Trial Outcomes & Findings for Effects of Dapagliflozin on Kidney Function (Glomerular Filtration Rate) in Subjects With Type 2 Diabetes (NCT NCT00976495)

NCT ID: NCT00976495

Last Updated: 2017-03-08

Results Overview

Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. If no Week 12 measurement was available, the last available post-baseline measurement obtained on or after Day 23 was used regardless of rescue medication. Measurements were obtained during radomization visit, and Week 12 in the double-blind period by a central laboratory.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

154 participants

Primary outcome timeframe

From Baseline to Week 12

Results posted on

2017-03-08

Participant Flow

Of 154 participants enrolled, 77 completed a qualification period. Of these 77 participants, 75 were randomized and received treatment. Of these 75 participants, 74 completed double-blind treatment period.

Participant milestones

Participant milestones
Measure
Placebo
Tablet, oral, once daily for 12 weeks
Dapagliflozin 10 mg
Tablet, oral, once daily for 12 weeks
Hydrochlorothiazide 25 mg
Tablet, oral, once daily for 12 weeks
Overall Study
STARTED
25
24
26
Overall Study
COMPLETED
25
23
26
Overall Study
NOT COMPLETED
0
1
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Placebo
Tablet, oral, once daily for 12 weeks
Dapagliflozin 10 mg
Tablet, oral, once daily for 12 weeks
Hydrochlorothiazide 25 mg
Tablet, oral, once daily for 12 weeks
Overall Study
Withdrawal by Subject
0
1
0

Baseline Characteristics

Effects of Dapagliflozin on Kidney Function (Glomerular Filtration Rate) in Subjects With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Placebo
n=25 Participants
Tablet, oral, once daily for 12 weeks
Dapagliflozin 10 mg
n=24 Participants
Tablet, oral, once daily for 12 weeks
Hydrochlorothiazide 25 mg
n=26 Participants
Tablet, oral, once daily for 12 weeks
Total
n=75 Participants
Total of all reporting groups
Age, Continuous
58.0 Years
STANDARD_DEVIATION 9.50 • n=99 Participants
53.7 Years
STANDARD_DEVIATION 9.38 • n=107 Participants
54.8 Years
STANDARD_DEVIATION 9.87 • n=206 Participants
55.5 Years
STANDARD_DEVIATION 9.63 • n=7 Participants
Age, Customized
Younger than 65 years
19 Participants
n=99 Participants
22 Participants
n=107 Participants
21 Participants
n=206 Participants
62 Participants
n=7 Participants
Age, Customized
65 - 75 years
6 Participants
n=99 Participants
2 Participants
n=107 Participants
5 Participants
n=206 Participants
13 Participants
n=7 Participants
Sex/Gender, Customized
Male
18 Participants
n=99 Participants
16 Participants
n=107 Participants
15 Participants
n=206 Participants
49 Participants
n=7 Participants
Sex/Gender, Customized
Female
7 Participants
n=99 Participants
8 Participants
n=107 Participants
11 Participants
n=206 Participants
26 Participants
n=7 Participants
Race/Ethnicity, Customized
White
17 Participants
n=99 Participants
19 Participants
n=107 Participants
20 Participants
n=206 Participants
56 Participants
n=7 Participants
Race/Ethnicity, Customized
Black/African American
4 Participants
n=99 Participants
4 Participants
n=107 Participants
4 Participants
n=206 Participants
12 Participants
n=7 Participants
Race/Ethnicity, Customized
Asian
3 Participants
n=99 Participants
0 Participants
n=107 Participants
2 Participants
n=206 Participants
5 Participants
n=7 Participants
Race/Ethnicity, Customized
Other
1 Participants
n=99 Participants
1 Participants
n=107 Participants
0 Participants
n=206 Participants
2 Participants
n=7 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 12

Population: All randomized participants who received study medication and had nonmissing HbA1c values at baseline and Week 12 (MLOCF)

Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. If no Week 12 measurement was available, the last available post-baseline measurement obtained on or after Day 23 was used regardless of rescue medication. Measurements were obtained during radomization visit, and Week 12 in the double-blind period by a central laboratory.

Outcome measures

Outcome measures
Measure
Placebo
n=25 Participants
Tablet, oral, once daily for 12 weeks
Dapagliflozin 10 mg
n=22 Participants
Tablet, oral, once daily for 12 weeks
Hydrochlorothiazide 25 mg
n=26 Participants
Tablet, oral, once daily for 12 weeks
Adjusted Percent Change From Baseline in Glomerular Filtration Rate (GFR) at Week 12 (Modified Last Observation Carried Forward [MLOCF])
-2.92 % Change of Baseline GFR
Standard Error 2.0133
-10.76 % Change of Baseline GFR
Standard Error 1.9684
-3.40 % Change of Baseline GFR
Standard Error 1.9756

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: All randomized participants who received study medication and had nonmissing ASBP values at baseline and Week 12 (LOCF)

Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Measurements were obtained during lead-in, and Week 12 in the double-blind period.

Outcome measures

Outcome measures
Measure
Placebo
n=25 Participants
Tablet, oral, once daily for 12 weeks
Dapagliflozin 10 mg
n=22 Participants
Tablet, oral, once daily for 12 weeks
Hydrochlorothiazide 25 mg
n=25 Participants
Tablet, oral, once daily for 12 weeks
Adjusted Mean Change From Baseline in 24-Hour Ambulatory Systolic Blood Pressure (ASBP) at Week 12 (Last Observation Carried Forward [LOCF])
-0.88 mmHg
Standard Error 1.6373
-3.28 mmHg
Standard Error 1.7674
-6.55 mmHg
Standard Error 1.6833

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: All randomized participants who received study medication and had nonmissing ASBP values at baseline and Week 12 (LOCF)

Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Measurements were obtained during lead-in, and Week 12 in the double-blind period.

Outcome measures

Outcome measures
Measure
Placebo
n=25 Participants
Tablet, oral, once daily for 12 weeks
Dapagliflozin 10 mg
n=22 Participants
Tablet, oral, once daily for 12 weeks
Hydrochlorothiazide 25 mg
n=25 Participants
Tablet, oral, once daily for 12 weeks
Adjusted Mean Change From Baseline in Daytime (0900 to 2100 Hours) Ambulatory Systolic Blood Pressure (ASBP) at Week 12 (Last Observation Carried Forward [LOCF])
-1.55 mmHg
Standard Error 1.7247
-5.93 mmHg
Standard Error 1.8673
-6.83 mmHg
Standard Error 1.7671

SECONDARY outcome

Timeframe: From Baseline to Week 12

Population: All randomized participants who received study medication and had nonmissing ASBP values at baseline and Week 12 (LOCF)

Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Measurements were obtained during lead-in, and Week 12 in the double-blind period.

Outcome measures

Outcome measures
Measure
Placebo
n=25 Participants
Tablet, oral, once daily for 12 weeks
Dapagliflozin 10 mg
n=22 Participants
Tablet, oral, once daily for 12 weeks
Hydrochlorothiazide 25 mg
n=25 Participants
Tablet, oral, once daily for 12 weeks
Adjusted Mean Change From Baseline in Nighttime (0100 to 0600 Hours) Ambulatory Systolic Blood Pressure (ASBP) at Week 12 (Last Observation Carried Forward [LOCF])
-0.61 mmHg
Standard Error 1.9468
-0.45 mmHg
Standard Error 2.0822
-7.76 mmHg
Standard Error 1.9857

Adverse Events

Placebo

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Dapagliflozin 10 mg

Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths

Hydrochlorothiazide 25 mg

Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Placebo
n=25 participants at risk
Tablet, oral, once daily for 12 weeks
Dapagliflozin 10 mg
n=24 participants at risk
Tablet, oral, once daily for 12 weeks
Hydrochlorothiazide 25 mg
n=26 participants at risk
Tablet, oral, once daily for 12 weeks
Infections and infestations
LOCALISED INFECTION
0.00%
0/25 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
4.2%
1/24 • Number of events 1 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
0.00%
0/26 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Injury, poisoning and procedural complications
INTERVERTEBRAL DISC INJURY
0.00%
0/25 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
4.2%
1/24 • Number of events 1 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
0.00%
0/26 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Respiratory, thoracic and mediastinal disorders
PLEURITIC PAIN
0.00%
0/25 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
4.2%
1/24 • Number of events 1 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
0.00%
0/26 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.

Other adverse events

Other adverse events
Measure
Placebo
n=25 participants at risk
Tablet, oral, once daily for 12 weeks
Dapagliflozin 10 mg
n=24 participants at risk
Tablet, oral, once daily for 12 weeks
Hydrochlorothiazide 25 mg
n=26 participants at risk
Tablet, oral, once daily for 12 weeks
Renal and urinary disorders
POLLAKIURIA
4.0%
1/25 • Number of events 1 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
12.5%
3/24 • Number of events 3 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
3.8%
1/26 • Number of events 1 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Renal and urinary disorders
NOCTURIA
4.0%
1/25 • Number of events 1 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
8.3%
2/24 • Number of events 2 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
0.00%
0/26 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Skin and subcutaneous tissue disorders
HYPERHIDROSIS
0.00%
0/25 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
0.00%
0/24 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
7.7%
2/26 • Number of events 2 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Skin and subcutaneous tissue disorders
INGROWING NAIL
0.00%
0/25 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
0.00%
0/24 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
7.7%
2/26 • Number of events 2 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Nervous system disorders
HEADACHE
0.00%
0/25 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
4.2%
1/24 • Number of events 2 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
15.4%
4/26 • Number of events 4 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
Metabolism and nutrition disorders
MALAISE
0.00%
0/25 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
0.00%
0/24 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.
7.7%
2/26 • Number of events 2 • Onset on or after the first date of double-blind treatment and on or prior to the last day of double-blind treatment 12 weeks plus 4 days for non-serious adverse event; plus 30 days for serious adverse event.

Additional Information

Anna Maria Langkilde

AstraZeneca

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place