The Safety and Efficacy of Dapagliflozin Therapy in Combination With Insulin in Japanese Subjects With T1DM

Type 1 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02582814
• Other study ID #: D1695C00001
• Status: Completed
• Phase: Phase 3
• Start date: October 26, 2015
• Est. completion date: June 15, 2017

Study information

• Verified date: January 2019
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 151
• Est. completion date: June 15, 2017
• Est. primary completion date: June 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 a-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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Drug:
• Dapagliflozin 5 mg
Dapagliflozin, a blood glucose lowering drug. Oral dose
• Dapagliflozin 10mg
Dapagliflozin, a blood glucose lowering drug. Oral dose

Locations

Country	Name	City	State
Japan	Research Site	Aizu Wakamatsu-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Fukuyama-shi
Japan	Research Site	Funabashi-shi
Japan	Research Site	Hamamatsu-shi
Japan	Research Site	Hirosaki-shi
Japan	Research Site	Ise-shi
Japan	Research Site	Kagoshima-shi
Japan	Research Site	Koriyama-shi
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Kunitachi-shi
Japan	Research Site	Minato-ku
Japan	Research Site	Nagoya-shi
Japan	Research Site	Oita-shi
Japan	Research Site	Otsu-shi
Japan	Research Site	Oyama-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shinjyuku-ku
Japan	Research Site	Suita-shi
Japan	Research Site	Tama-shi
Japan	Research Site	Tsukuba-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	Overall Adverse Event Summary	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.	From baseline to 52 weeks
Primary	Hypoglycemia	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.	From baseline to 52 weeks
Primary	Diabetic Ketoacidosis (DKA)	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.	From baseline to 52 weeks
Primary	Vital Signs (Heart Rate)	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.	From baseline to 52 weeks
Primary	ECGs	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.	From baseline to 52 weeks
Primary	Clinical Laboratory Measures, Urine Test Results (Any Marked Abnormality)	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.	From baseline to 52 weeks
Primary	Vital Signs (Blood Pressure)	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.	From baseline to 52 weeks
Secondary	Adjusted Change From Baseline in HbA1c	To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin therapy.	From baseline to 24/52 weeks
Secondary	Adjusted Percent Change From Baseline in Total Daily Insulin Dose	To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin therapy.	From baseline to 24/52 weeks
Secondary	Adjusted Percent Change From Baseline in Body Weight	To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin therapy.	From baseline to 24/52 weeks
Secondary	Adjusted Change From Baseline in Glycoalbumin	To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin therapy.	From baseline to 24/52 weeks
Secondary	Adjusted Change From Baseline in Average Daily Glucose Measured by 6-point SMBG	To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin therapy.	From baseline to 24/52 weeks
Secondary	Adjusted Change From Baseline in Post-prandial Glucose Measured by 6-point SMBG	To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin therapy.	From baseline to 24/52 weeks
Secondary	Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent Without Severe Hypoglycemia	To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin	From baseline to 24/52 weeks
Secondary	Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent	To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin	From baseline to 24/52 weeks
Secondary	Proportion of Subjects Achieving HbA1c < 7.0 Percent	To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin	From baseline to 24/52 weeks
Secondary	Adjusted Change From Baseline in SBP in Subjects With Baseline SBP/DBP >= 140/90 mmHg	To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin	From baseline to 24/52 weeks

External Links

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