Clinical trial NCT00757588: Safety and Efficacy of Saxagliptin Plus Insulin With or Without Metformin
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2008-09-23
Enrollment: 455
Sex: ALL
Minimum age (years): 18
Maximum age (years): 78
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Adjusted Mean Change From Baseline in A1C Levels (Last Observation Carried Forward [LOCF])
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Change From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Meal Tolerance Test (MTT)
timeFrame: Baseline to Week 24
measure: Change From Baseline in 120-minute PPG Values During an MTT
timeFrame: Baseline to Week 24
measure: Change From Baseline in Fasting Plasma Glucose Values
timeFrame: Baseline to Week 24
measure: Percentage of Participants Achieving a Therapeutic Glycemic Response
timeFrame: Baseline to Week 24
measure: Change From Baseline in Mean Total Daily Dose of Insulin (MTDDI) (LOCF)
timeFrame: Baseline to Week 24
Other outcomes:
measure: Number of Participants With Abnormal Changes From Baseline in Electrocardiogram (ECG) Results
timeFrame: Baseline to Week 52
measure: Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF)
timeFrame: Baseline and Weeks 24 and 52
measure: 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
timeFrame: Baseline to Week 52, continuously
measure: Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings
timeFrame: Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 52
measure: Mean Changes From Baseline in Heart Rate
timeFrame: Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 52
measure: Shift in Platelet Counts From Baseline to Selected Visits (LOCF)
timeFrame: Baseline and Weeks 24 and 52
measure: Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period
timeFrame: Baseline and during and up to 14 days after last dose of study drug (in Week 52)
measure: Percentage of Participants With Reported and Confirmed Hypoglycemia
timeFrame: Baseline to Week 52
Locations:
city: Tempe
country: United States
facility: Clinical Research Advantage, Inc
state: Arizona
city: Fresno
country: United States
facility: Valley Research
state: California
city: Lomita
country: United States
facility: Torrance-Lomita Medical Center
state: California
city: Northridge
country: United States
facility: Diabetes Medical Center Of California
state: California
city: San Diego
country: United States
facility: Ritchken & First M.D.'S
state: California
city: Spring Valley
country: United States
facility: Encompass Clinical Research
state: California
city: Altamonte Springs
country: United States
facility: Central Florida Clinical Trials, Inc.
state: Florida
city: Chipley
country: United States
facility: Family Care Associates Of Nw Florida
state: Florida
city: Marianna
country: United States
facility: Panhandle Family Care Assoc. & Coastal Palms Res. Grp Inc.
state: Florida
city: Roswell
country: United States
facility: Endocrine Research Solutions, Inc.
state: Georgia
city: Rolling Fork
country: United States
facility: Danny W. Jackson P.A.
state: Mississippi
city: West Seneca
country: United States
facility: Southgate Medical Group
state: New York
city: Taylors
country: United States
facility: Southeastern Research Associates, Inc.
state: South Carolina
city: Houston
country: United States
facility: Texas Center For Drug Development
state: Texas
city: San Antonio
country: United States
facility: Dgd Research, Inc.
state: Texas
city: Milwaukee
country: United States
facility: Aurora Advanced Healthcare
state: Wisconsin
city: Calgary
country: Canada
facility: Local Institution
state: Alberta
city: Vancouver
country: Canada
facility: Local Institution
state: British Columbia
city: Bathurst
country: Canada
facility: Local Institution
state: New Brunswick
city: London
country: Canada
facility: Local Institution
state: Ontario
city: Charlottetown
country: Canada
facility: Local Institution
state: Prince Edward Island
city: Gatineau
country: Canada
facility: Local Institution
state: Quebec
city: Laval
country: Canada
facility: Local Institution
state: Quebec
city: Sherbrooke
country: Canada
facility: Local Institution
state: Quebec
city: Regina
country: Canada
facility: Local Institution
state: Saskatchewan
city: Besancon Cedex
country: France
facility: Local Institution
city: Montpellier Cedex 5
country: France
facility: Local Institution
city: Nantes
country: France
facility: Local Institution
city: Valenciennes
country: France
facility: Local Institution
city: Balatonfured
country: Hungary
facility: Local Institution
city: Budapest
country: Hungary
facility: Local Institution
city: Budapest
country: Hungary
facility: Local Institution
city: Budapest
country: Hungary
facility: Local Institution
city: Szentes
country: Hungary
facility: Local Institution
city: Zalaegerszeg-Pozva
country: Hungary
facility: Local Institution
city: Indore
country: India
facility: Local Institution
state: Madhya Pradesh
city: Hariyana
country: India
facility: Local Institution
city: Mumbai
country: India
facility: Local Institution
city: Pune
country: India
facility: Local Institution
city: Pune
country: India
facility: Local Institution
city: Pune
country: India
facility: Local Institution
city: Vellore
country: India
facility: Local Institution
city: Ciudad De Mexico
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Zapopan, Jal.
country: Mexico
facility: Local Institution
state: Jalisco
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Monterrrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Aguascalientes
country: Mexico
facility: Local Institution
city: Aguascalientes
country: Mexico
facility: Local Institution
city: Mexico City
country: Mexico
facility: Local Institution
city: Veracruz
country: Mexico
facility: Local Institution
city: Elblag
country: Poland
facility: Local Institution
city: Gdansk
country: Poland
facility: Local Institution
city: Krakow
country: Poland
facility: Local Institution
city: Lodz
country: Poland
facility: Local Institution
city: Lublin
country: Poland
facility: Local Institution
city: Sopot
country: Poland
facility: Local Institution
city: Szczecin
country: Poland
facility: Local Institution
city: Wroclaw
country: Poland
facility: Local Institution
city: Zabrze
country: Poland
facility: Local Institution
city: Kursk
country: Russian Federation
facility: Local Institution
city: Saint-Petersburg
country: Russian Federation
facility: Local Institution
city: Saratov
country: Russian Federation
facility: Local Institution
city: Smolensk
country: Russian Federation
facility: Local Institution
city: St Petersburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: St.Petersburg
country: Russian Federation
facility: Local Institution
city: Yaroslaval
country: Russian Federation
facility: Local Institution
city: Parktown
country: South Africa
facility: Local Institution
state: Gauteng
city: Durban
country: South Africa
facility: Local Institution
state: Kwa Zulu Natal
city: Umhlanga Rocks
country: South Africa
facility: Local Institution
state: Kwa Zulu Natal
city: Goodwood
country: South Africa
facility: Local Institution
state: Western Cape
city: Tygerberg
country: South Africa
facility: Local Institution
state: Western Cape
city: Middlesborough
country: United Kingdom
facility: Local Institution
state: Cleveland
city: Salford
country: United Kingdom
facility: Local Institution
state: Greater Manchester
city: Newcastle Upon Tyne
country: United Kingdom
facility: Local Institution
state: Tyne And Wear
city: Birmingham
country: United Kingdom
facility: Local Institution
state: West Midlands
city: Sheffield
country: United Kingdom
facility: Local Institution
state: Yorkshire
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Cook 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.
citation: Barnett 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.
citation: Barnett 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.