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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00121667




Registration number
NCT00121667
Ethics application status
Date submitted
18/07/2005
Date registered
21/07/2005
Date last updated
29/04/2015

Titles & IDs
Public title
Study Assessing Saxagliptin Treatment In Type 2 Diabetic Subjects Who Are Not Controlled With Metformin Alone
Scientific 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"
Secondary ID [1] 0 0
CV181-014
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 2 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Saxagliptin + Metformin
Treatment: Drugs - Saxagliptin + Metformin
Treatment: Drugs - Saxagliptin + Metformin
Treatment: Drugs - Placebo + Metformin
Treatment: Drugs - Pioglitazone

Experimental: Saxagliptin + Metformin (A) - Pioglitazone 15-45 mg (as needed for rescue)

Experimental: Saxagliptin + Metformin (B) - Pioglitazone 15-45 mg (as needed for rescue)

Experimental: Saxagliptin + Metformin (C) - Pioglitazone 15-45 mg (as needed for rescue)

Placebo comparator: Placebo+ Metformin (D) - Pioglitazone 15-45 mg (as needed for rescue)


Treatment: Drugs: Saxagliptin + Metformin
Tablets, Oral, 2.5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT)

Treatment: Drugs: Saxagliptin + Metformin
Tablets, Oral, 5 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT)

Treatment: Drugs: Saxagliptin + Metformin
Tablets, Oral, 10 mg Saxagliptin (plus flexible metformin dose), Once daily (24 weeks ST, 42 months LT)

Treatment: Drugs: Placebo + Metformin
Tablets, Oral, 0 mg, Once daily (24 weeks ST, 42 months LT)

Treatment: Drugs: Pioglitazone
Tablets, Oral, 15 - 45 mg (as needed for rescue)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Baseline and Change From Baseline in Hemoglobin A1c (A1C) at Week 24
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [1] 0 0
Baseline and Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [2] 0 0
Percentage of Participants Achieving Therapeutic Glycemic Response (A1C < 7.0%) at Week 24
Timepoint [2] 0 0
Week 24
Secondary outcome [3] 0 0
Baseline and Change From Baseline at Week 24 in Postprandial Glucose (PPG) Area Under the Curve (AUC)
Timepoint [3] 0 0
Baseline, Week 24

Eligibility
Key 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
Minimum age
18 Years
Maximum age
77 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2010
Sample size
Target
Accrual to date
Final
1462
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
Local Institution - Sydney
Recruitment hospital [2] 0 0
Local Institution - Woollongong
Recruitment hospital [3] 0 0
Local Institution - Brisbane
Recruitment hospital [4] 0 0
Local Institution - Kippa Ring
Recruitment hospital [5] 0 0
Local Institution - Meadowbrook
Recruitment hospital [6] 0 0
Local Institution - Adelaide
Recruitment hospital [7] 0 0
Local Institution - Woodville South
Recruitment hospital [8] 0 0
Local Institution - Perth
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment postcode(s) [2] 0 0
- Woollongong
Recruitment postcode(s) [3] 0 0
- Brisbane
Recruitment postcode(s) [4] 0 0
- Kippa Ring
Recruitment postcode(s) [5] 0 0
- Meadowbrook
Recruitment postcode(s) [6] 0 0
- Adelaide
Recruitment postcode(s) [7] 0 0
- Woodville South
Recruitment postcode(s) [8] 0 0
- Perth
Recruitment outside Australia
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United States of America
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Alabama
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT00121667
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00121667