open-label phase with a documented negative result for hematuria microscopic urinalysis performed by the central laboratory.
  • NOTE: Female sub}ects with hematuria can be entered into the open-label phase and be randomized, but should be investigated according to local standards and best clinical practices. (See Appendix 3)
  • Other central laboratory test findings:
  • Abnormal free T4 values. Abnormal thyroid stimulating hormone (TSH) value at screening will be further evaluated by free T4. Sub}ects with abnormal free T4 values will be excluded.
  • Positive for hepatitis B surface antigen
  • Positive for anti-hepatitis C virus antibody
  • Allergies and Adverse Drug Reaction
  • Subjects who have contraindications to therapy as outlined in the dapagliflozin and saxagliptin Investigator Brochure, the local dapagliflozin or saxagliptin package insert or the local metformin package insert, including current treatment with potent cytochrome P450 3A4/5 inhibitors (in countries where dose adjustment would be required by the local Onglyza (saxagliptin) label.
  • Sex and Reproductive Status
  • Women who are pregnant
  • Other Exclusion Criteria
  • Prisoners or subjects who are involuntarily incarcerated
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
  • Subjects on a commercial weight loss program with ongoing weight loss, or on an intensive exercise program.
  • Employee of BMS, AstraZeneca (AZ), or their relatives.
  • Subject with any condition which, in the judgment of the Investigator, may render the subject unable to complete the study or which may pose a significant risk to the subject.
  • Subject is a participating investigator, study coordinator, employee of an investigator or immediate family member of any of the aforementioned.
  • Open Label Treatment Period
  • Note: Enrollment of subjects into the open-label (Stratum A) treatment period, beginning eee -16 of the study with HbA1c values at the lower bound (≥ 8.0% and ≤ 9.0%) and Enrollment of subjects into the open-label (Stratum B) eee -8, of the study with HbA1c values at the lower bound (≥ 7.5% and ≤ 8.5%) will be limited to approximately 50% of the total number of subjects randomized.
  • For subject in Stratum A:
  • At Week -10 and Week -2 a FPG qualification check will be performed. Subjects with a central laboratory FPG value meeting > 270 mg/dL will be scheduled for a follow-up visit (within 3 - 5 days) to obtain a second central laboratory FPG value. If the mean of the originally scheduled central laboratory FPG and the repeat central laboratory FPG value is > 270 mg/dL, the subject cannot be randomized and must be discontinued.
  • For subjects in Stratum B:
  • At Week -2 a FPG qualification check will be performed. Subjects with a central laboratory FPG value meeting > 270 mg/dL will be scheduled for a follow-up visit (within 3 - 5 days) to obtain a second central laboratory FPG value. If the mean of the originally scheduled central laboratory FPG and the repeat central laboratory FPG value is > 270 mg/dL, the subject cannot be randomized and must be discontinued
  • Double Blind Treatment Period

Trial locations and contacts

66 sites in 8 countries.

66 sites in 8 countries

United States26 sites

  • Associated Internal Medicine Specialists

    Battle Creek, Michigan, 49015

  • University Of Alabama At Birmingham

    Birmingham, Alabama, 35294

  • Metrolina Internal Medicine

    Charlotte, North Carolina, 28204

  • Cedar Crosse Research Center

    Chicago, Illinois, 60607

  • Sterling Research Grp, Ltd.

    Cincinnati, Ohio, 45246

  • Clinical Research Advantage

    Evansville, Indiana, 47714

  • Palm Springs Research Institute

    Hialeah, Florida, 33012

  • Endocrine Associates

    Houston, Texas, 77004

  • Fpa Clinical Research

    Kissimmee, Florida, 34741

  • Arkansas Clinical Research

    Little Rock, Arkansas, 72205

  • Torrance Clinical Research Institute Inc.

    Lomita, California, 90717

  • Randall G. Shue, Do, Inc.

    Los Angeles, California, 90023

  • National Research Institute

    Los Angeles, California, 90057

  • Clinical Research Advantage Inc/Desert Clinical Research Llc

    Mesa, Arizona, 85213

  • International Research Associates, Llc

    Miami, Florida, 33183

  • Diabetes Medical Center Of California

    Northridge, California, 91325

  • Omega Research Consultants, Llc

    Orlando, Florida, 32804

  • Compass Research East, Llc

    Oviedo, Florida, 32765

  • Palm Harbor Medical Associates

    Palm Harbor, Florida, 34684

  • Clinical Research Advantage, Inc.

    Phoenix, Arizona, 85018

  • Elite Clinical Studies, Llc

    Phoenix, Arizona, 85018

  • Jackson Clinic

    Rolling Fork, Mississippi, 39159

  • Sam Clinical Research Center

    San Antonio, Texas, 78229

  • Premier Research

    Trenton, New Jersey, 08611

  • Tidewater Integrated Medical Research

    Virginia Beach, Virginia, 23454

  • Cassidy Medical Group/Clinical Research Advantage

    Vista, California, 92083

Other trials in United States

Russia9 sites

  • Local Institution

    Kursk, 305035

  • Local Institution

    Moscow, 119034

  • Local Institution

    Saint Petersburg, 194044

  • Local Institution

    Saint Petersburg, 194156

  • Local Institution

    Saint Petersburg, 195112

  • Local Institution

    Saint Petersburg, 195257

  • Local Institution

    Saint Petersburg, 197022

  • Local Institution

    Saint Petersburg, 197136

  • Local Institution

    Yaroslaval, 150062

Other trials in Russia

Poland7 sites

  • Local Institution

    Bialystok, 15-435

  • Local Institution

    Krakow, 30-015

  • Local Institution

    Ruda Śląska, 41-709

  • Local Institution

    Warsaw, 00-465

  • Local Institution

    Warsaw, 01-868

  • Local Institution

    Warsaw, 03-003

  • Local Institution

    Żory, 44-240

Other trials in Poland

Mexico6 sites

  • Local Institution

    Aguascalientes, Aguascalientes, 20127

  • Local Institution

    Guadalajara, Jalisco, 44670

  • Local Institution

    Monterrey, Nuevo León, 64060

  • Local Institution

    Monterrey, Nuevo León, 64460

  • Local Institution

    Zapopan, Jalisco, 45116

  • Local Institution

    Zapopan, Jalisco, 45200

Other trials in Mexico

Romania6 sites

  • Local Institution

    Bucharest, Bucharest, 070208

  • Local Institution

    Bucharest, 010825

  • Local Institution

    Constanța, 900591

  • Local Institution

    Craiova, 200349

  • Local Institution

    Galati, 800098

  • Local Institution

    Ploieşti, 100097

Other trials in Romania

United Kingdom6 sites

  • Local Institution

    Bedfordshire, SG19 3JR

  • Local Institution

    Chippenham, Wiltshire, SN15 1HP

  • Local Institution

    Liverpool, Merseyside, L7 8XP

  • Local Institution

    London, W6 7HY

  • Local Institution

    Newport, Isle of Wight, PO30 5TG

  • Local Institution

    Portsmouth, Hants, PO3 6LY

Other trials in United Kingdom

Czechia5 sites

  • Local Institution

    Broumov, 550 01

  • Local Institution

    Pardubice, 530 02

  • Local Institution

    Prague, 100 00

  • Local Institution

    Prague, 149 00

  • Local Institution

    Pribram V, 261 95

Other trials in Czechia

Puerto Rico1 site

  • Clinical Research Puerto Rico

    San Juan, 00909

Other trials in Puerto Rico

About this study

Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Therapy With Dapagliflozin Added to Saxagliptin in Combination With Metformin Compared to Therapy With Placebo Added to Saxagliptin in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin and Saxagliptin

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.

Read the detailed description

Prior to randomization, all eligible subjects will receive open-label treatment with Saxagliptin 5mg and Metformin IR during the 16-week open-label treatment period.

Conditions
Type 2 Diabetes
Being tested
Dapagliflozin, Placebo matching with Dapagliflozin, Saxagliptin, Metformin immediate release (IR)
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DapagliflozinDrug

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

  • Placebo matching with DapagliflozinDrug

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

  • SaxagliptinDrug

    Also called Onglyza

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

  • Metformin immediate release (IR)Drug

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

Study groups in NCT01646320
Study groupRoleWhat they receive
Arm1: Dapagliflozin (10 mg) + Saxagliptin + Metformin IRExperimentalNot described
Receives: Drug: Dapagliflozin; Drug: Saxagliptin; Drug: Metformin immediate release (IR)
Arm 2: Placebo + Saxagliptin + Metformin IRExperimentalNot described
Receives: Drug: Placebo matching with Dapagliflozin; Drug: Saxagliptin; Drug: Metformin immediate release (IR)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: From Baseline to Week 24

Secondary outcomes (4)

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

    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. FPG 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

    Measured: From Baseline to Week 24

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

    2-hour postprandial glucose (PPG) from a liquid meal tolerance test (2-h MTT) Subject must be fasted for at least 8 hrs prior to the MTT.

    Measured: From Baseline to Week 24

  3. Adjusted Mean Change From Baseline in Body Weight at Week 24

    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. Body weights were measured during the qualification and lead-in periods and on Day 1 and Weeks 6, 12, 18, and 24 in the double-blind period.

    Measured: From baseline to Week 24

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

    Percent adjusted for baseline HbA1c. Therapeutic glycemic response is defined as HbA1c <7.0%. Data after rescue medication was excluded from this analysis.

    Measured: From baseline to week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jul 2012 (estimated)
  2. Study startSep 2012
  3. Primary completionAug 2014
  4. Study completionFeb 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
320 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01646320
Sponsor's protocol ID
MB102-129
Other IDs
2011-006324-20
Status last verified
May 2016
First submitted
18 Jul 2012
Last updated
22 Jun 2016
Data monitoring committee
No

Publications

  • 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.

    PubMed 38770818

  • 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.

    PubMed 29802530

  • 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.

    PubMed 26246458

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Dapagliflozin, Saxagliptin and Metformin immediate release (IR) in people with Type 2 Diabetes, run by AstraZeneca at 66 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 55 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 66 sites in United States, Russia, Poland, Mexico, Romania and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (time frame: From Baseline to Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01646320, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2016.

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