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

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

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)

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus, CKD and Albuminuria
• Intervention / Treatment: Drug: Dapagliflozin 10 mg; Drug: Saxagliptin 2.5 mg; Drug: Matching Placebo for Dapagliflozin 10 mg and Saxagliptin 2.5mg

• Study Type: Interventional
• Enrollment (Actual): 459
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia, 3128
    • Research Site
  • Campbelltown, Australia, 2560
    • Research Site
  • Geelong, Australia, 3220
    • Research Site
  • Herston, Australia, 4029
    • Research Site
• Canada
  • Quebec, Canada, G2J 0C4
    • Research Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 3P4
      • Research Site
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1G 1A7
      • Research Site
  • Ontario
    • Ajax, Ontario, Canada, L1Z 0M1
      • Research Site
    • Cambridge, Ontario, Canada, N1R 6V6
      • Research Site
    • Scarborough, Ontario, Canada, M1H 3G4
      • Research Site
    • Scarborough, Ontario, Canada, M1R 3A6
      • Research Site
    • Toronto, Ontario, Canada, M5C 2T2
      • Research Site
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 7K9
      • Research Site
    • Saint-Jerome, Quebec, Canada, J7Z 5T3
      • Research Site
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Research Site
• Japan
  • Chuo-ku, Japan, 103-0028
    • Research Site
  • Chuo-ku, Japan, 103-0027
    • Research Site
  • Chuo-ku, Japan, 103-0002
    • Research Site
  • Hachioji-shi, Japan, 192-0071
    • Research Site
  • Higashiosaka-shi, Japan, 577-0803
    • Research Site
  • Kisarazu-shi, Japan, 292-0038
    • Research Site
  • Kyoto-shi, Japan, 615-8125
    • Research Site
  • Neyagawa-shi, Japan, 572-0015
    • Research Site
  • Nishinomiya-shi, Japan, 663-8113
    • Research Site
  • Oita-shi, Japan, 870-0039
    • Research Site
  • Osaka-shi, Japan, 530-0001
    • Research Site
  • Osaka-shi, Japan, 559-0012
    • Research Site
  • Sendai-shi, Japan, 980-0021
    • Research Site
  • Shinjuku-ku, Japan, 160-0008
    • Research Site
  • Toyonaka-shi, Japan, 560-0082
    • Research Site
• Korea, Republic of
  • Ansan-si, Korea, Republic of, 15355
    • Research Site
  • Busan, Korea, Republic of, 47392
    • Research Site
  • Cheongju-si, Korea, Republic of, 28644
    • Research Site
  • Daejeon, Korea, Republic of, 35015
    • Research Site
  • Seongnam-si, Korea, Republic of, 13620
    • Research Site
  • Seoul, Korea, Republic of, 03080
    • Research Site
  • Seoul, Korea, Republic of, 02841
    • Research Site
  • Seoul, Korea, Republic of, 06351
    • Research Site
  • Suwon-si, Korea, Republic of, 16499
    • Research Site
  • Wonju-si, Korea, Republic of, 26426
    • Research Site
• Mexico
  • Aguascalientes, Mexico, 20230
    • Research Site
  • Guadalajara, Mexico, 44670
    • Research Site
  • Guadalajara, Mexico, 44160
    • Research Site
  • Guadalajara, Mexico, 44600
    • Research Site
  • Mexico, Mexico, 03800
    • Research Site
  • Mexico, Mexico, 06726
    • Research Site
  • Monterey, Mexico, 64060
    • Research Site
  • Monterrey, Mexico, 64460
    • Research Site
  • Monterrey, Mexico, 64465
    • Research Site
  • México, Mexico, 03300
    • Research Site
  • Queretaro, Mexico, 76000
    • Research Site
  • Zapopan, Mexico, 45116
    • Research Site
  • Zapopan, Jalisco, Mexico, 45200
    • Research Site
• South Africa
  • Benoni, South Africa, 1501
    • Research Site
  • Cape Town, South Africa, 1730
    • Research Site
  • Cape Town, South Africa, 7925
    • Research Site
  • Durban, South Africa, 4092
    • Research Site
  • Kuilsrivier, South Africa, 7580
    • Research Site
  • Mamelodi East, South Africa, 0184
    • Research Site
  • Muckleneuk, South Africa, 0002
    • Research Site
  • Paarl, South Africa, 7646
    • Research Site
  • Pretoria, South Africa, 184
    • Research Site
• Spain
  • A Coruña, Spain, 15006
    • Research Site
  • Barcelona, Spain, 08035
    • Research Site
  • Madrid, Spain, 28046
    • Research Site
  • Sabadell (Barcelona), Spain, 08208
    • Research Site
  • Santiago(A Coruña), Spain, 15706
    • Research Site
  • Valencia, Spain, 46017
    • Research Site
• Taiwan
  • Changhua, Taiwan, 500
    • Research Site
  • Kaohsiung Hsien, Taiwan, 83342
    • Research Site
  • New Taipei, Taiwan
    • Research Site
  • New Taipei City, Taiwan, 23148
    • Research Site
  • Taichung, Taiwan, 40705
    • Research Site
  • Taipei City, Taiwan, 112
    • Research Site
  • Yong-Kang City, Taiwan, 71004
    • Research Site
• United States
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Research Site
  • California
    • Chula Vista, California, United States, 91910
      • Research Site
    • Concord, California, United States, 94520
      • Research Site
    • El Centro, California, United States, 92243
      • Research Site
    • La Mesa, California, United States, 92123
      • Research Site
    • Long Beach, California, United States, 90807
      • Research Site
    • Los Gatos, California, United States, 95032
      • Research Site
    • North Hollywood, California, United States, 91606
      • Research Site
    • Riverside, California, United States, 92505
      • Research Site
    • San Diego, California, United States, 92111
      • Research Site
    • San Dimas, California, United States, 91773
      • Research Site
  • Florida
    • Hollywood, Florida, United States, 33024
      • Research Site
    • Miami, Florida, United States, 33126
      • Research Site
    • New Port Richey, Florida, United States, 34652
      • Research Site
    • Palm Harbor, Florida, United States, 34684
      • Research Site
    • Pompano Beach, Florida, United States, 33060
      • Research Site
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Research Site
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60643
      • Research Site
  • Maine
    • Bangor, Maine, United States, 04401
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Research Site
  • New York
    • Bronx, New York, United States, 10459
      • Research Site
    • Springfield Gardens, New York, United States, 11413
      • Research Site
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • Research Site
    • Morehead City, North Carolina, United States, 28557
      • Research Site
    • Rocky Mount, North Carolina, United States, 27804
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Research Site
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Research Site
  • Texas
    • Brownsville, Texas, United States, 78520
      • Research Site
    • Cypress, Texas, United States, 77429
      • Research Site
    • Houston, Texas, United States, 77004
      • Research Site
    • San Antonio, Texas, United States, 78215
      • Research Site
    • Sugar Land, Texas, United States, 77479
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Research Site
  • Virginia
    • Burke, Virginia, United States, 22015
      • Research Site
    • Richmond, Virginia, United States, 23219
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Change From Baseline in Glycosylated Haemoglobin (HbA1c): Comparison of Dapagliflozin 10 mg Plus Saxagliptin 2.5 mg and Placebo at 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.	Baseline and Week 24
Adjusted Mean Percent Change From Baseline in Urine Albumin-to-Creatinine Ratio (UACR) at 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.	Baseline and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Percent Change From Baseline in Total Body Weight at 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.	Baseline and Week 24
Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at 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.	Baseline and Week 24
Percentage of Patients Achieving at Least 30% Reduction in UACR at 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]).	From baseline up to Week 24
Percentage of Patients Achieving a Reduction in HbA1c of Less Than 7.0% at 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.	From baseline to Week 24
Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure (SBP) at 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.	Baseline and Week 24
Adjusted Mean Change From Baseline in HbA1c: Comparison of Dapagliflozin 10 mg and Placebo at 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.	Baseline and Week 24

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• 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.

Helpful Links

• D1690c00023_CSP_Redacted
• D1690c00023_SAP_Redacted

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2015
• Primary Completion (Actual): May 18, 2018
• Study Completion (Actual): May 18, 2018

Study Registration Dates

• First Submitted: August 31, 2015
• First Submitted That Met QC Criteria: September 10, 2015
• First Posted (Estimate): September 14, 2015

Study Record Updates

• Last Update Posted (Actual): August 21, 2019
• Last Update Submitted That Met QC Criteria: August 7, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Urological Manifestations; Endocrine System Diseases; Urination Disorders; Proteinuria; Diabetes Mellitus; Diabetes Mellitus, Type 2; Albuminuria; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Dapagliflozin; Saxagliptin
• Other Study ID Numbers: D1690C00023