A Multi-Center, Randomized, Double-Blind, Phase III Trial to Evaluate the Safety and Efficacy of Saxagliptin Co-administered With Dapagliflozin Compared to Saxagliptin or Dapagliflozin All Given as add-on Therapy to Metformin in Subject With Type 2 Diabetes

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Multi-Center, Randomized, Double-Blind, Active-Controlled , Parallel Group, Phase III Trial to Evaluate the Safety and Efficacy of Saxagliptin 5mg Co-administered With Dapagliflozin 5mg Compared to Saxagliptin 5mg or Dapagliflozin 5mg All Given as Add-on Therapy to Metformin inPatients With Type 2 Diabetes Who Have Inadequate Glycaemic Control on Metformin Alone

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02681094
• Other study ID #: D1683C00005
• Status: Completed
• Phase: Phase 3
• Start date: February 26, 2016
• Est. completion date: July 15, 2017

Study information

• Verified date: September 2018
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to evaluate safety and efficacy of therapy with saxagliptin 5mg co-administered with dapagliflozin 5mg, compared to therapy with saxagliptin 5mg or dapagliflozin 5mg in patients who are inadequately controlled on ≥1500mg/day of metformin monotherapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 905
• Est. completion date: July 15, 2017
• Est. primary completion date: July 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

1. Patients aged =18 years old at time of informed consent;

2. Patients with Type 2 diabetes mellitus (T2DM) defined as HbA1C=7.5% to =10.0% at screening visit;

3. Stable metformin therapy for at least 8 weeks prior to enrolment at a dose of =1500mg per day;

4. BMI =45.0kg/m2 at Enrolment visit;

5. Fasting Plasma Glucose (FPG) = 270mg/dl(15.0mmol/L) at the enrolment visit;

6. For Females Only: Women of childbearing potential (WOCBP) must be using an acceptable method of contraception to avoid pregnancy throughout the study and for at least 4 weeks after the last dose of study medication in such a manner that the risk of pregnancy is minimized.

Exclusion Criteria:

1. History of diabetes insipidus, Type 1 diabetes or Latent Autoimmune Diabetes of Adults, diabetic ketoacidosis or hyperosmolar nonketotic coma and Symptoms of poorly controlled diabetes that would preclude participation in this trial including but not limited to marked polyuria and polydipsia with greater than 10% weight loss during the 3 months prior to Enrolment (Visit 1), or other signs and symptoms.

2. History of pancreatitis.

3. Administration of any antihyperglycaemic therapy, other than metformin, for more than 14 days (consecutive or not) during the 8 weeks prior to enrolment

4. Any use of DPP-4 inhibitor or SGLT-2 inhibitor within 8 weeks prior to enrolment.

5. Significant hepatic disease, including, but not limited to, chronic active hepatitis and/or severe hepatic insufficiency and/or significant abnormal liver function, including patients with Alanine transaminase (ALT) and/or Aspartate transaminase (AST) =3x ULN (Upper Limit of Normal)and/or Total Bilirubin =2.0x ULN. History of severe hepatobiliary disease or hepatotoxicity with any medication. Positive serologic evidence of current infectious liver disease, including patients who are known to be positive for Hepatitis viral antibody ImmunoglobulinM (IgM), Hepatitis B surface antigen, and Hepatitis C virus antibody.

6. Moderate or severe impairment of renal function [defined as Estimated Glomerular Filtration Rate (eGFR) <60milliLitre/min/1.73 m2 (estimated by Modification in Diet and Renal Disease (MDRD)) or serum creatinine =1.5mg/dL in males or =1.4mg/dL in females]. Conditions of congenital renal glucosuria, history of unstable or rapidly progressing renal disease.

7. History of any clinically significant disease or disorder which, in the opinion of the investigator, may put the patient at risk because of participation in the study, may influence the results, or may limit the patient's ability to participate in or complete the study.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Inadequate Glycaemic Control
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Dapagliflozin
5mg, orally, Green, plain, diamond-shaped, film-coated tablet
• Placebo for Dapagliflozin
Does not contain active ingredient, orally, Green, plain, diamond-shaped, film-coated tablet
• Saxagliptin
5mg, orally, Plain, yellow, biconvex, round, film-coated tablet
• Placebo for Saxagliptin
Does not contain active ingredient, orally, Plain, yellow, biconvex, round, film-coated tablet

Locations

Country	Name	City	State
Canada	Research Site	Brampton	Ontario
Canada	Research Site	Bridgewater	Nova Scotia
Canada	Research Site	Chicoutimi	Quebec
Canada	Research Site	Etobicoke	Ontario
Canada	Research Site	Levis	Quebec
Canada	Research Site	London	Ontario
Canada	Research Site	Mirabel	Quebec
Canada	Research Site	Moncton	New Brunswick
Canada	Research Site	Pointe-Claire	Quebec
Canada	Research Site	Saint-Marc-des-Carrieres	Quebec
Canada	Research Site	Scarborough	Ontario
Canada	Research Site	Sudbury	Ontario
Canada	Research Site	Toronto	Ontario
Czechia	Research Site	Ceske Budejovice
Czechia	Research Site	Chrudim III
Czechia	Research Site	Jilove u Prahy
Czechia	Research Site	Ostrava
Czechia	Research Site	Pardubice
Czechia	Research Site	Plzen
Czechia	Research Site	Praha - Klanovice
Czechia	Research Site	Praha 10
Czechia	Research Site	Praha 4
Czechia	Research Site	Praha 4
Czechia	Research Site	Praha 8
Czechia	Research Site	Uherske Hradiste
Germany	Research Site	Berlin
Germany	Research Site	Bünde
Germany	Research Site	Essen
Germany	Research Site	Giengen
Germany	Research Site	Grossheirath
Germany	Research Site	Hof
Germany	Research Site	Hohenmölsen
Germany	Research Site	Karlsruhe
Germany	Research Site	Lichtenfels
Germany	Research Site	Meine
Germany	Research Site	Münster
Germany	Research Site	Rehburg Loccum
Germany	Research Site	Stolberg
Germany	Research Site	Villingen-Schwenningen
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mexico
Mexico	Research Site	Monterrey
Mexico	Research Site	Monterrey
Mexico	Research Site	Zapopan
Russian Federation	Research Site	Arkhangelsk
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Rostov-on-Don
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	St.Petersburg
Russian Federation	Research Site	Tver
Russian Federation	Research Site	Ufa
Russian Federation	Research Site	Vladikavkaz
United States	Research Site	Albany	New York
United States	Research Site	Asheville	North Carolina
United States	Research Site	Biloxi	Mississippi
United States	Research Site	Bronx	New York
United States	Research Site	Buford	Georgia
United States	Research Site	Chicago	Illinois
United States	Research Site	Columbus	Ohio
United States	Research Site	Cooper City	Florida
United States	Research Site	Dallas	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Denver	Colorado
United States	Research Site	Doral	Florida
United States	Research Site	East Providence	Rhode Island
United States	Research Site	El Paso	Texas
United States	Research Site	Fargo	North Dakota
United States	Research Site	Florissant	Missouri
United States	Research Site	Fort Worth	Texas
United States	Research Site	Fresno	California
United States	Research Site	Harbor City	California
United States	Research Site	Hawaiian Gardens	California
United States	Research Site	Hazel Crest	Illinois
United States	Research Site	Hialeah	Florida
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Lancaster	California
United States	Research Site	Los Angeles	California
United States	Research Site	Maumee	Ohio
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami Lakes	Florida
United States	Research Site	Montclair	California
United States	Research Site	Mooresville	North Carolina
United States	Research Site	New Orleans	Louisiana
United States	Research Site	Norfolk	Virginia
United States	Research Site	Northglenn	Colorado
United States	Research Site	Odessa	Texas
United States	Research Site	Pomona	California
United States	Research Site	Salt Lake City	Utah
United States	Research Site	Saraland	Alabama
United States	Research Site	Spring Valley	California
United States	Research Site	Sugar Land	Texas
United States	Research Site	Vallejo	California
United States	Research Site	Waco	Texas
United States	Research Site	Waterbury	Connecticut
United States	Research Site	West Columbia	South Carolina
United States	Research Site	Wheat Ridge	Colorado
United States	Research Site	Zachary	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Germany,  Mexico,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in HbA1c at Week 24	To demonstrate the superiority of the change from baseline HbA1c achieved with the co-administered saxagliptin 5 mg and dapagliflozin 5 mg to either agent individually after 24 weeks. Results were presented for the modified full analysis set.; Note: Baseline was defined as the last assessment on or prior to the date of the first dose of the study medication.	Baseline and week 24
Secondary	Proportion of Participants Achieving HbA1c <7.0% at 24 Weeks	To demonstrate the effect of the co-administered saxagliptin 5 mg and dapagliflozin 5 mg to either agent individually on proportion of participants achieving therapeutic glycaemic response after 24 weeks. Therapeutic glycaemic response was defined as an HbA1c value at Week 24 <7.0% irrespective of whether participant received rescue medication. Risk difference for each treatment was calculated as adjusted response rate. Participants who did not had an HbA1c measurement at Week 24 were regarded as non-responders. Results were presented for the modified full analysis set.	Baseline and week 24
Secondary	Change in Fasting Plasma Glucose at 24 Weeks	To demonstrate the effect of the co-administered saxagliptin 5 mg and dapagliflozin 5mg to either agent individually on fasting plasma glucose after 24 weeks. Results were presented for the modified full analysis set.	Baseline and week 24
Secondary	Change in Total Body Weight at 24 Weeks	To demonstrate the effect of the co-administered saxagliptin 5 mg and dapagliflozin 5 mg to saxagliptin 5 mg on total body weight after 24 weeks. Results were presented for the modified full analysis set.	Baseline and week 24

External Links

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