NCT02582814

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

Completed Phase 3 Results posted Last updated 12 April 2019

What this trial tests

Phase 3 trial testing Dapagliflozin 5 mg in Type 1 Diabetes Mellitus in 151 participants. Completed in 15 June 2017.

Timeline

26 October 2015

Primary endpoint
15 June 2017

15 June 2017

Quick facts

Lead sponsor	AstraZeneca
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	151
Start date	26 October 2015
Primary completion	15 June 2017
Estimated completion	15 June 2017
Sites	24 locations across Japan

Drugs / interventions tested

• Dapagliflozin 5 mg — full drug profile →
• Dapagliflozin 10mg — full drug profile →

Conditions studied

• Type 1 Diabetes Mellitus — all drugs for Type 1 Diabetes Mellitus →

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 18 to 75, any sex, with Type 1 Diabetes Mellitus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Adverse Event Summary Primary · 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.

Adverse Events

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	67
Dapagliflozin 10mg + Insulin	55

Related Adverse Events

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	23
Dapagliflozin 10mg + Insulin	22

SAE

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	7
Dapagliflozin 10mg + Insulin	3

AEs leading to discontinuation

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	4
Dapagliflozin 10mg + Insulin	4

Death

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	0
Dapagliflozin 10mg + Insulin	0

Hypoglycemia Primary · 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.

Any Hypoglycemia Episodes

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	75
Dapagliflozin 10mg + Insulin	75

Severe Hypoglycemia

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	2
Dapagliflozin 10mg + Insulin	5

Documented Symptomatic Hypoglycemia

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	67
Dapagliflozin 10mg + Insulin	73

Asymptomatic Hypoglycemia

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	60
Dapagliflozin 10mg + Insulin	64

Probable Symptomatic Hypoglycemia

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	13
Dapagliflozin 10mg + Insulin	14

Relative Hypoglycemia

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	14
Dapagliflozin 10mg + Insulin	11

Diabetic Ketoacidosis (DKA) Primary · 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.

Definite DKA

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	2
Dapagliflozin 10mg + Insulin	1

Possible DKA

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	1
Dapagliflozin 10mg + Insulin	0

Unlikely DKA

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	0
Dapagliflozin 10mg + Insulin	0

Adjusted Change From Baseline in HbA1c Secondary · From baseline to 24/52 weeks

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.

Week 24

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	-0.52	-0.66 – -0.38
Dapagliflozin 10mg + Insulin	-0.66	-0.80 – -0.53

Week 52

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	-0.33	-0.50 – -0.15
Dapagliflozin 10mg + Insulin	-0.36	-0.53 – -0.18

Adjusted Percent Change From Baseline in Total Daily Insulin Dose Secondary · From baseline to 24/52 weeks

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.

Week 24

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	-15.30	-18.55 – -11.92
Dapagliflozin 10mg + Insulin	-15.14	-18.43 – -11.73

Week 52

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	-12.27	-15.92 – -8.46
Dapagliflozin 10mg + Insulin	-13.13	-16.77 – -9.33

Adjusted Percent Change From Baseline in Body Weight Secondary · From baseline to 24/52 weeks

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.

Week 24

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	-3.88	-4.74 – -3.02
Dapagliflozin 10mg + Insulin	-5.26	-6.11 – -4.41

Week 52

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	-4.25	-5.29 – -3.21
Dapagliflozin 10mg + Insulin	-5.96	-6.98 – -4.93

Adjusted Change From Baseline in Glycoalbumin Secondary · From baseline to 24/52 weeks

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.

Week 24

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	-2.26	-2.83 – -1.70
Dapagliflozin 10mg + Insulin	-2.63	-3.22 – -2.04

Week 52

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	-1.49	-2.18 – -0.77
Dapagliflozin 10mg + Insulin	-1.68	-2.41 – -0.96

Adjusted Change From Baseline in Average Daily Glucose Measured by 6-point SMBG Secondary · From baseline to 24/52 weeks

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.

Week 24

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	-9.37	-15.80 – -2.94
Dapagliflozin 10mg + Insulin	-15.06	-21.62 – -8.51

Week 52

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	-11.62	-18.62 – -4.62
Dapagliflozin 10mg + Insulin	-12.93	-19.99 – -5.88

Adjusted Change From Baseline in Post-prandial Glucose Measured by 6-point SMBG Secondary · From baseline to 24/52 weeks

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.

Week 24

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	-2.33	-11.18 – 6.51
Dapagliflozin 10mg + Insulin	-10.08	-19.04 – -1.12

Week 52

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	-6.40	-15.45 – 2.64
Dapagliflozin 10mg + Insulin	-5.24	-14.32 – 3.83

Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent Without Severe Hypoglycemia Secondary · From baseline to 24/52 weeks

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

Week 24

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	60.8	48.8 – 72.0
Dapagliflozin 10mg + Insulin	61.3	49.4 – 72.4

Week 52

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	51.4	39.4 – 63.1
Dapagliflozin 10mg + Insulin	41.3	30.1 – 53.3

Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent Secondary · From baseline to 24/52 weeks

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

Week 24

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	62.2	50.1 – 73.2
Dapagliflozin 10mg + Insulin	66.7	54.8 – 77.1

Week 52

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	51.4	39.4 – 63.1
Dapagliflozin 10mg + Insulin	45.3	33.8 – 57.3

Proportion of Subjects Achieving HbA1c < 7.0 Percent Secondary · From baseline to 24/52 weeks

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

Week 24

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	9.5	3.9 – 18.5
Dapagliflozin 10mg + Insulin	5.3	1.5 – 13.1

Week 52

Group	Value	95% CI
Dapagliflozin 5mg + Insulin	6.8	2.2 – 15.1
Dapagliflozin 10mg + Insulin	2.7	0.3 – 9.3

Adverse events — posted to ClinicalTrials.gov

Time frame: 1 year. Non-serious adverse event (AE): onset on or after the 1st day of dose up to on or prior to the last day of dose plus 4 days. Serious AE: onset on or after the 1st day of dose up to on or prior to the last day of dose plus 30 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dapagliflozin 5mg + Insulin

Serious: 7/76 (9%)

Deaths: 0/76

Dapagliflozin 10mg + Insulin

Serious: 3/75 (4%)

Deaths: 0/75

Serious adverse events (9 terms)

Reaction	System	Dapagliflozin 5mg + Insulin	Dapagliflozin 10mg + Insulin
DIABETIC KETOACIDOSIS	Metabolism and nutrition disorders	—	—
VITREOUS HAEMORRHAGE	Eye disorders	—	—
COLITIS	Gastrointestinal disorders	—	—
HYPOGLYCAEMIC COMA	Nervous system disorders	—	—
ATRIAL FIBRILLATION	Cardiac disorders	—	—
HEPATIC FUNCTION ABNORMAL	Hepatobiliary disorders	—	—
GASTROENTERITIS	Infections and infestations	—	—
OSTEOARTHRITIS	Musculoskeletal and connective tissue disorders	—	—
ABORTION SPONTANEOUS	Pregnancy, puerperium and perinatal conditions	—	—

Other adverse events (12 terms — click to expand)

Reaction	System	Dapagliflozin 5mg + Insulin	Dapagliflozin 10mg + Insulin
NASOPHARYNGITIS	Infections and infestations	—	—
PHARYNGITIS	Infections and infestations	—	—
GASTROENTERITIS	Infections and infestations	—	—
POLLAKIURIA	Renal and urinary disorders	—	—
KETOSIS	Metabolism and nutrition disorders	—	—
HEADACHE	Nervous system disorders	—	—
BACK PAIN	Musculoskeletal and connective tissue disorders	—	—
DENTAL CARIES	Gastrointestinal disorders	—	—
ECZEMA	Skin and subcutaneous tissue disorders	—	—
THIRST	General disorders	—	—
BRONCHITIS	Infections and infestations	—	—
INFLUENZA	Infections and infestations	—	—

Most-reported serious reactions: DIABETIC KETOACIDOSIS, VITREOUS HAEMORRHAGE, COLITIS, HYPOGLYCAEMIC COMA, ATRIAL FIBRILLATION, HEPATIC FUNCTION ABNORMAL, GASTROENTERITIS, OSTEOARTHRITIS.

Data from ClinicalTrials.gov NCT02582814 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Efficacy and safety of dapagliflozin in Japanese patients with inadequately controlled type 1 diabetes (DEPICT-5): 52-week results from a randomized, open-label, phase III clinical trial.
   Araki E, Watada H, Uchigata Y, Tomonaga O, et al · · 2020 · cited 24× · PMID 31742898 · DOI 10.1111/dom.13922
2. Risk of diabetic ketoacidosis caused by sodium glucose cotransporter-2 inhibitors in patients with type 1 diabetes: a systematic review and network meta-analysis of randomized controlled trials.
   Liu Y, Yang S, Jiang A, Zou D, et al · · 2024 · cited 2× · PMID 39957850 · DOI 10.3389/fendo.2024.1453067