Trial Outcomes & Findings for Efficacy, Safety and Tolerability of AZD9977 and Dapagliflozin in Participants With Heart Failure and Chronic Kidney Disease (NCT NCT04595370)

NCT ID: NCT04595370

Last Updated: 2024-11-19

Results Overview

The effect of AZD9977 in combination with dapagliflozin compared with dapagliflozin alone on UACR assessed. Urine samples were collected for the analysis of UACR. UACR (milligrams per gram \[mg/g\]) was calculated as 10 x urine albumin (mg per deciliter \[mg/dL\])/urine creatinine (g/dL). Change from baseline in UACR at the end of 12 weeks of study treatment was calculated as the average of the UACR values at Week 12 and was analyzed by a mixed-effects model for repeated measures (MMRM). Due to early removal of arms (AZD9977 150 mg monotherapy and Placebo), the study objectives were revised and the MMRM analysis included the 4 remaining arms (AZD9977 15 mg + Dapagliflozin, AZD9977 50 mg + Dapagliflozin, AZD9977 150 mg + Dapagliflozin, and Dapagliflozin 10 mg). Since 2 arms were removed from the study resulting in fewer participants only descriptive statistics are shown for those two arms without formal comparison.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 153 participants
• Primary outcome timeframe: Baseline (Day 1) to Week 12
• Results posted on: 2024-11-19

Participant Flow

The study was conducted between 26-January-2021 (first subject first visit) to 22-September-2023 (last subject last visit).

Participants who signed the Informed Consent Form (ICF) were enrolled into study. The study included an optional pre-screening visit.

Participant milestones

Measure	AZD9977 15 mg + Dapagliflozin 10 mg Participants received AZD9977 15 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 50 mg + Dapagliflozin 10 mg Participants received AZD9977 50 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg + Dapagliflozin 10 mg Participants received AZD9977 150 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg Participants received AZD9977 150 mg and placebo matching to dapagliflozin orally once daily for 12 weeks.	Dapagliflozin 10 mg Participants received dapagliflozin 10 mg and placebo matching to AZD9977 orally once daily for 12 weeks.	Placebo Placebo participants received placebo matching to AZD9977 and dapagliflozin orally once daily for 12 weeks.
Overall Study STARTED	35	33	36	7	35	7
Overall Study COMPLETED	33	25	27	6	29	6
Overall Study NOT COMPLETED	2	8	9	1	6	1

Reasons for withdrawal

Measure	AZD9977 15 mg + Dapagliflozin 10 mg Participants received AZD9977 15 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 50 mg + Dapagliflozin 10 mg Participants received AZD9977 50 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg + Dapagliflozin 10 mg Participants received AZD9977 150 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg Participants received AZD9977 150 mg and placebo matching to dapagliflozin orally once daily for 12 weeks.	Dapagliflozin 10 mg Participants received dapagliflozin 10 mg and placebo matching to AZD9977 orally once daily for 12 weeks.	Placebo Placebo participants received placebo matching to AZD9977 and dapagliflozin orally once daily for 12 weeks.
Overall Study Subjects randomised, not treated, Protocol Deviation	1	0	0	0	0	0
Overall Study Subjects randomised, not treated, Withdrawal by Subject	0	0	1	0	0	0
Overall Study Adverse Event	0	4	3	1	1	1
Overall Study Withdrawal of Consent	1	1	1	0	0	0
Overall Study Death	0	1	0	0	1	0
Overall Study Protocol-Specified Withdrawal Criterion Met	0	0	1	0	0	0
Overall Study Withdrawal by Subject	0	0	1	0	2	0
Overall Study Lost to Follow-up	0	0	0	0	1	0
Overall Study Participants discontinued study treatment due to other reasons	0	2	2	0	1	0

Baseline Characteristics

Efficacy, Safety and Tolerability of AZD9977 and Dapagliflozin in Participants With Heart Failure and Chronic Kidney Disease

Baseline characteristics by cohort

Measure	AZD9977 15 mg + Dapagliflozin 10 mg n=34 Participants Participants received AZD9977 15 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 50 mg + Dapagliflozin 10 mg n=31 Participants Participants received AZD9977 50 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg + Dapagliflozin 10 mg n=35 Participants Participants received AZD9977 150 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg n=6 Participants Participants received AZD9977 150 mg and placebo matching to dapagliflozin orally once daily for 12 weeks.	Dapagliflozin 10 mg n=33 Participants Participants received dapagliflozin 10 mg and placebo matching to AZD9977 orally once daily for 12 weeks.	Placebo n=5 Participants Placebo participants received placebo matching to AZD9977 and dapagliflozin orally once daily for 12 weeks.	Total n=144 Participants Total of all reporting groups
Age, Continuous	70.9 Years STANDARD_DEVIATION 7.1 • n=5 Participants	72.4 Years STANDARD_DEVIATION 8.4 • n=7 Participants	73.7 Years STANDARD_DEVIATION 8.1 • n=5 Participants	77.0 Years STANDARD_DEVIATION 8.7 • n=4 Participants	72.2 Years STANDARD_DEVIATION 9.4 • n=21 Participants	77.2 Years STANDARD_DEVIATION 5.8 • n=10 Participants	72.7 Years STANDARD_DEVIATION 8.2 • n=115 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants	1 Participants n=4 Participants	10 Participants n=21 Participants	1 Participants n=10 Participants	36 Participants n=115 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	26 Participants n=7 Participants	27 Participants n=5 Participants	5 Participants n=4 Participants	23 Participants n=21 Participants	4 Participants n=10 Participants	108 Participants n=115 Participants
Race/Ethnicity, Customized Asian	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants	0 Participants n=10 Participants	17 Participants n=115 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants	1 Participants n=10 Participants	5 Participants n=115 Participants
Race/Ethnicity, Customized White	30 Participants n=5 Participants	27 Participants n=7 Participants	27 Participants n=5 Participants	6 Participants n=4 Participants	28 Participants n=21 Participants	4 Participants n=10 Participants	122 Participants n=115 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Week 12

Population: Full analysis set included all participants who were randomized and either received or did not receive any study intervention. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

The effect of AZD9977 in combination with dapagliflozin compared with dapagliflozin alone on UACR assessed. Urine samples were collected for the analysis of UACR. UACR (milligrams per gram [mg/g]) was calculated as 10 x urine albumin (mg per deciliter [mg/dL])/urine creatinine (g/dL). Change from baseline in UACR at the end of 12 weeks of study treatment was calculated as the average of the UACR values at Week 12 and was analyzed by a mixed-effects model for repeated measures (MMRM). Due to early removal of arms (AZD9977 150 mg monotherapy and Placebo), the study objectives were revised and the MMRM analysis included the 4 remaining arms (AZD9977 15 mg + Dapagliflozin, AZD9977 50 mg + Dapagliflozin, AZD9977 150 mg + Dapagliflozin, and Dapagliflozin 10 mg). Since 2 arms were removed from the study resulting in fewer participants only descriptive statistics are shown for those two arms without formal comparison.

Outcome measures

Measure	AZD9977 15 mg + Dapagliflozin 10 mg n=32 Participants Participants received AZD9977 15 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 50 mg + Dapagliflozin 10 mg n=23 Participants Participants received AZD9977 50 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg + Dapagliflozin 10 mg n=25 Participants Participants received AZD9977 150 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg n=5 Participants Participants received AZD9977 150 mg and placebo matching to dapagliflozin orally once daily for 12 weeks.	Dapagliflozin 10 mg n=28 Participants Participants received dapagliflozin 10 mg and placebo matching to AZD9977 orally once daily for 12 weeks.	Placebo n=3 Participants Placebo participants received placebo matching to AZD9977 and dapagliflozin orally once daily for 12 weeks.
Percent Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at Week 12	-56.391 Percent change from baseline Interval -71.528 to -33.207	-42.085 Percent change from baseline Interval -64.174 to -6.376	-58.047 Percent change from baseline Interval -73.56 to -33.43	-45.01 Percent change from baseline NA indicates that the lower and upper limits of the 95% CI were not calculated due to insufficient number of participants enrolled in this arm.	-34.318 Percent change from baseline Interval -58.204 to 3.22	230.32 Percent change from baseline NA indicates that the lower and upper limits of the 95% CI were not calculated due to insufficient number of participants enrolled in this arm.

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 12

Population: Full analysis set included all participants who were randomized and either received or did not receive any study intervention. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

The dose-response relationship of dapagliflozin alone and 3 doses of AZD9977 combined with dapagliflozin on UACR was assessed. Urine samples were collected for the analysis of UACR. UACR (mg/g) was calculated as 10 x urine albumin (mg/dL)/urine creatinine (g/dL). Change from baseline in UACR at the end of 12 weeks of study treatment was calculated as the average of the UACR values at Week 12 and was analyzed by a mixed-effects model for repeated measures (MMRM). Due to early removal of arms (AZD9977 150 mg monotherapy and Placebo), the study objectives were revised and the MMRM analysis included the 4 remaining arms (AZD9977 15 mg + Dapagliflozin, AZD9977 50 mg + Dapagliflozin, AZD9977 150 mg + Dapagliflozin, and Dapagliflozin 10 mg). Since 2 arms were removed from the study resulting in fewer participants, only descriptive statistics was shown for those two arms without formal comparison.

Outcome measures

Measure	AZD9977 15 mg + Dapagliflozin 10 mg n=32 Participants Participants received AZD9977 15 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 50 mg + Dapagliflozin 10 mg n=23 Participants Participants received AZD9977 50 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg + Dapagliflozin 10 mg n=25 Participants Participants received AZD9977 150 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg n=5 Participants Participants received AZD9977 150 mg and placebo matching to dapagliflozin orally once daily for 12 weeks.	Dapagliflozin 10 mg n=28 Participants Participants received dapagliflozin 10 mg and placebo matching to AZD9977 orally once daily for 12 weeks.	Placebo n=7 Participants Placebo participants received placebo matching to AZD9977 and dapagliflozin orally once daily for 12 weeks.
Percent Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) at 12 Weeks to Assess Dose-Response Relationship	-56.391 Percent change from baseline Interval -71.528 to -33.207	-42.085 Percent change from baseline Interval -64.174 to -6.376	-58.047 Percent change from baseline Interval -73.56 to -33.43	-45.01 Percent change from baseline NA indicates that the lower and upper limits of the 95% CI were not calculated due to insufficient number of participants enrolled in this arm.	-34.318 Percent change from baseline Interval -58.204 to 3.22	230.32 Percent change from baseline NA indicates that the lower and upper limits of the 95% CI were not calculated due to insufficient number of participants enrolled in this arm.

SECONDARY outcome

Timeframe: From baseline (Day 1) until Day 113

Population: Safety analysis set included all participants who were randomized and received any study intervention. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

The safety and tolerability of AZD9977 combined with dapagliflozin 10 mg, AZD9977 monotherapy, dapagliflozin 10 mg monotherapy and placebo was assessed.

Outcome measures

Measure	AZD9977 15 mg + Dapagliflozin 10 mg n=33 Participants Participants received AZD9977 15 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 50 mg + Dapagliflozin 10 mg n=31 Participants Participants received AZD9977 50 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg + Dapagliflozin 10 mg n=34 Participants Participants received AZD9977 150 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg n=6 Participants Participants received AZD9977 150 mg and placebo matching to dapagliflozin orally once daily for 12 weeks.	Dapagliflozin 10 mg n=33 Participants Participants received dapagliflozin 10 mg and placebo matching to AZD9977 orally once daily for 12 weeks.	Placebo n=5 Participants Placebo participants received placebo matching to AZD9977 and dapagliflozin orally once daily for 12 weeks.
Number of Participants With Adverse Events (AEs) Any AE leading to dose interruption	1 Participants	1 Participants	1 Participants	0 Participants	3 Participants	1 Participants
Number of Participants With Adverse Events (AEs) Any AE	9 Participants	12 Participants	18 Participants	5 Participants	14 Participants	3 Participants
Number of Participants With Adverse Events (AEs) Any SAE	1 Participants	3 Participants	2 Participants	0 Participants	4 Participants	2 Participants
Number of Participants With Adverse Events (AEs) Any SAE with outcome death	0 Participants	2 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Adverse Events (AEs) Any AE leading to discontinuation of IP	0 Participants	4 Participants	3 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With Adverse Events (AEs) Any AE leading to withdrawal from study	0 Participants	5 Participants	2 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 12

Population: Safety analysis set included all participants who were randomized and received any study intervention. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

Effect of AZD9977 combined with dapagliflozin 10 mg, AZD9977 monotherapy, dapagliflozin 10 mg monotherapy and placebo on serum K+ was assessed.

Outcome measures

Measure	AZD9977 15 mg + Dapagliflozin 10 mg n=27 Participants Participants received AZD9977 15 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 50 mg + Dapagliflozin 10 mg n=21 Participants Participants received AZD9977 50 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg + Dapagliflozin 10 mg n=25 Participants Participants received AZD9977 150 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg n=4 Participants Participants received AZD9977 150 mg and placebo matching to dapagliflozin orally once daily for 12 weeks.	Dapagliflozin 10 mg n=25 Participants Participants received dapagliflozin 10 mg and placebo matching to AZD9977 orally once daily for 12 weeks.	Placebo n=3 Participants Placebo participants received placebo matching to AZD9977 and dapagliflozin orally once daily for 12 weeks.
Change From Baseline in Serum Potassium (K+)	0.056 millimoles per liter (mmol/L) Interval -0.106 to 0.219	0.003 millimoles per liter (mmol/L) Interval -0.184 to 0.19	0.109 millimoles per liter (mmol/L) Interval -0.061 to 0.279	0.55 millimoles per liter (mmol/L) NA indicates that the lower and upper limits of the 95% CI were not calculated due to insufficient number of participants enrolled in this arm.	0.040 millimoles per liter (mmol/L) Interval -0.129 to 0.209	0.03 millimoles per liter (mmol/L) NA indicates that the lower and upper limits of the 95% CI were not calculated due to insufficient number of participants enrolled in this arm.

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 12

Population: Safety analysis set included all participants who were randomized and received any study intervention. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

Effect of AZD9977 combined with dapagliflozin 10 mg, AZD9977 monotherapy, dapagliflozin 10 mg monotherapy and placebo on serum K+ was assessed.

Outcome measures

Measure	AZD9977 15 mg + Dapagliflozin 10 mg n=30 Participants Participants received AZD9977 15 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 50 mg + Dapagliflozin 10 mg n=25 Participants Participants received AZD9977 50 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg + Dapagliflozin 10 mg n=29 Participants Participants received AZD9977 150 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg n=5 Participants Participants received AZD9977 150 mg and placebo matching to dapagliflozin orally once daily for 12 weeks.	Dapagliflozin 10 mg n=33 Participants Participants received dapagliflozin 10 mg and placebo matching to AZD9977 orally once daily for 12 weeks.	Placebo n=5 Participants Placebo participants received placebo matching to AZD9977 and dapagliflozin orally once daily for 12 weeks.
Absolute Value of Serum Potassium Over Time Baseline	4.60 mmol/L Standard Deviation 0.38	4.44 mmol/L Standard Deviation 0.61	4.46 mmol/L Standard Deviation 0.44	4.50 mmol/L Standard Deviation 0.38	4.60 mmol/L Standard Deviation 0.66	4.50 mmol/L Standard Deviation 0.28
Absolute Value of Serum Potassium Over Time Week 12	4.62 mmol/L Standard Deviation 0.50	4.53 mmol/L Standard Deviation 0.43	4.63 mmol/L Standard Deviation 0.43	5.00 mmol/L Standard Deviation 0.61	4.64 mmol/L Standard Deviation 0.40	4.33 mmol/L Standard Deviation 0.32

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 12

Population: Safety analysis set included all participants who were randomized and received any study intervention. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

Effect of AZD9977 combined with dapagliflozin 10 mg, AZD9977 monotherapy, dapagliflozin 10 mg monotherapy and placebo on eGFR was assessed.

Outcome measures

Measure	AZD9977 15 mg + Dapagliflozin 10 mg n=26 Participants Participants received AZD9977 15 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 50 mg + Dapagliflozin 10 mg n=21 Participants Participants received AZD9977 50 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg + Dapagliflozin 10 mg n=24 Participants Participants received AZD9977 150 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg n=4 Participants Participants received AZD9977 150 mg and placebo matching to dapagliflozin orally once daily for 12 weeks.	Dapagliflozin 10 mg n=23 Participants Participants received dapagliflozin 10 mg and placebo matching to AZD9977 orally once daily for 12 weeks.	Placebo n=3 Participants Placebo participants received placebo matching to AZD9977 and dapagliflozin orally once daily for 12 weeks.
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)	-1.432 mL/min/1.73 m^2 Interval -4.305 to 1.441	-1.160 mL/min/1.73 m^2 Interval -4.351 to 2.03	-5.307 mL/min/1.73 m^2 Interval -8.295 to -2.32	-0.923 mL/min/1.73 m^2 NA indicates that the lower and upper limits of the 95% CI were not calculated due to insufficient number of participants enrolled in this arm.	-3.498 mL/min/1.73 m^2 Interval -6.528 to -0.469	6.880 mL/min/1.73 m^2 NA indicates that the lower and upper limits of the 95% CI were not calculated due to insufficient number of participants enrolled in this arm.

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 12

Population: Safety analysis set included all participants who were randomized and received any study intervention. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

Effect of all doses of AZD9977 combined with dapagliflozin 10 mg, AZD9977 monotherapy, dapagliflozin 10 mg monotherapy and placebo on eGFR was assessed

Outcome measures

Measure	AZD9977 15 mg + Dapagliflozin 10 mg n=32 Participants Participants received AZD9977 15 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 50 mg + Dapagliflozin 10 mg n=31 Participants Participants received AZD9977 50 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg + Dapagliflozin 10 mg n=33 Participants Participants received AZD9977 150 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg n=5 Participants Participants received AZD9977 150 mg and placebo matching to dapagliflozin orally once daily for 12 weeks.	Dapagliflozin 10 mg n=32 Participants Participants received dapagliflozin 10 mg and placebo matching to AZD9977 orally once daily for 12 weeks.	Placebo n=5 Participants Placebo participants received placebo matching to AZD9977 and dapagliflozin orally once daily for 12 weeks.
Absolute Value of eGFR Over Time Baseline	41.341 mL/min/1.73 m^2 Standard Deviation 12.902	38.586 mL/min/1.73 m^2 Standard Deviation 10.155	43.663 mL/min/1.73 m^2 Standard Deviation 16.168	36.874 mL/min/1.73 m^2 Standard Deviation 12.626	41.895 mL/min/1.73 m^2 Standard Deviation 12.791	40.288 mL/min/1.73 m^2 Standard Deviation 15.176
Absolute Value of eGFR Over Time Week 12	41.219 mL/min/1.73 m^2 Standard Deviation 15.112	39.429 mL/min/1.73 m^2 Standard Deviation 8.998	39.063 mL/min/1.73 m^2 Standard Deviation 13.819	34.075 mL/min/1.73 m^2 Standard Deviation 21.071	37.973 mL/min/1.73 m^2 Standard Deviation 11.571	48.920 mL/min/1.73 m^2 Standard Deviation 21.111

Adverse Events

AZD9977 15 mg + Dapagliflozin 10 mg

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

AZD9977 50 mg + Dapagliflozin 10 mg

Serious events: 3 serious events

Other events: 4 other events

Deaths: 2 deaths

AZD9977 150 mg + Dapagliflozin 10 mg

Serious events: 2 serious events

Other events: 13 other events

Deaths: 0 deaths

AZD9977 150 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Dapagliflozin 10 mg

Serious events: 4 serious events

Other events: 7 other events

Deaths: 1 deaths

Placebo

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	AZD9977 15 mg + Dapagliflozin 10 mg n=33 participants at risk Participants received AZD9977 15 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 50 mg + Dapagliflozin 10 mg n=31 participants at risk Participants received AZD9977 50 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg + Dapagliflozin 10 mg n=34 participants at risk Participants received AZD9977 150 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg n=6 participants at risk Participants received AZD9977 150 mg and placebo matching to dapagliflozin orally once daily for 12 weeks.	Dapagliflozin 10 mg n=33 participants at risk Participants received dapagliflozin 10 mg and placebo matching to AZD9977 orally once daily for 12 weeks.	Placebo n=5 participants at risk Placebo participants received placebo matching to AZD9977 and dapagliflozin orally once daily for 12 weeks.
Infections and infestations COVID-19	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	3.2% 1/31 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/34 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	20.0% 1/5 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Nervous system disorders Transient ischaemic attack	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	2.9% 1/34 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Cardiac disorders Cardiac failure	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	3.2% 1/31 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	2.9% 1/34 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	20.0% 1/5 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Cardiac disorders Cardiac failure congestive	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/34 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	3.0% 1/33 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Cardiac disorders Left ventricular failure	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	3.2% 1/31 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/34 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/34 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	3.0% 1/33 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	3.2% 1/31 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/34 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
General disorders Peripheral swelling	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/34 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	3.0% 1/33 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
General disorders Sudden cardiac death	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/34 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	3.0% 1/33 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Investigations Hepatic enzyme increased	3.0% 1/33 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/34 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.

Other adverse events

Measure	AZD9977 15 mg + Dapagliflozin 10 mg n=33 participants at risk Participants received AZD9977 15 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 50 mg + Dapagliflozin 10 mg n=31 participants at risk Participants received AZD9977 50 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg + Dapagliflozin 10 mg n=34 participants at risk Participants received AZD9977 150 mg and dapagliflozin 10 mg orally once daily for 12 weeks.	AZD9977 150 mg n=6 participants at risk Participants received AZD9977 150 mg and placebo matching to dapagliflozin orally once daily for 12 weeks.	Dapagliflozin 10 mg n=33 participants at risk Participants received dapagliflozin 10 mg and placebo matching to AZD9977 orally once daily for 12 weeks.	Placebo n=5 participants at risk Placebo participants received placebo matching to AZD9977 and dapagliflozin orally once daily for 12 weeks.
Infections and infestations Nasopharyngitis	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	8.8% 3/34 • Number of events 3 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	3.0% 1/33 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Infections and infestations Urinary tract infection	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	3.2% 1/31 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	2.9% 1/34 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	9.1% 3/33 • Number of events 3 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Infections and infestations Urinary tract infection bacterial	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	6.5% 2/31 • Number of events 2 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	2.9% 1/34 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	3.2% 1/31 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	5.9% 2/34 • Number of events 2 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	16.7% 1/6 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	9.1% 3/33 • Number of events 3 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Vascular disorders Hypertensive crisis	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	5.9% 2/34 • Number of events 2 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Gastrointestinal disorders Diarrhoea	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	5.9% 2/34 • Number of events 2 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	20.0% 1/5 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Gastrointestinal disorders Nausea	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	5.9% 2/34 • Number of events 2 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Renal and urinary disorders Chronic kidney disease	3.0% 1/33 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	3.2% 1/31 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	5.9% 2/34 • Number of events 2 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	16.7% 1/6 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	3.0% 1/33 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Injury, poisoning and procedural complications Fall	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	2.9% 1/34 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	6.1% 2/33 • Number of events 2 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Vascular disorders Hypotension	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/34 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	16.7% 1/6 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Vascular disorders Syncope	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	2.9% 1/34 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	20.0% 1/5 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Nervous system disorders Headache	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/34 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	16.7% 1/6 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Musculoskeletal and connective tissue disorders Spinal pain	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/34 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	16.7% 1/6 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Gastrointestinal disorders Gingival recession	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/34 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	16.7% 1/6 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/5 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Gastrointestinal disorders Colitis	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/34 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	20.0% 1/5 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Endocrine disorders Hyperthyroidism	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/34 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	20.0% 1/5 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/34 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	20.0% 1/5 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.
Endocrine disorders Diabetes mellitus	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/31 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/34 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/6 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	0.00% 0/33 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.	20.0% 1/5 • Number of events 1 • From baseline (Day 1) until Day 113 Safety set included all participants who were randomized and received any study intervention. All AEs that were reported with an onset date and time, or worsening, on or after date and time of first dose of IP up to and including 28 days after last dose of IP were included in the safety analysis.

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee No unpublished information may be disclosed without prior written approval from AstraZeneca AB.
• Publication restrictions are in place

Restriction type: OTHER