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.

NCT02157298 | Completed Phase 4 Results

• 1 other identifier: D1692C00013
• Study Type: interventional
• Target: 266
• Locations: 1 country
• Sites: 14

Brief 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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Japanese patients with type 2 diabetes with inadequate glycemic control on insulin

Outcome Measures

Primary Outcomes (1)

• Adjusted Mean Change in HbA1c Levels

  Mean change in HbA1c levels from baseline to Week 16 between dapagliflozin 5 mg versus placebo

  Baseline to Week 16

Secondary Outcomes (4)

• Fasting Plasma Glucose

  Baseline to Week 16

• Total Body Weight

  Baseline to Week 16

• Total Mean Daily Insulin Dose

  Baseline to Week 16

• Proportion of Participants With Mean Daily Insulin Dose Reduction of Greater Than or Equal 10%

  Baseline to Week 16

Study Arms (2)

dapagliflozin 5mg

EXPERIMENTAL

dapagliflozin tablet 5mg

Drug: Dapagliflozin 5 mg

Placebo

PLACEBO COMPARATOR

dapagliflozin tablet 5mg placebo

Drug: Placebo tablet

Interventions

Dapagliflozin 5 mg DRUG

Dapagliflozin, a blood glucose lowering drug. Oral dose

dapagliflozin 5mg

Placebo tablet DRUG

Placebo tablet. Oral dose

Placebo

Eligibility Criteria

• Age: 20 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 malignancy within the last 5 years prior to enrolment, excluding successful treatment of basal or squamous cell skin cancer.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (14)

Research Site

Adachi-ku, Japan

Location

Research Site

Chitose-shi, Japan

Location

Research Site

Chiyoda-ku, Japan

Location

Research Site

Chūōku, Japan

Location

Research Site

Fukuoka, Japan

Location

Research Site

Hirosaki-shi, Japan

Location

Research Site

Kamakura-shi, Japan

Location

Research Site

Koriyama-shi, Japan

Location

Research Site

Mitaka-shi, Japan

Location

Research Site

Osaka, Japan

Location

Research Site

Ōita, Japan

Location

Research Site

Sendai, Japan

Location

Research Site

Shizuoka, Japan

Location

Research Site

Yokohama, Japan

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Limitations and Caveats

For HbA1c, FPG and TBW: excluding data after insulin up-titration and for Mean Daily Insulin Dose: including data after insulin up-titration were used. For participants who did not complete week 16 last observation carried forward (LOCF) was used.

Results Point of Contact

• Title: Yuji Ageishi
• Organization: AstraZeneca K.K.

Yuji.Ageishi@astrazeneca.com

+81-3-6268-2740

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2014
• First Posted: June 6, 2014
• Study Start: June 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: November 1, 2015
• Last Updated: May 11, 2016
• Results First Posted: March 17, 2016

Record last verified: 2016-03

Locations

JP (14)