Phase IV Study With a 36-week Extension Period to Evaluate the Efficacy and Safety of Dapagliflozin Therapy When Added to the Therapy of Japanese Patients With Type 2 Diabetes With Inadequate Glycemic Control on Insulin.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02157298
First received: June 2, 2014
Last updated: March 29, 2016
Last verified: March 2016
  Purpose
Japanese male and female patients with Type 2 Diabetes and aged ≥ 20 years old, with inadequate glycemic control on insulin defined as Haemoglobin A1c ≥ 7.2% and < 11% will be enrolled into the wash-out phase or directly into the lead-in phase depending on whether the patient has been receiving an Oral antidiabetic drug (including Glucagon-Like Peptide-1 agonists and excluding Thiazolidinedions) other than a Dipeptidyl Peptidase-4 inhibitor as part of the baseline treatment. Additional treatment with a concomitant Dipeptidyl Peptidase-4 inhibitor is allowed. And around 180 eligible patients in total will be randomized into the study with a 2:1 randomization scheme (i.e.120 patients into the dapagliflozin treatment group and 60 patients into the placebo treatment group. All subjects who completed a 16 weeks double-blind treatment period will shift to a 36 weeks open extension treatment period.

Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Dapagliflozin 5 mg
Drug: Placebo tablet
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 16-week Multicenter, Randomized, Parallel-group, Double-blind, Placebo-controlled Phase IV Study With a 36-week Extension Period to Evaluate the Efficacy and Safety of Dapagliflozin Therapy When Added to the Therapy of Japanese Patients With Type 2 Diabetes With Inadequate Glycemic Control on Insulin

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Adjusted Mean Change in HbA1c Levels [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    Mean change in HbA1c levels from baseline to Week 16 between dapagliflozin 5 mg versus placebo


Secondary Outcome Measures:
  • Fasting Plasma Glucose [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    Mean change in fasting plasma glucose from baseline to Week 16 between dapagliflozin 5 mg versus placebo

  • Total Body Weight [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    Mean change in total body weight from baseline to Week 16 between dapagliflozin 5 mg versus placebo

  • Total Mean Daily Insulin Dose [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    Mean change in calculated mean daily insulin dose from baseline to Week 16 between dapagliflozin 5 mg versus placebo

  • Proportion of Participants With Mean Daily Insulin Dose Reduction of Greater Than or Equal 10% [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    Proportion of participants with mean daily insulin dose reduction greater than or equal 10% from baseline to week 16 (LOCF) between dapagliflozin 5 mg versus placebo


Enrollment: 266
Study Start Date: June 2014
Study Completion Date: November 2015
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: dapagliflozin 5mg
dapagliflozin tablet 5mg
Drug: Dapagliflozin 5 mg
Dapagliflozin, a blood glucose lowering drug. Oral dose
Placebo Comparator: Placebo
dapagliflozin tablet 5mg placebo
Drug: Placebo tablet
Placebo tablet. Oral dose

  Eligibility

Ages Eligible for Study:   20 Years to 130 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provision of informed consent prior to any study specific procedures
  • Diagnosis of Type 2 Diabetes according the criteria specified by the Japan Diabetes Society
  • Japanese Men or women age ≥ 20 years at time of consenting.
  • Stable (unless adjustment is required based on Fasting Plasma Glucose values) dose insulin* mono-therapy with the mean insulin [up to two types of insulin within authorized indication in Japan] dose of ≥ 0.2 IU/kg/day AND ≥ 15 IU/body/day over the past 8 weeks prior to enrolment.
  • HbA1c ≥ 7.2% and < 11% from the blood samples collected at Visit 1 (enrolment) and Visit 3, observed from the central laboratory

Exclusion Criteria:

  • Diagnosis of Type 1 diabetes mellitus, known diagnosis of Maturity Onset Diabetes of the Young, secondary diabetes mellitus or diabetes insipidus
  • History of diabetic ketoacidosis.
  • Thyroid-stimulating hormone and free T4 values outside normal range, observed from the central laboratory; an abnormal Thyroid-stimulating hormone value needs to be followed up with a free T4 test. Patients with abnormal free T4 values will be excluded at Visit 1
  • Fasting Plasma Glucose >240 mg/dL (twice in a row) despite the permitted dose adjustment of insulin therapy during washout period and lead-in period.
  • Recent cardiovascular events in a patient.
  • eGFR <45 mL/min/1.73 m2 at Visit 3, observed from the central laboratory.
  • History of unstable or rapidly progressing renal disease.
  • History of unexplained microscopic or gross hematuria, or microscopic hematuria at Visit 1, confirmed by a follow-up sample at next scheduled visit, where according to the investigator a satisfactory evaluation of hematuria has not been conducted.
  • Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN, observed from the central laboratory at Visit 1.
  • Total bilirubin >2.0 mg/dL (34.2 μmol/L), observed from the central laboratory at Visit 1.
  • Positive serologic evidence of current infectious liver disease including Hepatitis A viral antibody IgM, Hepatitis B surface antigen and Hepatitis C virus antibody, observed from the central laboratory.
  • Haemoglobin <10 g/dL (<100 g/L) or 6.2 mmol/L for men; haemoglobin <9.0 g/dL (<90 g/L) or 5.9 mmol/L for women, observed from the central laboratory at Visit 1.
  • History of chronic haemolytic anaemia or haemoglobinopathies (for example, sickle cell anaemia, thalassemia, sideroblastic anaemia). Mild haemolysis due to artificial heart valves or due to sickle cell trait is not an exclusion criterion except when haemoglobin levels are too low (as defined in haemoglobin criteria above).
  • History of malignancy within the last 5 years prior to enrolment, excluding successful treatment of basal or squamous cell skin cancer.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT02157298

Locations
Japan
Research Site
Adachi-ku, Japan
Research Site
Chitose-shi, Japan
Research Site
Chiyoda-ku, Japan
Research Site
Chuo-ku, Japan
Research Site
Fukuoka-shi, Japan
Research Site
Hirosaki-shi, Japan
Research Site
Kamakura-shi, Japan
Research Site
Koriyama-shi, Japan
Research Site
Mitaka-shi, Japan
Research Site
Oita-Shi, Japan
Research Site
Osaka-shi, Japan
Research Site
Sendai-shi, Japan
Research Site
Shizuoka-shi, Japan
Research Site
Yokohama-shi, Japan
Sponsors and Collaborators
AstraZeneca
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02157298     History of Changes
Other Study ID Numbers: D1692C00013 
Study First Received: June 2, 2014
Results First Received: February 18, 2016
Last Updated: March 29, 2016
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by AstraZeneca:
Japanese patients with type 2 diabetes with inadequate glycemic control on insulin

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 29, 2016