AzTrials
AzTrials

Type 2 DiabetesPhase 3NCT01619059

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

A Phase 3 study testing Saxagliptin, Dapagliflozin and Metformin IR in people with Type 2 Diabetes, run by AstraZeneca at 83 sites in 9 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-477118 (Saxagliptin) 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?
Saxagliptin, Dapagliflozin and Metformin IR
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
315 participants
Where
83 sitesin 9 countries
Study dates
Jun 2012to Jan 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
  • 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)
  • Stable metformin therapy for at least 8 weeks prior to screening visit at a dose ≥ 1500 mg per day.
  • C-peptide ≥ 1.0 ng/mL (0.34 nmol/L) at screening visit.
Show all 13Show fewer
  • 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. See Section 3.3.3 for the definition of WOCBP.
  • WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of investigational product.
  • Women must not be breastfeeding
  • Sexually active fertile men must use effective birth control if their partners are WOCBP.

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 43Show 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 recommended as per 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.
  • Note: Subjects with SBP ≥ 160mmHg and < 180mmHg or a DBP ≥ 100 mmHg and < 110mmHg will be able to enter the lead-in period, provided their hypertension treatment is adjusted as deemed appropriate by the investigator. These subjects cannot be randomized if their blood pressure remains with SBP ≥ 160 mmHg or DBP ≥ 100 mmHg measured at Day 1.
  • 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 (see Appendix 1), unstable or acute congestive heart failure. Note: eligible patients with congestive heart failure, especially those who are on diuretic therapy, should have careful monitoring of their volumes status throughout the study.
  • Renal Diseases:
  • Moderate or severe impairment of renal function [defined as eGFR < 60 mL/min/1.73 m2 (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, for more than 14 days (consecutive or not) during the 12 weeks prior to screening, as well as previous participation in any DPP-4 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 saxagliptin 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 CV181-169 or MB102-129 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
  • Male subjects with microscopic hematuria present at Week -18 or Week -16 AND no common cause that can be confirmed. 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 subjects 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. Subjects 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 saxagliptin and dapagliflozin Investigator Brochure, the local saxagliptin or dapagliflozin 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 saxagliptin label).
  • Sex and Reproductive Status
  • Women who are pregnant
  • Other Exclusion Criteria
  • Prisoners or subjects who are involuntarily incarcerated.
  • Subject who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Trial locations and contacts

83 sites in 9 countries.

83 sites in 9 countries

United States34 sites

  • University Of Alabama At Birmingham

    Birmingham, Alabama, 35294

  • Holston Medical Group

    Bristol, Tennessee, 37620

  • Barat Research Group, Inc.

    Charlotte, North Carolina, 28262

  • Southeast Clinical Research, Llc

    Chiefland, Florida, 32626

  • Sterling Research Grp, Ltd.

    Cincinnati, Ohio, 45219

  • Tlm Medical Services

    Columbia, South Carolina, 29204

  • Clinical Therapeutics Corporation

    Coral Gables, Florida, 33134

  • Padre Coast Clinical Research

    Corpus Christi, Texas, 78404

  • Clinical Research Advantage, Inc.

    Evansville, Indiana, 47725

  • Clinical Research Advantage

    Evansville, Indiana, 7714

  • New West Physicians, Pc

    Golden, Colorado, 80401

  • Medical Research Unlimited, Llc

    Hialeah, Florida, 33012

  • Beach Physicians Clinical Research Corp.

    Huntington Beach, California, 92647

  • University Of Florida Endocrinology & Diabetes

    Jacksonville, Florida, 32207

  • Care Partners Clinical Research, Llc

    Jacksonville, Florida, 32277

  • Clinical Research Advantage, Inc.

    Las Vegas, Nevada, 89128

  • Torrance Clinical Research

    Lomita, California, 90717

  • Randall G. Shue, Do, Inc.

    Los Angeles, California, 90023

  • National Research Institute

    Los Angeles, California, 90057

  • Mesa Family Medical Center

    Mesa, Arizona, 85203

  • Clinical Research Advantage Inc/Desert Clinical Research Llc

    Mesa, Arizona, 85213

  • Clinical Research Of Miami, Inc.

    Miami, Florida, 33126

  • Terence T. Hart, Md

    Muscle Shoals, Alabama, 35662

  • Family Medicine Of Sayebrook

    Myrtle Beach, South Carolina, 29588

  • Joslin Diabetes Center Affiliate Of Snhmc

    Nashua, New Hampshire, 03063

  • Vanderbilt Diabetes Center

    Nashville, Tennessee, 37232

  • N. Shore Diabetes & Endoc Assoc

    New Hyde Park, New York, 11042

  • Digiovanna Institute For Medical Education & Research

    North Massapequa, New York, 11758

  • Clinical Research Advantage, Inc

    Phoenix, Arizona, 85020

  • Clinical Research Advantage, Inc./ Stonecreek Medical Associates, Pc

    Phoenix, Arizona, 85028

  • Mercy Health Research

    St Louis, Missouri, 63141

  • Cassidy Medical Group/Clinical Research Advantage

    Vista, California, 92083

  • Infosphere Clinical Research, Inc.

    West Hills, California, 91307

  • Physicians Research, Inc.

    Zanesville, Ohio, 43701

Other trials in United States

Poland10 sites

  • Local Institution

    Bialystok, 15-435

  • Local Institution

    Katowice, 40-750

  • Local Institution

    Katowice, 40954

  • Local Institution

    Krakow, 31-530

  • Local Institution

    Pszczyna, 43-200

  • Local Institution

    Puławy, 24-100

  • Local Institution

    Szczecin, 70-376

  • Local Institution

    Warsaw, 01-868

  • Local Institution

    Węgrów, 07-100

  • Local Institution

    Wroclaw, 50-349

Other trials in Poland

Russia9 sites

  • Local Institution

    Kursk, 305035

  • Local Institution

    Moscow, 119034

  • Local Institution

    Saint Petersburg, 194044

  • Local Institution

    Saint Petersburg, 195112

  • Local Institution

    Saint Petersburg, 195257

  • Local Institution

    Saint Petersburg, 197022

  • Local Institution

    Saint Petersburg, 197136

  • Local Institution

    Saint Petersburg, 197341

  • Local Institution

    Yaroslaval, 150062

Other trials in Russia

Romania8 sites

  • Local Institution

    Brasov, Brașov County, 500365

  • Local Institution

    Bucharest, Bucharest, 070208

  • Local Institution

    Bucharest, 020045

  • Local Institution

    Bucharest, 77108

  • Local Institution

    Constanța, 900591

  • Local Institution

    Craiova, 200349

  • Local Institution

    Galati, 800098

  • Local Institution

    Ploieşti, 100097

Other trials in Romania

Canada7 sites

  • Local Institution

    Brampton, Ontario, L6T-0G1

  • Local Institution

    Halifax, Nova Scotia, B3K2M5

  • Local Institution

    Moncton, New Brunswick, E1G 1A7

  • Local Institution

    Montreal, Quebec, H2R 1V6

  • Local Institution

    Québec, Quebec, G3K 2P8

  • Local Institution

    Sarnia, Ontario, N7T 4X3

  • Local Institution

    St. John's, Newfoundland and Labrador, A1E 2E2

Other trials in Canada

Mexico7 sites

  • Local Institution

    Del. Benito Juarez, 03100

  • Local Institution

    Guadalajara, Jalisco, 44600

  • Local Institution

    Guadalajara, Jalisco, 44650

  • Local Institution

    Guadalajara, Jalisco, 44670

  • Local Institution

    Monterrey, Nuevo León, 64460

  • Local Institution

    Morelia, Michioacan, 58070

  • Local Institution

    Veracruz, 91910

Other trials in Mexico

Hungary4 sites

  • Local Institution

    Balatonfüred, H-8230

  • Local Institution

    Budaörs, 2040

  • Local Institution

    Budapest, 1138

  • Local Institution

    Zalaegerszeg, 8900

Other trials in Hungary

Czechia3 sites

  • Local Institution

    Hradec Králové, 500 05

  • Local Institution

    Karlovy Vary, 360 01

  • Local Institution

    Prague, 150 98

Other trials in Czechia

Puerto Rico1 site

  • Research & Cardiovascular Corp

    Ponce, 00717

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 Triple Therapy With Saxagliptin Added to Dapagliflozin in Combination With Metformin Compared to Therapy With Placebo Added to Dapagliflozin in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin and Dapagliflozin

The purpose of this study is to learn if BMS-477118 (Saxagliptin) 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
Being tested
Saxagliptin, Dapagliflozin, Metformin IR, Placebo matching with Saxagliptin
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.

  • SaxagliptinDrug

    Also called Onglyza

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

  • DapagliflozinDrug

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

  • Metformin IRDrug

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

  • Placebo matching with SaxagliptinDrug

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

Study groups in NCT01619059
Study groupRoleWhat they receive
Arm 1: Saxagliptin+Dapagliflozin+Metformin IRExperimentalNot described
Receives: Drug: Saxagliptin; Drug: Dapagliflozin; Drug: Metformin IR
Arm 2: Placebo+Dapagliflozin+Metformin IRExperimentalNot described
Receives: Drug: Dapagliflozin; Drug: Metformin IR; Drug: Placebo matching with Saxagliptin

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. 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 at Week 24 in the double-blind period, including observations prior to rescue.

    Measured: From Baseline to Week 24

Secondary outcomes (3)

  1. Adjusted Mean Change From Baseline in 2-hour Post Prandial Glucose (PPG) From a Liquid Meal Tolerance Test (MTT) at Week 24

    Baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. PPG measurements were obtained at Week 24 in the double-blind period, including observations prior to rescue.

    Measured: From Baseline to Week 24

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

    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 at Week 24 in the double-blind period, including observations prior to rescue.

    Measured: From Baseline to Week 24

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

    Therapeutic glycemic response is defined as HbA1c <7.0%. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.

    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 posted14 Jun 2012 (estimated)
  2. Study startJun 2012
  3. Primary completionJun 2014
  4. Study completionJan 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
315 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01619059
Sponsor's protocol ID
CV181-168
Other IDs
2011-006323-37
Status last verified
Mar 2016
First submitted
12 Jun 2012
Last updated
22 Apr 2016
Data monitoring committee
No

Publications

  • 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

  • Matthaei S, Catrinoiu D, Celinski A, Ekholm E, Cook W, Hirshberg B, Chen H, Iqbal N, Hansen L. Randomized, Double-Blind Trial of Triple Therapy With Saxagliptin Add-on to Dapagliflozin Plus Metformin in Patients With Type 2 Diabetes. Diabetes Care. 2015 Nov;38(11):2018-24. doi: 10.2337/dc15-0811. Epub 2015 Aug 31.

    PubMed 26324329

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Saxagliptin, Dapagliflozin and Metformin IR in people with Type 2 Diabetes, run by AstraZeneca at 83 sites in 9 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 13 inclusion and 43 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 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 83 sites in United States, Poland, Russia, Romania, Canada and 4 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 17 Mar 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 NCT01619059, which also lists 2 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 Apr 2016.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in