A 52-week International, Multicenter Trial With a Long -Term Extension to Evaluate Saxagliptin With Dapagliflozin in Combination With Metformin Compared to Glimepiride in Combination With Metformin in Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone

Diabetes Clinical Trial

Official title:

A 52-week International, Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel Group, Phase 3bTrial With a Blinded 104-week Long -Term Extension Period to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin in Combination With Metformin Compared to Glimepiride in Combination With Metformin ≥1500 mg in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Therapy Alone

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02419612
• Other study ID #: CV181-365
• Status: Completed
• Phase: Phase 3
• Start date: August 14, 2015
• Est. completion date: September 18, 2019

Study information

• Verified date: June 2020
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clincial trial is evaluating if the co-administration of saxagliptin and dapagliflozin, in addition to metformin, results in better glycemic control, as measured by HbA1c, over a treatment period of 52 weeks, compared to the addition of glimepiride to metformin in subjects with Type 2 Diabetes Mellitus who have inadequate glycemic control on Metformin Alone. We will compare the change from baseline in HbA1c achieved with saxagliptin, in co-administration with dapagliflozin, added to current background therapy with metformin compared to glimepiride added to current background therapy with metformin ≥1500 mg at Week 52.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 444
• Est. completion date: September 18, 2019
• Est. primary completion date: August 29, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Subjects must be willing and able to give signed and dated written informed consent

• Patients with Type 2 diabetes mellitus (T2DM) with inadequate glycemic control

• Subjects should have been taking the same daily dose of metformin = 1500 mg

• Fasting Plasma Glucose = 270 mg/dL (=15 mmol/L)

• Males and females, aged =18 years old at time of screening visit

• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test

• WOCBP and males must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug

Exclusion Criteria:

• Clinical diagnosis of type I diabetes

• History of diabetic ketoacidosis

• Cardiovascular/vascular diseases within 3 months of the enrollment

• Renal disease

• Hepatic diseases

• History of, or currently, acute or chronic pancreatitis

• Hematological and oncological disease/conditions

• Patients who have contraindications to therapy being studied

• Patients on weight loss program(s)

• Replacement or chronic systemic corticosteroid therapy

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus

Intervention

Drug:
• Saxagliptin

• Dapagliflozin

• Glimepiride

Other:
• Placebo

Locations

Country	Name	City	State
Czechia	Research Site	Cheb
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Krnov
Czechia	Research Site	Kromeriz
Czechia	Research Site	Nachod
Czechia	Research Site	Praha 4
Czechia	Research Site	Praha 4
Germany	Research Site	Dresden
Germany	Research Site	Leipzig
Hungary	Research Site	Ajka
Hungary	Research Site	Balatonfüred
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Eger
Hungary	Research Site	Gyula
Hungary	Research Site	Kaposvár
Hungary	Research Site	Kecskemét
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Zalaegerszeg
Mexico	Research Site	Aguascalientes
Mexico	Research Site	Chihuahua
Mexico	Research Site	Cuautla
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guanajuato
Mexico	Research Site	Monterrey
Mexico	Research Site	Veracruz
Poland	Research Site	Bialystok
Poland	Research Site	Katowice
Poland	Research Site	Kraków
Poland	Research Site	Kraków
Poland	Research Site	Lódz
Poland	Research Site	Opole
Poland	Research Site	Oswiecim
Poland	Research Site	Poznan
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Romania	Research Site	Brasov
Romania	Research Site	Bucuresti
Romania	Research Site	Bucuresti
Romania	Research Site	Buzau
Romania	Research Site	Galati
Romania	Research Site	Oradea
Romania	Research Site	Oradea
Romania	Research Site	Ploiesti
Romania	Research Site	Ploiesti
Romania	Research Site	Satu-Mare
Romania	Research Site	Targu
Romania	Research Site	Timisoara
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Smolensk
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St.-Petersburg
Sweden	Research Site	Göteborg
Sweden	Research Site	Helsingborg
Sweden	Research Site	Rättvik
United Kingdom	Research Site	Dundee
United States	Research Site	Birmingham	Alabama
United States	Research Site	Bristol	Tennessee
United States	Research Site	Chandler	Arizona
United States	Research Site	Dallas	Texas
United States	Research Site	Edina	Minnesota
United States	Research Site	Greer	South Carolina
United States	Research Site	Huntington Park	California
United States	Research Site	Jacksonville	Florida
United States	Research Site	Jacksonville	Florida
United States	Research Site	Kissimmee	Florida
United States	Research Site	Knoxville	Tennessee
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Los Angeles	California
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	New Port Richey	Florida
United States	Research Site	Palm Harbor	Florida
United States	Research Site	Sacramento	California
United States	Research Site	San Antonio	Texas
United States	Research Site	Tarzana	California
United States	Research Site	Tempe	Arizona
United States	Research Site	Waterbury	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Czechia,  Germany,  Hungary,  Mexico,  Poland,  Romania,  Russian Federation,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Hemoglobin A1c (HbA1c) at Week 52	To examine whether the mean change from baseline in HbA1c with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin is superior to titrated glimepiride plus metformin after 52 weeks of double-blind treatment.	Baseline and Week 52
Secondary	Change From Baseline in Total Body Weight at Week 52	To examine whether the mean change from baseline in total body weight with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin is superior to titrated glimepiride plus metformin after 52 weeks of double-blind treatment.	Baseline and Week 52
Secondary	Percentage of Subjects Achieving a Therapeutic Glycemic Response, Defined as HbA1c < 7.0%, at Week 52	Therapeutic glycemic response was defined as HbA1c <7.0%. Subjects rescued or discontinued prior to, and subjects with missing measurements at Week 52 were treated as non-responders. The percentage of subjects with a therapeutic glycemic response is based on the logistic regression method with adjustment for baseline HbA1c.	At Week 52
Secondary	Change From Baseline in Systolic Blood Pressure (SBP) at Week 52	To examine whether the change from baseline in SBP with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin is superior to titrated glimepiride plus metformin after 52 weeks of double-blind treatment.	Baseline and Week 52
Secondary	Percentage of Subjects With Treatment Intensification During the 52-week Short-term Treatment Period	Treatment intensification was defined as the addition of insulin or other glucose-lowering agent for rescue therapy or discontinuation for lack of glycemic control. Time to treatment intensification was censored after the 52-week treatment period if treatment intensification had not occurred by then. Subjects rescued at Week 52 were counted as having an event for the analysis. The values presented are the percentage of subjects requiring the addition of insulin or other glucose-lowering agent for rescue therapy or discontinuation for lack of glycemic control during the 52-week short -term treatment period.	Up to Week 52
Secondary	Percentage of Subjects With Treatment Intensification During the 156-Week Short-term Plus Long-Term Treatment Period.	Treatment intensification was defined as the addition of insulin or other glucose-lowering agent for rescue therapy or discontinuation for lack of glycemic control. Time to treatment intensification was censored after 156-week treatment period if treatment intensification had not occurred by then. Subjects rescued at Week 156 were counted as having an event for the analysis. The values presented are the percentage of subjects requiring the addition of insulin or other glucose-lowering agent for rescue therapy or discontinuation for lack of glycemic control during the 156-week treatment period.	Up to Week 156
Secondary	Percentage of Subjects Achieving a Therapeutic Glycemic Response, Defined as HbA1c < 7.0%, at Week 156	Therapeutic glycemic response was defined as HbA1c <7.0%. Subjects rescued or discontinued prior to, and subjects with missing measurements at Week 156 were treated as non-responders. The percentage of subjects with a therapeutic glycemic response is based on the logistic regression method with adjustment for baseline HbA1c.	At Week 156
Secondary	Time to Treatment Intensification During the 156-Week Short-term Plus Long-Term Treatment Period.	Treatment intensification was defined as the addition of insulin or other glucose-lowering agent for rescue therapy or discontinuation for lack of glycemic control. Time to treatment intensification was censored after 156-week treatment period if treatment intensification had not occurred by then. Subjects rescued at Week 156 were counted as having an event for the analysis. Time to treatment intensification curves were generated using Kaplan-Meier estimates and compared using a Cox proportional hazards model.	Up to Week 156

External Links

•   CV181365_CSP_redacted
•   cv181365_SAP_redacted