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

NCT01619059 | Completed Phase 3 Results

• 2 other identifiers: CV181-1682011-006323-37
• Study Type: interventional
• Target: 315
• Locations: 9 countries
• Sites: 83

Brief 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.

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. 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.

  From Baseline to Week 24

Secondary Outcomes (3)

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

  From Baseline to Week 24

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

  From Baseline to Week 24

• Percentage of Participants 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)

Arm 1: Saxagliptin+Dapagliflozin+Metformin IR

EXPERIMENTAL

Drug: Saxagliptin; Drug: Dapagliflozin; Drug: Metformin IR

Arm 2: Placebo+Dapagliflozin+Metformin IR

EXPERIMENTAL

Drug: Dapagliflozin; Drug: Metformin IR; Drug: Placebo matching with Saxagliptin

Interventions

Saxagliptin DRUG

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

Also known as: Onglyza

Arm 1: Saxagliptin+Dapagliflozin+Metformin IR

Dapagliflozin DRUG

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

Arm 1: Saxagliptin+Dapagliflozin+Metformin IR; Arm 2: Placebo+Dapagliflozin+Metformin IR

Metformin IR DRUG

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

Arm 1: Saxagliptin+Dapagliflozin+Metformin IR; Arm 2: Placebo+Dapagliflozin+Metformin IR

Placebo matching with Saxagliptin DRUG

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

Arm 2: Placebo+Dapagliflozin+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
• a) 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.
• 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.

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 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:

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (83)

University Of Alabama At Birmingham

Birmingham, Alabama, 35294, United States

Location

Terence T. Hart, Md

Muscle Shoals, Alabama, 35662, United States

Location

Mesa Family Medical Center

Mesa, Arizona, 85203, United States

Location

Clinical Research Advantage Inc/Desert Clinical Research Llc

Mesa, Arizona, 85213, United States

Location

Clinical Research Advantage, Inc

Phoenix, Arizona, 85020, United States

Location

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

Phoenix, Arizona, 85028, United States

Location

Beach Physicians Clinical Research Corp.

Huntington Beach, California, 92647, United States

Location

Torrance Clinical Research

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

Cassidy Medical Group/Clinical Research Advantage

Vista, California, 92083, United States

Location

Infosphere Clinical Research, Inc.

West Hills, California, 91307, United States

Location

New West Physicians, Pc

Golden, Colorado, 80401, United States

Location

Southeast Clinical Research, Llc

Chiefland, Florida, 32626, United States

Location

Clinical Therapeutics Corporation

Coral Gables, Florida, 33134, United States

Location

Medical Research Unlimited, Llc

Hialeah, Florida, 33012, United States

Location

University Of Florida Endocrinology & Diabetes

Jacksonville, Florida, 32207, United States

Location

Care Partners Clinical Research, Llc

Jacksonville, Florida, 32277, United States

Location

Clinical Research Of Miami, Inc.

Miami, Florida, 33126, United States

Location

Clinical Research Advantage, Inc.

Evansville, Indiana, 47725, United States

Location

Clinical Research Advantage

Evansville, Indiana, 7714, United States

Location

Mercy Health Research

St Louis, Missouri, 63141, United States

Location

Clinical Research Advantage, Inc.

Las Vegas, Nevada, 89128, United States

Location

Joslin Diabetes Center Affiliate Of Snhmc

Nashua, New Hampshire, 03063, United States

Location

N. Shore Diabetes & Endoc Assoc

New Hyde Park, New York, 11042, United States

Location

Digiovanna Institute For Medical Education & Research

North Massapequa, New York, 11758, United States

Location

Barat Research Group, Inc.

Charlotte, North Carolina, 28262, United States

Location

Sterling Research Grp, Ltd.

Cincinnati, Ohio, 45219, United States

Location

Physicians Research, Inc.

Zanesville, Ohio, 43701, United States

Location

Tlm Medical Services

Columbia, South Carolina, 29204, United States

Location

Family Medicine Of Sayebrook

Myrtle Beach, South Carolina, 29588, United States

Location

Holston Medical Group

Bristol, Tennessee, 37620, United States

Location

Vanderbilt Diabetes Center

Nashville, Tennessee, 37232, United States

Location

Padre Coast Clinical Research

Corpus Christi, Texas, 78404, United States

Location

Local Institution

Moncton, New Brunswick, E1G 1A7, Canada

Location

Local Institution

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

Location

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Halifax, Nova Scotia, B3K2M5, Canada

Location

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Brampton, Ontario, L6T-0G1, Canada

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Sarnia, Ontario, N7T 4X3, Canada

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Montreal, Quebec, H2R 1V6, Canada

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Québec, Quebec, G3K 2P8, Canada

Location

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Hradec Králové, 500 05, Czechia

Location

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Karlovy Vary, 360 01, Czechia

Location

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Prague, 150 98, Czechia

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Balatonfüred, H-8230, Hungary

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Budaörs, 2040, Hungary

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Budapest, 1138, Hungary

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Zalaegerszeg, 8900, Hungary

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Guadalajara, Jalisco, 44600, Mexico

Location

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Guadalajara, Jalisco, 44650, Mexico

Location

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Guadalajara, Jalisco, 44670, Mexico

Location

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Morelia, Michioacan, 58070, Mexico

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Monterrey, Nuevo León, 64460, Mexico

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Del. Benito Juarez, 03100, Mexico

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Veracruz, 91910, Mexico

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Bialystok, 15-435, Poland

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Katowice, 40-750, Poland

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Katowice, 40954, Poland

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Krakow, 31-530, Poland

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Pszczyna, 43-200, Poland

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Puławy, 24-100, Poland

Location

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Szczecin, 70-376, Poland

Location

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Warsaw, 01-868, Poland

Location

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Węgrów, 07-100, Poland

Location

Local Institution

Wroclaw, 50-349, Poland

Location

Research & Cardiovascular Corp

Ponce, 00717, Puerto Rico

Location

Local Institution

Brasov, Brașov County, 500365, Romania

Location

Local Institution

Bucharest, Bucharest, 070208, Romania

Location

Local Institution

Bucharest, 020045, Romania

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Bucharest, 77108, 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

Location

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Saint Petersburg, 195112, Russia

Location

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Saint Petersburg, 195257, Russia

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Saint Petersburg, 197022, Russia

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Saint Petersburg, 197136, Russia

Location

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Saint Petersburg, 197341, Russia

Location

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Yaroslaval, 150062, Russia

Location

Related Publications (2)

• 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

• 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.

  PMID: 26324329 DERIVED

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

saxagliptin; dapagliflozin

Condition Hierarchy (Ancestors)

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

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: June 12, 2012
• First Posted: June 14, 2012
• Study Start: June 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: January 1, 2015
• Last Updated: April 22, 2016
• Results First Posted: March 17, 2016

Record last verified: 2016-03

Locations

CA (7); ME (7); RU (9); US (34); PL (10); PR (1); HU (4); RO (8); CZ (3)