Type 1 Diabetes MellitusPhase 3NCT02582814
The Safety and Efficacy of Dapagliflozin Therapy in Combination With Insulin in Japanese Subjects With T1DM
A Phase 3 study testing Dapagliflozin 5 mg and Dapagliflozin 10mg in people with Type 1 Diabetes Mellitus, run by AstraZeneca at 24 sites in Japan.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Dapagliflozin 5 mg and Dapagliflozin 10mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 151 participants
- Where
- 24 sitesJapan
- Study dates
- 26 Oct 2015to 15 Jun 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
24 sites in 1 country.
24 sites in 1 country
Japan24 sites
Research Site
Aizu Wakamatsu-shi
Research Site
Chūōku
Research Site
Fukuoka
Research Site
Fukuyama-shi
Research Site
Funabashi-shi
Research Site
Hamamatsu
Research Site
Hirosaki-shi
Research Site
Ise-shi
Research Site
Kagoshima
Research Site
Koriyama-shi
Research Site
Kumamoto
Research Site
Kunitachi-shi
Research Site
Minatoku
Research Site
Nagoya
Research Site
Ōita
Research Site
Ōtsu
Research Site
Oyama-shi
Research Site
Sapporo
Research Site
Sendai
Research Site
Shinjyuku-ku
Research Site
Suita-shi
Research Site
Tama-shi
Research Site
Tsukuba
Research Site
Yokohama
About this study
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
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
- Being tested
- Dapagliflozin 5 mg, Dapagliflozin 10mg
- Keywords
- Japanese patients with type 1 diabetes with inadequate glycemic control on insulin
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapagliflozin 5 mgDrug
Dapagliflozin, a blood glucose lowering drug. Oral dose
Dapagliflozin 10mgDrug
Dapagliflozin, a blood glucose lowering drug. Oral dose
| Study group | Role | What they receive |
|---|---|---|
| dapagliflozin 5mg + insulin | Experimental | dapagliflozin tablet 5mg + adjustable insulin Receives: Drug: Dapagliflozin 5 mg |
| dapagliflozin 10mg + insulin | Experimental | dapagliflozin tablet 10mg + adjustable insulin Receives: Drug: Dapagliflozin 10mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From baseline to 52 weeks
Secondary outcomes (10)
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.
Measured: From baseline to 24/52 weeks
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.
Measured: From baseline to 24/52 weeks
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.
Measured: From baseline to 24/52 weeks
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.
Measured: From baseline to 24/52 weeks
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.
Measured: From baseline to 24/52 weeks
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.
Measured: From baseline to 24/52 weeks
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
Measured: From baseline to 24/52 weeks
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
Measured: From baseline to 24/52 weeks
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
Measured: From baseline to 24/52 weeks
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
Measured: From baseline to 24/52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2015 (estimated)
- Study start26 Oct 2015
- Primary completion15 Jun 2017
- Study completion15 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 151 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02582814
- Sponsor's protocol ID
- D1695C00001
- Status last verified
- Jan 2019
- First submitted
- 20 Oct 2015
- Last updated
- 12 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02582814
- Acronym / sponsor ID
- D1695C00001
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- Japanese patients with type 1 diabetes with inadequate glycemic control on insulin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 151 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 26 Oct 2015 (actual)
- Primary completion
- 15 Jun 2017 (actual)
- Study completion
- 15 Jun 2017 (actual)
- First posted
- 21 Oct 2015 (estimated)
- Results
- Posted 12 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| dapagliflozin 5mg + insulin | Experimental | Drug: Dapagliflozin 5 mgdapagliflozin tablet 5mg + adjustable insulin |
| dapagliflozin 10mg + insulin | Experimental | Drug: Dapagliflozin 10mgdapagliflozin tablet 10mg + adjustable insulin |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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%
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dapagliflozin 5 mgDapagliflozin, a blood glucose lowering drug. Oral dose | Drug | dapagliflozin 5mg + insulin |
| Dapagliflozin 10mgDapagliflozin, a blood glucose lowering drug. Oral dose | Drug | dapagliflozin 10mg + insulin |
Primary outcome
Overall Adverse Event Summary
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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.
ECGs
Time frame: 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)
Time frame: 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)
Time frame: 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.
10 secondary outcomes
Adjusted Change From Baseline in HbA1c
Time frame: From baseline to 24/52 weeks
Adjusted Percent Change From Baseline in Total Daily Insulin Dose
Time frame: From baseline to 24/52 weeks
Adjusted Percent Change From Baseline in Body Weight
Time frame: From baseline to 24/52 weeks
Adjusted Change From Baseline in Glycoalbumin
Time frame: From baseline to 24/52 weeks
Adjusted Change From Baseline in Average Daily Glucose Measured by 6-point SMBG
Time frame: From baseline to 24/52 weeks
Adjusted Change From Baseline in Post-prandial Glucose Measured by 6-point SMBG
Time frame: From baseline to 24/52 weeks
Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent Without Severe Hypoglycemia
Time frame: From baseline to 24/52 weeks
Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent
Time frame: From baseline to 24/52 weeks
Proportion of Subjects Achieving HbA1c < 7.0 Percent
Time frame: From baseline to 24/52 weeks
Adjusted Change From Baseline in SBP in Subjects With Baseline SBP/DBP >= 140/90 mmHg
Time frame: From baseline to 24/52 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- D1695C00001\_SAP\_redactedLink provided by the sponsor.
- D1695C00001\_CSP\_redactedLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dapagliflozin 5 mg and Dapagliflozin 10mg in people with Type 1 Diabetes Mellitus, run by AstraZeneca at 24 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Adverse Event Summary (time frame: From baseline to 52 weeks). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2019.