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.

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02157298
• Other study ID #: D1692C00013
• Status: Completed
• Phase: Phase 4
• First received: June 2, 2014
• Last updated: February 18, 2016
• Start date: June 2014
• Est. completion date: November 2015

Study information

• Verified date: February 2016
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 266
• Est. completion date: November 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 130 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Dapagliflozin 5 mg
Dapagliflozin, a blood glucose lowering drug. Oral dose
• Placebo tablet
Placebo tablet. Oral dose

Locations

Country	Name	City	State
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

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adjusted Mean Change in HbA1c Levels	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.	Baseline to Week 16	No
Secondary	Fasting Plasma Glucose	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.	Baseline to Week 16	No
Secondary	Total Body Weight	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	Baseline to Week 16	No
Secondary	Total Mean Daily Insulin Dose	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.	Baseline to Week 16	No
Secondary	Porportion of Participants With Mean Daily Insulin Dose Reduction of Greater Than or Equal 10%	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 (LOCF) as compared to placebo added to insulin treatment.	Baseline to Week 16	No