The Safety and Efficacy of Dapagliflozin Therapy in Combi... | NCT02582814

NCT02582814

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
Dapagliflozin 5 mg	Drug	Dapagliflozin, a blood glucose lowering drug. Oral dose	dapagliflozin 5mg + insulin

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.

Secondary Outcomes

Measure	Description	Time Frame
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.	From baseline to 24/52 weeks
Adjusted Percent Change From Baseline in Total Daily Insulin Dose

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

- 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

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Aizu Wakamatsu-shi			Japan
Research Site

References Module

Label	URL
D1695C00001\_SAP\_redacted	View source
D1695C00001\_CSP\_redacted	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

ID	Title	Description
FG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
FG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Mar 16, 2017	Jun 5, 2018

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Arm/Group Information

ID	Title	Description
BG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
BG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00047.7± 12.85 BG00148.9± 12.93 BG00248.3± 12.86

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00033 BG00142 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Asian	BG00076 BG00175 BG002

Body Mass Index

Mean

Standard Deviation

kg/m2

Title

Denominators

Categories

Title	Measurements
	BG00025.28± 3.635 BG00124.66± 2.806 BG002

Duration of T1DM

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00014.60± 8.420 BG00115.94± 10.328 BG002

HbA1c

Mean

Standard Deviation

Percent

Title

Denominators

Categories

Title	Measurements
	BG0008.43± 0.711 BG0018.40± 0.715 BG002

C-peptide

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
< 0.1 ng/mL	BG00063 BG00165 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Posted

Count of Participants

Participants

From baseline to 52 weeks

ID	Title	Description
OG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
OG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin

Units	Counts
Participants	OG00076 OG00175

Title

Denominators

Categories

Adverse Events

Title	Measurements
At least one events	OG00067 OG00155

Related Adverse Events

Title	Measurements
At least one events	OG000

Primary

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.

Posted

Count of Participants

Participants

From baseline to 52 weeks

ID	Title	Description
OG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
OG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin

Units	Counts
Participants	OG000

Primary

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.

Posted

Count of Participants

Participants

From baseline to 52 weeks

ID	Title	Description
OG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
OG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin

Units	Counts
Participants	OG000

Secondary

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.

All available post-baseline data were included in analysis. Nubmer of observations at each time point is presented in the table below.

Posted

Least Squares Mean

95% Confidence Interval

percent

From baseline to 24/52 weeks

ID	Title	Description
OG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
OG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin

Units	Counts
Participants	OG000

Secondary

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.

All available post-baseline data were included in analysis. Nubmer of observations at each time point is presented in the table below.

Posted

Least Squares Mean

95% Confidence Interval

percent change

From baseline to 24/52 weeks

ID	Title	Description
OG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
OG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin

Units	Counts
Participants	OG000

Secondary

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.

All available post-baseline data were included in analysis. Nubmer of observations at each time point is presented in the table below.

Posted

Least Squares Mean

95% Confidence Interval

percent change

From baseline to 24/52 weeks

ID	Title	Description
OG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
OG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin

Units	Counts
Participants	OG000

Secondary

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.

All available post-baseline data were included in analysis. Nubmer of observations at each time point is presented in the table below.

Posted

Least Squares Mean

95% Confidence Interval

percent

From baseline to 24/52 weeks

ID	Title	Description
OG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
OG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin

Units	Counts
Participants	OG000

Secondary

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.

All available post-baseline data were included in analysis. Nubmer of observations at each time point is presented in the table below.

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

From baseline to 24/52 weeks

ID	Title	Description
OG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
OG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin

Units	Counts
Participants	OG000

Secondary

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.

All available post-baseline data were included in analysis. Nubmer of observations at each time point is presented in the table below.

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

From baseline to 24/52 weeks

ID	Title	Description
OG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
OG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin

Units	Counts
Participants	OG000

Secondary

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

Subjects with non-missing HbA1c baseline and Week24/52 (LOCF) values were included.

Posted

Number

95% Confidence Interval

percentage of participants

From baseline to 24/52 weeks

ID	Title	Description
OG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
OG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin

Units	Counts
Participants	OG000

Secondary

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

Subjects with non-missing HbA1c baseline and Week24/52 (LOCF) values were included.

Posted

Number

95% Confidence Interval

percentage of participants

From baseline to 24/52 weeks

ID	Title	Description
OG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
OG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin

Units	Counts
Participants	OG000

Secondary

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

Subjects with non-missing HbA1c baseline and Week24/52 (LOCF) values were included.

Posted

Number

95% Confidence Interval

percentage of participants

From baseline to 24/52 weeks

ID	Title	Description
OG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
OG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin

Units	Counts
Participants	OG000

Secondary

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

Subjects with baseline SBP >= 140mmHg and/or baselien DBP >= 90mmHg were included in analysis.

Posted

Least Squares Mean

95% Confidence Interval

mmHg

From baseline to 24/52 weeks

ID	Title	Description
OG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
OG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin

Units	Counts
Participants	OG000

Primary

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.

Subjects with both non-missing baseline and non-missing Week 52 were included.

Posted

Mean

Standard Deviation

bpm

From baseline to 52 weeks

ID	Title	Description
OG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
OG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin

Units	Counts
Participants	OG000

Primary

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.

Posted

Count of Participants

Participants

From baseline to 52 weeks

ID	Title	Description
OG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
OG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin

Units	Counts
Participants	OG000

Primary

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.

Subjects with non-missing post-baseilne measurements were included.

Posted

Count of Participants

Participants

From baseline to 52 weeks

ID	Title	Description
OG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
OG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin

Units	Counts
Participants	OG000

Primary

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.

Subjects with both non-missing baseline and non-missing Week 52 were included.

Posted

Mean

Standard Deviation

mmHg

From baseline to 52 weeks

ID	Title	Description
OG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin
OG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Dapagliflozin 5mg + Insulin	dapagliflozin tablet 5mg + adjustable insulin	0	76	7	76	66	76
EG001	Dapagliflozin 10mg + Insulin	dapagliflozin tablet 10mg + adjustable insulin	0	75	3	75	55	75

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
VITREOUS HAEMORRHAGE	Eye disorders	MedDRA version 19.0	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0011 events1 affected75 at risk
COLITIS	Gastrointestinal disorders	MedDRA version 19.0	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0011 events1 affected75 at risk
DIABETIC KETOACIDOSIS	Metabolism and nutrition disorders	MedDRA version 19.0	Non-systematic Assessment	EG0002 events2 affected76 at risk EG0011 events1 affected75 at risk
HYPOGLYCAEMIC COMA	Nervous system disorders	MedDRA version 19.0	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0011 events1 affected75 at risk
ATRIAL FIBRILLATION	Cardiac disorders	MedDRA version 19.0	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected75 at risk
HEPATIC FUNCTION ABNORMAL	Hepatobiliary disorders	MedDRA version 19.0	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected75 at risk
GASTROENTERITIS	Infections and infestations	MedDRA version 19.0	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected75 at risk
OSTEOARTHRITIS	Musculoskeletal and connective tissue disorders	MedDRA version 19.0	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected75 at risk
ABORTION SPONTANEOUS	Pregnancy, puerperium and perinatal conditions	MedDRA version 19.0	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected75 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
NASOPHARYNGITIS	Infections and infestations	MedDRA version 19.0	Non-systematic Assessment	EG00039 events25 affected76 at risk EG00144 events32 affected75 at risk
PHARYNGITIS	Infections and infestations	MedDRA version 19.0	Non-systematic Assessment	EG0006 events5 affected76 at risk EG00113 events9 affected75 at risk
GASTROENTERITIS	Infections and infestations	MedDRA version 19.0	Non-systematic Assessment	EG0008 events7 affected76 at risk EG00110 events8 affected75 at risk
DENTAL CARIES	Gastrointestinal disorders	MedDRA version 19.0	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0015 events5 affected75 at risk
ECZEMA	Skin and subcutaneous tissue disorders	MedDRA version 19.0	Non-systematic Assessment	EG0004 events4 affected76 at risk EG0014 events4 affected75 at risk
THIRST	General disorders	MedDRA version 19.0	Non-systematic Assessment	EG0004 events4 affected76 at risk EG0014 events4 affected75 at risk
HEADACHE	Nervous system disorders	MedDRA version 19.0	Non-systematic Assessment	EG0004 events4 affected76 at risk EG00112 events6 affected75 at risk
POLLAKIURIA	Renal and urinary disorders	MedDRA version 19.0	Non-systematic Assessment	EG0007 events7 affected76 at risk EG0016 events6 affected75 at risk
KETOSIS	Metabolism and nutrition disorders	MedDRA version 19.0	Non-systematic Assessment	EG0008 events4 affected76 at risk EG00115 events7 affected75 at risk
BRONCHITIS	Infections and infestations	MedDRA version 19.0	Systematic Assessment	EG0005 events2 affected76 at risk EG0014 events4 affected75 at risk
INFLUENZA	Infections and infestations	MedDRA version 19.0	Systematic Assessment	EG0004 events4 affected76 at risk EG0012 events2 affected75 at risk
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA version 19.0	Systematic Assessment	EG0009 events6 affected76 at risk EG0011 events1 affected75 at risk

ID	Term
D003922	Diabetes Mellitus, Type 1

Ancestor Terms

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
C529054	dapagliflozin