Clinical trial NCT02547935: A Study to Evaluate the Effect of Dapagliflozin With and Without Saxagliptin on Albuminuria, and to Investigate the Effect of Dapagliflozin and Saxagliptin on HbA1c in Patients With Type 2 Diabetes and CKD
Official title: An Exploratory Phase II/III, Randomized, Double-blind, Placebo Controlled, Parallel Design Study to Evaluate the Efficacy, Safety and Pharmacodynamics of Dapagliflozin and Dapagliflozin in Combination With Saxagliptin in CKD Patients With Type 2 Diabetes Mellitus and Albuminuria Treated With ACEi or ARB
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Type 2 Diabetes Mellitus, CKD and Albuminuria
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2015-09-14
Enrollment: 459
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 purpose of this clinical research study is to determine whether dapagliflozin alone or in combination with saxagliptin can decrease albuminuria and improve glycemic control in patients with Type 2 diabetes, albuminuria and renal impairment (CKD). The study is planned to randomize a total of 450 patients (150 patients per treatment arm)


Eligibility criteria: Inclusion Criteria:

* Provision of informed consent prior to any study specific procedures
* Female or male aged ≥18 years
* History of type 2 diabetes mellitus for more than 12 months
* HbA1c≥7.0% and ≤11.0%
* Stable antidiabetic treatment during the last 12 weeks up to randomization
* eGFR 25-75 mL/minute/1.73m2, inclusive
* Micro or macroalbuminuria (UACR 30 - 3500 mg/g)
* Treatment with ACE inhibitor or an ARB for at least 3 months prior to screening
* Body mass index between 20 and 45 kg/m2

Exclusion Criteria:

* Any of the following CV/Vascular Diseases within 3 month prior to signing the consent at Visit 1:

  * Myocardial infarction
  * cardiac surgery or revascularization (CABG/PTCA)
  * unstable angina
  * unstable HF
  * New York Heart Association (NYHA) Class III-IV
  * transient ischemic attack (TIA) or significant cerebrovascular disease
  * unstable or previously undiagnosed arrhythmia
* Significant hepatic disease, including, but not limited to, chronic active hepatitis and/or severe hepatic insufficiency
* Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) \> 3X ULN
* Total Bilirubin (TB) \>2 mg/dL (34.2 μmol/L)
* History of acute kidney injury requiring renal replacement therapy (dialysis or ultrafiltration) or any biopsy or imaging verifying intercurrent kidney disease other than diabetic nephropathy or diabetic nephropathy with nephrosclerosis
* Ongoing treatment with a SGLT2 inhibitor, GLP-1 agonist or DPP4 inhibitors
* Any condition which, in the judgment of the Investigator, may render the patient unable to complete the study or which may pose a significant risk to the patient or patient suspected or with confirmed poor protocol or medication compliance

Primary outcomes:
measure: Adjusted Mean Change From Baseline in Glycosylated Haemoglobin (HbA1c): Comparison of Dapagliflozin 10 mg Plus Saxagliptin 2.5 mg and Placebo at Week 24
timeFrame: Baseline and Week 24
measure: Adjusted Mean Percent Change From Baseline in Urine Albumin-to-Creatinine Ratio (UACR) at Week 24
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Adjusted Mean Percent Change From Baseline in Total Body Weight at Week 24
timeFrame: Baseline and Week 24
measure: Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Patients Achieving at Least 30% Reduction in UACR at Week 24
timeFrame: From baseline up to Week 24
measure: Percentage of Patients Achieving a Reduction in HbA1c of Less Than 7.0% at Week 24
timeFrame: From baseline to Week 24
measure: Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (SBP) at Week 24
timeFrame: Baseline and Week 24
measure: Adjusted Mean Change From Baseline in HbA1c: Comparison of Dapagliflozin 10 mg and Placebo at Week 24
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Research Site
state: Arizona
city: Chula Vista
country: United States
facility: Research Site
state: California
city: Concord
country: United States
facility: Research Site
state: California
city: El Centro
country: United States
facility: Research Site
state: California
city: La Mesa
country: United States
facility: Research Site
state: California
city: Long Beach
country: United States
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state: California
city: Los Gatos
country: United States
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state: California
city: North Hollywood
country: United States
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state: California
city: Riverside
country: United States
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state: California
city: San Diego
country: United States
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state: California
city: San Dimas
country: United States
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state: California
city: Hollywood
country: United States
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state: Florida
city: Miami
country: United States
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state: Florida
city: New Port Richey
country: United States
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state: Florida
city: Palm Harbor
country: United States
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state: Florida
city: Pompano Beach
country: United States
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state: Florida
city: Augusta
country: United States
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state: Georgia
city: Meridian
country: United States
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state: Idaho
city: Chicago
country: United States
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state: Illinois
city: Bangor
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state: Maine
city: Kansas City
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state: Missouri
city: Las Vegas
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state: Nevada
city: Bronx
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state: New York
city: Springfield Gardens
country: United States
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state: New York
city: Greensboro
country: United States
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state: North Carolina
city: Morehead City
country: United States
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state: North Carolina
city: Rocky Mount
country: United States
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state: North Carolina
city: Philadelphia
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state: Pennsylvania
city: Greenville
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state: South Carolina
city: Brownsville
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state: Texas
city: Cypress
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state: Texas
city: Houston
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city: San Antonio
country: United States
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state: Texas
city: Sugar Land
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state: Texas
city: Salt Lake City
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state: Utah
city: Burke
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state: Virginia
city: Richmond
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state: Virginia
city: Box Hill
country: Australia
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city: Campbelltown
country: Australia
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city: Geelong
country: Australia
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city: Herston
country: Australia
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city: Winnipeg
country: Canada
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state: Manitoba
city: Moncton
country: Canada
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state: New Brunswick
city: Ajax
country: Canada
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state: Ontario
city: Cambridge
country: Canada
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state: Ontario
city: Scarborough
country: Canada
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state: Ontario
city: Scarborough
country: Canada
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state: Ontario
city: Toronto
country: Canada
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state: Ontario
city: Chicoutimi
country: Canada
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state: Quebec
city: Saint-Jerome
country: Canada
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state: Quebec
city: Sherbrooke
country: Canada
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state: Quebec
city: Quebec
country: Canada
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city: Chuo-ku
country: Japan
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city: Chuo-ku
country: Japan
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city: Chuo-ku
country: Japan
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city: Hachioji-shi
country: Japan
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city: Higashiosaka-shi
country: Japan
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city: Kisarazu-shi
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
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city: Neyagawa-shi
country: Japan
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city: Nishinomiya-shi
country: Japan
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city: Oita-shi
country: Japan
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city: Osaka-shi
country: Japan
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city: Osaka-shi
country: Japan
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city: Sendai-shi
country: Japan
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city: Shinjuku-ku
country: Japan
facility: Research Site
city: Toyonaka-shi
country: Japan
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city: Ansan-si
country: Korea, Republic of
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Daejeon
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Wonju-si
country: Korea, Republic of
facility: Research Site
city: Aguascalientes
country: Mexico
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: Mexico
country: Mexico
facility: Research Site
city: Monterey
country: Mexico
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city: Monterrey
country: Mexico
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city: Monterrey
country: Mexico
facility: Research Site
city: México
country: Mexico
facility: Research Site
city: Queretaro
country: Mexico
facility: Research Site
city: Zapopan, Jalisco
country: Mexico
facility: Research Site
city: Zapopan
country: Mexico
facility: Research Site
city: Benoni
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Durban
country: South Africa
facility: Research Site
city: Kuilsrivier
country: South Africa
facility: Research Site
city: Mamelodi East
country: South Africa
facility: Research Site
city: Muckleneuk
country: South Africa
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city: Paarl
country: South Africa
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city: Pretoria
country: South Africa
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city: A Coruña
country: Spain
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city: Barcelona
country: Spain
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city: Madrid
country: Spain
facility: Research Site
city: Sabadell (Barcelona)
country: Spain
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city: Santiago(A Coruña)
country: Spain
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city: Valencia
country: Spain
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city: Changhua
country: Taiwan
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city: Kaohsiung Hsien
country: Taiwan
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city: New Taipei City
country: Taiwan
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city: New Taipei
country: Taiwan
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city: Taichung
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Yong-Kang City
country: Taiwan
facility: Research Site
Study officials:
References:
citation: Pollock C, Stefansson B, Reyner D, Rossing P, Sjostrom CD, Wheeler DC, Langkilde AM, Heerspink HJL. Albuminuria-lowering effect of dapagliflozin alone and in combination with saxagliptin and effect of dapagliflozin and saxagliptin on glycaemic control in patients with type 2 diabetes and chronic kidney disease (DELIGHT): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2019 Jun;7(6):429-441. doi: 10.1016/S2213-8587(19)30086-5. Epub 2019 Apr 13.