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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

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ClinicalTrials.gov Identifier: NCT02547935
Recruitment Status : Completed
First Posted : September 14, 2015
Results First Posted : June 4, 2019
Last Update Posted : August 21, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE August 31, 2015
First Posted Date  ICMJE September 14, 2015
Results First Submitted Date  ICMJE May 15, 2019
Results First Posted Date  ICMJE June 4, 2019
Last Update Posted Date August 21, 2019
Actual Study Start Date  ICMJE September 21, 2015
Actual Primary Completion Date May 18, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2019)
  • Adjusted Mean Change From Baseline in Glycosylated Haemoglobin (HbA1c): Comparison of Dapagliflozin 10 mg Plus Saxagliptin 2.5 mg and Placebo at Week 24 [ Time Frame: Baseline and Week 24 ]
    HbA1c was analysed at baseline and every 4 weeks during the 24-week treatment period. Only measurements prior to rescue or treatment discontinuation were analysed. The adjusted mean change from baseline at Week 24 was analysed using a mixed model repeated measures (MMRM) model.
  • Adjusted Mean Percent Change From Baseline in Urine Albumin-to-Creatinine Ratio (UACR) at Week 24 [ Time Frame: Baseline and Week 24 ]
    UACR was analysed at baseline and every 4 weeks during the 24-week treatment period. All measurements regardless of rescue medication or treatment discontinuation were analysed. UACR values were first transformed to logarithms and the results were based on exponentiation of model estimates and expressed as adjusted mean percent change from baseline at Week 24.
Original Primary Outcome Measures  ICMJE
 (submitted: September 10, 2015)
  • Change from baseline in HbA1c at Week 24 (dapagliflozin 10 mg + saxagliptin 2.5 mg) [ Time Frame: 24 weeks of treatment ]
    To compare the mean change from baseline to week 24 in HbA1c between dapagliflozin 10 mg plus saxagliptin 2.5 mg and placebo
  • Percent change from baseline in Urine albumin to creatinine ratio (UACR) at Week 24 (dapagliflozin 10 mg + saxagliptin 2.5 mg) [ Time Frame: 24 weeks of treatment ]
    To compare the mean persent change from baseline to week 24 in Urine albumin to creatinine ratio (UACR) between dapagliflozin 10 mg plus saxagliptin 2.5 mg and placebo.
  • Percent change from baseline in Urine albumin to creatinine ratio (UACR) at Week 24 (dapagliflozin 10 mg) [ Time Frame: 24 weeks of treatment ]
    To compare the mean percent change from baseline to week 24 in Urine albumin to creatinine ratio (UACR)between dapagliflozin 10 mg and placebo
Change History Complete list of historical versions of study NCT02547935 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2019)
  • Adjusted Mean Percent Change From Baseline in Total Body Weight at Week 24 [ Time Frame: Baseline and Week 24 ]
    Total body weight was measured in kilograms (kg) at baseline and at Week 1 then every 4 weeks during the 24-week treatment period. All measurements regardless of rescue medication or treatment discontinuation were analysed. Total body weight values were first transformed to logarithms and the results were based on exponentiation of model estimates and expressed as adjusted mean percent change from baseline at Week 24.
  • Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 [ Time Frame: Baseline and Week 24 ]
    FPG was analysed at baseline and Week 1 then every 4 weeks during the 24-week treatment period. Only measurements prior to rescue or treatment discontinuation were analysed. The adjusted mean change from baseline at Week 24 was analysed using a MMRM model.
  • Percentage of Patients Achieving at Least 30% Reduction in UACR at Week 24 [ Time Frame: From baseline up to Week 24 ]
    The percentage of patients meeting the criteria of at least a 30% reduction in UACR, was analysed using a logistic regression model. If no measurement was available at Week 24 the last available post-baseline measurement was carried forward (Last Observation Carried Forward [LOCF]).
  • Percentage of Patients Achieving a Reduction in HbA1c of Less Than 7.0% at Week 24 [ Time Frame: From baseline to Week 24 ]
    The percentage of patients meeting the criteria of a less than 7% reduction in HbA1c, was analysed using a logistic regression model. If no measurement was available at Week 24 the last available post-baseline measurement was carried forward (LOCF). Only measurements prior to rescue or treatment discontinuation were analysed.
  • Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (SBP) at Week 24 [ Time Frame: Baseline and Week 24 ]
    Seated SBP was analysed at baseline, Week 1 and every 4 weeks during the 24-week treatment period. All measurements regardless of rescue medication or treatment discontinuation were analysed. The adjusted mean change from baseline at Week 24 was analysed using a MMRM model.
  • Adjusted Mean Change From Baseline in HbA1c: Comparison of Dapagliflozin 10 mg and Placebo at Week 24 [ Time Frame: Baseline and Week 24 ]
    HbA1c was analysed at baseline and every 4 weeks during the 24-week treatment period. Only measurements prior to rescue or treatment discontinuation were analysed. The adjusted mean change from baseline at Week 24 was analysed using a MMRM model.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2015)
  • Percent change from baseline in total body weight at Week 24 [ Time Frame: 24 weeks of treatment ]
    To compare the mean percent change from baseline in total body weight between dapagliflozin 10 mg with and, separately, without saxagliptin 2.5 mg and placebo.
  • Change from baseline in FPG at Week 24 [ Time Frame: 24 weeks of treatment ]
    To compare the mean change from baseline in fasting plasma glucose (FPG) between dapagliflozin 10 mg with and, separately, without saxagliptin 2.5 mg and placebo.
  • Proportion of patients that achieve 30% reduction in UACR [ Time Frame: 24 weeks of treatment ]
    To compare the proportion of patients achieving a 30% reduction in UACR between dapagliflozin 10 mg with and, separately, without saxagliptin 2.5 mg and placebo
  • Proportion of patients which achieve HbA1c<7% [ Time Frame: 24 weeks of treatment ]
    To compare the proportion of patients achieving a reduction in HbA1c <7.0% between dapagliflozin 10 mg with and, separately, without saxagliptin 2.5 mg and placebo
  • Change from baseline in seated SBP at Week 24 [ Time Frame: 24 weeks of treatment ]
    To compare the mean change from baseline in seated systolic blood pressure (SBP) between dapagliflozin 10 mg with and, separately, without saxagliptin 2.5 mg and placebo
  • Change from baseline in HbA1c at Week 24 [ Time Frame: 24 weeks of treatment ]
    To compare the mean change from baseline in HbA1c between dapagliflozin 10 mg and placebo
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Type 2 Diabetes Mellitus, CKD and Albuminuria
Intervention  ICMJE
  • Drug: Dapagliflozin 10 mg
    Tablets administered orally once daily for 24 weeks.
    Other Name: Forxiga™
  • Drug: Saxagliptin 2.5 mg
    Tablets administered orally once daily for 24 weeks.
    Other Name: Onglyza™
  • Drug: Matching Placebo for Dapagliflozin 10 mg and Saxagliptin 2.5mg
    Tablets administered orally once daily for 24 weeks.
Study Arms  ICMJE
  • Experimental: Dapagliflozin 10mg
    Tablets administered orally once daily for 24 weeks
    Intervention: Drug: Dapagliflozin 10 mg
  • Experimental: Dapagliflozin 10mg + Saxagliptin 2.5mg
    Tablets administered orally once daily for 24 weeks
    Intervention: Drug: Saxagliptin 2.5 mg
  • Placebo Comparator: Placebo
    Tablets administered orally once daily for 24 weeks
    Intervention: Drug: Matching Placebo for Dapagliflozin 10 mg and Saxagliptin 2.5mg
Publications * Pollock C, Stefánsson B, Reyner D, Rossing P, Sjöström 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 19, 2018)
459
Original Estimated Enrollment  ICMJE
 (submitted: September 10, 2015)
450
Actual Study Completion Date  ICMJE May 18, 2018
Actual Primary Completion Date May 18, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Mexico,   Australia,   Japan,   Korea, Republic of,   South Africa,   Spain,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02547935
Other Study ID Numbers  ICMJE D1690C00023
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP