Safety and Efficacy of Saxagliptin Plus Insulin With or Without Metformin

Type 2 Diabetes Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00757588
• Other study ID #: CV181-057
• Secondary ID: Eudract-2008-001
• Status: Completed
• Phase: Phase 3
• First received: September 22, 2008
• Last updated: May 8, 2015
• Start date: November 2008
• Est. completion date: April 2010

Study information

• Verified date: May 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationRussia: Ethics CommitteeIndia: Central Drugs Standard Control OrganizationPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Brazil: National Health Surveillance AgencySouth Africa: Medicines Control CouncilCanada: Canadian Institutes of Health Research
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 455
• Est. completion date: April 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 78 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Saxagliptin, 5 mg + insulin
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 + insulin
Placebo tablets given orally once daily for 24 weeks (short-term period)+ insulin with metformin

Locations

Country	Name	City	State
Canada	Local Institution	Bathurst	New Brunswick
Canada	Local Institution	Calgary	Alberta
Canada	Local Institution	Charlottetown	Prince Edward Island
Canada	Local Institution	Gatineau	Quebec
Canada	Local Institution	Laval	Quebec
Canada	Local Institution	London	Ontario
Canada	Local Institution	Regina	Saskatchewan
Canada	Local Institution	Sherbrooke	Quebec
Canada	Local Institution	Vancouver	British Columbia
France	Local Institution	Besancon Cedex
France	Local Institution	Montpellier Cedex 5
France	Local Institution	Nantes
France	Local Institution	Valenciennes
Hungary	Local Institution	Balatonfured
Hungary	Local Institution	Budapest
Hungary	Local Institution	Budapest
Hungary	Local Institution	Budapest
Hungary	Local Institution	Szentes
Hungary	Local Institution	Zalaegerszeg-Pozva
India	Local Institution	Hariyana
India	Local Institution	Indore	Madhya Pradesh
India	Local Institution	Mumbai
India	Local Institution	Pune
India	Local Institution	Pune
India	Local Institution	Pune
India	Local Institution	Vellore
Mexico	Local Institution	Aguascalientes
Mexico	Local Institution	Aguascalientes
Mexico	Local Institution	Ciudad De Mexico	Distrito Federal
Mexico	Local Institution	Mexico City
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	Monterrrey	Nuevo Leon
Mexico	Local Institution	Veracruz
Mexico	Local Institution	Zapopan, Jal.	Jalisco
Poland	Local Institution	Elblag
Poland	Local Institution	Gdansk
Poland	Local Institution	Krakow
Poland	Local Institution	Lodz
Poland	Local Institution	Lublin
Poland	Local Institution	Sopot
Poland	Local Institution	Szczecin
Poland	Local Institution	Wroclaw
Poland	Local Institution	Zabrze
Russian Federation	Local Institution	Kursk
Russian Federation	Local Institution	Saint-Petersburg
Russian Federation	Local Institution	Saratov
Russian Federation	Local Institution	Smolensk
Russian Federation	Local Institution	St Petersburg
Russian Federation	Local Institution	St. Petersburg
Russian Federation	Local Institution	St. Petersburg
Russian Federation	Local Institution	St.Petersburg
Russian Federation	Local Institution	Yaroslaval
South Africa	Local Institution	Durban	Kwa Zulu Natal
South Africa	Local Institution	Goodwood	Western Cape
South Africa	Local Institution	Parktown	Gauteng
South Africa	Local Institution	Tygerberg	Western Cape
South Africa	Local Institution	Umhlanga Rocks	Kwa Zulu Natal
United Kingdom	Local Institution	Birmingham	West Midlands
United Kingdom	Local Institution	Middlesborough	Cleveland
United Kingdom	Local Institution	Newcastle Upon Tyne	Tyne And Wear
United Kingdom	Local Institution	Salford	Greater Manchester
United Kingdom	Local Institution	Sheffield	Yorkshire
United States	Central Florida Clinical Trials, Inc.	Altamonte Springs	Florida
United States	Family Care Associates Of Nw Florida	Chipley	Florida
United States	Valley Research	Fresno	California
United States	Texas Center For Drug Development	Houston	Texas
United States	Torrance-Lomita Medical Center	Lomita	California
United States	Panhandle Family Care Assoc. & Coastal Palms Res. Grp Inc.	Marianna	Florida
United States	Aurora Advanced Healthcare	Milwaukee	Wisconsin
United States	Diabetes Medical Center Of California	Northridge	California
United States	Danny W. Jackson P.A.	Rolling Fork	Mississippi
United States	Endocrine Research Solutions, Inc.	Roswell	Georgia
United States	Dgd Research, Inc.	San Antonio	Texas
United States	Ritchken & First M.D.'S	San Diego	California
United States	Encompass Clinical Research	Spring Valley	California
United States	Southeastern Research Associates, Inc.	Taylors	South Carolina
United States	Clinical Research Advantage, Inc	Tempe	Arizona
United States	Southgate Medical Group	West Seneca	New York

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Canada,  France,  Hungary,  India,  Mexico,  Poland,  Russian Federation,  South Africa,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Abnormal Changes From Baseline in Electrocardiogram (ECG) Results	ECG abnormalities included those in nonspecific "other" categories (Other nonspecific ST/T, Other intraventricular conduction defect, Other, and Other rhythm abnormalities)and nonspecific findings, such as sinus bradycardia, sinus arrythmia, sinus tachycardia, poor R-wave progression, and ventricular premature contractions.	Baseline to Week 52	Yes
Other	Shift in Absolute Lymphocyte Counts From Baseline to Selected Visits (LOCF)	Absolute lymphocyte count=value*10^3 c/uL	Baseline and Weeks 24 and 52	Yes
Other	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	An AE is any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; requires inpatient hospitalization; or prolongs existing hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment.	Baseline to Week 52, continuously	Yes
Other	Mean Changes From Baseline in Systolic and Diastolic Blood Pressure Readings		Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 52	Yes
Other	Mean Changes From Baseline in Heart Rate		Baseline to Weeks 2, 4, 6, 8, 12, 16, 20, 24, 28, 36, 44, and 52	Yes
Other	Shift in Platelet Counts From Baseline to Selected Visits (LOCF)	Platelet count=value*10^9 c/L	Baseline and Weeks 24 and 52	Yes
Other	Number of Participants With Marked Laboratory Abnormalities During the 24-Week ST + 52-Week LT Treatment Period	Marked abnormality=a laboratory value lying outside the predefined criteria and more extreme (farther from the limit)on-treatment than at baseline. ULN=upper limit of normal; LLN=lower limit of normal; prx=pre-RX=pretreatment.; Criteria 1: if prx=0 use >=2, if prx=0.5 or 1 use >=3, if prx=2 use 4.	Baseline and during and up to 14 days after last dose of study drug (in Week 52)	Yes
Other	Percentage of Participants With Reported and Confirmed Hypoglycemia	Confirmed hypoglycemia=fingerstick glucose measurement of =50 mg/dL with associated symptoms/	Baseline to Week 52	Yes
Primary	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	No
Secondary	Change From Baseline in Postprandial Glucose (PPG) Area Under the Curve (AUC) Response to an Meal Tolerance Test (MTT)	An MTT is a 2-part test that measures glucose and insulin levels after an overnight fast and before ingesting a meal consisting of a nutritional drink and power bar and again at prespecified times (30, 60, 120, and 180 minutes) after the start of ingestion of the meal	Baseline to Week 24	No
Secondary	Change From Baseline in 120-minute PPG Values During an MTT	An MTT is a 2-part test that measures glucose and insulin levels after an overnight fast and before ingesting a meal consisting of a nutritional drink and power bar and again at prespecified times (30, 60, 120, and 180 minutes) after the start of ingestion of the meal.	Baseline to Week 24	No
Secondary	Change From Baseline in Fasting Plasma Glucose Values		Baseline to Week 24	No
Secondary	Percentage of Participants Achieving a Therapeutic Glycemic Response	Therapeutic glycemic response is defined as an A1C<7%. Significance was not interpreted with a p value.	Baseline to Week 24	No
Secondary	Change From Baseline in Mean Total Daily Dose of Insulin (MTDDI) (LOCF)	Based on information recorded in the participant's daily diary. The MTDDI was calculated at every visit using the values patients recorded since the last regularly scheduled visit (minimum of 80% of days with a value). At every visit, the MTDDI was compared with the participant's baseline MTDDI (measured during a 4-week lead-in period) to identify any changes in insulin use at that visit compared with insulin use at baseline.	Baseline to Week 24	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form