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 is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by AstraZeneca
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02157298
First received: June 2, 2014
Last updated: September 11, 2014
Last verified: September 2014
  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:
  • Change in Haemoglobin A1c [ Time Frame: from baseline to 16 weeks ] [ Designated as safety issue: No ]
    To assess the efficacy of 16 weeks double blind treatment with 5 mg dapagliflozin compared to placebo as add-on therapy to insulin in improving glycemic control in subjects with Type 2 Diabetes, as determined by the change in Haemoglobin A1c levels from the baseline to Week 16.


Secondary Outcome Measures:
  • Change in Fasting Plasma Glucose [ Time Frame: from baseline 16 weeks ] [ Designated as safety issue: No ]
    To examine whether treatment with dapagliflozin in combination with insulin is superior in reducing Fasting Plasma Glucose after 16 weeks of double blind treatment as compared to placebo added to insulin treatment.

  • Change in body weight [ Time Frame: from baseline to 16 weeks ] [ Designated as safety issue: No ]
    To examine whether treatment with dapagliflozin in combination with insulin is superior in reducing body weight or causing less weight gain after 16 weeks of double blind treatment as compared to placebo added to insulin treatment.

  • Absolute change in calculated mean daily insulin dose [ Time Frame: from baseline to 16 weeks ] [ Designated as safety issue: No ]
    To examine whether treatment with dapagliflozin in combination with insulin leads to a lower absolute calculated mean daily insulin dose from baseline to week 16 as compared to placebo added to insulin treatment.

  • Proportion of subjects with calculated mean daily insulin dose reduction of at least 10% [ Time Frame: from baseline to 16 weeks ] [ Designated as safety issue: No ]
    To examine whether treatment with dapagliflozin in combination with insulin leads to higher percentage of patients with calculated mean daily insulin dose reduction from baseline to week 16 as compared to placebo added to insulin treatment.


Other Outcome Measures:
  • Change in Haemoglobin A1c by subgroup defined by baseline Haemoglobin A1c (< 7.5%, ≥ 7.5% and < 8.5%, ≥ 8.5%) and by baseline Body Mass Index(≥ 25 kg/m, ≥ 27 kg/m2) [ Time Frame: from baseline to 16 weeks ] [ Designated as safety issue: No ]
    Mean change in Haemoglobin A1c from baseline to week 16 in patients with baseline Haemoglobin A1c ≥ 8.5%, baseline Haemoglobin A1c ≥ 7.5% and < 8.5%, baseline Haemoglobin A1c < 7.5%, baseline Body Mass Index ≥ 25 kg/m2, and baseline Body Mass Index ≥ 27 kg/m2

  • Proportion of patients achieving a therapeutic glycemic response defined as Haemoglobin A1c < 7% [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
    Proportion of patients achieving a therapeutic glycemic response defined as Haemoglobin A1c< 7% at week 16

  • Change in 2h-Postprandial glucose(Self Monitoring of Blood Glucose) [ Time Frame: from baseline to 16 weeks ] [ Designated as safety issue: No ]
    Mean change in 2h-Postprandial glucose (Self Monitoring of Blood Glucose) from baseline to week 16 in all patients

  • Change in body weight by subgroup defined by baseline Body Mass Index (< 25 kg/m2, ≥ 25 kg/m2, ≥ 27 kg/m2) [ Time Frame: from baseline to 16 weeks ] [ Designated as safety issue: No ]
    Mean change in body weight from baseline to week 16 in patients with a baseline Body Mass Index< 25 kg/m2, ≥ 25 kg/m2, and ≥ 27 kg/m2

  • Change in waist circumference [ Time Frame: from baseline to 16 weeks ] [ Designated as safety issue: No ]
    Mean change in waist circumference from baseline to week 16

  • Change in seated systolic and diastolic blood pressure [ Time Frame: from baseline to 16 weeks ] [ Designated as safety issue: No ]
    To assess the change from baseline in seated systolic and diastolic blood pressure after 16 weeks of double-blind treatment

  • Changes in Haemoglobin A1c and Fasting Plasma Glucose (excluding data after insulin up-titration) [ Time Frame: from pre-titration to 16 weeks and 8 weeks, respectively, after up-titration, 52 weeks ] [ Designated as safety issue: No ]
    To examine whether uptitration of dapagliflozin 5 to 10 mg in combination with insulin brings about additional glycemic control in open extension phase

  • Proportion of subjects with further reduction of Haemoglobin A1c measured - overall, > 0% and ≤ 0.3%, > 0.3% and ≤ 0.5%, > 0.5% and ≤1.0%, greater than 1.0% reduction (excluding data after insulin up-titration) [ Time Frame: 16 weeks after up-titration, 52 weeks ] [ Designated as safety issue: No ]
    To examine whether uptitration of dapagliflozin 5 to 10 mg in combination with insulin brings about additional glycemic control in open extension phase

  • Proportion of subjects achieving Haemoglobin A1c of < 7.5% measured (excluding data after insulin up-titration) [ Time Frame: 16 weeks after up-titration , 52 weeks ] [ Designated as safety issue: No ]
    To examine whether uptitration of dapagliflozin 5 to 10 mg in combination with insulin brings about additional glycemic control in open extension phase

  • Proportion of subjects with Haemoglobin A1c of ≥ 7.5% before up-titration achieving Haemoglobin A1c of < 7.5% measured (excluding data after insulin up-titration) [ Time Frame: 16 weeks after up-titration, 52 weeks ] [ Designated as safety issue: No ]
    To examine whether uptitration of dapagliflozin 5 to 10 mg in combination with insulin brings about additional glycemic control in open extension phase

  • Proportion of subjects achieving Fasting Plasma Glucose of < 126 mg/dL measured (excluding data after insulin up-titration) [ Time Frame: 8 weeks after up-titration, 52 weeks ] [ Designated as safety issue: No ]
    To examine whether uptitration of dapagliflozin 5 to 10 mg in combination with insulin brings about additional glycemic control in open extension phase

  • Proportion of subjects with Fasting Plasma Glucose of ≥ 126 mg/dL before up-titration achieving Fasting Plasma Glucose of < 126 mg/dL measured (excluding data after insulin up-titration) [ Time Frame: 8 weeks after up-titration, 52 weeks ] [ Designated as safety issue: No ]
    To examine whether uptitration of dapagliflozin 5 to 10 mg in combination with insulin brings about additional glycemic control in open extension phase

  • Change in Haemoglobin A1c (including and excluding data after insulin up-titration during open-label treatment period) [ Time Frame: from baseline over time during the double blind and open-label treatment period, 52 weeks ] [ Designated as safety issue: No ]
    To assess the maintenance efficacy of 5 mg and 10 mg dapagliflozin plus insulin over 52 weeks of treatment.

  • Change in Fasting Plasma Glucose (including and excluding data after insulin up-titration during open-label treatment period) [ Time Frame: from baseline over time during the double blind and open-label treatment period, 52 weeks ] [ Designated as safety issue: No ]
    To assess the maintenance efficacy of 5 mg and 10 mg dapagliflozin plus insulin over 52 weeks of treatment.

  • Change in weight (including and excluding data after insulin up-titration during open-label treatment period) [ Time Frame: from baseline over time during the double blind and open-label treatment period, 52 weeks ] [ Designated as safety issue: No ]
    To assess the maintenance efficacy of 5 mg and 10 mg dapagliflozin plus insulin over 52 weeks of treatment.

  • Change in seated systolic Blood pressure and seated diastolic Blood pressure (including data after insulin up-titration during open-label treatment period) [ Time Frame: from baseline over time during the open-label treatment period, 52 weeks ] [ Designated as safety issue: No ]
    To assess the maintenance efficacy of 5 mg and 10 mg dapagliflozin plus insulin over 52 weeks of treatment.

  • Percent change in fasting lipids (Total Cholesterol, Low-Density Lipoprotein Cholesterol, High-Density Lipoprotein Cholesterol, Triglyceride and Free Fatty Acid) (including and excluding data after insulin up-titration during open-label treatment period) [ Time Frame: from baseline over time during the open-label treatment period until week 52 ] [ Designated as safety issue: No ]
    To assess the maintenance efficacy of 5 mg and 10 mg dapagliflozin plus insulin over 52 weeks of treatment.

  • Change in serum uric acid (including and excluding data after insulin up-titration during open-label treatment period) [ Time Frame: from baseline over time during the open-label treatment period until week 52 ] [ Designated as safety issue: No ]
    To assess the maintenance efficacy of 5 mg and 10 mg dapagliflozin plus insulin over 52 weeks of treatment.

  • Change in waist circumference(including and excluding data after insulin up-titration during open-label treatment period) [ Time Frame: from baseline over time during the open-label treatment period until week 52 ] [ Designated as safety issue: No ]
    To assess the maintenance efficacy of 5 mg and 10 mg dapagliflozin plus insulin over 52 weeks of treatment.

  • Change in mean daily insulin dose (including data after insulin up-titration during open-label treatment period) [ Time Frame: from baseline over time during the open-label treatment period until week 52 ] [ Designated as safety issue: No ]
    To assess the maintenance efficacy of 5 mg and 10 mg dapagliflozin plus insulin over 52 weeks of treatment.

  • Percent changes in fasting Total Cholesterol, fasting Low-Density Lipoprotein Cholesterol, fasting High-Density Lipoprotein Cholesterol, fasting Triglyceride, fasting Free Fatty Acid and glycoalbumin [ Time Frame: from baseline to 16 weeks ] [ Designated as safety issue: No ]
    To examine mean change in serum uric acid, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, free fatty acids and glycoalbumin from baseline to week 16

  • Change in serum uric acid [ Time Frame: from baseline to week 16 ] [ Designated as safety issue: No ]
    To examine mean change in serum uric acid, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, free fatty acids and glycoalbumin from baseline to week 16

  • Adverse events, laboratory values, electrocardiogram, pulse, blood pressure, hypoglycaemic events, estimated glomerular filtration rate, total albumin/creatinine ratio (mg/g) and physical examination findings [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
    To evaluate the safety and tolerability of 5 mg dapagliflozin as add-on therapy to insulin up to 16 weeks of double blind treatment.

  • Adverse events, laboratory values, electrocardiogram, pulse, blood pressure, hypoglycaemic events, estimated glomerular filtration rate, total albumin/creatinine ratio (mg/g) and physical examination findings [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    To assess the safety of 5 mg and 10 mg dapagliflozin plus insulin over 52 weeks of treatment.


Estimated Enrollment: 224
Study Start Date: June 2014
Estimated Study Completion Date: November 2015
Estimated 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 and older
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02157298

Contacts
Contact: Yuji Ageishi, Study Leader 81 3 6268 2740 ClinicalTrialTransparency@astrazeneca.com

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

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02157298     History of Changes
Other Study ID Numbers: D1692C00013
Study First Received: June 2, 2014
Last Updated: September 11, 2014
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
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Insulin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 28, 2014