Trial Outcomes & Findings for A Study to Evaluate the Safety and Efficacy of AZD5718 in Participants With Proteinuric Chronic Kidney Disease (NCT NCT04492722)
NCT ID: NCT04492722
Last Updated: 2024-12-20
Results Overview
The dose response effect of AZD5718 on urine ACR at 20 weeks was evaluated. Values less than 1 indicate improvement from baseline.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
613 participants
Primary outcome timeframe
Week 1 (Baseline) to Week 20
Results posted on
2024-12-20
Participant Flow
Participants were enrolled in this study from 01 October 2020 to 06 September 2022. The study was terminated early on 01 July 2022 due to lack of efficacy.
The screening period was for 4 weeks. Participants who met all the inclusion and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment.
Participant milestones
| Measure |
AZD5718 Dose 1 + Dapagliflozin 10 mg
Participants received once daily oral dose of AZD5718 Dose 1 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 2 + Dapagliflozin 10 mg
Participants received once daily oral dose of AZD5718 Dose 2 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 3 + Dapagliflozin 10 mg
Participants received once daily oral dose of AZD5718 Dose 3 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
Placebo + Dapagliflozin 10 mg
Participants received once daily oral dose of placebo matched to AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
154
|
153
|
153
|
153
|
|
Overall Study
COMPLETED
|
72
|
82
|
82
|
82
|
|
Overall Study
NOT COMPLETED
|
82
|
71
|
71
|
71
|
Reasons for withdrawal
| Measure |
AZD5718 Dose 1 + Dapagliflozin 10 mg
Participants received once daily oral dose of AZD5718 Dose 1 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 2 + Dapagliflozin 10 mg
Participants received once daily oral dose of AZD5718 Dose 2 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 3 + Dapagliflozin 10 mg
Participants received once daily oral dose of AZD5718 Dose 3 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
Placebo + Dapagliflozin 10 mg
Participants received once daily oral dose of placebo matched to AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
7
|
2
|
3
|
0
|
|
Overall Study
Death
|
0
|
0
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
1
|
|
Overall Study
Physician Decision
|
0
|
3
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
6
|
6
|
0
|
3
|
|
Overall Study
Development of Study Specific Withdrawal Criteria
|
3
|
1
|
2
|
2
|
|
Overall Study
Due to Covid-19 pandemic
|
7
|
3
|
7
|
6
|
|
Overall Study
Failure to meet randomisation criteria
|
2
|
3
|
4
|
2
|
|
Overall Study
Early termination from the study
|
54
|
51
|
50
|
50
|
|
Overall Study
Missing
|
3
|
0
|
0
|
5
|
|
Overall Study
Participants who did not receive treatment
|
0
|
1
|
4
|
0
|
Baseline Characteristics
A Study to Evaluate the Safety and Efficacy of AZD5718 in Participants With Proteinuric Chronic Kidney Disease
Baseline characteristics by cohort
| Measure |
AZD5718 Dose 1 + Dapagliflozin 10 mg
n=154 Participants
Participants received once daily oral dose of AZD5718 Dose 1 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 2 + Dapagliflozin 10 mg
n=152 Participants
Participants received once daily oral dose of AZD5718 Dose 2 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 3 + Dapagliflozin 10 mg
n=149 Participants
Participants received once daily oral dose of AZD5718 Dose 3 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
Placebo + Dapagliflozin 10 mg
n=153 Participants
Participants received once daily oral dose of placebo matched to AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
Total
n=608 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
64.9 Years
STANDARD_DEVIATION 10.70 • n=5 Participants
|
63.7 Years
STANDARD_DEVIATION 10.63 • n=7 Participants
|
65.1 Years
STANDARD_DEVIATION 9.39 • n=5 Participants
|
64.3 Years
STANDARD_DEVIATION 10.71 • n=4 Participants
|
64.5 Years
STANDARD_DEVIATION 10.37 • n=21 Participants
|
|
Sex: Female, Male
Female
|
57 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
53 Participants
n=4 Participants
|
208 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
97 Participants
n=5 Participants
|
99 Participants
n=7 Participants
|
104 Participants
n=5 Participants
|
100 Participants
n=4 Participants
|
400 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
32 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
32 Participants
n=4 Participants
|
129 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
122 Participants
n=5 Participants
|
115 Participants
n=7 Participants
|
121 Participants
n=5 Participants
|
121 Participants
n=4 Participants
|
479 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
54 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
52 Participants
n=4 Participants
|
217 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
20 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
66 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
68 Participants
n=5 Participants
|
73 Participants
n=7 Participants
|
67 Participants
n=5 Participants
|
77 Participants
n=4 Participants
|
285 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
12 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
40 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Week 1 (Baseline) to Week 20Population: Per-protocol analysis set consisted of all participants who received the additional treatment with dapagliflozin post-Week 12 and who did not violate the terms of the protocol in a way that could affect the primary efficacy endpoint significantly.
The dose response effect of AZD5718 on urine ACR at 20 weeks was evaluated. Values less than 1 indicate improvement from baseline.
Outcome measures
| Measure |
AZD5718 Dose 1 + Dapagliflozin 10 mg
n=69 Participants
Participants received once daily oral dose of AZD5718 Dose 1 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 2 + Dapagliflozin 10 mg
n=67 Participants
Participants received once daily oral dose of AZD5718 Dose 2 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 3 + Dapagliflozin 10 mg
n=75 Participants
Participants received once daily oral dose of AZD5718 Dose 3 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
Placebo + Dapagliflozin 10 mg
n=76 Participants
Participants received once daily oral dose of placebo matched to AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in Reduction of Urine Albumin to Creatinine Ratio (ACR) to Week 20
|
0.79 milligram/gram (mg/g)
Interval 0.69 to 0.9
|
0.81 milligram/gram (mg/g)
Interval 0.7 to 0.92
|
0.77 milligram/gram (mg/g)
Interval 0.67 to 0.87
|
0.84 milligram/gram (mg/g)
Interval 0.73 to 0.95
|
SECONDARY outcome
Timeframe: Week 1 (Baseline) to Week 12Population: Per-protocol analysis set consisted of all participants who received the additional treatment with dapagliflozin post-Week 12 and who did not violate the terms of the protocol in a way that could affect the primary efficacy endpoint significantly.
The dose response effect of AZD5718 on urine ACR at 12 weeks was evaluated. Values less than 1 indicate improvement from baseline.
Outcome measures
| Measure |
AZD5718 Dose 1 + Dapagliflozin 10 mg
n=99 Participants
Participants received once daily oral dose of AZD5718 Dose 1 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 2 + Dapagliflozin 10 mg
n=97 Participants
Participants received once daily oral dose of AZD5718 Dose 2 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 3 + Dapagliflozin 10 mg
n=101 Participants
Participants received once daily oral dose of AZD5718 Dose 3 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
Placebo + Dapagliflozin 10 mg
n=104 Participants
Participants received once daily oral dose of placebo matched to AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in Reduction of Urine ACR to Week 12
|
0.94 mg/g
Interval 0.84 to 1.04
|
1.03 mg/g
Interval 0.92 to 1.15
|
0.96 mg/g
Interval 0.86 to 1.06
|
1.10 mg/g
Interval 0.99 to 1.22
|
SECONDARY outcome
Timeframe: From Screening (Week -4 to 0) to Week 24Population: All participants who were randomised and received any study treatment. Participants were evaluated according to the actual treatment they received. If a participant had received a different treatment dose than randomised throughout the study, they would have been analysed according to the treated dose, not the randomisation dose.
The safety and tolerability profile of AZD5718 treatment was assessed
Outcome measures
| Measure |
AZD5718 Dose 1 + Dapagliflozin 10 mg
n=154 Participants
Participants received once daily oral dose of AZD5718 Dose 1 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 2 + Dapagliflozin 10 mg
n=152 Participants
Participants received once daily oral dose of AZD5718 Dose 2 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 3 + Dapagliflozin 10 mg
n=149 Participants
Participants received once daily oral dose of AZD5718 Dose 3 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
Placebo + Dapagliflozin 10 mg
n=153 Participants
Participants received once daily oral dose of placebo matched to AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
|---|---|---|---|---|
|
Number of Participants With Adverse Events and Serious Adverse Events
Any AE
|
82 Participants
|
81 Participants
|
104 Participants
|
80 Participants
|
|
Number of Participants With Adverse Events and Serious Adverse Events
Any AE with outcome = death
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events and Serious Adverse Events
Any SAE (including events with outcome = death)
|
12 Participants
|
8 Participants
|
11 Participants
|
6 Participants
|
|
Number of Participants With Adverse Events and Serious Adverse Events
Any AE leading to discontinuation of study treatment
|
12 Participants
|
2 Participants
|
3 Participants
|
6 Participants
|
|
Number of Participants With Adverse Events and Serious Adverse Events
Any AE leading to dose interruption
|
7 Participants
|
6 Participants
|
5 Participants
|
10 Participants
|
|
Number of Participants With Adverse Events and Serious Adverse Events
Any AE leading to withdrawal from study
|
7 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events and Serious Adverse Events
Any AE possibly related to study treatment as assessed by investigator
|
14 Participants
|
12 Participants
|
8 Participants
|
14 Participants
|
SECONDARY outcome
Timeframe: Week 1 (Baseline) to Week 12Population: All participants in the Full Analysis Population who had valid Ambulatory Blood Pressure data for change from baseline analyses.
The effect of AZD5718 on ambulatory blood pressure was assessed
Outcome measures
| Measure |
AZD5718 Dose 1 + Dapagliflozin 10 mg
n=69 Participants
Participants received once daily oral dose of AZD5718 Dose 1 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 2 + Dapagliflozin 10 mg
n=78 Participants
Participants received once daily oral dose of AZD5718 Dose 2 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 3 + Dapagliflozin 10 mg
n=70 Participants
Participants received once daily oral dose of AZD5718 Dose 3 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
Placebo + Dapagliflozin 10 mg
n=85 Participants
Participants received once daily oral dose of placebo matched to AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in 24-hours Mean Systolic Blood Pressure to Week 12
|
-2.06 millimeter mercury (mm Hg)
Standard Deviation 10.782
|
1.56 millimeter mercury (mm Hg)
Standard Deviation 11.407
|
-1.83 millimeter mercury (mm Hg)
Standard Deviation 9.986
|
3.76 millimeter mercury (mm Hg)
Standard Deviation 11.779
|
SECONDARY outcome
Timeframe: From Week 2 to Week 20Population: All participants in the Full Analysis Population who have at least one detectable AZD5718 plasma concentration measurement post-treatment. The Pharmacokinetic Population was used for all PK analyses. Here "n" is the number of participants included in the analysis.
The PK of AZD5718 after repeated oral dosing for 20 weeks was evaluated
Outcome measures
| Measure |
AZD5718 Dose 1 + Dapagliflozin 10 mg
n=88 Participants
Participants received once daily oral dose of AZD5718 Dose 1 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 2 + Dapagliflozin 10 mg
n=91 Participants
Participants received once daily oral dose of AZD5718 Dose 2 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 3 + Dapagliflozin 10 mg
n=96 Participants
Participants received once daily oral dose of AZD5718 Dose 3 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
Placebo + Dapagliflozin 10 mg
Participants received once daily oral dose of placebo matched to AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
|---|---|---|---|---|
|
Plasma Concentrations of AZD5718
Week 2 (pre-dose)
|
4.771 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 113.047
|
12.181 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 116.038
|
37.346 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 138.565
|
—
|
|
Plasma Concentrations of AZD5718
Week 4 (pre-dose)
|
3.975 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 85.449
|
11.207 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 111.951
|
37.525 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 127.660
|
—
|
|
Plasma Concentrations of AZD5718
Week 8 (pre-dose)
|
3.947 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 77.097
|
11.579 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 113.404
|
35.903 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 116.207
|
—
|
|
Plasma Concentrations of AZD5718
Week 12 (pre-dose)
|
4.107 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 79.068
|
11.041 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 81.967
|
33.568 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 127.405
|
—
|
|
Plasma Concentrations of AZD5718
Week 16 (pre-dose)
|
4.115 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 76.378
|
10.006 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 97.216
|
35.662 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 130.148
|
—
|
|
Plasma Concentrations of AZD5718
Week 20 (pre-dose)
|
3.813 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 65.605
|
10.200 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 122.277
|
33.063 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 100.320
|
—
|
|
Plasma Concentrations of AZD5718
Week 4 (post-dose, 1-2 hours)
|
16.321 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 115.673
|
71.279 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 128.551
|
340.794 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 147.394
|
—
|
|
Plasma Concentrations of AZD5718
Week 4 (post-dose, 2-5 hours)
|
18.376 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 77.409
|
86.464 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 103.733
|
464.721 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 79.567
|
—
|
|
Plasma Concentrations of AZD5718
Week 4 (post-dose, 5-8 hours)
|
16.713 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 65.648
|
76.834 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 59.503
|
343.531 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 90.628
|
—
|
|
Plasma Concentrations of AZD5718
Week 4 (post dose, 8-12 hours)
|
14.434 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 52.414
|
53.706 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 68.160
|
234.913 nanomoles per liter (nmol/L)
Geometric Coefficient of Variation 97.174
|
—
|
SECONDARY outcome
Timeframe: Week 1 (Baseline), Week 2, Week 4, Week 8, and Week 12Population: Per-protocol analysis set consisted of all participants who received the additional treatment with dapagliflozin post-Week 12.
The effect of AZD5718 on renal function was evaluated
Outcome measures
| Measure |
AZD5718 Dose 1 + Dapagliflozin 10 mg
n=100 Participants
Participants received once daily oral dose of AZD5718 Dose 1 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 2 + Dapagliflozin 10 mg
n=101 Participants
Participants received once daily oral dose of AZD5718 Dose 2 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 3 + Dapagliflozin 10 mg
n=105 Participants
Participants received once daily oral dose of AZD5718 Dose 3 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
Placebo + Dapagliflozin 10 mg
n=106 Participants
Participants received once daily oral dose of placebo matched to AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
|---|---|---|---|---|
|
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) to Week 12
Week 12
|
-0.612 milliliter/minute/1.73m^2
Standard Deviation 6.2138
|
-1.149 milliliter/minute/1.73m^2
Standard Deviation 6.1783
|
-0.394 milliliter/minute/1.73m^2
Standard Deviation 6.4678
|
-0.257 milliliter/minute/1.73m^2
Standard Deviation 6.4508
|
|
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) to Week 12
Week 2
|
-0.470 milliliter/minute/1.73m^2
Standard Deviation 6.3936
|
-0.140 milliliter/minute/1.73m^2
Standard Deviation 5.2801
|
-0.429 milliliter/minute/1.73m^2
Standard Deviation 5.7175
|
0.547 milliliter/minute/1.73m^2
Standard Deviation 5.7124
|
|
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) to Week 12
Week 4
|
-0.735 milliliter/minute/1.73m^2
Standard Deviation 6.5764
|
0.140 milliliter/minute/1.73m^2
Standard Deviation 5.2628
|
-0.817 milliliter/minute/1.73m^2
Standard Deviation 6.1986
|
0.058 milliliter/minute/1.73m^2
Standard Deviation 6.3583
|
|
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) to Week 12
Week 8
|
-0.760 milliliter/minute/1.73m^2
Standard Deviation 6.0304
|
-0.535 milliliter/minute/1.73m^2
Standard Deviation 5.8865
|
-1.144 milliliter/minute/1.73m^2
Standard Deviation 6.5142
|
-0.068 milliliter/minute/1.73m^2
Standard Deviation 5.3729
|
Adverse Events
AZD5718 Dose 1 + Dapagliflozin 10 mg
Serious events: 12 serious events
Other events: 16 other events
Deaths: 0 deaths
AZD5718 Dose 2 + Dapagliflozin 10 mg
Serious events: 8 serious events
Other events: 8 other events
Deaths: 0 deaths
AZD5718 Dose 3 + Dapagliflozin 10 mg
Serious events: 11 serious events
Other events: 9 other events
Deaths: 0 deaths
Placebo + Dapagliflozin 10 mg
Serious events: 6 serious events
Other events: 8 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
AZD5718 Dose 1 + Dapagliflozin 10 mg
n=154 participants at risk
Participants received once daily oral dose of AZD5718 Dose 1 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 2 + Dapagliflozin 10 mg
n=152 participants at risk
Participants received once daily oral dose of AZD5718 Dose 2 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 3 + Dapagliflozin 10 mg
n=149 participants at risk
Participants received once daily oral dose of AZD5718 Dose 3 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
Placebo + Dapagliflozin 10 mg
n=153 participants at risk
Participants received once daily oral dose of placebo matched to AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
|---|---|---|---|---|
|
Infections and infestations
Pneumonia
|
0.65%
1/154 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
1.3%
2/149 • Number of events 2 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Infections and infestations
Urinary tract infection
|
0.65%
1/154 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.67%
1/149 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Infections and infestations
COVID-19
|
0.65%
1/154 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Infections and infestations
COVID-19 pneumonia
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.67%
1/149 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Infections and infestations
Liver abscess
|
0.65%
1/154 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Infections and infestations
Pelvic abscess
|
0.65%
1/154 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Infections and infestations
Peritonitis bacterial
|
0.65%
1/154 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Infections and infestations
Septic shock
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.67%
1/149 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Infections and infestations
Cellulitis
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.65%
1/153 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute leukaemia
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.66%
1/152 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.65%
1/154 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.66%
1/152 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Endocrine disorders
Pituitary apoplexy
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.67%
1/149 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.67%
1/149 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Psychiatric disorders
Conversion disorder
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.66%
1/152 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Nervous system disorders
Ischaemic stroke
|
0.65%
1/154 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.65%
1/153 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
|
Eye disorders
Cataract
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.66%
1/152 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Eye disorders
Vitreous haemorrhage
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.66%
1/152 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Cardiac disorders
Acute myocardial infarction
|
0.65%
1/154 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Cardiac disorders
Cardiac failure
|
0.65%
1/154 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Cardiac disorders
Cardiac failure chronic
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.66%
1/152 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.67%
1/149 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.65%
1/153 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
|
Vascular disorders
Peripheral ischaemia
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.66%
1/152 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Vascular disorders
Venous haemorrhage
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.66%
1/152 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Gastrointestinal disorders
Diverticulum
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.66%
1/152 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.65%
1/153 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
|
Hepatobiliary disorders
Cholangitis
|
0.65%
1/154 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.65%
1/154 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.65%
1/153 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.65%
1/153 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
|
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome
|
0.65%
1/154 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.66%
1/152 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Renal and urinary disorders
Chronic kidney disease
|
0.65%
1/154 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Renal and urinary disorders
Diabetic nephropathy
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.67%
1/149 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.65%
1/153 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
|
General disorders
Asthenia
|
0.65%
1/154 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
General disorders
Chest pain
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.67%
1/149 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
General disorders
Sudden death
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.65%
1/153 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
|
Injury, poisoning and procedural complications
Foreign body ingestion
|
0.65%
1/154 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.67%
1/149 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.67%
1/149 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Injury, poisoning and procedural complications
Limb traumatic amputation
|
0.00%
0/154 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.67%
1/149 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.65%
1/154 • Number of events 1 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/152 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/149 • From Screening (Week -4 to 0) to Week 24
|
0.00%
0/153 • From Screening (Week -4 to 0) to Week 24
|
Other adverse events
| Measure |
AZD5718 Dose 1 + Dapagliflozin 10 mg
n=154 participants at risk
Participants received once daily oral dose of AZD5718 Dose 1 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 2 + Dapagliflozin 10 mg
n=152 participants at risk
Participants received once daily oral dose of AZD5718 Dose 2 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
AZD5718 Dose 3 + Dapagliflozin 10 mg
n=149 participants at risk
Participants received once daily oral dose of AZD5718 Dose 3 for 12 weeks, and thereafter an add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
Placebo + Dapagliflozin 10 mg
n=153 participants at risk
Participants received once daily oral dose of placebo matched to AZD5718 for 12 weeks, thereafter add-on therapy of 10 mg dapagliflozin for 8 weeks.
|
|---|---|---|---|---|
|
Infections and infestations
Urinary tract infection
|
5.2%
8/154 • Number of events 8 • From Screening (Week -4 to 0) to Week 24
|
5.3%
8/152 • Number of events 8 • From Screening (Week -4 to 0) to Week 24
|
0.67%
1/149 • Number of events 2 • From Screening (Week -4 to 0) to Week 24
|
3.9%
6/153 • Number of events 6 • From Screening (Week -4 to 0) to Week 24
|
|
Investigations
Glomerular filtration rate decreased
|
5.2%
8/154 • Number of events 9 • From Screening (Week -4 to 0) to Week 24
|
2.0%
3/152 • Number of events 3 • From Screening (Week -4 to 0) to Week 24
|
3.4%
5/149 • Number of events 9 • From Screening (Week -4 to 0) to Week 24
|
5.2%
8/153 • Number of events 10 • From Screening (Week -4 to 0) to Week 24
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
3.9%
6/154 • Number of events 6 • From Screening (Week -4 to 0) to Week 24
|
4.6%
7/152 • Number of events 7 • From Screening (Week -4 to 0) to Week 24
|
6.0%
9/149 • Number of events 9 • From Screening (Week -4 to 0) to Week 24
|
3.9%
6/153 • Number of events 9 • From Screening (Week -4 to 0) to Week 24
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee No unpublished information contained herein may be disclosed without prior written approval from AstraZeneca. Access to this document must be restricted to relevant parties.
- Publication restrictions are in place
Restriction type: OTHER