Safety and Efficacy of Saxagliptin Plus Insulin With or Without Metformin
A Multicenter, Randomized, Double-Blind, Phase 3 Trial to Evaluate the Efficacy and Safety of Saxagliptin Added to Insulin Monotherapy or to Insulin in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Insulin Alone or on Insulin in Combination With Metformin
2 other identifiers
interventional
455
10 countries
80
Brief Summary
The purpose of this study is to compare the effects of saxagliptin with those of placebo as add-on therapy to insulin and insulin with metformin in improving glycemic control at 24 and 52 weeks.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 type-2-diabetes
Started Nov 2008
Shorter than P25 for phase_3 type-2-diabetes
80 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 22, 2008
CompletedFirst Posted
Study publicly available on registry
September 23, 2008
CompletedStudy Start
First participant enrolled
November 1, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2010
CompletedResults Posted
Study results publicly available
December 13, 2011
CompletedJune 1, 2015
May 1, 2015
1.4 years
September 22, 2008
August 10, 2011
May 8, 2015
Conditions
Outcome Measures
Primary Outcomes (1)
Adjusted Mean Change From Baseline in A1C Levels (Last Observation Carried Forward [LOCF])
Change from baseline: post-pre. Adjusted for baseline (value and metformin use). ANCOVA model: difference between week t and baseline values=baseline values + treatment + metformin use
Baseline to Week 24
Secondary Outcomes (5)
Change From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Meal Tolerance Test (MTT)
Baseline to Week 24
Change From Baseline in 120-minute PPG Values During an MTT
Baseline to Week 24
Change From Baseline in Fasting Plasma Glucose Values
Baseline to Week 24
Percentage of Participants Achieving a Therapeutic Glycemic Response
Baseline to Week 24
Change From Baseline in Mean Total Daily Dose of Insulin (MTDDI) (LOCF)
Baseline to Week 24
Other Outcomes (8)
Number of Participants With Abnormal Changes From Baseline in Electrocardiogram (ECG) Results
Baseline to Week 52
Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF)
Baseline and Weeks 24 and 52
Number of Participants With at Least 1 Adverse Event (AE), at Least 1 Treatment-related AE, Death as Outcome, at Least 1 Serious Adverse Event (SAE), at Least 1 Treatment-related SAE, Discontinuations Due to SAEs, and Discontinuations Due to AEs
Baseline to Week 52, continuously
- +5 more other outcomes
Study Arms (2)
Saxagliptin, 5 mg + insulin
EXPERIMENTALSaxagliptin, 5 mg, plus insulin, administered to participants with Type 2 diabetes inadequately controlled with insulin alone or with insulin plus metformin
Placebo + insulin
PLACEBO COMPARATORPlacebo administered to participants with Type 2 diabetes inadequately controlled with insulin alone or with insulin plus metformin
Interventions
Saxagliptin, 5-mg tablets (plus stable insulin dose), given orally once daily (24 weeks short-term, 28 weeks long-term); participants stratified by use of stable metformin dose; flexible insulin dose (as needed for rescue)
Placebo tablets given orally once daily for 24 weeks (short-term period)+ insulin with metformin
Eligibility Criteria
You may qualify if:
- Type 2 diabetes mellitus
- Must have been taking a stable dose of basal or premixed insulin for 8 weeks or longer prior to screening
- If taking metformin, must have been taking the same daily dose for 8 weeks or longer prior to screening
- Insulin type should be intermediate- or long-acting (basal) or premixed (premixed formulation may include short- or rapid-acting insulin as 1 component).
- Inadequate glycemic control (A1C of 7.5% to 11.0%, inclusive)
- Body mass index of 45 kg/m² or lower
- Fasting C-peptide level of 0.8 ng/mL or higher
You may not qualify if:
- Symptoms of poorly controlled diabetes, including but not limited to marked polyuria and polydipsia with greater than 10% weight loss during the last 3 months prior to screening or other signs and symptoms
- History of diabetic ketoacidosis or hyperosmolar nonketotic coma
- Women of childbearing potential unable or unwilling to use acceptable birth control
- Women who are pregnant or breastfeeding
- Active liver disease
- Anemia
- Chronic or repeated intermittent corticosteroid treatment (participants receiving stable doses of replacement corticosteroid (except dexamethasone) therapy may be enrolled)
- Use of short- or rapid-acting insulin
- Significant cardiovascular history defined as: myocardial infarction, coronary angioplasty or bypass graft, valvular disease or repair, unstable angina pectoris, transient ischemic attack, or cerebrovascular accident
- Congestive heart failure
- Unstable or rapidly progressing renal disease
- History of alcohol or drug abuse within the previous year
- History of hemoglobinopathies
- Unstable major psychiatric disorders
- Immunocompromised status
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (80)
Clinical Research Advantage, Inc
Tempe, Arizona, 85282, United States
Valley Research
Fresno, California, 93720, United States
Torrance-Lomita Medical Center
Lomita, California, 90717, United States
Diabetes Medical Center Of California
Northridge, California, 91325, United States
Ritchken & First M.D.'S
San Diego, California, 92117, United States
Encompass Clinical Research
Spring Valley, California, 91978, United States
Central Florida Clinical Trials, Inc.
Altamonte Springs, Florida, 32701, United States
Family Care Associates Of Nw Florida
Chipley, Florida, 32428, United States
Panhandle Family Care Assoc. & Coastal Palms Res. Grp Inc.
Marianna, Florida, 32446, United States
Endocrine Research Solutions, Inc.
Roswell, Georgia, 30076, United States
Danny W. Jackson P.A.
Rolling Fork, Mississippi, 39159, United States
Southgate Medical Group
West Seneca, New York, 14224, United States
Southeastern Research Associates, Inc.
Taylors, South Carolina, 29687, United States
Texas Center For Drug Development
Houston, Texas, 77081, United States
Dgd Research, Inc.
San Antonio, Texas, 78229, United States
Aurora Advanced Healthcare
Milwaukee, Wisconsin, 53209, United States
Local Institution
Calgary, Alberta, T3B 0M3, Canada
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Vancouver, British Columbia, V6E 1M7, Canada
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Bathurst, New Brunswick, E2A 4X7, Canada
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London, Ontario, N6A 4V2, Canada
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Charlottetown, Prince Edward Island, C1A 5Y9, Canada
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Gatineau, Quebec, J8V 2P5, Canada
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Laval, Quebec, H7T 2P5, Canada
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Sherbrooke, Quebec, J1G 5K2, Canada
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Regina, Saskatchewan, S4P 0W5, Canada
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Besançon, 25030, France
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Montpellier, 34295, France
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Nantes, 44093, France
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Valenciennes, 59300, France
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Balatonfüred, 8230, Hungary
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Budapest, 1041, Hungary
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Budapest, 1083, Hungary
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Budapest, 1212, Hungary
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Szentes, 6600, Hungary
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Zalaegerszeg-Pozva, 8900, Hungary
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Indore, Madhya Pradesh, 452001, India
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Hariyāna, 132001, India
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Mumbai, 400007, India
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Pune, 411 030, India
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Pune, 411011, India
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Pune, 411037, India
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Vellore, 632004, India
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Aguascalientes, Aguascalientes, 20127, Mexico
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Aguascalientes, Aguascalientes, 20230, Mexico
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Zapopan, Jal., Jalisco, 45150, Mexico
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Mexico City, Mexico City, 06700, Mexico
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Mexico City, Mexico City, 14000, Mexico
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Monterrey, Nuevo León, 64060, Mexico
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Monterrey, Nuevo León, 64240, Mexico
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Monterrey, Nuevo León, 64710, Mexico
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Monterrrey, Nuevo León, 64700, Mexico
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Veracruz, Veracruz, 91700, Mexico
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Elblag, 82-300, Poland
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Gdansk, 80-286, Poland
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Krakow, 30-510, Poland
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Lodz, 90-153, Poland
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Lublin, 20-950, Poland
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Sopot, 81-756, Poland
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Szczecin, 71-455, Poland
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Wroclaw, 50-088, Poland
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Zabrze, 41-800, Poland
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Kursk, 305035, Russia
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Saint Petersburg, 191015, Russia
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Saint Petersburg, 194156, Russia
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Saint Petersburg, 195257, Russia
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Saint Petersburg, 197022, Russia
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Saint Petersburg, 198013, Russia
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Saratov, 410031, Russia
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Smolensk, 214018, Russia
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Yaroslaval, 150062, Russia
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Parktown, Gauteng, 2193, South Africa
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Durban, KwaZulu-Natal, 4001, South Africa
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Umhlanga, KwaZulu-Natal, 4319, South Africa
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Goodwood, Western Cape, 7460, South Africa
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Tygerberg, Western Cape, 7505, South Africa
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Middlesbrough, Cleveland, TS4 3BW, United Kingdom
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Salford, Greater Manchester, M6 8HD, United Kingdom
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Newcastle upon Tyne, Tyne and Wear, NE4 6BE, United Kingdom
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Birmingham, West Midlands, B9 5SS, United Kingdom
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Sheffield, Yorkshire, S5 7AU, United Kingdom
Related Publications (4)
Perl S, Cook W, Wei C, Iqbal N, Hirshberg B. Saxagliptin Efficacy and Safety in Patients With Type 2 Diabetes and Moderate Renal Impairment. Diabetes Ther. 2016 Sep;7(3):527-35. doi: 10.1007/s13300-016-0184-9. Epub 2016 Jul 11.
PMID: 27402391DERIVEDCook W, Minervini G, Bryzinski B, Hirshberg B. Saxagliptin efficacy and safety in patients with type 2 diabetes mellitus stratified by cardiovascular disease history and cardiovascular risk factors: analysis of 3 clinical trials. Postgrad Med. 2014 Oct;126(6):19-32. doi: 10.3810/pgm.2014.10.2818.
PMID: 25414932DERIVEDBarnett AH, Charbonnel B, Li J, Donovan M, Fleming D, Iqbal N. Saxagliptin add-on therapy to insulin with or without metformin for type 2 diabetes mellitus: 52-week safety and efficacy. Clin Drug Investig. 2013 Oct;33(10):707-17. doi: 10.1007/s40261-013-0107-8.
PMID: 23949898DERIVEDBarnett AH, Charbonnel B, Donovan M, Fleming D, Chen R. Effect of saxagliptin as add-on therapy in patients with poorly controlled type 2 diabetes on insulin alone or insulin combined with metformin. Curr Med Res Opin. 2012 Apr;28(4):513-23. doi: 10.1185/03007995.2012.665046. Epub 2012 Mar 1.
PMID: 22313154DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Boaz Hirschberg
- Organization
- AstraZeneca Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Bristol-Myers Squibb
Bristol-Myers Squibb
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 22, 2008
First Posted
September 23, 2008
Study Start
November 1, 2008
Primary Completion
April 1, 2010
Study Completion
April 1, 2010
Last Updated
June 1, 2015
Results First Posted
December 13, 2011
Record last verified: 2015-05