Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes

Phase 3

Completed

• Conditions: Type 1 Diabetes Mellitus
• Interventions: Drug: Dapagliflozin; Other: Placebo for dapagliflozin

• Registration Number: NCT02460978
• Lead Sponsor: AstraZeneca

Brief Summary

The purpose of this study is to determine if adding dapagliflozin to insulin is a safe and effective therapy to improve glycemic control in patients with type 1 diabetes.

Detailed Description

Study Classification: Safety, Efficacy and Pharmacokinetics/dynamics

Study Timeline

• Study First Submitted: 2015-06-01
• Study First Submitted QC: 2015-06-01
• Study First Posted: 2015-06-03
• Study Start: 2015-07-08
• Primary Completion: 2017-09-02
• Study Completion: 2018-04-18
• Results First Submitted: 2018-08-24
• Results First Submitted QC: 2018-10-09
• Results First Posted: 2018-11-06
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-14
• Last Update Posted: 2019-03-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 815

Inclusion Criteria

• Diagnosis of Type 1 Diabetes mellitus (T1DM)
• Central laboratory C-peptide < 0.7 ng/ml (0.23 nmol/L)
• Insulin use for at least 12 months per patient reported or medical records
• Method of insulin administration (MDI or CSII) must have been unchanged for at least 3 months prior to screening
• Subjects must be on a total insulin dose of ≥ 0.3 U/kg/day for at least 3 months prior to screening
• If on MDI insulin administration, subject must be on ≥ 3x injections per day
• Screening Visit: Central laboratory HbA1c ≥ 7.7% and ≤ 11.0%
• Body mass index (BMI) ≥ 18.5 kg/m2

Exclusion Criteria

• History of Type 2 Diabetes mellitus (T2DM) or maturity onset diabetes of the young (MODY), pancreatic surgery, or chronic pancreatitis that could result in decreased beta cell capacity
• Taking any non-insulin antihyperglicemic agent within 1 month prior to screening
• Taking GLP-1 receptor agonist within 2 months prior to screening for once weekly administration and within 1 month prior to screening for once or twice daily administration
• Taking metformin and/or thiazolidinediones within 2 months prior to screening
• History of diabetes ketoacidosis requiring medical intervention within 1 month prior to screening
• History of hospital admission for glycemic control (either hyperglycemia or hypoglycemia) within 1 month prior to screening
• Frequent episodes of severe hypoglycemia (more than one episode requiring medical assistance, emergency care), and/or glucagon therapy administered by a third-party individual within 1 month prior to screening
• History of Addison's disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dapagliflozin 10 mg	Dapagliflozin	Dapagliflozin 10 mg tablet orally, once daily for 52 weeks
Placebo	Placebo for dapagliflozin	Placebo tablet orally, once daily for 52 weeks
Dapagliflozin 5 mg	Dapagliflozin	Dapagliflozin 5 mg tablet orally, once daily for 52 weeks

Primary Outcome Measures

Name	Time	Method
Adjusted Mean Change From Baseline in HbA1c at Week 24	Baseline and 24 weeks	To compare the change from baseline in HbA1c between dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment

Secondary Outcome Measures

Name	Time	Method
Adjusted Mean Percentage Change From Baseline in Total Daily Insulin Dose at Week 24	Baseline and 24 weeks	To compare the percent change from baseline in total daily insulin dose with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment
Adjusted Mean Percentage Change From Baseline in Body Weight at Week 24	Baseline and 24 weeks	To compare the percentage change from baseline in body weight with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment
Adjusted Mean Change From Baseline in 24-hour Continuous Glucose Monitoring (CGM) Mean Value at Week 24	Baseline and 24 weeks	To compare the change from baseline in mean value of 24-hour glucose readings obtained from CGM with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment
Adjusted Mean Change From Baseline in 24-hour CGM Mean Amplitude of Glycemic Excursion (MAGE) Value at Week 24	Baseline and 24 weeks	To compare the change from baseline in mean amplitude of glucose excursions (MAGE) of 24-hour glucose readings obtained from CGM with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment
Change From Baseline in the Percent of 24-hour Glucose Readings Obtained From CGM That Falls Within the Target Range of > 70 mg/dL and <= 180 mg/dL (%) at Week 24	Baseline and 24 weeks	To compare the change from baseline in the percent of 24-hour glucose readings obtained from CGM that falls within the target range of \>70 mg/dL and \<=180 mg/dL with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment
Percentage of Subjects With HbA1c Reduction From Baseline to Week 24 Last Observation Carried Forward (LOCF) >= 0.5% and Without Severe Hypoglycemia Events at Week 24	Baseline and 24 weeks	To compare dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin for the proportion of subjects achieving an HbA1c reduction from baseline to Week 24 visit \>=0.5% without severe hypoglycemia events

Trial Locations

Locations (1)

Research Site; 🇬🇧 Wakefield, United Kingdom