Effect of Dapagliflozin on 24-hour Blood Glucose in T2DM Patients Inadequately Controlled With Either Metformin Or Insulin

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02429258
• Collaborator: (none)
• Enrollment: 226
• Locations: 26
• Arms: 2
• Duration (Months): 5
• Patients Per Site: 8.7
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

Effect of Dapagliflozin on 24-hour Blood Glucose in Type 2 Diabetes Patients Inadequately Controlled With Either Metformin Or Insulin

Condition or Disease	Intervention/Treatment	Phase
Type II Diabetes	Drug: Farxiga; Drug: Placebo; Drug: Metformin; Drug: Insulin	Phase 4

Detailed Description

Effect of Dapagliflozin on 24-hour Blood Glucose in 92 Type 2 Diabetes Patients Inadequately Controlled With Either Metformin Or Insulin

Study Design

• Study Type: Interventional
• Actual Enrollment: 226 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect of Dapagliflozin on 24-hour Blood Glucose in T2DM Patients Inadequately Controlled With Either Metformin Or Insulin
• Study Start Date: May 1, 2015
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Farxiga with metformin or insulin Farxiga with metformin (>/=1500mg/day) or insulin (>/=30 units/day) and up to 2 OAD medications	Drug: Farxiga; Farxiga 10mg/day; Drug: Metformin; Metformin background therapy >/= 1500mg/day; Drug: Insulin; Insulin >/= 30 units
Placebo Comparator: Placebo with metformin or insulin Placebo with metformin (>/=1500mg/day) or insulin (>/=30 units/day) and up to 2 OAD medications	Drug: Placebo; Placebo; Drug: Metformin; Metformin background therapy >/= 1500mg/day; Drug: Insulin; Insulin >/= 30 units

Outcome Measures

Primary Outcome Measures

1. Change in 24-hour Mean Weighted Glucose (MWG) From Baseline to End of Treatment (Week 4) Using the Continuous Glucose Monitoring (CGM) System [Baseline to Week 4]

Secondary Outcome Measures

1. Change in the 24-hour Mean Ampitude of Glucose Excursions (MAGE) From Baseline to Week 4 [Baseline to Week 4]

2. Change in Percentage of CGM Readings Over 24-hours With Plasma Glucose <70 mg/dL From Baseline to Week 4 - ITT Population [Baseline to Week 4]

3. Change in Percentage of CGM Readings Over 24-hours With Plasma Glucose Between 70 mg/dL and 180 mg/dL From Baseline to Week 4 - ITT Population [Baseline to Week 4]

4. Change in Percentage of CGM Readings Over 24-hours With Plasma Glucose >180 mg/dL From Baseline to Week 4 - ITT Population [Baseline to Week 4]

5. Change in Fasting Plasma Glucose (FPG) From Baseline to Week 4 [Baseline to Week 4]

6. Change in 4-hour Mean Weighted Post-prandial Glucose (PPG) (After the Standardized Breakfast Meal) From Baseline to Week 4 [Baseline to Week 4]

7. Change in HbA1c From Baseline to Week 4 [Baseline to Week 4]

8. Change in Fructosamine From Baseline to Week 4 [Baseline to Week 4]

9. Change in 2-hour Mean Weighted PPG (After the Standardized Breakfast Meal) From Baseline to Week 4 [Baseline to Week 4]

10. Change in Static Insulin Secretion Rate (10^-9 Min^-1) From Baseline to Week 4 - ITT Population [Baseline to Week 4]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 2 diabetes mellitus (T2DM)

• Treated with either stable dose of metformin alone > or = to 1500mg/day or stable dose of insulin > or = to 30 units/day and up to 2 OAD medications for at least 8 weeks

• Hemoglobin A1c (HbA1c) 7.5% to 10.5% at screening

• Body mass index (BMI) < or = to 45 kg/m2

Exclusion Criteria:

• For patients who enter the study taking a stable dose of metformin, history of taking OAD medications other than metformin during the 8 weeks prior to screening or have been on insulin therapy within 1 year of screening

• For patients who enter the study taking insulin, history of taking any other therapy outside of the stable insulin and up to 2 OAD medications for 8 weeks prior to screening.

• Use of sulfonylureas during the 8 weeks prior to screening

• Prior exposure to dapagliflozin or any sodium-glucose co-transporter 2 (SGLT-2) inhibitor

• Ingestion of any medication know to affect glucose metabolism for >7 consecutive days during the 3 months prior to screening

• Ingestion of prescription or over the counter weight loss medication during 3 months prior to screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States
2	Research Site	Phoenix	Arizona	United States
3	Research Site	Huntington Park	California	United States
4	Research Site	Los Angeles	California	United States
5	Research Site	Sacramento	California	United States
6	Research Site	San Diego	California	United States
7	Research Site	West Hills	California	United States
8	Research Site	Cooper City	Florida	United States
9	Research Site	Miami	Florida	United States
10	Research Site	Evanston	Illinois	United States
11	Research Site	Oxon Hill	Maryland	United States
12	Research Site	Henderson	Nebraska	United States
13	Research Site	Brooklyn	New York	United States
14	Research Site	Rochester	New York	United States
15	Research Site	Greensboro	North Carolina	United States
16	Research Site	Cincinnati	Ohio	United States
17	Research Site	Dublin	Ohio	United States
18	Research Site	Franklin	Ohio	United States
19	Research Site	Eugene	Oregon	United States
20	Research Site	Lansdale	Pennsylvania	United States
21	Research Site	Spartanburg	South Carolina	United States
22	Research Site	Bartlett	Tennessee	United States
23	Research Site	Dallas	Texas	United States
24	Research Site	Houston	Texas	United States
25	Research Site	Hurst	Texas	United States
26	Research Site	Renton	Washington	United States

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02429258
• Other Study ID Numbers: D1690L00026
• First Posted: Apr 29, 2015
• Last Update Posted: Jun 14, 2017
• Last Verified: Apr 1, 2017

• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Metformin; Dapagliflozin

Study Results

Participant Flow

Pre-assignment Detail	226 subjects signed the informed consent form (ICF), and 132 subjects were screened to randomize a total of 100 subjects.

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin + Metformin or Insulin	Placebo + Metformin or Insulin
Period Title: Overall Study
STARTED	50	50
COMPLETED	48	49
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Dapagliflozin	Placebo	Total
Arm/Group Description	Dapagliflozin + Metformin or Insulin	Placebo + Metformin or Insulin	Total of all reporting groups
Overall Participants	50	50	100
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.9 (7.11)	56.8 (9.71)	56.9 (8.47)
Sex: Female, Male (Count of Participants)
Female	24 48%	25 50%	49 49%
Male	26 52%	25 50%	51 51%
Race/Ethnicity, Customized (Number) [Number]
Black or African American	11 22%	14 28%	25 25%
White	39 78%	36 72%	75 75%
American Indian and Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Other	0 0%	0 0%	0 0%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	34.3 (5.92)	33.2 (5.59)	33.8 (5.75)
Hemoglobin A1c (HbA1c) (Percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage]	8.31 (0.785)	8.37 (0.810)	8.34 (0.794)

Outcome Measures

1. Primary Outcome

Title	Change in 24-hour Mean Weighted Glucose (MWG) From Baseline to End of Treatment (Week 4) Using the Continuous Glucose Monitoring (CGM) System
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin + Metformin or Insulin	Placebo + Metformin or Insulin
Measure Participants	50	50
Least Squares Mean (Standard Error) [mg/dL]	-18.2 (4.33)	5.8 (4.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-24.0
	Confidence Interval	() 95%; -36.1 to -12.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.08
	Estimation Comments

2. Secondary Outcome

Title	Change in the 24-hour Mean Ampitude of Glucose Excursions (MAGE) From Baseline to Week 4
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin + Metformin or Insulin	Placebo + Metformin or Insulin
Measure Participants	50	50
Least Squares Mean (Standard Error) [mg/dL]	-10.0 (4.14)	5.3 (4.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-15.3
	Confidence Interval	() 95%; -26.8 to -3.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.80
	Estimation Comments

3. Secondary Outcome

Title	Change in Percentage of CGM Readings Over 24-hours With Plasma Glucose <70 mg/dL From Baseline to Week 4 - ITT Population
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin + Metformin or Insulin	Placebo + Metformin or Insulin
Measure Participants	50	50
Least Squares Mean (Standard Error) [Change in percentage]	0.3 (0.30)	-0.6 (0.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.023
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.0
	Confidence Interval	() 95%; 0.1 to 1.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.42
	Estimation Comments

4. Secondary Outcome

Title	Change in Percentage of CGM Readings Over 24-hours With Plasma Glucose Between 70 mg/dL and 180 mg/dL From Baseline to Week 4 - ITT Population
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin + Metformin or Insulin	Placebo + Metformin or Insulin
Measure Participants	50	50
Least Squares Mean (Standard Error) [Change in percentage]	12.2 (2.60)	-2.8 (2.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	15.0
	Confidence Interval	() 95%; 7.7 to 22.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.65
	Estimation Comments

5. Secondary Outcome

Title	Change in Percentage of CGM Readings Over 24-hours With Plasma Glucose >180 mg/dL From Baseline to Week 4 - ITT Population
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin + Metformin or Insulin	Placebo + Metformin or Insulin
Measure Participants	50	50
Least Squares Mean (Standard Error) [Change in percentage]	-12.6 (2.65)	3.5 (2.60)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-16.1
	Confidence Interval	() 95%; -23.5 to -8.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.72
	Estimation Comments

6. Secondary Outcome

Title	Change in Fasting Plasma Glucose (FPG) From Baseline to Week 4
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin + Metformin or Insulin	Placebo + Metformin or Insulin
Measure Participants	50	50
Least Squares Mean (Standard Error) [mg/dL]	-26.2 (5.99)	3.6 (5.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-29.7
	Confidence Interval	() 95%; -46.6 to -12.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.47
	Estimation Comments

7. Secondary Outcome

Title	Change in 4-hour Mean Weighted Post-prandial Glucose (PPG) (After the Standardized Breakfast Meal) From Baseline to Week 4
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin + Metformin or Insulin	Placebo + Metformin or Insulin
Measure Participants	50	50
Least Squares Mean (Standard Error) [mg/dL]	-50.9 (6.54)	-10.0 (6.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-40.8
	Confidence Interval	() 95%; -59.0 to -22.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.14
	Estimation Comments

8. Secondary Outcome

Title	Change in HbA1c From Baseline to Week 4
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin + Metformin or Insulin	Placebo + Metformin or Insulin
Measure Participants	50	50
Least Squares Mean (Standard Error) [% Alc]	-0.51 (0.07)	-0.28 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.024
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.23
	Confidence Interval	() 95%; -0.43 to -0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

9. Secondary Outcome

Title	Change in Fructosamine From Baseline to Week 4
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin + Metformin or Insulin	Placebo + Metformin or Insulin
Measure Participants	50	50
Least Squares Mean (Standard Error) [mmol/L]	-20.4 (3.22)	-9.6 (3.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.019
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-10.8
	Confidence Interval	() 95%; -19.9 to -1.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.55
	Estimation Comments

10. Secondary Outcome

Title	Change in 2-hour Mean Weighted PPG (After the Standardized Breakfast Meal) From Baseline to Week 4
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin + Metformin or Insulin	Placebo + Metformin or Insulin
Measure Participants	50	50
Least Squares Mean (Standard Error) [mg/dL]	-49.5 (6.61)	-13.2 (6.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-36.3
	Confidence Interval	() 95%; -54.7 to -17.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 9.25
	Estimation Comments

11. Secondary Outcome

Title	Change in Static Insulin Secretion Rate (10^-9 Min^-1) From Baseline to Week 4 - ITT Population
Time Frame	Baseline to Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dapagliflozin	Placebo
Arm/Group Description	Dapagliflozin + Metformin or Insulin	Placebo + Metformin or Insulin
Measure Participants	50	50
Least Squares Mean (Standard Error) [10^-9 min^-1]	8.4 (2.07)	1.4 (1.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dapagliflozin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.017
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7.0
	Confidence Interval	() 95%; 1.3 to 12.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.86
	Estimation Comments

Adverse Events

Arm/Group Title	Dapagliflozin		Placebo
Arm/Group Description	Dapagliflozin + Metformin or Insulin		Placebo + Metformin or Insulin
All Cause Mortality
	Dapagliflozin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dapagliflozin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/50 (0%)
Other (Not Including Serious) Adverse Events
	Dapagliflozin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/50 (6%)		3/50 (6%)
Infections and infestations
Urinary Tract Infection	3/50 (6%)	3	3/50 (6%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Institution & PI agree they will not use or disclose and confidential information to third parties for a period of 10 years from receipt