Clinical trial NCT02582814: The Safety and Efficacy of Dapagliflozin Therapy in Combination With Insulin in Japanese Subjects With T1DM
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 1 Diabetes Mellitus
Keywords: Japanese patients with type 1 diabetes with inadequate glycemic control on insulin
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2015-10-21
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

* Signed Written Informed Consent
* 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.
* Japanese men and women
* Screening Visit: Central laboratory HbA1c ≥ 7.5% and ≤ 10.5%
* BMI ≥ 20.0 kg/m² at visit 1
* Age 18 to 75 years, inclusive

Exclusion Criteria:

- Target Disease Exceptions History of T2DM Maturity onset diabetes of young (MODY) Any anti-hyperglycemic agent use, other than α-GI or insulin, within 1 month prior to the enrolment.

Use of thiazolidinediones within 6 months prior to the enrolment History of DKA requiring medical intervention 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

* Medical History and Concurrent Diseases 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

Primary outcomes:
measure: Overall Adverse Event Summary
timeFrame: From baseline to 52 weeks
measure: Hypoglycemia
timeFrame: From baseline to 52 weeks
measure: Diabetic Ketoacidosis (DKA)
timeFrame: From baseline to 52 weeks
measure: Vital Signs (Heart Rate)
timeFrame: From baseline to 52 weeks
measure: ECGs
timeFrame: From baseline to 52 weeks
measure: Clinical Laboratory Measures, Urine Test Results (Any Marked Abnormality)
timeFrame: From baseline to 52 weeks
measure: Vital Signs (Blood Pressure)
timeFrame: From baseline to 52 weeks
Secondary outcomes:
measure: Adjusted Change From Baseline in HbA1c
timeFrame: From baseline to 24/52 weeks
measure: Adjusted Percent Change From Baseline in Total Daily Insulin Dose
timeFrame: From baseline to 24/52 weeks
measure: Adjusted Percent Change From Baseline in Body Weight
timeFrame: From baseline to 24/52 weeks
measure: Adjusted Change From Baseline in Glycoalbumin
timeFrame: From baseline to 24/52 weeks
measure: Adjusted Change From Baseline in Average Daily Glucose Measured by 6-point SMBG
timeFrame: From baseline to 24/52 weeks
measure: Adjusted Change From Baseline in Post-prandial Glucose Measured by 6-point SMBG
timeFrame: From baseline to 24/52 weeks
measure: Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent Without Severe Hypoglycemia
timeFrame: From baseline to 24/52 weeks
measure: Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent
timeFrame: From baseline to 24/52 weeks
measure: Proportion of Subjects Achieving HbA1c < 7.0 Percent
timeFrame: From baseline to 24/52 weeks
measure: Adjusted Change From Baseline in SBP in Subjects With Baseline SBP/DBP >= 140/90 mmHg
timeFrame: From baseline to 24/52 weeks
Other outcomes:
Locations:
city: Aizu Wakamatsu-shi
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Fukuyama-shi
country: Japan
facility: Research Site
city: Funabashi-shi
country: Japan
facility: Research Site
city: Hamamatsu-shi
country: Japan
facility: Research Site
city: Hirosaki-shi
country: Japan
facility: Research Site
city: Ise-shi
country: Japan
facility: Research Site
city: Kagoshima-shi
country: Japan
facility: Research Site
city: Koriyama-shi
country: Japan
facility: Research Site
city: Kumamoto-shi
country: Japan
facility: Research Site
city: Kunitachi-shi
country: Japan
facility: Research Site
city: Minato-ku
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Oita-shi
country: Japan
facility: Research Site
city: Otsu-shi
country: Japan
facility: Research Site
city: Oyama-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Shinjyuku-ku
country: Japan
facility: Research Site
city: Suita-shi
country: Japan
facility: Research Site
city: Tama-shi
country: Japan
facility: Research Site
city: Tsukuba-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
Study officials:
References: