Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes

Phase 3

Completed

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

• Registration Number: NCT02268214
• 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: 2014-10-15
• Study First Submitted QC: 2014-10-15
• Study First Posted: 2014-10-20
• Study Start: 2014-11-11
• Primary Completion: 2017-01-04
• Study Completion: 2017-08-25
• Results First Submitted: 2018-03-02
• Results First Submitted QC: 2018-03-02
• Results First Posted: 2018-03-29
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-16
• Last Update Posted: 2018-09-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 833

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 metformin and/or thiazolidinediones within 2 months prior to screening

• Taking any antidiabetic medication (other than insulin), 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

• 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
Arm C: Placebo for Dapagliflozin	Placebo for dapagliflozin	Placebo tablet orally, once daily for 52 weeks
Arm A: Dapagliflozin	Dapagliflozin	Dapagliflozin 5 mg tablet orally, once daily for 52 weeks
Arm B: Dapagliflozin	Dapagliflozin	Dapagliflozin 10 mg tablet orally, once daily for 52 weeks

Primary Outcome Measures

Name	Time	Method
Adjusted Mean Change in HbA1c From Baseline at Week 24	From Baseline to Week 24	Adjusted mean change from baseline in HbA1c at Week 24 (Repeated Measures Model\[RMM\]).

Secondary Outcome Measures

Name	Time	Method
Adjusted Mean Change in Percent 24-hour Continuous Glucose Monitoring Glucose > 70 and <= 180 (mg/dL) From Baseline at Week 24	From Baseline to Week 24	Adjusted Mean Change in Percent 24-hour Continuous Glucose Monitoring Glucose \> 70 and \<= 180 (mg/dL) from Baseline at Week 24 (Repeated Measures Model\[RMM\])
Adjusted Mean Percent Change in Body Weight From Baseline at Week 24	From Baseline to Week 24	Adjusted mean percent change from baseline in body weight at Week 24 (Repeated Measures Model\[RMM\])
Adjusted Mean Percent Change in Total Daily Insulin Dose From Baseline at Week 24	From Baseline to Week 24	Adjusted mean change from baseline in Total Daily Insulin Dose at Week 24 (Repeated Measures Model\[RMM\])
Adjusted Mean Change in 24-hour Mean Continuous Glucose Monitoring Glucose From Baseline at Week 24	From Baseline to Week 24	Adjusted mean change in 24-hour mean Continuous Glucose Monitoring glucose from baseline at Week 24 (Repeated Measures Model\[RMM\])
Adjusted Mean Change in 24-hour Continuous Glucose Monitoring MAGE From Baseline at Week 24	From Baseline to Week 24	Adjusted Mean Change in 24-hour Continuous Glucose Monitoring Mean Amplitude of Glucose Excursions (MAGE) from Baseline at Week 24 (Repeated Measures Model\[RMM\])
Subjects With HbA1c Reduction From Baseline to Week 24 (LOCF) >= 0.5% and Without Severe Hypoglycemia Events	From Baseline to Week 24	Subjects with HbA1c reduction from baseline to week 24 (LOCF) \>= 0.5% and without severe hypoglycemia events

Trial Locations

Locations (1)

Research Site; 🇬🇧 Welwyn Garden City, United Kingdom