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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

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)

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus, CKD and Albuminuria Drug: Dapagliflozin 10 mg Drug: Saxagliptin 2.5 mg Drug: Matching Placebo for Dapagliflozin 10 mg and Saxagliptin 2.5mg Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 459 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : September 21, 2015
Actual Primary Completion Date : May 18, 2018
Actual Study Completion Date : May 18, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dapagliflozin 10mg
Tablets administered orally once daily for 24 weeks
Drug: Dapagliflozin 10 mg
Tablets administered orally once daily for 24 weeks.
Other Name: Forxiga™

Experimental: Dapagliflozin 10mg + Saxagliptin 2.5mg
Tablets administered orally once daily for 24 weeks
Drug: Saxagliptin 2.5 mg
Tablets administered orally once daily for 24 weeks.
Other Name: Onglyza™

Placebo Comparator: Placebo
Tablets administered orally once daily for 24 weeks
Drug: Matching Placebo for Dapagliflozin 10 mg and Saxagliptin 2.5mg
Tablets administered orally once daily for 24 weeks.




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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]).

  4. 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.

  5. 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.

  6. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02547935


  Show 112 Study Locations
Sponsors and Collaborators
AstraZeneca
  Study Documents (Full-Text)

Documents provided by AstraZeneca:
Study Protocol  [PDF] September 18, 2017
Statistical Analysis Plan  [PDF] June 5, 2018


Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02547935     History of Changes
Other Study ID Numbers: D1690C00023
First Posted: September 14, 2015    Key Record Dates
Results First Posted: June 4, 2019
Last Update Posted: August 21, 2019
Last Verified: July 2019
Additional relevant MeSH terms:
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Albuminuria
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Signs and Symptoms
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Saxagliptin
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors