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A Multi-Center, Randomized, Double-Blind, Phase III Trial to Evaluate the Safety and Efficacy of Saxagliptin Co-administered With Dapagliflozin Compared to Saxagliptin or Dapagliflozin All Given as add-on Therapy to Metformin in Subject With Type 2 Diabetes

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ClinicalTrials.gov Identifier: NCT02681094
Recruitment Status : Completed
First Posted : February 12, 2016
Results First Posted : October 10, 2018
Last Update Posted : October 10, 2018
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
The aim of this study is to evaluate safety and efficacy of therapy with saxagliptin 5mg co-administered with dapagliflozin 5mg, compared to therapy with saxagliptin 5mg or dapagliflozin 5mg in patients who are inadequately controlled on ≥1500mg/day of metformin monotherapy.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Inadequate Glycaemic Control Drug: Dapagliflozin Drug: Placebo for Dapagliflozin Drug: Saxagliptin Drug: Placebo for Saxagliptin Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 905 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-Center, Randomized, Double-Blind, Active-Controlled , Parallel Group, Phase III Trial to Evaluate the Safety and Efficacy of Saxagliptin 5mg Co-administered With Dapagliflozin 5mg Compared to Saxagliptin 5mg or Dapagliflozin 5mg All Given as Add-on Therapy to Metformin inPatients With Type 2 Diabetes Who Have Inadequate Glycaemic Control on Metformin Alone
Actual Study Start Date : February 26, 2016
Actual Primary Completion Date : July 15, 2017
Actual Study Completion Date : July 15, 2017


Arm Intervention/treatment
Active Comparator: Saxagliptin+Dapagliflozin+Metformin
5 mg Tablets, Oral, Once daily, 24 weeks for Saxagliptin and Dapagliflozin
Drug: Dapagliflozin
5mg, orally, Green, plain, diamond-shaped, film-coated tablet
Other Name: Forxiga

Drug: Saxagliptin
5mg, orally, Plain, yellow, biconvex, round, film-coated tablet
Other Name: Onglyza™

Active Comparator: Dapagliflozin+Saxagliptin placebo+Metformin
5 mg Tablets, Oral, Once daily, 24 weeks for Dapagliflozin and Saxagliptin Placebo
Drug: Dapagliflozin
5mg, orally, Green, plain, diamond-shaped, film-coated tablet
Other Name: Forxiga

Drug: Placebo for Saxagliptin
Does not contain active ingredient, orally, Plain, yellow, biconvex, round, film-coated tablet

Active Comparator: Saxagliptin+Dapagliflozin placebo+metformin
5 mg Tablets, Oral, Once daily, 24 weeks for Saxagliptin and Dapagliflozin placebo
Drug: Placebo for Dapagliflozin
Does not contain active ingredient, orally, Green, plain, diamond-shaped, film-coated tablet

Drug: Saxagliptin
5mg, orally, Plain, yellow, biconvex, round, film-coated tablet
Other Name: Onglyza™




Primary Outcome Measures :
  1. Change From Baseline in HbA1c at Week 24 [ Time Frame: Baseline and week 24 ]

    To demonstrate the superiority of the change from baseline HbA1c achieved with the co-administered saxagliptin 5 mg and dapagliflozin 5 mg to either agent individually after 24 weeks. Results were presented for the modified full analysis set.

    Note: Baseline was defined as the last assessment on or prior to the date of the first dose of the study medication.



Secondary Outcome Measures :
  1. Proportion of Participants Achieving HbA1c <7.0% at 24 Weeks [ Time Frame: Baseline and week 24 ]
    To demonstrate the effect of the co-administered saxagliptin 5 mg and dapagliflozin 5 mg to either agent individually on proportion of participants achieving therapeutic glycaemic response after 24 weeks. Therapeutic glycaemic response was defined as an HbA1c value at Week 24 <7.0% irrespective of whether participant received rescue medication. Risk difference for each treatment was calculated as adjusted response rate. Participants who did not had an HbA1c measurement at Week 24 were regarded as non-responders. Results were presented for the modified full analysis set.

  2. Change in Fasting Plasma Glucose at 24 Weeks [ Time Frame: Baseline and week 24 ]
    To demonstrate the effect of the co-administered saxagliptin 5 mg and dapagliflozin 5mg to either agent individually on fasting plasma glucose after 24 weeks. Results were presented for the modified full analysis set.

  3. Change in Total Body Weight at 24 Weeks [ Time Frame: Baseline and week 24 ]
    To demonstrate the effect of the co-administered saxagliptin 5 mg and dapagliflozin 5 mg to saxagliptin 5 mg on total body weight after 24 weeks. Results were presented for the modified full analysis set.



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:

  1. Patients aged ≥18 years old at time of informed consent;
  2. Patients with Type 2 diabetes mellitus (T2DM) defined as HbA1C≥7.5% to ≤10.0% at screening visit;
  3. Stable metformin therapy for at least 8 weeks prior to enrolment at a dose of ≥1500mg per day;
  4. BMI ≤45.0kg/m2 at Enrolment visit;
  5. Fasting Plasma Glucose (FPG) ≤ 270mg/dl(15.0mmol/L) at the enrolment visit;
  6. For Females Only: Women of childbearing potential (WOCBP) must be using an acceptable method of contraception to avoid pregnancy throughout the study and for at least 4 weeks after the last dose of study medication in such a manner that the risk of pregnancy is minimized.

Exclusion Criteria:

  1. History of diabetes insipidus, Type 1 diabetes or Latent Autoimmune Diabetes of Adults, diabetic ketoacidosis or hyperosmolar nonketotic coma and Symptoms of poorly controlled diabetes that would preclude participation in this trial including but not limited to marked polyuria and polydipsia with greater than 10% weight loss during the 3 months prior to Enrolment (Visit 1), or other signs and symptoms.
  2. History of pancreatitis.
  3. Administration of any antihyperglycaemic therapy, other than metformin, for more than 14 days (consecutive or not) during the 8 weeks prior to enrolment
  4. Any use of DPP-4 inhibitor or SGLT-2 inhibitor within 8 weeks prior to enrolment.
  5. Significant hepatic disease, including, but not limited to, chronic active hepatitis and/or severe hepatic insufficiency and/or significant abnormal liver function, including patients with Alanine transaminase (ALT) and/or Aspartate transaminase (AST) ≥3x ULN (Upper Limit of Normal)and/or Total Bilirubin ≥2.0x ULN. History of severe hepatobiliary disease or hepatotoxicity with any medication. Positive serologic evidence of current infectious liver disease, including patients who are known to be positive for Hepatitis viral antibody ImmunoglobulinM (IgM), Hepatitis B surface antigen, and Hepatitis C virus antibody.
  6. Moderate or severe impairment of renal function [defined as Estimated Glomerular Filtration Rate (eGFR) <60milliLitre/min/1.73 m2 (estimated by Modification in Diet and Renal Disease (MDRD)) or serum creatinine ≥1.5mg/dL in males or ≥1.4mg/dL in females]. Conditions of congenital renal glucosuria, history of unstable or rapidly progressing renal disease.
  7. History of any clinically significant disease or disorder which, in the opinion of the investigator, may put the patient at risk because of participation in the study, may influence the results, or may limit the patient's ability to participate in or complete the study.

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): NCT02681094


  Show 110 Study Locations
Sponsors and Collaborators
AstraZeneca
  Study Documents (Full-Text)

Documents provided by AstraZeneca:
Study Protocol  [PDF] August 4, 2016
Statistical Analysis Plan  [PDF] August 9, 2017


Additional Information:
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02681094     History of Changes
Other Study ID Numbers: D1683C00005
First Posted: February 12, 2016    Key Record Dates
Results First Posted: October 10, 2018
Last Update Posted: October 10, 2018
Last Verified: September 2018
Keywords provided by AstraZeneca:
Diabetes Mellitus Type 2,
saxagliptin,
dapagliflozin,
metformin
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Saxagliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors