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

August 7, 2019 updated by: AstraZeneca

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
459

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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
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.
Baseline and Week 24
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.
Baseline and Week 24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Baseline and 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.
Baseline and Week 24
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]).
From baseline up to Week 24
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.
From baseline to Week 24
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.
Baseline and Week 24
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.
Baseline and Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AstraZeneca

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 21, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 18, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 18, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 31, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 10, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 14, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 21, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 7, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • D1690C00023

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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