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

NCT02582814 | Completed Phase 3 Results

• 1 other identifier: D1695C00001
• Study Type: interventional
• Target: 151
• Locations: 1 country
• Sites: 24

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.

Conditions

Type 1 Diabetes Mellitus

Keywords

Japanese patients with type 1 diabetes with inadequate glycemic control on insulin

Outcome Measures

Primary Outcomes (7)

• 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

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (10)

• 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

Study Arms (2)

dapagliflozin 5mg + insulin

EXPERIMENTAL

dapagliflozin tablet 5mg + adjustable insulin

Drug: Dapagliflozin 5 mg

dapagliflozin 10mg + insulin

EXPERIMENTAL

dapagliflozin tablet 10mg + adjustable insulin

Drug: Dapagliflozin 10mg

Interventions

Dapagliflozin 5 mg DRUG

Dapagliflozin, a blood glucose lowering drug. Oral dose

dapagliflozin 5mg + insulin

Dapagliflozin 10mg DRUG

Dapagliflozin, a blood glucose lowering drug. Oral dose

dapagliflozin 10mg + insulin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \- 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (24)

Research Site

Aizu Wakamatsu-shi, Japan

Location

Research Site

Chūōku, Japan

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Research Site

Fukuoka, Japan

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Fukuyama-shi, Japan

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Funabashi-shi, Japan

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Hamamatsu, Japan

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Hirosaki-shi, Japan

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Ise-shi, Japan

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Kagoshima, Japan

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Koriyama-shi, Japan

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Research Site

Kumamoto, Japan

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Kunitachi-shi, Japan

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Research Site

Minatoku, Japan

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Nagoya, Japan

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Research Site

Oyama-shi, Japan

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Research Site

Ōita, Japan

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Ōtsu, Japan

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Research Site

Sapporo, Japan

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Research Site

Sendai, Japan

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Research Site

Shinjyuku-ku, Japan

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Research Site

Suita-shi, Japan

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Research Site

Tama-shi, Japan

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Research Site

Tsukuba, Japan

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Research Site

Yokohama, Japan

Location

Related Links

• D1695C00001\_SAP\_redacted
• D1695C00001\_CSP\_redacted

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: A clinical pharmacology and long-term safety study
• Organization: AstraZeneca

Yu.Shimizuishi@astrazeneca.com

+819039706431

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2015
• First Posted: October 21, 2015
• Study Start: October 26, 2015
• Primary Completion: June 15, 2017
• Study Completion: June 15, 2017
• Last Updated: April 12, 2019
• Results First Posted: April 12, 2019

Record last verified: 2019-01

Locations

JP (24)