Overview

This trial is active, not recruiting.

Condition type 1 diabetes mellitus
Treatments dapagliflozin 5 mg, dapagliflozin 10mg
Phase phase 3
Sponsor AstraZeneca
Start date October 2015
End date October 2017
Trial size 170 participants
Trial identifier NCT02582814, D1695C00001

Summary

This study will enroll eligible subjects into a long-term safety study (Part B).

Japanese male and female patients with T1DM and age 18 to 75 years, with inadequate glycemic control on insulin defined as HbA1c ≥ 7.5% and ≤ 10.5% at screening visit. As a condition of enrollment, subjects must be on a total daily insulin dose of ≥ 0.3 U/kg/day for at least 3 months prior to the screening visit. The study design of Part B is a randomized, open-label, 2 arm, parallel-group design. 140 Japanese subjects in total will be randomized in a 1:1 ratio into one of the two treatment arms; dapagliflozin 5 mg or dapagliflozin 10 mg.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
dapagliflozin tablet 5mg
dapagliflozin 5 mg
Dapagliflozin, a blood glucose lowering drug. Oral dose
(Experimental)
dapagliflozin tablet 10mg
dapagliflozin 10mg
Dapagliflozin, a blood glucose lowering drug. Oral dose

Primary Outcomes

Measure
<Part B>Incidence of adverse event
time frame: from baseline to 52 weeks
<Part B>Physical examination
time frame: from baseline to 52 weeks
<Part B>Vital signs (blood pressure, heart rate)
time frame: from baseline to 52 weeks
<Part B>ECG
time frame: from baseline to 52 weeks
<Part B>Clinical laboratory measures, urine test results.
time frame: from baseline to 52 weeks

Secondary Outcomes

Measure
<Part B>Change from baseline in HbA1c
time frame: From baseline to 24 weeks
<Part B>Change from baseline in HbA1c
time frame: From baseline to 52 weeks
<Part B>Change from baseline in Glycoalbumin
time frame: From baseline to 24 weeks
<Part B>Change from baseline in Glycoalbumin
time frame: From baseline to 52 weeks
<Part B>Change from baseline in Average glucose values measured by 6-point Self monitored blood glucose (SMBG)
time frame: From baseline to 24 weeks
<Part B>Change from baseline in Average glucose values measured by 6-point SMBG
time frame: From baseline to 52 weeks
<Part B>Percent change from baseline in Total daily insulin dose
time frame: From baseline to 24 weeks
<Part B>Percent change from baseline in Total daily insulin dose
time frame: From baseline to 52 weeks
<Part B>Percent change from baseline in Body weight
time frame: From baseline to 24 weeks
<Part B>Percent change from baseline in Body weight
time frame: From baseline to 52 weeks
<Part B>Proportion of subjects with HbA1c reduction from baseline of at least 0.5% without severe hypoglycemia
time frame: From baseline to 24 weeks
<Part B>Proportion of subjects with HbA1c reduction from baseline of at least 0.5% without severe hypoglycemia
time frame: From baseline to 52 weeks
<Part B>Change from baseline in Seated SBP among subjects with hypertension at baseline seated Systolic blood pressure (SBP) ≥ 140 mmHg and/or seated Diastolic blood pressure (DBP) ≥ 90 mmHg
time frame: From baseline to 24 weeks
<Part B>Change from baseline in Seated SBP among subjects with hypertension at baseline seated SBP ≥ 140 mmHg and/or seated DBP ≥ 90 mmHg
time frame: From baseline to 52 weeks
<Part B>Proportion of subjects with HbA1c reduction from baseline of at least 0.5%
time frame: From baseline to 24 weeks
<Part B>Proportion of subjects with HbA1c reduction from baseline of at least 0.5%
time frame: From baseline to 52 weeks
<Part B>Proportion of subjects with HbA1c < 7.0%
time frame: From baseline to 24 weeks
<Part B>Proportion of subjects with HbA1c < 7.0%
time frame: From baseline to 52 weeks

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

Inclusion Criteria: - Signed Written Informed Consent Subjects or their legally responsible representatives must be willing and able to give signed and dated written informed consent. - Target Population Diagnosis of T1DM. In addition, the following criteria also needs to be met; Central laboratory test of C-peptide < 0.7 ng/mL - Insulin use for at least 12 months prior to the enrolment per subject report or medical records and Method of insulin administration (MDI or CSII) must have been unchanged for at least 3 months prior to the enrolment per subject report or medical records. Subjects must be taking a total daily insulin dose of ≥ 0.3 U/kg/day for at least 3 months prior to the enrolment. If on MDI insulin administration subject must be on ≥ 3x injections per day. - Gender and reproductive Status Japanese men and women. - HbA1c eligibility criteria include: Screening Visit: Central laboratory HbA1c ≥ 7.5% and ≤ 10.5% (One repeat HbA1c test for subjects in screening if their initial test result was an HbA1c ± 0.2% of the cut off values) - BMI ≥ 20.0 kg/m² at visit 1 - Age 18 to 75 years, inclusive - ≥ 18 years old and < 20 years old must have assent forms signed and dated by their parents or guardians Exclusion Criteria: - Target Disease Exceptions History of Type 2 diabetes mellitus (T2DM) In cases where the subject has a history of T2DM and has a documented history of being auto-antibody positive for GAD65, tyrosine phosphatase IA-2/IA-2β, or Zinc Transporter 8 (ZnT8), or fasting c-peptide value below the lower limit of detection performed by local or central laboratory, the subject will be eligible for screening - Maturity onset diabetes of young (MODY) - Pancreatic surgery, chronic pancreatitis, or other pancreatic disorders that could result in decreased β-cell capacity (eg, pancreatogenous diabetes) - Any anti-hyperglycemic agent use, other than α-GI or insulin, within 1 month prior to the enrolment. α-GI users at the enrolment or within 1 month prior to the enrolment are permitted to enter this study, if subjects can conduct wash-out of the drug. Use of thiazolidinediones within 6 months prior to the enrolment - History of Diabetic Ketoacidosis (DKA) requiring medical intervention (eg, emergency room visit and/or hospitalization) within 1 month prior to the enrolment - History of hospital admission for glycemic control (either hyperglycemia or hypoglycemia) within 1 month prior to the enrolment - Malignancy within 5 years of the enrolment (with the exception of treated basal cell or treated squamous cell carcinoma) - History of bladder cancer - History of radiation therapy to the lower abdomen or pelvis at any time - Physical and Laboratory Test Findings Aspartate aminotransferase (AST) > 3x upper limit of normal (ULN) Alanine aminotransferase (ALT) > 3x ULN Serum total bilirubin (TB) > 2.0 mg/dL (34.2 µmol/L) Estimated GFR (eGFR) by the Japanese Society of Nephrology formula ≤ 45 mL/min/1.73m2 Hemoglobin ≤ 11.0 g/dL (110 g/L) for men; hemoglobin ≤ 10.0 g/dL (100 g/L) for women. Positive for hepatitis B surface antigen or anti-hepatitis C virus antibody Abnormal Free T4

Additional Information

Official title A Clinical Pharmacology and Long Term Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Dapagliflozin Therapy in Combination With Insulin in Japanese Subjects With Type 1 Diabetes Who Have Inadequate Glycemic Control
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by AstraZeneca.