Clinical trial NCT00885378: Efficacy and Safety Study of Saxagliptin + Metformin Immediate Release (IR) Versus Metformin IR Alone in Type 2 Diabetes Mellitus
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 3 Trial to Evaluate the Efficacy and Safety of 2.5 mg Saxagliptin, Twice Daily, in Combination With Metformin IR in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin IR Alone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2009-04-22
Enrollment: 166
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 reduction in hemoglobin A1C (A1C) for participants taking saxagliptin in combination with metformin immediate release (IR) versus metformin IR alone.


Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes
* 18-78 years of age
* Taking stable twice daily (BID) dosing of metformin IR (at least 1500 mg) for at least 8 weeks
* A1C: 7-10%
* C-peptide: ≥ 0.8 ng/mL
* Body mass index (BMI): ≤45 kg/m\^2

Exclusion Criteria:

* Women of childbearing potential unable or unwilling to use acceptable birth control
* Women who are pregnant or breastfeeding
* Fasting plasma glucose (FPG) \>270 mg/dL
* Significant cardiovascular history
* Symptoms of poorly controlled diabetes
* History of diabetic ketoacidosis or hyperosmolar nonketotic coma
* Insulin therapy within one year of screening
* Cardiovascular even within the prior 6 months
* New York Heart Association Stage III/IV congestive heart failure and/or known left ventricular ejection fraction \<=40%
* Significant history of renal or hepatic disease
* History of a psychiatric disorder, alcohol or drug abuse within the previous year
* Treatment with potent CYP3A4 inhibitors or inducers
* Immunocompromised participants
* Active liver disease or clinically significant abnormal hepatic, renal , endocrine, metabolic, or hematological screening tests

Primary outcomes:
measure: Mean Hemoglobin A1C (A1c) and Change From Baseline to Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Mean Baseline and Change From Baseline in Fasting Plasma Glucose (FPG)
timeFrame: Baseline, Week 12
measure: Percentage of Participants Achieving a Therapeutic Glycemic Response (A1C < 7.0%) at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving a Therapeutic Glycemic Response (A1C <= 6.5%) at Week 12
timeFrame: Week 12
Other outcomes:
measure: Participant Adverse Event (AE), Related AE, Serious Adverse Event (SAE), Related SAE, and Discontinued Due to AEs Summary
timeFrame: Week 1 to Week 12; AEs are included up to the last treatment day + 1 day or the last visit in the double-blind (DB) period. SAEs are included up to the last of 1) the last treatment day + 30 days or 2) the last visit day + 30 days in the DB period.
measure: Participants With Reported Hypoglycemia AEs During Double-Blind Treatment Period
timeFrame: Week 1 to Week 12; AEs are included up to the last treatment day + 1 day or the last visit in the DB period. SAEs are included up to the last of 1) the last treatment day + 30 days or 2) the last visit day + 30 days in the DB period.
measure: Participants With Confirmed Hypoglycemia
timeFrame: Week 1 to Week 12; AEs are included up to the last treatment day + 1 day or the last visit in the DB period. SAEs are included up to the last of 1) the last treatment day + 30 days or 2) the last visit day + 30 days in the DB period.
measure: Participant Electrocardiogram (ECG) Status at Baseline and Week 12
timeFrame: Baseline, Week 12
measure: Baseline and Mean Change From Baseline in Participant Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: Baseline, Week 4, Week 8, Week 12
measure: Baseline and Mean Change From Baseline in Participant Heart Rate (HR)
timeFrame: Baseline, Week 4, Week 8, Week 12
measure: Participants Experiencing Changes From Baseline in Laboratory Parameters That Met the Marked Abnormality Criteria
timeFrame: Baseline, Week 12
measure: Participants Experiencing Changes From Baseline in Urinalysis Parameters That Met the Marked Abnormality Criteria
timeFrame: Baseline, Week 12
Locations:
city: Concord
country: United States
facility: John Muir Physician Network Clinical Research Center
state: California
city: Fountain Valley
country: United States
facility: Southland Clinical Research Center, Inc.
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research
state: California
city: San Diego
country: United States
facility: Ritchken & First M.D.'S
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: Coral Gables
country: United States
facility: Clinical Therapeutics Corporation
state: Florida
city: Miami
country: United States
facility: Nextphase Clinical Trials, Inc.
state: Florida
city: Perry
country: United States
facility: Middle Georgia Drug Study Center, Llc
state: Georgia
city: Slidell
country: United States
facility: Louisiana Heart Center Research
state: Louisiana
city: Rolling Fork
country: United States
facility: Jackson Clinic
state: Mississippi
city: Akron
country: United States
facility: Community Health Care Of Manchester
state: Ohio
city: Bellbrook
country: United States
facility: Midwest Regional Research, Inc.
state: Ohio
city: Kettering
country: United States
facility: Wells Institute For Health Awareness
state: Ohio
city: Newark
country: United States
facility: Newark Physician Associates
state: Ohio
city: Oklahoma
country: United States
facility: Integris Family Care South
state: Oklahoma
city: Yukon
country: United States
facility: Integris Family Care Yukon
state: Oklahoma
city: Eugene
country: United States
facility: Williamette Valley Clinical Studies
state: Oregon
city: Fleetwood
country: United States
facility: Integrated Medical Group Pc/Fleetwood Clinical Research
state: Pennsylvania
city: Taylors
country: United States
facility: Southeastern Research Associates, Inc
state: South Carolina
city: Kingsport
country: United States
facility: Holston Medical Group
state: Tennessee
city: Houston
country: United States
facility: Village Family Practice
state: Texas
city: Pearland
country: United States
facility: Southwest Clinical Research Centers, Llc
state: Texas
city: San Antonio
country: United States
facility: Jolene K. Berg, Md., Dgd Research, Inc.
state: Texas
city: Virginia Beach
country: United States
facility: Tidewater Integrated Medical Research
state: Virginia
city: Ludwigshafen
country: Germany
facility: Local Institution
city: Magdeberg
country: Germany
facility: Local Institution
city: Pirna
country: Germany
facility: Local Institution
city: Saarbrucken
country: Germany
facility: Local Institution
city: Saarlouis
country: Germany
facility: Local Institution
city: Tann
country: Germany
facility: Local Institution
city: Wuestensachsen
country: Germany
facility: Local Institution
city: Balatonfured
country: Hungary
facility: Local Institution
city: Budapest
country: Hungary
facility: Local Institution
city: Eger
country: Hungary
facility: Local Institution
city: Szigetvar
country: Hungary
facility: Local Institution
city: Zalaegerszeg
country: Hungary
facility: Local Institution
city: Ponce
country: Puerto Rico
facility: Local Institution
city: San Juan
country: Puerto Rico
facility: Local Institution
city: San Juan
country: Puerto Rico
facility: Local Institution
city: San Juan
country: Puerto Rico
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: White JL, Buchanan P, Li J, Frederich R. A randomized controlled trial of the efficacy and safety of twice-daily saxagliptin plus metformin combination therapy in patients with type 2 diabetes and inadequate glycemic control on metformin monotherapy. BMC Endocr Disord. 2014 Feb 24;14:17. doi: 10.1186/1472-6823-14-17.