Trial Outcomes & Findings for A Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes With Inadequately Controlled Hypertension on an ACEI or ARB and an Additional Antihypertensive Medication (NCT NCT01195662)
NCT ID: NCT01195662
Last Updated: 2016-12-29
Results Overview
Systolic blood pressure (SBP) was measured in millimeters of mercury (mmHg) on Day -1, Day 1, Weeks 2, 4, 8, and 12 of the Double Blind Period. Blood pressure (BP) values were obtained after the participant was seated for quietly for 10 minutes; a mean of 3 replicate measurements was taken at least 1 minute apart. However, if the 3 consecutive seated BP readings were not within 8 mm Hg of each other, an additional 2 BP readings were obtained (total = 5) and incorporated into the calculated mean. BP was measured in both arms. If the BP was higher in one arm than the other, then this arm was used; if no difference, the participant's dominant arm was used for all future BP measurements. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. Participants refrained from ingestion of caffeine, alcohol, or nicotine at least 10 hours prior to their visit and having their BP measured.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
2245 participants
Primary outcome timeframe
Baseline to Week 12
Results posted on
2016-12-29
Participant Flow
Recruitment: 29-Oct-2010 to 04-Oct-2012. Original study had 3 arms but 5 mg dapagliflozin arm was discontinued with Protocol Amendment 8 (implemented 01-Nov-2011) because totality of data in development program showed that once daily 10-mg dapagliflozin provides optimal efficacy with safety and tolerance. Study continued to enroll with 2 arms.
2245 enrolled. 1213 completed enrollment;1032 not completed:1 adverse event (AE), 65 withdrew consent (WC), 7 lost to follow up (LTF), 2 administrative (admin), 934 criteria not met, 2 non-compliant, 21 other. Lead-In: 588 randomized; 625 not randomized: 6 AE, 69 WC, 13 LTF, 8 admin, 2 at request, 497 criteria not met, 11 non-compliant, 19 other.
Participant milestones
| Measure |
Placebo Matching Dapagliflozin
Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dapagliflozin 10 mg
Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)
Dapagliflozin: Tablets, Oral, 5 mg, once a day for up to12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
This arm was discontinued with Amendment 8 to the protocol (implemented 1 November 2011) and the other 2 arms continued to enroll. This arm is not included in primary and secondary efficacy analysis.
|
|---|---|---|---|
|
Double Blind Treatment Period
STARTED
|
224
|
225
|
133
|
|
Double Blind Treatment Period
COMPLETED
|
202
|
211
|
119
|
|
Double Blind Treatment Period
NOT COMPLETED
|
22
|
14
|
14
|
|
Follow-Up(Week 13/1 Week Post Last Dose)
STARTED
|
203
|
209
|
120
|
|
Follow-Up(Week 13/1 Week Post Last Dose)
COMPLETED
|
200
|
209
|
119
|
|
Follow-Up(Week 13/1 Week Post Last Dose)
NOT COMPLETED
|
3
|
0
|
1
|
Reasons for withdrawal
| Measure |
Placebo Matching Dapagliflozin
Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dapagliflozin 10 mg
Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)
Dapagliflozin: Tablets, Oral, 5 mg, once a day for up to12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
This arm was discontinued with Amendment 8 to the protocol (implemented 1 November 2011) and the other 2 arms continued to enroll. This arm is not included in primary and secondary efficacy analysis.
|
|---|---|---|---|
|
Double Blind Treatment Period
Adverse Event
|
4
|
1
|
2
|
|
Double Blind Treatment Period
Withdrawal by Subject
|
6
|
4
|
4
|
|
Double Blind Treatment Period
Lost to Follow-up
|
3
|
2
|
3
|
|
Double Blind Treatment Period
Administrative reason
|
2
|
1
|
1
|
|
Double Blind Treatment Period
Requested discontinue treatment
|
1
|
0
|
1
|
|
Double Blind Treatment Period
No Longer Meets Criteria
|
1
|
5
|
2
|
|
Double Blind Treatment Period
Lack of Efficacy
|
2
|
0
|
0
|
|
Double Blind Treatment Period
Non-specified
|
3
|
0
|
0
|
|
Double Blind Treatment Period
Missing disposition information
|
0
|
1
|
1
|
|
Follow-Up(Week 13/1 Week Post Last Dose)
Withdrawal by Subject
|
2
|
0
|
1
|
|
Follow-Up(Week 13/1 Week Post Last Dose)
non-specified
|
1
|
0
|
0
|
Baseline Characteristics
A Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes With Inadequately Controlled Hypertension on an ACEI or ARB and an Additional Antihypertensive Medication
Baseline characteristics by cohort
| Measure |
Placebo Matching Dapagliflozin
n=224 Participants
Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dapagliflozin 10 mg
n=225 Participants
Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)
n=133 Participants
Dapagliflozin: Tablets, Oral, 5 mg, once daily, Up to 12 weeks. This arm discontinued with implementation of Amendment 8 to the protocol (1 November 2011). Study continued to enroll participants in other 2 arms post Amendment 8. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Total
n=582 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
Less than (<) 65 years
|
198 participants
n=5 Participants
|
198 participants
n=7 Participants
|
118 participants
n=5 Participants
|
514 participants
n=4 Participants
|
|
Age, Customized
Greater than, equal (>=) to 65 and < 75 years
|
25 participants
n=5 Participants
|
23 participants
n=7 Participants
|
14 participants
n=5 Participants
|
62 participants
n=4 Participants
|
|
Age, Customized
>= 75 years
|
1 participants
n=5 Participants
|
4 participants
n=7 Participants
|
1 participants
n=5 Participants
|
6 participants
n=4 Participants
|
|
Gender
Female
|
95 Participants
n=5 Participants
|
107 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
254 Participants
n=4 Participants
|
|
Gender
Male
|
129 Participants
n=5 Participants
|
118 Participants
n=7 Participants
|
81 Participants
n=5 Participants
|
328 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
157 participants
n=5 Participants
|
160 participants
n=7 Participants
|
84 participants
n=5 Participants
|
401 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
17 participants
n=5 Participants
|
19 participants
n=7 Participants
|
9 participants
n=5 Participants
|
45 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
38 participants
n=5 Participants
|
34 participants
n=7 Participants
|
36 participants
n=5 Participants
|
108 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Other Race
|
12 participants
n=5 Participants
|
12 participants
n=7 Participants
|
4 participants
n=5 Participants
|
28 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Ethnicity Hispanic/Latino
|
41 participants
n=5 Participants
|
47 participants
n=7 Participants
|
21 participants
n=5 Participants
|
109 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Ethnicity Not Hispanic/Latino
|
40 participants
n=5 Participants
|
38 participants
n=7 Participants
|
16 participants
n=5 Participants
|
94 participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Ethnicity Not Reported
|
143 participants
n=5 Participants
|
140 participants
n=7 Participants
|
96 participants
n=5 Participants
|
379 participants
n=4 Participants
|
|
Body Mass Index (BMI)
< 25 kg/m^2
|
21 participants
n=5 Participants
|
17 participants
n=7 Participants
|
9 participants
n=5 Participants
|
47 participants
n=4 Participants
|
|
Body Mass Index (BMI)
>=25 kg/m^2
|
203 participants
n=5 Participants
|
208 participants
n=7 Participants
|
124 participants
n=5 Participants
|
535 participants
n=4 Participants
|
|
Body Mass Index (BMI)
>=27 kg/m^2
|
179 participants
n=5 Participants
|
178 participants
n=7 Participants
|
101 participants
n=5 Participants
|
458 participants
n=4 Participants
|
|
Body Mass Index (BMI)
>=30 kg/m^2
|
147 participants
n=5 Participants
|
141 participants
n=7 Participants
|
73 participants
n=5 Participants
|
361 participants
n=4 Participants
|
|
Hypertension Medication
Thiazide or thiazide-like diuretics, no insulin
|
94 participants
n=5 Participants
|
95 participants
n=7 Participants
|
54 participants
n=5 Participants
|
243 participants
n=4 Participants
|
|
Hypertension Medication
Calcium channel and beta blockers, no insulin
|
114 participants
n=5 Participants
|
112 participants
n=7 Participants
|
79 participants
n=5 Participants
|
305 participants
n=4 Participants
|
|
Hypertension Medication
Thiazide or thiazide-like diuretics, insulin
|
5 participants
n=5 Participants
|
6 participants
n=7 Participants
|
0 participants
n=5 Participants
|
11 participants
n=4 Participants
|
|
Hypertension Medication
Calcium channel and beta blockers, insulin
|
11 participants
n=5 Participants
|
12 participants
n=7 Participants
|
0 participants
n=5 Participants
|
23 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 12Population: All randomized participants who received double-blind medication and had non-missing Baseline and on-study measurement. Data after rescue excluded from analyses
Systolic blood pressure (SBP) was measured in millimeters of mercury (mmHg) on Day -1, Day 1, Weeks 2, 4, 8, and 12 of the Double Blind Period. Blood pressure (BP) values were obtained after the participant was seated for quietly for 10 minutes; a mean of 3 replicate measurements was taken at least 1 minute apart. However, if the 3 consecutive seated BP readings were not within 8 mm Hg of each other, an additional 2 BP readings were obtained (total = 5) and incorporated into the calculated mean. BP was measured in both arms. If the BP was higher in one arm than the other, then this arm was used; if no difference, the participant's dominant arm was used for all future BP measurements. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. Participants refrained from ingestion of caffeine, alcohol, or nicotine at least 10 hours prior to their visit and having their BP measured.
Outcome measures
| Measure |
Placebo Matching Dapagliflozin
n=218 Participants
Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dapagliflozin 10 mg
n=221 Participants
Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)
Dapagliflozin: Tablets, Oral, 5 mg, once a day for up to12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
This arm was discontinued with Amendment 8 to the protocol (implemented 1 November 2011) and the other 2 arms continued to enroll. This arm is not included in primary and secondary efficacy analysis.
|
|---|---|---|---|
|
Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure for 12 Week Double-Blind Treatment Period - Randomized Participants
Week 2 (N=218, 221)
|
-5.13 mmHg
Standard Error 0.9489
|
-7.93 mmHg
Standard Error 0.9357
|
—
|
|
Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure for 12 Week Double-Blind Treatment Period - Randomized Participants
Week 4 (N=213, 220)
|
-6.05 mmHg
Standard Error 1.0232
|
-9.69 mmHg
Standard Error 1.0097
|
—
|
|
Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure for 12 Week Double-Blind Treatment Period - Randomized Participants
Week 8 (N=205, 212)
|
-6.80 mmHg
Standard Error 1.0374
|
-11.38 mmHg
Standard Error 1.0251
|
—
|
|
Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure for 12 Week Double-Blind Treatment Period - Randomized Participants
Week 12 (N=199, 205)
|
-7.62 mmHg
Standard Error 1.0701
|
-11.90 mmHg
Standard Error 1.0585
|
—
|
PRIMARY outcome
Timeframe: Baseline to Week 12Population: All randomized participants who received double-blind medication and had non-missing Baseline and on-study measurement. Data after rescue included.
Adjusted mean change in glycosylated hemoglobin ( HbA1c) from baseline at Week 12 was calculated. HbA1c was measured as percent of hemoglobin by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. HbA1c values were obtained at enrollment and lead-in (Day -28) periods, and at Day 1, Weeks 4, 8, and 12, in the double-blind period.
Outcome measures
| Measure |
Placebo Matching Dapagliflozin
n=214 Participants
Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dapagliflozin 10 mg
n=219 Participants
Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)
Dapagliflozin: Tablets, Oral, 5 mg, once a day for up to12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
This arm was discontinued with Amendment 8 to the protocol (implemented 1 November 2011) and the other 2 arms continued to enroll. This arm is not included in primary and secondary efficacy analysis.
|
|---|---|---|---|
|
Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) for 12 Week Double-Blind Treatment Period - Randomized Participants
Week 12 (N=197, 204)
|
-0.02 Percent of Hemoglobin
Standard Error 0.0673
|
-0.63 Percent of Hemoglobin
Standard Error 0.0668
|
—
|
|
Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) for 12 Week Double-Blind Treatment Period - Randomized Participants
Week 4 (N=214, 219)
|
-0.06 Percent of Hemoglobin
Standard Error 0.0498
|
-0.41 Percent of Hemoglobin
Standard Error 0.0496
|
—
|
|
Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) for 12 Week Double-Blind Treatment Period - Randomized Participants
Week 8 (N=207, 211)
|
-0.07 Percent of Hemoglobin
Standard Error 0.0606
|
-0.58 Percent of Hemoglobin
Standard Error 0.0602
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: All randomized participants who received double-blind medication and had non-missing Baseline and Week 12 (LOCF) values. Data after rescue excluded from analyses.
Ambulatory 24 hour (hr) blood pressure monitoring (ABPM) was performed at baseline, which was during the lead-in period (between Day -7 and Day -1 prior to randomization) and 1 week prior to the Week 12 visit/end of treatment visit. If no Week 12 measurement was available, the last available earlier post-baseline measurement was used (LOCF) for analysis. Initiation of the 24-hr ABPM began between 6am and 11am to ensure trough BP measurements were obtained.The ABPM units were calibrated, and used per the manufacturer's and central ABPM vendor instructions. BP was measured in mmHg. Participants had to have a mean 24-hour ABPM ≥ 130/80 mmHg prior to randomization. All medication was withheld on the morning of the study visit and brought to the visit site by the participant. Once the ABPM cuff was in place, all morning medication was taken while at the site.
Outcome measures
| Measure |
Placebo Matching Dapagliflozin
n=186 Participants
Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dapagliflozin 10 mg
n=187 Participants
Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)
Dapagliflozin: Tablets, Oral, 5 mg, once a day for up to12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
This arm was discontinued with Amendment 8 to the protocol (implemented 1 November 2011) and the other 2 arms continued to enroll. This arm is not included in primary and secondary efficacy analysis.
|
|---|---|---|---|
|
Adjusted Mean Change From Baseline in 24-hour Ambulatory Systolic Blood Pressure at Week 12 Last Observation Carried Forward (LOCF)
|
-6.88 mmHg
Standard Error 1.5793
|
-11.33 mmHg
Standard Error 1.6031
|
—
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: All randomized participants who received double-blind medication and had non-missing Baseline and on-study measurement. Data after rescue excluded from analyses
Diastolic BP was measured in millimeters of mercury (mmHg) on Day -1, Day 1, Weeks 2, 4, 8, and 12 of the Double Blind Period. Diastolic BP values were obtained after the participant was seated for quietly for 10 minutes; a mean of 3 replicate measurements was taken at least 1 minute apart. However, if the 3 consecutive seated BP readings were not within 8 mm Hg of each other, an additional 2 BP readings were obtained (total = 5) and incorporated into the calculated mean. BP was measured in both arms. If the pressure was higher in one arm than the other, then this arm was used; if no difference, the participant's dominant arm was used for all future BP measurements. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. Participants refrained from ingestion of caffeine, alcohol, or nicotine at least 10 hours prior to their visit and having their BP measured.
Outcome measures
| Measure |
Placebo Matching Dapagliflozin
n=218 Participants
Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dapagliflozin 10 mg
n=221 Participants
Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)
Dapagliflozin: Tablets, Oral, 5 mg, once a day for up to12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
This arm was discontinued with Amendment 8 to the protocol (implemented 1 November 2011) and the other 2 arms continued to enroll. This arm is not included in primary and secondary efficacy analysis.
|
|---|---|---|---|
|
Adjusted Mean Change From Baseline in Seated Diastolic Blood Pressure (DBP) for 12 Week Double-Blind Treatment Period - Randomized Participants
Week 2 (N=218, 221)
|
-3.84 mmHg
Standard Error 0.5691
|
-5.22 mmHg
Standard Error 0.5613
|
—
|
|
Adjusted Mean Change From Baseline in Seated Diastolic Blood Pressure (DBP) for 12 Week Double-Blind Treatment Period - Randomized Participants
Week 4 (N=213, 220)
|
-4.28 mmHg
Standard Error 0.5894
|
-5.57 mmHg
Standard Error 0.5818
|
—
|
|
Adjusted Mean Change From Baseline in Seated Diastolic Blood Pressure (DBP) for 12 Week Double-Blind Treatment Period - Randomized Participants
Week 8 (N=205, 212)
|
-4.76 mmHg
Standard Error 0.6247
|
-6.53 mmHg
Standard Error 0.6170
|
—
|
|
Adjusted Mean Change From Baseline in Seated Diastolic Blood Pressure (DBP) for 12 Week Double-Blind Treatment Period - Randomized Participants
Week 12 (N=199, 205)
|
-5.33 mmHg
Standard Error 0.6377
|
-6.30 mmHg
Standard Error 0.6308
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: All randomized participants who received double-blind medication and had non-missing Baseline and on-study measurement (Week 12 LOCF). Data after rescue excluded from analyses.
Ambulatory 24 hour (hr) BP monitoring (ABPM) was performed at baseline, which was during the lead-in period (between Day -7 and Day -1 prior to randomization) and 1 week prior to the Week 12 visit/end of treatment visit. If no Week 12 measurement was available, the last available earlier post-baseline measurement was used (LOCF). Initiation of the 24-hr ABPM began between 6am and 11am to ensure trough BP measurements were obtained. The ABPM units were calibrated, and used per the manufacturer's and central ABPM vendor instructions. BP was measured in mmHg. Participants had to have a mean 24-hour ABPM ≥ 130/80 mmHg prior to randomization. All medication was withheld on the morning of the study visit and brought to the visit site by the participant. Once the ABPM cuff was in place, all morning medication was taken while at the site.
Outcome measures
| Measure |
Placebo Matching Dapagliflozin
n=186 Participants
Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dapagliflozin 10 mg
n=187 Participants
Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)
Dapagliflozin: Tablets, Oral, 5 mg, once a day for up to12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
This arm was discontinued with Amendment 8 to the protocol (implemented 1 November 2011) and the other 2 arms continued to enroll. This arm is not included in primary and secondary efficacy analysis.
|
|---|---|---|---|
|
Adjusted Mean Change From Baseline in 24-hr Ambulatory Diastolic Blood Pressure at Week 12 (LOCF)
|
-5.57 mmHg
Standard Error 1.0042
|
-7.56 mmHg
Standard Error 1.0183
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: All randomized participants who received double-blind medication and had non-missing Baseline and on-study measurement. Data after rescue was included.
Adjusted mean change in serum uric acid from baseline at Week 12 was calculated. Serum uric acid was measured in milligrams per deciliter (mg/dL) by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. Serum uric acid measurements were obtained at qualification and lead-in (Day -28) periods, and at Day 1, Weeks 4, 8, and 12, in the double-blind period but only the change from baseline at Week 12 was considered a secondary endpoint and is presented.
Outcome measures
| Measure |
Placebo Matching Dapagliflozin
n=210 Participants
Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dapagliflozin 10 mg
n=219 Participants
Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)
Dapagliflozin: Tablets, Oral, 5 mg, once a day for up to12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
This arm was discontinued with Amendment 8 to the protocol (implemented 1 November 2011) and the other 2 arms continued to enroll. This arm is not included in primary and secondary efficacy analysis.
|
|---|---|---|---|
|
Adjusted Mean Change From Baseline in Serum Uric Acid at Week 12 in Double-Blind Treatment Period - Randomized Participants
|
-0.03 mg/dL
Standard Error 0.0890
|
-0.43 mg/dL
Standard Error 0.0883
|
—
|
SECONDARY outcome
Timeframe: Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic eventPopulation: Randomized participants who received double-blind study medication in the double-blind period.
Medical Dictionary for Regulatory Activities (MedDRA), version 15.1 AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or missing relationship to study drug as per the investigator. Events captured from baseline to last double blind dose plus 4 days for AEs, plus 30 days for SAEs during the Double Blind 12 Week Period. Only hypoglycemia reported as an SAE is included in AE/SAE categories . All reported hypoglycemia events within 4 days of last day of treatment are included as hypoglycemic events.
Outcome measures
| Measure |
Placebo Matching Dapagliflozin
n=224 Participants
Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dapagliflozin 10 mg
n=225 Participants
Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)
n=133 Participants
Dapagliflozin: Tablets, Oral, 5 mg, once a day for up to12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
This arm was discontinued with Amendment 8 to the protocol (implemented 1 November 2011) and the other 2 arms continued to enroll. This arm is not included in primary and secondary efficacy analysis.
|
|---|---|---|---|
|
Number of Participants With Deaths,Serious Adverse Events (SAEs), Adverse Events (AEs), Hypoglycemia Events, Discontinuation Due to AEs, SAEs and Hypoglycemia, During the 12 Week Double Blind Period, Including Data After Rescue
Deaths
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Deaths,Serious Adverse Events (SAEs), Adverse Events (AEs), Hypoglycemia Events, Discontinuation Due to AEs, SAEs and Hypoglycemia, During the 12 Week Double Blind Period, Including Data After Rescue
SAEs
|
2 participants
|
6 participants
|
1 participants
|
|
Number of Participants With Deaths,Serious Adverse Events (SAEs), Adverse Events (AEs), Hypoglycemia Events, Discontinuation Due to AEs, SAEs and Hypoglycemia, During the 12 Week Double Blind Period, Including Data After Rescue
Related SAEs
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Deaths,Serious Adverse Events (SAEs), Adverse Events (AEs), Hypoglycemia Events, Discontinuation Due to AEs, SAEs and Hypoglycemia, During the 12 Week Double Blind Period, Including Data After Rescue
AEs
|
93 participants
|
98 participants
|
60 participants
|
|
Number of Participants With Deaths,Serious Adverse Events (SAEs), Adverse Events (AEs), Hypoglycemia Events, Discontinuation Due to AEs, SAEs and Hypoglycemia, During the 12 Week Double Blind Period, Including Data After Rescue
Hypoglycemia AEs
|
6 participants
|
13 participants
|
2 participants
|
|
Number of Participants With Deaths,Serious Adverse Events (SAEs), Adverse Events (AEs), Hypoglycemia Events, Discontinuation Due to AEs, SAEs and Hypoglycemia, During the 12 Week Double Blind Period, Including Data After Rescue
Related AEs
|
12 participants
|
15 participants
|
8 participants
|
|
Number of Participants With Deaths,Serious Adverse Events (SAEs), Adverse Events (AEs), Hypoglycemia Events, Discontinuation Due to AEs, SAEs and Hypoglycemia, During the 12 Week Double Blind Period, Including Data After Rescue
Discontinued due to AE
|
4 participants
|
1 participants
|
2 participants
|
|
Number of Participants With Deaths,Serious Adverse Events (SAEs), Adverse Events (AEs), Hypoglycemia Events, Discontinuation Due to AEs, SAEs and Hypoglycemia, During the 12 Week Double Blind Period, Including Data After Rescue
Discontinued due to SAE
|
1 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Deaths,Serious Adverse Events (SAEs), Adverse Events (AEs), Hypoglycemia Events, Discontinuation Due to AEs, SAEs and Hypoglycemia, During the 12 Week Double Blind Period, Including Data After Rescue
Discontinued due to Hypoglycemia
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1) to last dose double blind medication (Week 12) plus 4 daysPopulation: N=All randomized participants who received at least one dose of double-blind medication. n=all treated participants who had non-missing Baseline and on-study measurement. Data after rescue included.
Samples obtained: Day 1, Weeks 4, 8,12 in Double Blind Period. Baseline: last assessment prior to start of first dose of double-blind treatment. Pretreatment (PreRX); grams per deciliter (g/dL); upper limit of normal (ULN); milliequivalent per liter (mEq/L); greater than (\>) less than (\<); Units per liter (U/L), Marked abnormality Low (High): hemoglobin \<6 (\>18 females or \>20 males) g/dL; creatinine (\>=1.5\*preRX, \>=2.5 mg/dL); glucose \< 54 or (\> 350) mg/dL; albumin \<= 2 or (\> 6) g/dL; creatine kinase \>5\*ULN; albumin/creatinine ratio (\>1800 mg/G); calcium \<7.5 (\>1 and \>0.5 from PreRX) mg/dL; bicarbonate \<=13 meq/dL; potassium \<=2.5 (\>6) meq/L; magnesium \<1 (\>4) mEq/L; sodium \< 130 mEq/L (\>150 mEq/L; phosphorus (\>=5.6 mg/dL age 17-65, \>=5.1 is \>=66 years); Albumin/creatinine ratio (\>1800 mg/g). Note: Hepatic tests are presented separately in next outcome measure.
Outcome measures
| Measure |
Placebo Matching Dapagliflozin
n=218 Participants
Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dapagliflozin 10 mg
n=223 Participants
Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)
Dapagliflozin: Tablets, Oral, 5 mg, once a day for up to12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
This arm was discontinued with Amendment 8 to the protocol (implemented 1 November 2011) and the other 2 arms continued to enroll. This arm is not included in primary and secondary efficacy analysis.
|
|---|---|---|---|
|
Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue
Hemoglobin High >18 g/dL (n=218, 223)
|
1 participants
|
0 participants
|
—
|
|
Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue
Creatinine >=1.5PreRx (n=218,223)
|
1 participants
|
3 participants
|
—
|
|
Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue
Glucose, plasma unspecif <54 mg/dL (n=218,222)
|
0 participants
|
1 participants
|
—
|
|
Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue
Glucose, plasma unspecif >350 mg/dL (n=218,222)
|
2 participants
|
1 participants
|
—
|
|
Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue
Creatine Kinase >5*ULN (n=218,223)
|
2 participants
|
0 participants
|
—
|
|
Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue
Creatine Kinase >10*ULN (n=218,223)
|
1 participants
|
0 participants
|
—
|
|
Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue
Calcium, total <7.5 mg (n=218,223)
|
0 participants
|
1 participants
|
—
|
|
Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue
Potassium, serum≥6 mEq/L (n=218,222)
|
0 participants
|
4 participants
|
—
|
|
Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue
Magnesium <1 mEq/L (n=218,223)
|
0 participants
|
2 participants
|
—
|
|
Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue
Sodium, serum <130 mEq/L (n=218,222)
|
1 participants
|
0 participants
|
—
|
|
Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue
Sodium, serum >150 mEq/L (n=218,222)
|
1 participants
|
1 participants
|
—
|
|
Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue
Phosphorus inorganic High (n=218,223)
|
0 participants
|
2 participants
|
—
|
|
Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue
Albumin/Creatinine Ratio High (n=218, 223)
|
5 participants
|
3 participants
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1) to last dose double blind medication (Week 12) Plus 30 daysPopulation: N=All randomized participants who received at least 1 dose of study medication. n=number of participants treated with double blind study medication with at least one non-missing post-baseline value. Data after rescue included.
Laboratories were obtained at Day 1, Weeks 4, 8 and 12 in the Double Blind Period. Baseline: last assessment prior to start of first dose of double-blind treatment. Includes laboratory values measured after the first date of double-blind treatment and up to and including the last day of double blind treatment plus 30 days. Upper limit of normal (ULN);, alanine aminotransferase (ALT); aspartate aminotransferase (AST); alkaline phosphatase (ALP). Marked abnormality (High): AST and ALT (\>3\*ULN); ALP (\>1.5\*ULN); bilirubin (\>1.5\*ULN). Participants with abnormally elevated liver laboratory tests were followed 30 days after the last dose of study drug.
Outcome measures
| Measure |
Placebo Matching Dapagliflozin
n=221 Participants
Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dapagliflozin 10 mg
n=224 Participants
Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)
Dapagliflozin: Tablets, Oral, 5 mg, once a day for up to12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
This arm was discontinued with Amendment 8 to the protocol (implemented 1 November 2011) and the other 2 arms continued to enroll. This arm is not included in primary and secondary efficacy analysis.
|
|---|---|---|---|
|
Number of Participants With Elevated Liver Laboratory Tests in Participants Treated With Double Blind 10 mg Dapagliflozin or Placebo , Including Data After Rescue
AST >3*ULN (n=221, 224)
|
0 participants
|
3 participants
|
—
|
|
Number of Participants With Elevated Liver Laboratory Tests in Participants Treated With Double Blind 10 mg Dapagliflozin or Placebo , Including Data After Rescue
AST >5*ULN (n=221, 224)
|
0 participants
|
1 participants
|
—
|
|
Number of Participants With Elevated Liver Laboratory Tests in Participants Treated With Double Blind 10 mg Dapagliflozin or Placebo , Including Data After Rescue
AST >10*ULN (n=221, 224)
|
0 participants
|
1 participants
|
—
|
|
Number of Participants With Elevated Liver Laboratory Tests in Participants Treated With Double Blind 10 mg Dapagliflozin or Placebo , Including Data After Rescue
AST >20*ULN (n=221, 224)
|
0 participants
|
1 participants
|
—
|
|
Number of Participants With Elevated Liver Laboratory Tests in Participants Treated With Double Blind 10 mg Dapagliflozin or Placebo , Including Data After Rescue
ALT >3*ULN (n=221, 224)
|
0 participants
|
3 participants
|
—
|
|
Number of Participants With Elevated Liver Laboratory Tests in Participants Treated With Double Blind 10 mg Dapagliflozin or Placebo , Including Data After Rescue
ALT >5*ULN (n=221, 224)
|
0 participants
|
2 participants
|
—
|
|
Number of Participants With Elevated Liver Laboratory Tests in Participants Treated With Double Blind 10 mg Dapagliflozin or Placebo , Including Data After Rescue
ALT >10*ULN (n=221, 224)
|
0 participants
|
1 participants
|
—
|
|
Number of Participants With Elevated Liver Laboratory Tests in Participants Treated With Double Blind 10 mg Dapagliflozin or Placebo , Including Data After Rescue
ALT >20*ULN (n=221, 224)
|
0 participants
|
1 participants
|
—
|
|
Number of Participants With Elevated Liver Laboratory Tests in Participants Treated With Double Blind 10 mg Dapagliflozin or Placebo , Including Data After Rescue
Total Bilirubin >1.5*ULN (n=221, 224)
|
0 participants
|
2 participants
|
—
|
|
Number of Participants With Elevated Liver Laboratory Tests in Participants Treated With Double Blind 10 mg Dapagliflozin or Placebo , Including Data After Rescue
Total Bilirubin >2*ULN (n=221, 224)
|
0 participants
|
1 participants
|
—
|
|
Number of Participants With Elevated Liver Laboratory Tests in Participants Treated With Double Blind 10 mg Dapagliflozin or Placebo , Including Data After Rescue
ALP >1.5*ULN (n=221, 224)
|
5 participants
|
4 participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: N= All randomized participants who received double-blind medication. Data after rescue included.
12-Lead electrocardiograms (ECGs) were performed at Enrollment, Day 1 of Double Blind Period and Week 12/End of treatment visit (last observation carried forward) on participants who were supine. ECGs were assessed by the investigator as normal or abnormal. Baseline (BL) was Day 1 prior to dosing or last observation prior to dosing.
Outcome measures
| Measure |
Placebo Matching Dapagliflozin
n=224 Participants
Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dapagliflozin 10 mg
n=225 Participants
Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)
Dapagliflozin: Tablets, Oral, 5 mg, once a day for up to12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
This arm was discontinued with Amendment 8 to the protocol (implemented 1 November 2011) and the other 2 arms continued to enroll. This arm is not included in primary and secondary efficacy analysis.
|
|---|---|---|---|
|
Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 12 (LOCF), Including Data After Rescue
Baseline normal/Week 12 normal
|
137 participants
|
130 participants
|
—
|
|
Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 12 (LOCF), Including Data After Rescue
Baseline normal/Week 12 abnormal
|
9 participants
|
10 participants
|
—
|
|
Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 12 (LOCF), Including Data After Rescue
Baseline normal/ Week 12 not reported
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 12 (LOCF), Including Data After Rescue
Baseline abnormal/Week 12 normal
|
10 participants
|
22 participants
|
—
|
|
Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 12 (LOCF), Including Data After Rescue
Baselline abnormal/Week 12 abnormal
|
48 participants
|
50 participants
|
—
|
|
Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 12 (LOCF), Including Data After Rescue
Baseline abnormal/Week 12 not reported
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 12 (LOCF), Including Data After Rescue
Baseline not reported/Week 12 normal
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 12 (LOCF), Including Data After Rescue
Baseline not reported/Week 12 abnormal
|
0 participants
|
0 participants
|
—
|
|
Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 12 (LOCF), Including Data After Rescue
Baseline not reported/Week 12 not reported
|
20 participants
|
13 participants
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1), Week 12Population: N= All randomized participants who received double-blind medication and had non-missing Week (t) values. Week 12 includes participants with orthostatic hypotension during Week 12 visit window. Data after rescue included.
Orthostatic hypotension was defined as a decrease from supine to standing of \> 20 mmHg in systolic BP or \>10 mmHg in diastolic BP. Proportion was calculated from number of participants with orthostatic hypotension (n) divided by the number of treated participants (N). n/N presented as a percent (%). Baseline was Day 1 of the double blind Period. Measurements for orthostatic hypotension were taken on Day 1 and at Week 12 visit and does not reflect AEs reported by the investigator.
Outcome measures
| Measure |
Placebo Matching Dapagliflozin
n=220 Participants
Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dapagliflozin 10 mg
n=222 Participants
Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)
Dapagliflozin: Tablets, Oral, 5 mg, once a day for up to12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
This arm was discontinued with Amendment 8 to the protocol (implemented 1 November 2011) and the other 2 arms continued to enroll. This arm is not included in primary and secondary efficacy analysis.
|
|---|---|---|---|
|
Proportion of Participants With Orthostatic Hypotension at Baseline and Week 12, Including Data After Rescue
Baseline n/N (2/220, 2/222)
|
0.9 Percent of Participants
|
0.9 Percent of Participants
|
—
|
|
Proportion of Participants With Orthostatic Hypotension at Baseline and Week 12, Including Data After Rescue
Week 12 n/N (4/199, 7/203)
|
2.0 Percent of Participants
|
3.4 Percent of Participants
|
—
|
Adverse Events
Placebo Matching Dapagliflozin
Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths
Dapagliflozin 10 mg
Serious events: 6 serious events
Other events: 0 other events
Deaths: 0 deaths
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo Matching Dapagliflozin
n=224 participants at risk
Placebo matching dapagliflozin: Tablets, Oral, 0 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dapagliflozin 10 mg
n=225 participants at risk
Dapagliflozin: Tablets, Oral, 10 mg, once daily, Up to 12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
|
Dagagliflozin 5 mg (Arm Discontinued With Amendment 8)
n=133 participants at risk
Dapagliflozin: Tablets, Oral, 5 mg, once a day for up to12 weeks. Non-investigational medications used in this study were antidiabetic drug(s), including oral antidiabetic drugs and insulin, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and an additional antihypertensive drug. All non-investigational medications were commercially available and were not supplied by the Sponsor.
This arm was discontinued with Amendment 8 to the protocol (implemented 1 November 2011) and the other 2 arms continued to enroll. This arm is not included in primary and secondary efficacy analysis.
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/224 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.44%
1/225 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.00%
0/133 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
|
Infections and infestations
Hepatitis E
|
0.00%
0/224 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.44%
1/225 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.00%
0/133 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
|
Injury, poisoning and procedural complications
Avulsion fracture
|
0.00%
0/224 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.44%
1/225 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.00%
0/133 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
0.00%
0/224 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.00%
0/225 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.75%
1/133 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
|
Cardiac disorders
Angina pectoris
|
0.45%
1/224 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.00%
0/225 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.00%
0/133 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/224 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.44%
1/225 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.00%
0/133 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.45%
1/224 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.00%
0/225 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.00%
0/133 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
|
Gastrointestinal disorders
Diverticular perforation
|
0.00%
0/224 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.44%
1/225 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.00%
0/133 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
|
Infections and infestations
Bronchitis
|
0.00%
0/224 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.44%
1/225 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.00%
0/133 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/224 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.44%
1/225 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
0.00%
0/133 • 12 Weeks plus 30 days
Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER