Trial Outcomes & Findings for A Study of AZD8233 in Participants With Dyslipidemia. (NCT NCT04823611)

NCT ID: NCT04823611

Last Updated: 2024-12-24

Results Overview

Part B: Change from baseline in LDL-C at week 12. Results are based on Mixed Model Repeated Measures (MMRM) analysis on the log-transformed change from baseline. Log-transformed change from baseline is calculated as the visit value in log minus the baseline value in log. The results from the model are then back transformed. Note: log(week 12 data) - log(baseline data) = log(week12/baseline), which is a ratio

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 87 participants
• Primary outcome timeframe: Baseline to week 12
• Results posted on: 2024-12-24

Participant Flow

Participant milestones

Measure	Part A:AZD8233 90mg AZD8233 for subcutaneous injection.	Part A:Placebo Placebo solution for subcutaneous injection.	Part B:AZD8233 50mg AZD8233 medium dose for subcutaneous injection.	Part B:AZD8233 15mg AZD8233 low dose for subcutaneous injection.	Part B:Placebo Placebo solution for subcutaneous injection.	Part C: AZD8233 60mg AZD8233 medium dose for subcutaneous injection.	Part C: Placebo Placebo solution for subcutaneous injection.
Overall Study STARTED	8	3	22	22	21	8	3
Overall Study COMPLETED	6	3	21	22	21	8	3
Overall Study NOT COMPLETED	2	0	1	0	0	0	0

Reasons for withdrawal

Measure	Part A:AZD8233 90mg AZD8233 for subcutaneous injection.	Part A:Placebo Placebo solution for subcutaneous injection.	Part B:AZD8233 50mg AZD8233 medium dose for subcutaneous injection.	Part B:AZD8233 15mg AZD8233 low dose for subcutaneous injection.	Part B:Placebo Placebo solution for subcutaneous injection.	Part C: AZD8233 60mg AZD8233 medium dose for subcutaneous injection.	Part C: Placebo Placebo solution for subcutaneous injection.
Overall Study Adverse Event	2	0	1	0	0	0	0

Baseline Characteristics

A Study of AZD8233 in Participants With Dyslipidemia.

Baseline characteristics by cohort

Measure	Part A:AZD8233 90mg n=8 Participants AZD8233 for subcutaneous injection.	Part A:Placebo n=3 Participants Placebo solution for subcutaneous injection.	Part B:AZD8233 50mg n=22 Participants AZD8233 medium dose for subcutaneous injection.	Part B:AZD8233 15mg n=22 Participants AZD8233 low dose for subcutaneous injection.	Part B:Placebo n=21 Participants Placebo solution for subcutaneous injection.	Part C: AZD8233 60mg n=8 Participants AZD8233 medium dose for subcutaneous injection.	Part C: Placebo n=3 Participants Placebo solution for subcutaneous injection.	Total n=87 Participants Total of all reporting groups
Age, Continuous	53.1 Years STANDARD_DEVIATION 5.38 • n=5 Participants	47.0 Years STANDARD_DEVIATION 11.36 • n=7 Participants	60.6 Years STANDARD_DEVIATION 6.29 • n=5 Participants	64.4 Years STANDARD_DEVIATION 5.50 • n=4 Participants	61.9 Years STANDARD_DEVIATION 7.04 • n=21 Participants	52.0 Years STANDARD_DEVIATION 6.37 • n=8 Participants	52.0 Years STANDARD_DEVIATION 3.61 • n=8 Participants	59.6 Years STANDARD_DEVIATION 7.86 • n=24 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	12 Participants n=5 Participants	7 Participants n=4 Participants	9 Participants n=21 Participants	2 Participants n=8 Participants	0 Participants n=8 Participants	33 Participants n=24 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	2 Participants n=7 Participants	10 Participants n=5 Participants	15 Participants n=4 Participants	12 Participants n=21 Participants	6 Participants n=8 Participants	3 Participants n=8 Participants	54 Participants n=24 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	8 Participants n=5 Participants	3 Participants n=7 Participants	22 Participants n=5 Participants	22 Participants n=4 Participants	21 Participants n=21 Participants	8 Participants n=8 Participants	3 Participants n=8 Participants	87 Participants n=24 Participants

PRIMARY outcome

Timeframe: Baseline to week 12

Population: Full Analysis Set (Part B only). These data were not pre-specified for parts A and C

Part B: Change from baseline in LDL-C at week 12. Results are based on Mixed Model Repeated Measures (MMRM) analysis on the log-transformed change from baseline. Log-transformed change from baseline is calculated as the visit value in log minus the baseline value in log. The results from the model are then back transformed. Note: log(week 12 data) - log(baseline data) = log(week12/baseline), which is a ratio

Outcome measures

Measure	Part A:AZD8233 90mg AZD8233 for subcutaneous injection.	Part A:Placebo Placebo solution for subcutaneous injection.	Part B:AZD8233 50mg n=20 Participants AZD8233 medium dose for subcutaneous injection.	Part B:AZD8233 15mg n=22 Participants AZD8233 low dose for subcutaneous injection.	Part B:Placebo n=21 Participants Placebo solution for subcutaneous injection.	Part C: AZD8233 60mg AZD8233 medium dose for subcutaneous injection.	Part C: Placebo Placebo solution for subcutaneous injection.
Part B: Change in LDL-C in Serum at Week 12	—	—	0.198 Ratio Interval 0.167 to 0.235	0.458 Ratio Interval 0.388 to 0.541	0.953 Ratio Interval 0.806 to 1.128	—	—

SECONDARY outcome

Timeframe: Measurement at baseline and week 12

Population: Full Analysis Set (Part B only). These data were not pre-specified for parts A and C

Percentage change from baseline to week 12 in Low-density Lipoprotein Cholesterol (LDL-C) in serum

Outcome measures

Measure	Part A:AZD8233 90mg AZD8233 for subcutaneous injection.	Part A:Placebo Placebo solution for subcutaneous injection.	Part B:AZD8233 50mg n=21 Participants AZD8233 medium dose for subcutaneous injection.	Part B:AZD8233 15mg n=22 Participants AZD8233 low dose for subcutaneous injection.	Part B:Placebo n=21 Participants Placebo solution for subcutaneous injection.	Part C: AZD8233 60mg AZD8233 medium dose for subcutaneous injection.	Part C: Placebo Placebo solution for subcutaneous injection.
Part B: Percentage Change From Baseline in LDL-C in Serum at Week 12	—	—	-77.13 % change from baseline Interval -83.67 to -70.59	-52.48 % change from baseline Interval -58.85 to -46.11	-3.24 % change from baseline Interval -9.68 to 3.19	—	—

SECONDARY outcome

Timeframe: Baseline to week 12

Population: Full Analysis Set (Part B only). These data were not pre-specified for parts A and C

Part B: Change from baseline in PCSK9 in plasma at week 12. Results are based on Mixed Model Repeated Measures (MMRM) analysis on the log-transformed change from baseline. Log-transformed change from baseline is calculated as the visit value in log minus the baseline value in log. The results from the model are then back transformed. Note: log(week 12 data) - log(baseline data) = log(week12/baseline), which is a ratio

Outcome measures

Measure	Part A:AZD8233 90mg AZD8233 for subcutaneous injection.	Part A:Placebo Placebo solution for subcutaneous injection.	Part B:AZD8233 50mg n=21 Participants AZD8233 medium dose for subcutaneous injection.	Part B:AZD8233 15mg n=22 Participants AZD8233 low dose for subcutaneous injection.	Part B:Placebo n=21 Participants Placebo solution for subcutaneous injection.	Part C: AZD8233 60mg AZD8233 medium dose for subcutaneous injection.	Part C: Placebo Placebo solution for subcutaneous injection.
Part B: Change in PCSK9 in Plasma at Week 12	—	—	0.066 Ratio Interval 0.055 to 0.079	0.296 Ratio Interval 0.248 to 0.352	0.874 Ratio Interval 0.731 to 1.045	—	—

SECONDARY outcome

Timeframe: Measurement at baseline and week 12

Population: Full Analysis Set (Part B only). These data were not pre-specified for parts A and C

Percentage change from baseline to week 12 in proprotein convertase subtilisin/kexin type-9 (PCSK9) in plasma

Outcome measures

Measure	Part A:AZD8233 90mg AZD8233 for subcutaneous injection.	Part A:Placebo Placebo solution for subcutaneous injection.	Part B:AZD8233 50mg n=21 Participants AZD8233 medium dose for subcutaneous injection.	Part B:AZD8233 15mg n=22 Participants AZD8233 low dose for subcutaneous injection.	Part B:Placebo n=21 Participants Placebo solution for subcutaneous injection.	Part C: AZD8233 60mg AZD8233 medium dose for subcutaneous injection.	Part C: Placebo Placebo solution for subcutaneous injection.
Part B: Percentage Change From Baseline in PCSK9 in Plasma at Week 12	—	—	-92.91 % change from baseline Interval -99.0 to -86.82	-65.07 % change from baseline Interval -71.03 to -59.12	-11.92 % change from baseline Interval -18.01 to -5.82	—	—

SECONDARY outcome

Timeframe: Day 1 and Day 57

Population: Pharmacokinetic Analysis Set (Parts A and C only). These data were not pre-specified for part B

Area Under the plasma concentration time curve from time 0 to time 24 hours

Outcome measures

Measure	Part A:AZD8233 90mg n=8 Participants AZD8233 for subcutaneous injection.	Part A:Placebo Placebo solution for subcutaneous injection.	Part B:AZD8233 50mg AZD8233 medium dose for subcutaneous injection.	Part B:AZD8233 15mg AZD8233 low dose for subcutaneous injection.	Part B:Placebo Placebo solution for subcutaneous injection.	Part C: AZD8233 60mg n=8 Participants AZD8233 medium dose for subcutaneous injection.	Part C: Placebo Placebo solution for subcutaneous injection.
Part A & Part C: AUC (0-24) of AZD8233 Day 1	5736 h.ng/mL Geometric Coefficient of Variation 53.55	—	—	—	—	3906 h.ng/mL Geometric Coefficient of Variation 26.56	—
Part A & Part C: AUC (0-24) of AZD8233 Day 57	5377 h.ng/mL Geometric Coefficient of Variation 50.57	—	—	—	—	3493 h.ng/mL Geometric Coefficient of Variation 32.47	—

SECONDARY outcome

Timeframe: Day 1 and Day 57

Population: Pharmacokinetic Analysis Set (Parts A and C only). These data were not pre-specified for part B

Maximum plasma concentration

Outcome measures

Measure	Part A:AZD8233 90mg n=8 Participants AZD8233 for subcutaneous injection.	Part A:Placebo Placebo solution for subcutaneous injection.	Part B:AZD8233 50mg AZD8233 medium dose for subcutaneous injection.	Part B:AZD8233 15mg AZD8233 low dose for subcutaneous injection.	Part B:Placebo Placebo solution for subcutaneous injection.	Part C: AZD8233 60mg n=8 Participants AZD8233 medium dose for subcutaneous injection.	Part C: Placebo Placebo solution for subcutaneous injection.
Part A & Part C: Cmax of AZD8233 Day 1	1525 ng/mL Geometric Coefficient of Variation 62.11	—	—	—	—	830.8 ng/mL Geometric Coefficient of Variation 23.90	—
Part A & Part C: Cmax of AZD8233 Day 57	1271 ng/mL Geometric Coefficient of Variation 70.63	—	—	—	—	781.2 ng/mL Geometric Coefficient of Variation 50.34	—

SECONDARY outcome

Timeframe: Day 1 and Day 57

Population: Pharmacokinetic Analysis Set (Parts A and C only). These data were not pre-specified for part B

Terminal half-life

Outcome measures

Measure	Part A:AZD8233 90mg n=8 Participants AZD8233 for subcutaneous injection.	Part A:Placebo Placebo solution for subcutaneous injection.	Part B:AZD8233 50mg AZD8233 medium dose for subcutaneous injection.	Part B:AZD8233 15mg AZD8233 low dose for subcutaneous injection.	Part B:Placebo Placebo solution for subcutaneous injection.	Part C: AZD8233 60mg n=8 Participants AZD8233 medium dose for subcutaneous injection.	Part C: Placebo Placebo solution for subcutaneous injection.
Part A & Part C: t1/2 of AZD8233 Day 1	3.459 hours Geometric Coefficient of Variation 45.69	—	—	—	—	2.751 hours Geometric Coefficient of Variation 35.94	—
Part A & Part C: t1/2 of AZD8233 Day 57	2.848 hours Geometric Coefficient of Variation 44.73	—	—	—	—	2.527 hours Geometric Coefficient of Variation 28.36	—

SECONDARY outcome

Timeframe: Day 1 and Day 57

Population: Pharmacokinetic Analysis Set (Parts A and C only). These data were not pre-specified for part B

Apparent plasma clearance

Outcome measures

Measure	Part A:AZD8233 90mg n=8 Participants AZD8233 for subcutaneous injection.	Part A:Placebo Placebo solution for subcutaneous injection.	Part B:AZD8233 50mg AZD8233 medium dose for subcutaneous injection.	Part B:AZD8233 15mg AZD8233 low dose for subcutaneous injection.	Part B:Placebo Placebo solution for subcutaneous injection.	Part C: AZD8233 60mg n=8 Participants AZD8233 medium dose for subcutaneous injection.	Part C: Placebo Placebo solution for subcutaneous injection.
Part A & Part C: CL/F (L/h) of AZD8233 Day 1	15.58 L/h Geometric Coefficient of Variation 52.84	—	—	—	—	15.31 L/h Geometric Coefficient of Variation 26.36	—
Part A & Part C: CL/F (L/h) of AZD8233 Day 57	16.62 L/h Geometric Coefficient of Variation 50.44	—	—	—	—	17.14 L/h Geometric Coefficient of Variation 32.25	—

SECONDARY outcome

Timeframe: Day 1 and Day 57

Population: Pharmacokinetic Analysis Set (Parts A and C only). These data were not pre-specified for part B

Apparent Volume of distribution during the terminal phase

Outcome measures

Measure	Part A:AZD8233 90mg n=8 Participants AZD8233 for subcutaneous injection.	Part A:Placebo Placebo solution for subcutaneous injection.	Part B:AZD8233 50mg AZD8233 medium dose for subcutaneous injection.	Part B:AZD8233 15mg AZD8233 low dose for subcutaneous injection.	Part B:Placebo Placebo solution for subcutaneous injection.	Part C: AZD8233 60mg n=8 Participants AZD8233 medium dose for subcutaneous injection.	Part C: Placebo Placebo solution for subcutaneous injection.
Part A & Part C: Vz/F (L) Day 1	77.74 L Geometric Coefficient of Variation 106.7	—	—	—	—	60.77 L Geometric Coefficient of Variation 56.66	—
Part A & Part C: Vz/F (L) Day 57	68.30 L Geometric Coefficient of Variation 58.04	—	—	—	—	62.49 L Geometric Coefficient of Variation 56.80	—

Adverse Events

Part A:AZD8233 90mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Part A:Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part B:AZD8233 50mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Part B:AZD8233 15mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Part B:Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Part C: AZD8233 60mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part C: Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Part A:AZD8233 90mg n=8 participants at risk AZD8233 for subcutaneous injection.	Part A:Placebo n=3 participants at risk Placebo solution for subcutaneous injection.	Part B:AZD8233 50mg n=22 participants at risk AZD8233 medium dose for subcutaneous injection.	Part B:AZD8233 15mg n=22 participants at risk AZD8233 low dose for subcutaneous injection.	Part B:Placebo n=21 participants at risk Placebo solution for subcutaneous injection.	Part C: AZD8233 60mg n=8 participants at risk AZD8233 medium dose for subcutaneous injection.	Part C: Placebo n=3 participants at risk Placebo solution for subcutaneous injection.
Cardiac disorders Ventricular extrasystoles	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.5% 1/22 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/21 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Infections and infestations Oral herpes	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.5% 1/22 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/21 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Infections and infestations Nasopharyngitis	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.5% 1/22 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.5% 1/22 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/21 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Nervous system disorders Carpal tunnel syndrome	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.8% 1/21 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.8% 1/21 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.8% 1/21 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Gastrointestinal disorders Dental caries	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.8% 1/21 • Number of events 2 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Gastrointestinal disorders Toothache	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.5% 1/22 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/21 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Skin and subcutaneous tissue disorders Blister	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.5% 1/22 • Number of events 2 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/21 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Skin and subcutaneous tissue disorders Hand dermatitis	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.8% 1/21 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.8% 1/21 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.5% 1/22 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/21 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.8% 1/21 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
General disorders Injection site reaction	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.5% 1/22 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.5% 1/22 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/21 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
General disorders Oedema peripheral	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.8% 1/21 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Injury, poisoning and procedural complications Bite	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.8% 1/21 • Number of events 2 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Injury, poisoning and procedural complications Contusion	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.8% 1/21 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Injury, poisoning and procedural complications Fall	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.5% 1/22 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/21 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Injury, poisoning and procedural complications Rib fracture	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.8% 1/21 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Infections and infestations COVID-19	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/21 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	25.0% 2/8 • Number of events 2 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/21 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	12.5% 1/8 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
General disorders Pyrexia	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/21 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	12.5% 1/8 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Investigations Blood creatine phosphokinase increased	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/21 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	33.3% 1/3 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Hepatobiliary disorders Hepatic function abnormal	75.0% 6/8 • Number of events 6 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	33.3% 1/3 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/21 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	33.3% 1/3 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/21 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Infections and infestations Cystitis	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.5% 1/22 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/21 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C
Infections and infestations Myringitis	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/22 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	4.5% 1/22 • Number of events 1 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/21 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/8 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C	0.00% 0/3 • From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C. MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B \& C

Additional Information

Global Clinical Lead

AstraZeneca Clinical Study Information Center

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

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