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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 151
- 试验地点
- 1
- 主要终点
- ECGs
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open Label
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
dapagliflozin 5mg + insulin
dapagliflozin tablet 5mg + adjustable insulin
干预措施: Dapagliflozin 5 mg (Drug)
dapagliflozin 10mg + insulin
dapagliflozin tablet 10mg + adjustable insulin
干预措施: Dapagliflozin 10mg (Drug)
结局指标
主要结局
ECGs
时间窗: From baseline to 52 weeks
To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.
Hypoglycemia
时间窗: From baseline to 52 weeks
To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.
Diabetic Ketoacidosis (DKA)
时间窗: From baseline to 52 weeks
To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.
Vital Signs (Blood Pressure)
时间窗: From baseline to 52 weeks
To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.
Overall Adverse Event Summary
时间窗: From baseline to 52 weeks
To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.
Vital Signs (Heart Rate)
时间窗: From baseline to 52 weeks
To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.
Clinical Laboratory Measures, Urine Test Results (Any Marked Abnormality)
时间窗: From baseline to 52 weeks
To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.
次要结局
- Adjusted Change From Baseline in HbA1c(From baseline to 24/52 weeks)
- Adjusted Percent Change From Baseline in Total Daily Insulin Dose(From baseline to 24/52 weeks)
- Adjusted Percent Change From Baseline in Body Weight(From baseline to 24/52 weeks)
- Adjusted Change From Baseline in Glycoalbumin(From baseline to 24/52 weeks)
- Adjusted Change From Baseline in Average Daily Glucose Measured by 6-point SMBG(From baseline to 24/52 weeks)
- Adjusted Change From Baseline in Post-prandial Glucose Measured by 6-point SMBG(From baseline to 24/52 weeks)
- Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent Without Severe Hypoglycemia(From baseline to 24/52 weeks)
- Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent(From baseline to 24/52 weeks)
- Proportion of Subjects Achieving HbA1c < 7.0 Percent(From baseline to 24/52 weeks)
- Adjusted Change From Baseline in SBP in Subjects With Baseline SBP/DBP >= 140/90 mmHg(From baseline to 24/52 weeks)