Clinical trial NCT00121667: Study Assessing Saxagliptin Treatment In Type 2 Diabetic Subjects Who Are Not Controlled With Metformin Alone
Official title: "A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial to Evaluate the Efficacy and Safety of BMS-477118 in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone"
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2005-07-21
Enrollment: 1462
Sex: ALL
Minimum age (years): 18
Maximum age (years): 77
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical research study is to learn whether Saxagliptin added to Metformin therapy is more effective than Metformin alone as a treatment for type 2 diabetic subjects who are not sufficiently controlled with Metformin alone

Detailed description: All subjects will participate in a lead-in period, and qualifying subjects will continue into a short-term randomized treatment period. Subjects who complete the short-term period will be eligible to enter the long term extension period. Also, subjects in the short-term period who have an elevated blood sugar that requires additional medication for blood sugar control will be eligible to enter the long-term treatment extension period where they will receive pioglitizone added onto their blinded study medication

Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes mellitus requiring treatment with at least 1500 mg but not greater than 2550 mg of a maximum tolerated dose of Metformin therapy for at least 8 weeks prior to screening.
* HbA1c \>= 7.0% and \<= 10.0 %
* Body mass index \<= 40 kg/m2
* Fasting C-peptide \>= 1 ng/dL

Exclusion Criteria:

* Symptomatic poorly controlled diabetes
* Recent cardiac or cerebrovascular event
* Serum creatinine \>= 1.5 mg/dL for males and \>= 1.4 mg/dL for females

Primary outcomes:
measure: Baseline and Change From Baseline in Hemoglobin A1c (A1C) at Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Baseline and Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants Achieving Therapeutic Glycemic Response (A1C < 7.0%) at Week 24
timeFrame: Week 24
measure: Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC)
timeFrame: Baseline, Week 24
Other outcomes:
measure: Overall Summary of Adverse Events During ST+LT Treatment Period
timeFrame: AEs: up to last treatment day + 1 day or last visit day in the ST+LT period; SAEs: up to last treatment day + 30 days or last visit day + 30 days in the LT+ST period. Mean duration of exposure: 124, 118, 130, 95 wks respectively for 2.5mg, 5mg, 10 mg, pla
measure: Marked Laboratory Abnormalities - During ST + LT Treatment Period
timeFrame: Lab assessments taken during and up to 14 days after the last dose of study drug during the ST + LT Treatment Period. Mean duration of exposure: 124, 118, 130, 95 weeks, respectively, for 2.5mg, 5mg, 10 mg, placebo.
measure: Baseline and Changes From Baseline in Hemoglobin During the ST + LT Period
timeFrame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
measure: Baseline and Changes From Baseline in Hematocrit During the ST + LT Period
timeFrame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
measure: Baseline and Changes From Baseline in Red Blood Cell Counts (x 10^6 c/µL) During the ST + LT Period
timeFrame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
measure: Baseline and Changes From Baseline in Platelet Counts (x 10^9 c/L) During the ST + LT Period
timeFrame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
measure: Baseline and Changes From Baseline in White Blood Cell Counts (x 10^3 c/µL) During the ST + LT Period
timeFrame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
measure: Baseline and Changes From Baseline in Absolute Neutrophil Counts (x 10^3 c/µL) During the ST + LT Period
timeFrame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
measure: Baseline and Changes From Baseline in Absolute Lymphocyte Counts (x 10^3 c/µL) During the ST + LT Period
timeFrame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
measure: Baseline and Changes From Baseline in Absolute Monocyte Counts (x 10^3 c/µL) During the ST + LT Period
timeFrame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
measure: Baseline and Changes From Baseline in Absolute Basophil Counts (x 10^3 c/µL) During the ST + LT Period
timeFrame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
measure: Baseline and Changes From Baseline in Absolute Eosinophil Counts (x 10^3 c/µL) During the ST + LT Period
timeFrame: Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
measure: Changes From Baseline in Systolic Blood Pressure During the ST + LT Period
timeFrame: Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
measure: Changes From Baseline in Diastolic Blood Pressure During the ST + LT Period
timeFrame: Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
measure: Changes From Baseline in Heart Rate During the ST + LT Period
timeFrame: Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 30, 37, 50, 63, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206
measure: Electrocardiogram (ECG) Tracings - Shift Table From Baseline (BL) to Selected Visits During ST + LT Treatment Period
timeFrame: Baseline, Weeks 12, 24, 76, 102, 154, 206,
measure: All Reported Hypoglycemic Adverse Events During the ST + LT Treatment Period
timeFrame: AEs: up to last treatment day + 1 day or last visit day in the ST+LT period; SAEs: up to last treatment day + 30 days or last visit day + 30 days in the LT+ST period. Mean duration of exposure: 124, 118, 130, 95 wks respectively for 2.5mg, 5mg, 10 mg, pla
measure: Confirmed Hypoglycemia During the ST + LT Treatment Period
timeFrame: AEs: up to last treatment day + 1 day or last visit day in the ST+LT period; SAEs: up to last treatment day + 30 days or last visit day + 30 days in the LT+ST period. Mean duration of exposure: 124, 118, 130, 95 wks respectively for 2.5mg, 5mg, 10 mg, pla
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city: Chester
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city: Greensboro
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city: Morehead City
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city: Austin
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city: Bryan
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city: St. John's
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city: St. Johns
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city: Aylmer
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city: London
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city: Oakville
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state: Ontario
city: Sarnia
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state: Ontario
city: Thornhill
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state: Ontario
city: Toronto
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state: Ontario
city: Woodstock
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state: Ontario
city: Charlottetown
country: Canada
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state: Prince Edward Island
city: Drummondville
country: Canada
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state: Quebec
city: Fleurimont
country: Canada
facility: Local Institution
state: Quebec
city: Longueuil
country: Canada
facility: Local Institution
state: Quebec
city: St. Leonard
country: Canada
facility: Local Institution
state: Quebec
city: Saskatoon
country: Canada
facility: Local Institution
state: Saskatchewan
city: Santiago De Chile
country: Chile
facility: Local Institution
state: Metropolitana
city: Santiago
country: Chile
facility: Local Institution
state: Metropolitana
city: Celaya
country: Mexico
facility: Local Institution
state: Guanajuato
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Morelia
country: Mexico
facility: Local Institution
state: Michioacan
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Hermosillo
country: Mexico
facility: Local Institution
state: Sonora
city: Merida
country: Mexico
facility: Local Institution
state: Yucatan
city: Distrito Federal
country: Mexico
facility: Local Institution
city: Durango
country: Mexico
facility: Local Institution
city: Carolina
country: Puerto Rico
facility: Local Institution
city: Ponce
country: Puerto Rico
facility: Local Institution
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country: Puerto Rico
facility: Local Institution
city: San Juan
country: Puerto Rico
facility: Local Institution
city: Hualien
country: Taiwan
facility: Local Institution
city: Taichung
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
Study officials:
References:
citation: DeFronzo RA, Hissa MN, Garber AJ, Luiz Gross J, Yuyan Duan R, Ravichandran S, Chen RS; Saxagliptin 014 Study Group. The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone. Diabetes Care. 2009 Sep;32(9):1649-55. doi: 10.2337/dc08-1984. Epub 2009 May 28.
citation: Bailey CJ, Del Prato S, Wei C, Reyner D, Saraiva G. Durability of glycaemic control with dapagliflozin, an SGLT2 inhibitor, compared with saxagliptin, a DPP4 inhibitor, in patients with inadequately controlled type 2 diabetes. Diabetes Obes Metab. 2019 Nov;21(11):2564-2569. doi: 10.1111/dom.13841. Epub 2019 Aug 26.
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: Bonora E, Bryzinski B, Hirshberg B, Cook W. A post hoc analysis of saxagliptin efficacy and safety in patients with type 2 diabetes stratified by UKPDS 10-year cardiovascular risk score. Nutr Metab Cardiovasc Dis. 2016 May;26(5):374-9. doi: 10.1016/j.numecd.2015.11.004. Epub 2015 Dec 1.
citation: Rosenstock J, Gross JL, Aguilar-Salinas C, Hissa M, Berglind N, Ravichandran S, Fleming D. Long-term 4-year safety of saxagliptin in drug-naive and metformin-treated patients with Type 2 diabetes. Diabet Med. 2013 Dec;30(12):1472-6. doi: 10.1111/dme.12267. Epub 2013 Jul 19.
citation: Karyekar CS, Frederich R, Ravichandran S. Clinically relevant reductions in HbA1c without hypoglycaemia: results across four studies of saxagliptin. Int J Clin Pract. 2013 Aug;67(8):759-67. doi: 10.1111/ijcp.12212. Epub 2013 Jun 24.
citation: Karyekar C, Donovan M, Allen E, Fleming D, Ravichandran S, Chen R. Efficacy and safety of saxagliptin combination therapy in US patients with type 2 diabetes. Postgrad Med. 2011 Jul;123(4):63-70. doi: 10.3810/pgm.2011.07.2305.