Clinical trial NCT02681094: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Inadequate Glycaemic Control
Keywords: Diabetes Mellitus Type 2,
saxagliptin,
dapagliflozin,
metformin
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2016-02-12
Enrollment: 905
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in HbA1c at Week 24
timeFrame: Baseline and week 24
Secondary outcomes:
measure: Proportion of Participants Achieving HbA1c <7.0% at 24 Weeks
timeFrame: Baseline and week 24
measure: Change in Fasting Plasma Glucose at 24 Weeks
timeFrame: Baseline and week 24
measure: Change in Total Body Weight at 24 Weeks
timeFrame: Baseline and week 24
Other outcomes:
Locations:
city: Saraland
country: United States
facility: Research Site
state: Alabama
city: Fresno
country: United States
facility: Research Site
state: California
city: Harbor City
country: United States
facility: Research Site
state: California
city: Hawaiian Gardens
country: United States
facility: Research Site
state: California
city: Lancaster
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Montclair
country: United States
facility: Research Site
state: California
city: Pomona
country: United States
facility: Research Site
state: California
city: Spring Valley
country: United States
facility: Research Site
state: California
city: Vallejo
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Northglenn
country: United States
facility: Research Site
state: Colorado
city: Wheat Ridge
country: United States
facility: Research Site
state: Colorado
city: Waterbury
country: United States
facility: Research Site
state: Connecticut
city: Cooper City
country: United States
facility: Research Site
state: Florida
city: Doral
country: United States
facility: Research Site
state: Florida
city: Hialeah
country: United States
facility: Research Site
state: Florida
city: Miami Lakes
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
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state: Florida
city: Buford
country: United States
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state: Georgia
city: Chicago
country: United States
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state: Illinois
city: Hazel Crest
country: United States
facility: Research Site
state: Illinois
city: New Orleans
country: United States
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state: Louisiana
city: Zachary
country: United States
facility: Research Site
state: Louisiana
city: Biloxi
country: United States
facility: Research Site
state: Mississippi
city: Florissant
country: United States
facility: Research Site
state: Missouri
city: Albany
country: United States
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state: New York
city: Bronx
country: United States
facility: Research Site
state: New York
city: Asheville
country: United States
facility: Research Site
state: North Carolina
city: Mooresville
country: United States
facility: Research Site
state: North Carolina
city: Fargo
country: United States
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state: North Dakota
city: Columbus
country: United States
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state: Ohio
city: Maumee
country: United States
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state: Ohio
city: East Providence
country: United States
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state: Rhode Island
city: West Columbia
country: United States
facility: Research Site
state: South Carolina
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: El Paso
country: United States
facility: Research Site
state: Texas
city: Fort Worth
country: United States
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state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
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state: Texas
city: Houston
country: United States
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state: Texas
city: Odessa
country: United States
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state: Texas
city: Sugar Land
country: United States
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state: Texas
city: Waco
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state: Texas
city: Salt Lake City
country: United States
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state: Utah
city: Norfolk
country: United States
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state: Virginia
city: Moncton
country: Canada
facility: Research Site
state: New Brunswick
city: Bridgewater
country: Canada
facility: Research Site
state: Nova Scotia
city: Brampton
country: Canada
facility: Research Site
state: Ontario
city: Etobicoke
country: Canada
facility: Research Site
state: Ontario
city: London
country: Canada
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state: Ontario
city: Scarborough
country: Canada
facility: Research Site
state: Ontario
city: Sudbury
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
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state: Ontario
city: Chicoutimi
country: Canada
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state: Quebec
city: Levis
country: Canada
facility: Research Site
state: Quebec
city: Mirabel
country: Canada
facility: Research Site
state: Quebec
city: Pointe-Claire
country: Canada
facility: Research Site
state: Quebec
city: Saint-Marc-des-Carrieres
country: Canada
facility: Research Site
state: Quebec
city: Ceske Budejovice
country: Czechia
facility: Research Site
city: Chrudim III
country: Czechia
facility: Research Site
city: Jilove u Prahy
country: Czechia
facility: Research Site
city: Ostrava
country: Czechia
facility: Research Site
city: Pardubice
country: Czechia
facility: Research Site
city: Plzen
country: Czechia
facility: Research Site
city: Praha - Klanovice
country: Czechia
facility: Research Site
city: Praha 10
country: Czechia
facility: Research Site
city: Praha 4
country: Czechia
facility: Research Site
city: Praha 4
country: Czechia
facility: Research Site
city: Praha 8
country: Czechia
facility: Research Site
city: Uherske Hradiste
country: Czechia
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bünde
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Giengen
country: Germany
facility: Research Site
city: Grossheirath
country: Germany
facility: Research Site
city: Hof
country: Germany
facility: Research Site
city: Hohenmölsen
country: Germany
facility: Research Site
city: Karlsruhe
country: Germany
facility: Research Site
city: Lichtenfels
country: Germany
facility: Research Site
city: Meine
country: Germany
facility: Research Site
city: Münster
country: Germany
facility: Research Site
city: Rehburg Loccum
country: Germany
facility: Research Site
city: Stolberg
country: Germany
facility: Research Site
city: Villingen-Schwenningen
country: Germany
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Mexico
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: Zapopan
country: Mexico
facility: Research Site
city: Arkhangelsk
country: Russian Federation
facility: Research Site
city: Ekaterinburg
country: Russian Federation
facility: Research Site
city: Ekaterinburg
country: Russian Federation
facility: Research Site
city: Izhevsk
country: Russian Federation
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Perm
country: Russian Federation
facility: Research Site
city: Perm
country: Russian Federation
facility: Research Site
city: Rostov-on-Don
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: St.Petersburg
country: Russian Federation
facility: Research Site
city: Tver
country: Russian Federation
facility: Research Site
city: Ufa
country: Russian Federation
facility: Research Site
city: Vladikavkaz
country: Russian Federation
facility: Research Site
Study officials:
References: