Trial Outcomes & Findings for To Investigate the Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI) (NCT NCT01689207)

Last Updated: 2017-09-06

Results Overview

from screening visit (Day -28) to 3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

222 participants

Primary outcome timeframe

Informed consent (up to 28 days before first dose) to follow up period (max of 22 days after first dose for Part A, a max of 28 days after first dose in Part B, max 17 days in Part C)

Results posted on

2017-09-06

Participant Flow

First subject enrolled 27 September 2012 and last subject last visit was 30 December 2014. Subjects were healthy male and female volunteers both young and elderly. Healthy volunteers were given full and adequate oral and written information about the nature, purpose, possible risk and benefit of the study and could discontinue at any time.

A Screening visit was conducted within 28 days before admission to the study centre. 222 volunteers were screend, 92 volunteers were entered into the study. Healthy volunteers were admitted to the study centre on Day -1 of either Part A, Part B or Part C.

Participant milestones

Participant milestones
Measure	Part A: Placebo Placebo	Part A: Drug Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)	Part B: Placebo Placebo	Part B: Cohort 1 Drug ATM (2000mg) + AVI (375mg)	Part B: Cohort 2 Drug ATM (2000mg) + AVI (600mg)	Part B: Cohort 3 Drug ATM (1500mg) + AVI (600mg)	Part B: Cohort 4 Drug ATM (1500mg) + AVI (450mg)	Part B: Cohort 5 Drug ATM (1500mg) + AVI (410mg)	Part C: Placebo Placebo	Part C: Cohort 1 Drug Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)	Part C: Cohort 2 Drug Aged \>65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)
Overall Study STARTED	4	8	16	8	4	8	10	10	6	10	8
Overall Study COMPLETED	4	7	16	8	2	7	10	10	5	10	8
Overall Study NOT COMPLETED	0	1	0	0	2	1	0	0	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: Placebo Placebo	Part A: Drug Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)	Part B: Placebo Placebo	Part B: Cohort 1 Drug ATM (2000mg) + AVI (375mg)	Part B: Cohort 2 Drug ATM (2000mg) + AVI (600mg)	Part B: Cohort 3 Drug ATM (1500mg) + AVI (600mg)	Part B: Cohort 4 Drug ATM (1500mg) + AVI (450mg)	Part B: Cohort 5 Drug ATM (1500mg) + AVI (410mg)	Part C: Placebo Placebo	Part C: Cohort 1 Drug Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)	Part C: Cohort 2 Drug Aged \>65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)
Overall Study Adverse Event	0	1	0	0	2	1	0	0	1	0	0

Baseline Characteristics

To Investigate the Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: Placebo n=4 Participants Placebo	Part A: Drug n=8 Participants Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)	Part B: Placebo n=16 Participants Placebo	Part B: Cohort 1 Drug n=8 Participants ATM (2000mg) + AVI (375mg)	Part B: Cohort 2 Drug n=4 Participants ATM (2000mg) + AVI (600mg)	Part B: Cohort 3 Drug n=8 Participants ATM (1500mg) + AVI (600mg)	Part B: Cohort 4 Drug n=10 Participants ATM (1500mg) + AVI (450mg)	Part B: Cohort 5 Drug n=10 Participants ATM (1500mg) + AVI (410mg)	Part C: Placebo n=6 Participants Placebo	Part C: Cohort 1 Drug n=10 Participants Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)	Part C: Cohort 2 Drug n=8 Participants Aged \>65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)	Total n=92 Participants Total of all reporting groups
Age, Continuous	33.8 years STANDARD_DEVIATION 6.9 • n=5 Participants	31.3 years STANDARD_DEVIATION 7.1 • n=7 Participants	27.4 years STANDARD_DEVIATION 5.0 • n=5 Participants	30.3 years STANDARD_DEVIATION 4.9 • n=4 Participants	27.8 years STANDARD_DEVIATION 1.9 • n=21 Participants	29.4 years STANDARD_DEVIATION 9.9 • n=10 Participants	29.7 years STANDARD_DEVIATION 7.3 • n=115 Participants	30.6 years STANDARD_DEVIATION 6.3 • n=6 Participants	51.3 years STANDARD_DEVIATION 19.4 • n=6 Participants	32.9 years STANDARD_DEVIATION 8.4 • n=64 Participants	68.5 years STANDARD_DEVIATION 2.9 • n=17 Participants	34.8 years STANDARD_DEVIATION 14.0 • n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	1 Participants n=6 Participants	0 Participants n=64 Participants	2 Participants n=17 Participants	3 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants	8 Participants n=4 Participants	4 Participants n=21 Participants	8 Participants n=10 Participants	10 Participants n=115 Participants	10 Participants n=6 Participants	5 Participants n=6 Participants	10 Participants n=64 Participants	6 Participants n=17 Participants	89 Participants n=21 Participants

PRIMARY outcome

Timeframe: Informed consent (up to 28 days before first dose) to follow up period (max of 22 days after first dose for Part A, a max of 28 days after first dose in Part B, max 17 days in Part C)

Population: Safety population

Outcome measures

Outcome measures
Measure	Part A: Placebo n=4 Participants Placebo	Part A: Drug n=8 Participants Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)	Part B: Placebo n=16 Participants Placebo	Part B: Cohort 1 Drug n=8 Participants ATM (2000mg) + AVI (375mg)	Part B: Cohort 2 Drug n=4 Participants ATM (2000mg) + AVI (600mg)	Part B: Cohort 3 Drug n=8 Participants ATM (1500mg) + AVI (600mg)	Part B: Cohort 4 Drug n=10 Participants ATM (1500mg) + AVI (450mg)	Part B: Cohort 5 Drug n=10 Participants ATM (1500mg) + AVI (410mg)	Part C: Placebo n=6 Participants Placebo	Part C: Cohort 1 Drug n=10 Participants Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)	Part C: Cohort 2 Drug n=8 Participants Aged \>65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)	Part A: Aztreonam (ATM) 2000mg n=7 Participants Crossover period ATm 2000mg	Part A: Avibactam (AVI) 600mg n=8 Participants Crossover period AVI 600mg	Part A: ATM 2000mg + AVI 600mg n=7 Participants Crossover period ATM 2000mg + AVI 600mg
Safety Profile - Number of Subjects With at Least 1 AE Number of subjects with at least 1 AE	1 Participants	2 Participants	3 Participants	4 Participants	2 Participants	6 Participants	8 Participants	3 Participants	3 Participants	5 Participants	7 Participants	0 Participants	2 Participants	0 Participants
Safety Profile - Number of Subjects With at Least 1 AE Subjects with at least 1 AE with outcome of death	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Safety Profile - Number of Subjects With at Least 1 AE At least 1 AE leading to discontinuation	0 Participants	1 Participants	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 0 to 24 hours post-dose on Day 1 in Part A. 0 to 24 hours post-dose on Days 1, 2, 4 and 11 in Part B (varied intervals per cohort). 0 to 6 hours post-dose on Days 1, 4, 7 and 10 in Part C. Steady state measure on Day 11 in Part B or Day 10 in Part C

Population: Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in \<3 subjects as this is considered to lack robustness.

Area under the plasma concentration-time curve from zero extrapolated to infinity (AUC µg\*h/mL) or AUC(0-last) in Part A on Day 1 after single infusion, area under the plasma concentration-time curve at steady state after multiple infusion (AUCss µg\*h/mL).

Outcome measures

Outcome measures
Measure	Part A: Placebo n=4 Participants Placebo	Part A: Drug n=8 Participants Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)	Part B: Placebo n=16 Participants Placebo	Part B: Cohort 1 Drug n=8 Participants ATM (2000mg) + AVI (375mg)	Part B: Cohort 2 Drug n=4 Participants ATM (2000mg) + AVI (600mg)	Part B: Cohort 3 Drug n=8 Participants ATM (1500mg) + AVI (600mg)	Part B: Cohort 4 Drug n=10 Participants ATM (1500mg) + AVI (450mg)	Part B: Cohort 5 Drug n=10 Participants ATM (1500mg) + AVI (410mg)	Part C: Placebo n=6 Participants Placebo	Part C: Cohort 1 Drug n=10 Participants Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)	Part C: Cohort 2 Drug n=8 Participants Aged \>65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)	Part A: Aztreonam (ATM) 2000mg Crossover period ATm 2000mg	Part A: Avibactam (AVI) 600mg Crossover period AVI 600mg	Part A: ATM 2000mg + AVI 600mg Crossover period ATM 2000mg + AVI 600mg
PK- Plasma Pharmacokinetic Parameter AUC (ugh/mL) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C AUC (ugh/mL) - Aztreonam (ATM) alone	NA ug*h/mL Geometric Coefficient of Variation NA Not evaluated	372 ug*h/mL Geometric Coefficient of Variation 15.2	NA ug*h/mL Geometric Coefficient of Variation NA Not evaluated	NA ug*h/mL Geometric Coefficient of Variation NA ATM not administered alone	NA ug*h/mL Geometric Coefficient of Variation NA ATM not administered alone	NA ug*h/mL Geometric Coefficient of Variation NA ATM not administered alone	NA ug*h/mL Geometric Coefficient of Variation NA ATM not administered alone	NA ug*h/mL Geometric Coefficient of Variation NA ATM not administered alone	NA ug*h/mL Geometric Coefficient of Variation NA Not evaluated	NA ug*h/mL Geometric Coefficient of Variation NA ATM not administered alone	NA ug*h/mL Geometric Coefficient of Variation NA ATM not administered alone	—	—	—
PK- Plasma Pharmacokinetic Parameter AUC (ugh/mL) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C AUC (ugh/mL) - Avibactam (AVI)alone	NA ug*h/mL Geometric Coefficient of Variation NA Not evaluated	52.6 ug*h/mL Geometric Coefficient of Variation 22.5	NA ug*h/mL Geometric Coefficient of Variation NA Not evaluated	NA ug*h/mL Geometric Coefficient of Variation NA AVI not administered alone	NA ug*h/mL Geometric Coefficient of Variation NA AVI not administered alone	NA ug*h/mL Geometric Coefficient of Variation NA AVI not administered alone	NA ug*h/mL Geometric Coefficient of Variation NA AVI not administered alone	NA ug*h/mL Geometric Coefficient of Variation NA AVI not administered alone	NA ug*h/mL Geometric Coefficient of Variation NA Not evaluated	NA ug*h/mL Geometric Coefficient of Variation NA AVI not administered alone	NA ug*h/mL Geometric Coefficient of Variation NA AVI not administered alone	—	—	—
PK- Plasma Pharmacokinetic Parameter AUC (ugh/mL) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C AUC (ugh/mL) - ATM in combination (Day 1)	NA ug*h/mL Geometric Coefficient of Variation NA Not evaluated	375 ug*h/mL Geometric Coefficient of Variation 12.8	NA ug*h/mL Geometric Coefficient of Variation NA Not evaluated	345 ug*h/mL Geometric Coefficient of Variation 16.3	326 ug*h/mL Geometric Coefficient of Variation 5.5	283 ug*h/mL Geometric Coefficient of Variation 17.7	270 ug*h/mL Geometric Coefficient of Variation 9.8	250 ug*h/mL Geometric Coefficient of Variation 13.3	NA ug*h/mL Geometric Coefficient of Variation NA Not evaluated	276 ug*h/mL Geometric Coefficient of Variation 13.5	308 ug*h/mL Geometric Coefficient of Variation 12.0	—	—	—
PK- Plasma Pharmacokinetic Parameter AUC (ugh/mL) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C AUCss (ugh/mL) - ATM in combination	NA ug*h/mL Geometric Coefficient of Variation NA Not evaluated	NA ug*h/mL Geometric Coefficient of Variation NA No multiple dosing	NA ug*h/mL Geometric Coefficient of Variation NA Not evaluated	275 ug*h/mL Geometric Coefficient of Variation 14.0	NA ug*h/mL Geometric Coefficient of Variation NA Not determined as only 2 subjects	231 ug*h/mL Geometric Coefficient of Variation 15.9	223 ug*h/mL Geometric Coefficient of Variation 7.9	203 ug*h/mL Geometric Coefficient of Variation 11.1	NA ug*h/mL Geometric Coefficient of Variation NA Not evaluated	211 ug*h/mL Geometric Coefficient of Variation 15.7	259 ug*h/mL Geometric Coefficient of Variation 12.1	—	—	—
PK- Plasma Pharmacokinetic Parameter AUC (ugh/mL) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C AUC (ugh/mL) - AVI in combination (Day 1)	NA ug*h/mL Geometric Coefficient of Variation NA Not evaluated	58.3 ug*h/mL Geometric Coefficient of Variation 17.7	NA ug*h/mL Geometric Coefficient of Variation NA Not evaluated	31.8 ug*h/mL Geometric Coefficient of Variation 12.5	47.8 ug*h/mL Geometric Coefficient of Variation 12.5	53.1 ug*h/mL Geometric Coefficient of Variation 12.9	35.7 ug*h/mL Geometric Coefficient of Variation 11.8	31.4 ug*h/mL Geometric Coefficient of Variation 14.7	NA ug*h/mL Geometric Coefficient of Variation NA Not evaluated	41.9 ug*h/mL Geometric Coefficient of Variation 17.1	52.3 ug*h/mL Geometric Coefficient of Variation 11.0	—	—	—
PK- Plasma Pharmacokinetic Parameter AUC (ugh/mL) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C AUCss (ugh/mL) - AVI in combination	NA ug*h/mL Geometric Coefficient of Variation NA Not evaluated	NA ug*h/mL Geometric Coefficient of Variation NA No multiple dosing in Part A	NA ug*h/mL Geometric Coefficient of Variation NA Not evaluated	26.1 ug*h/mL Geometric Coefficient of Variation 13.0	NA ug*h/mL Geometric Coefficient of Variation NA Not determined as only 2 subjects	43.3 ug*h/mL Geometric Coefficient of Variation 11.7	29.0 ug*h/mL Geometric Coefficient of Variation 10.2	26.7 ug*h/mL Geometric Coefficient of Variation 12.6	NA ug*h/mL Geometric Coefficient of Variation NA Not evaluated	29.3 ug*h/mL Geometric Coefficient of Variation 19.6	38.8 ug*h/mL Geometric Coefficient of Variation 14.0	—	—	—

SECONDARY outcome

Population: Pharmacokinetic analysis set. Please note, PK parameters have not been calculated where data is available in \<3 subjects as this is considered to lack robustness. Placebo arms are not evaluated. Values shown where analysed (eg. not applicable for ATM alone in combination cohorts)

Terminal half-life (t1/2), on Day 1 after single infusion and at steady state after multiple infusion.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=4 Participants Placebo	Part A: Drug n=8 Participants Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)	Part B: Placebo n=16 Participants Placebo	Part B: Cohort 1 Drug n=8 Participants ATM (2000mg) + AVI (375mg)	Part B: Cohort 2 Drug n=4 Participants ATM (2000mg) + AVI (600mg)	Part B: Cohort 3 Drug n=8 Participants ATM (1500mg) + AVI (600mg)	Part B: Cohort 4 Drug n=10 Participants ATM (1500mg) + AVI (450mg)	Part B: Cohort 5 Drug n=10 Participants ATM (1500mg) + AVI (410mg)	Part C: Placebo n=6 Participants Placebo	Part C: Cohort 1 Drug n=10 Participants Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)	Part C: Cohort 2 Drug n=8 Participants Aged \>65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)	Part A: Aztreonam (ATM) 2000mg Crossover period ATm 2000mg	Part A: Avibactam (AVI) 600mg Crossover period AVI 600mg	Part A: ATM 2000mg + AVI 600mg Crossover period ATM 2000mg + AVI 600mg
PK- Plasma Pharmacokinetic Parameter t1/2(h) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C t1/2 (h) - Aztreonam (ATM) alone	NA h Geometric Coefficient of Variation NA Not evaluated	1.98 h Geometric Coefficient of Variation 18.9	NA h Geometric Coefficient of Variation NA Not evaluated	NA h Geometric Coefficient of Variation NA ATM not dosed alone	NA h Geometric Coefficient of Variation NA ATM not dosed alone	NA h Geometric Coefficient of Variation NA ATM not dosed alone	NA h Geometric Coefficient of Variation NA ATM not dosed alone	NA h Geometric Coefficient of Variation NA ATM not dosed alone	NA h Geometric Coefficient of Variation NA Not evaluated	NA h Geometric Coefficient of Variation NA ATM not dosed alone	NA h Geometric Coefficient of Variation NA ATM not dosed alone	—	—	—
PK- Plasma Pharmacokinetic Parameter t1/2(h) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C t1/2 (h) - Avibactam (AVI)alone	NA h Geometric Coefficient of Variation NA Not evaluated	2.22 h Geometric Coefficient of Variation 26.3	NA h Geometric Coefficient of Variation NA Not evaluated	NA h Geometric Coefficient of Variation NA AVI not dosed alone	NA h Geometric Coefficient of Variation NA AVI not dosed alone	NA h Geometric Coefficient of Variation NA AVI not dosed alone	NA h Geometric Coefficient of Variation NA AVI not dosed alone	NA h Geometric Coefficient of Variation NA AVI not dosed alone	NA h Geometric Coefficient of Variation NA Not evaluated	NA h Geometric Coefficient of Variation NA AVI not dosed alone	NA h Geometric Coefficient of Variation NA AVI not dosed alone	—	—	—
PK- Plasma Pharmacokinetic Parameter t1/2(h) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C t1/2 (h) - ATM in combination	NA h Geometric Coefficient of Variation NA Not evaluated	2.09 h Geometric Coefficient of Variation 14.0	NA h Geometric Coefficient of Variation NA Not evaluated	2.24 h Geometric Coefficient of Variation 16.6	1.98 h Geometric Coefficient of Variation 3.3	1.90 h Geometric Coefficient of Variation 16.2	2.14 h Geometric Coefficient of Variation 21.2	2.28 h Geometric Coefficient of Variation 25.9	NA h Geometric Coefficient of Variation NA Not evaluated	NA h Geometric Coefficient of Variation NA Not evaluated	NA h Geometric Coefficient of Variation NA Not evaluated	—	—	—
PK- Plasma Pharmacokinetic Parameter t1/2(h) for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C t1/2 (h) - AVI in combination	NA h Geometric Coefficient of Variation NA Not evaluated	2.35 h Geometric Coefficient of Variation 25.4	NA h Geometric Coefficient of Variation NA Not evaluated	2.17 h Geometric Coefficient of Variation 30.9	2.82 h Geometric Coefficient of Variation 41.1	2.61 h Geometric Coefficient of Variation 10.1	2.26 h Geometric Coefficient of Variation 30.1	1.85 h Geometric Coefficient of Variation 27.4	NA h Geometric Coefficient of Variation NA Not evaluated	NA h Geometric Coefficient of Variation NA Not evaluated	NA h Geometric Coefficient of Variation NA Not evaluated	—	—	—

SECONDARY outcome

Timeframe: Day 1

Time to Cmax (tmax)

Outcome measures

Outcome measures
Measure	Part A: Placebo n=4 Participants Placebo	Part A: Drug n=8 Participants Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)	Part B: Placebo n=16 Participants Placebo	Part B: Cohort 1 Drug n=8 Participants ATM (2000mg) + AVI (375mg)	Part B: Cohort 2 Drug n=4 Participants ATM (2000mg) + AVI (600mg)	Part B: Cohort 3 Drug n=8 Participants ATM (1500mg) + AVI (600mg)	Part B: Cohort 4 Drug n=10 Participants ATM (1500mg) + AVI (450mg)	Part B: Cohort 5 Drug n=10 Participants ATM (1500mg) + AVI (410mg)	Part C: Placebo n=6 Participants Placebo	Part C: Cohort 1 Drug n=10 Participants Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)	Part C: Cohort 2 Drug n=8 Participants Aged \>65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)	Part A: Aztreonam (ATM) 2000mg Crossover period ATm 2000mg	Part A: Avibactam (AVI) 600mg Crossover period AVI 600mg	Part A: ATM 2000mg + AVI 600mg Crossover period ATM 2000mg + AVI 600mg
PK- Plasma Pharmacokinetic Parameter Tmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) on Day 1 in Parts A, B and C tmax (h) - AVI in combination (Day 1)	NA (h) Not evaluated	0.98 (h) Interval 0.98 to 0.98	NA (h) Not evaluated	0.98 (h) Interval 0.98 to 0.98	0.98 (h) Interval 0.98 to 1.0	1.98 (h) Interval 1.5 to 1.98	2.98 (h) Interval 2.0 to 3.0	2.50 (h) Interval 2.5 to 3.05	NA (h) Not evaluated	2.98 (h) Interval 2.0 to 3.0	2.98 (h) Interval 2.5 to 3.03	—	—	—
PK- Plasma Pharmacokinetic Parameter Tmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) on Day 1 in Parts A, B and C tmax (h) - ATM alone	NA (h) Not evaluated	0.98 (h) Interval 0.98 to 0.98	NA (h) Not evaluated	NA (h) ATM not dosed alone	NA (h) ATM not dosed alone	NA (h) ATM not dosed alone	NA (h) ATM not dosed alone	NA (h) ATM not dosed alone	NA (h) Not evaluated	NA (h) ATM not dosed alone	NA (h) ATM not dosed alone	—	—	—
PK- Plasma Pharmacokinetic Parameter Tmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) on Day 1 in Parts A, B and C tmax (h) - AVI alone	NA (h) Not evaluated	0.98 (h) Interval 0.98 to 1.12	NA (h) Not evaluated	NA (h) AVI not dosed alone	NA (h) AVI not dosed alone	NA (h) AVI not dosed alone	NA (h) AVI not dosed alone	NA (h) AVI not dosed alone	NA (h) Not evaluated	NA (h) AVI not dosed alone	NA (h) AVI not dosed alone	—	—	—
PK- Plasma Pharmacokinetic Parameter Tmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) on Day 1 in Parts A, B and C tmax (h) - ATM in combination (Day 1)	NA (h) Not evaluated	0.98 (h) Interval 0.98 to 0.98	NA (h) Not evaluated	0.98 (h) Interval 0.98 to 1.25	0.98 (h) Interval 0.98 to 1.0	1.98 (h) Interval 1.5 to 1.98	2.98 (h) Interval 2.0 to 3.0	2.98 (h) Interval 2.5 to 3.03	NA (h) Not evaluated	2.98 (h) Interval 2.98 to 3.0	2.98 (h) Interval 2.68 to 3.03	—	—	—

SECONDARY outcome

Maximum plasma concentration (Cmax µg/mL) on Day 1 after single infusion , maximum plasma concentration at steady state (Css,max µg/mL) after multiple infusion.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=4 Participants Placebo	Part A: Drug n=8 Participants Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)	Part B: Placebo n=16 Participants Placebo	Part B: Cohort 1 Drug n=8 Participants ATM (2000mg) + AVI (375mg)	Part B: Cohort 2 Drug n=4 Participants ATM (2000mg) + AVI (600mg)	Part B: Cohort 3 Drug n=8 Participants ATM (1500mg) + AVI (600mg)	Part B: Cohort 4 Drug n=10 Participants ATM (1500mg) + AVI (450mg)	Part B: Cohort 5 Drug n=10 Participants ATM (1500mg) + AVI (410mg)	Part C: Placebo n=6 Participants Placebo	Part C: Cohort 1 Drug n=10 Participants Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)	Part C: Cohort 2 Drug n=8 Participants Aged \>65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)	Part A: Aztreonam (ATM) 2000mg Crossover period ATm 2000mg	Part A: Avibactam (AVI) 600mg Crossover period AVI 600mg	Part A: ATM 2000mg + AVI 600mg Crossover period ATM 2000mg + AVI 600mg
PK- Plasma Pharmacokinetic Parameter Cmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C Cmax (ug/mL) - ATM alone	NA ug/mL Geometric Coefficient of Variation NA Not evaluated	143 ug/mL Geometric Coefficient of Variation 14.0	NA ug/mL Geometric Coefficient of Variation NA Not evaluated	NA ug/mL Geometric Coefficient of Variation NA ATM not administered alone	NA ug/mL Geometric Coefficient of Variation NA ATM not administered alone	NA ug/mL Geometric Coefficient of Variation NA ATM not administered alone	NA ug/mL Geometric Coefficient of Variation NA ATM not administered alone	NA ug/mL Geometric Coefficient of Variation NA ATM not administered alone	NA ug/mL Geometric Coefficient of Variation NA Not evaluated	NA ug/mL Geometric Coefficient of Variation NA ATM not administered alone	NA ug/mL Geometric Coefficient of Variation NA ATM not administered alone	—	—	—
PK- Plasma Pharmacokinetic Parameter Cmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C Cmax (ug/mL) - AVI alone	NA ug/mL Geometric Coefficient of Variation NA Not evaluated	26.8 ug/mL Geometric Coefficient of Variation 14.2	NA ug/mL Geometric Coefficient of Variation NA Not evaluated	NA ug/mL Geometric Coefficient of Variation NA AVI not administered alone	NA ug/mL Geometric Coefficient of Variation NA AVI not administered alone	NA ug/mL Geometric Coefficient of Variation NA AVI not administered alone	NA ug/mL Geometric Coefficient of Variation NA AVI not administered alone	NA ug/mL Geometric Coefficient of Variation NA AVI not administered alone	NA ug/mL Geometric Coefficient of Variation NA Not evaluated	NA ug/mL Geometric Coefficient of Variation NA AVI not administered alone	NA ug/mL Geometric Coefficient of Variation NA AVI not administered alone	—	—	—
PK- Plasma Pharmacokinetic Parameter Cmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C Cmax (ug/mL) - ATM in combination (Day1)	NA ug/mL Geometric Coefficient of Variation NA Not evaluated	137 ug/mL Geometric Coefficient of Variation 11.3	NA ug/mL Geometric Coefficient of Variation NA Not evaluated	123 ug/mL Geometric Coefficient of Variation 16.7	123 ug/mL Geometric Coefficient of Variation 6.2	82.4 ug/mL Geometric Coefficient of Variation 16.0	63.2 ug/mL Geometric Coefficient of Variation 9.4	59.2 ug/mL Geometric Coefficient of Variation 13.1	NA ug/mL Geometric Coefficient of Variation NA Not evaluated	75.6 ug/mL Geometric Coefficient of Variation 13.8	81.6 ug/mL Geometric Coefficient of Variation 11.8	—	—	—
PK- Plasma Pharmacokinetic Parameter Cmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C Css, max (ug/mL) - ATM in combination	NA ug/mL Geometric Coefficient of Variation NA Not evaluated	NA ug/mL Geometric Coefficient of Variation NA No multiple dosing in Part A	NA ug/mL Geometric Coefficient of Variation NA Not evaluated	124 ug/mL Geometric Coefficient of Variation 9.0	NA ug/mL Geometric Coefficient of Variation NA Not determined as only 2 subjects	80.9 ug/mL Geometric Coefficient of Variation 12.9	62.6 ug/mL Geometric Coefficient of Variation 9.1	55.7 ug/mL Geometric Coefficient of Variation 9.0	NA ug/mL Geometric Coefficient of Variation NA Not evaluated	57.2 ug/mL Geometric Coefficient of Variation 14.9	66.2 ug/mL Geometric Coefficient of Variation 13.3	—	—	—
PK- Plasma Pharmacokinetic Parameter Cmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C Cmax (ug/mL) - AVI in combination (Day1)	NA ug/mL Geometric Coefficient of Variation NA Not evaluated	137 ug/mL Geometric Coefficient of Variation 11.3	NA ug/mL Geometric Coefficient of Variation NA Not evaluated	16.0 ug/mL Geometric Coefficient of Variation 10.1	25.1 ug/mL Geometric Coefficient of Variation 5.8	19.3 ug/mL Geometric Coefficient of Variation 16.4	9.99 ug/mL Geometric Coefficient of Variation 11.2	8.68 ug/mL Geometric Coefficient of Variation 14.0	NA ug/mL Geometric Coefficient of Variation NA Not evaluated	12.1 ug/mL Geometric Coefficient of Variation 18.4	15.2 ug/mL Geometric Coefficient of Variation 13.6	—	—	—
PK- Plasma Pharmacokinetic Parameter Cmax for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C Css, max (ug/mL) - AVI in combination	NA ug/mL Geometric Coefficient of Variation NA Not evaluated	NA ug/mL Geometric Coefficient of Variation NA No multiple dosing in Part A	NA ug/mL Geometric Coefficient of Variation NA Not evaluated	14.5 ug/mL Geometric Coefficient of Variation 15.9	NA ug/mL Geometric Coefficient of Variation NA Not determined as only 2 subjects	17.6 ug/mL Geometric Coefficient of Variation 12.2	8.69 ug/mL Geometric Coefficient of Variation 9.9	8.36 ug/mL Geometric Coefficient of Variation 16.5	NA ug/mL Geometric Coefficient of Variation NA Not evaluated	8.88 ug/mL Geometric Coefficient of Variation 19.9	11.6 ug/mL Geometric Coefficient of Variation 15.1	—	—	—

SECONDARY outcome

Systemic clearence (CL) and renal clearance (CLr) on Day 1 after single infusion and at steady state after multiple infusion.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=4 Participants Placebo	Part A: Drug n=8 Participants Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)	Part B: Placebo n=16 Participants Placebo	Part B: Cohort 1 Drug n=8 Participants ATM (2000mg) + AVI (375mg)	Part B: Cohort 2 Drug n=4 Participants ATM (2000mg) + AVI (600mg)	Part B: Cohort 3 Drug n=8 Participants ATM (1500mg) + AVI (600mg)	Part B: Cohort 4 Drug n=10 Participants ATM (1500mg) + AVI (450mg)	Part B: Cohort 5 Drug n=10 Participants ATM (1500mg) + AVI (410mg)	Part C: Placebo n=6 Participants Placebo	Part C: Cohort 1 Drug n=10 Participants Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)	Part C: Cohort 2 Drug n=8 Participants Aged \>65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)	Part A: Aztreonam (ATM) 2000mg Crossover period ATm 2000mg	Part A: Avibactam (AVI) 600mg Crossover period AVI 600mg	Part A: ATM 2000mg + AVI 600mg Crossover period ATM 2000mg + AVI 600mg
PK- Plasma Pharmacokinetic Parameters CL and CLr for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C CL (L/h) - ATM alone	NA L/h Geometric Coefficient of Variation NA Not evaluated	5.37 L/h Geometric Coefficient of Variation 15.2	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA ATM not dosed alone	NA L/h Geometric Coefficient of Variation NA ATM not dosed alone	NA L/h Geometric Coefficient of Variation NA ATM not dosed alone	NA L/h Geometric Coefficient of Variation NA ATM not dosed alone	NA L/h Geometric Coefficient of Variation NA ATM not dosed alone	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA ATM not dosed alone	NA L/h Geometric Coefficient of Variation NA ATM not dosed alone	—	—	—
PK- Plasma Pharmacokinetic Parameters CL and CLr for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C CL(L/h) - AVI alone	NA L/h Geometric Coefficient of Variation NA Not evaluated	11.4 L/h Geometric Coefficient of Variation 22.4	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA AVI not dosed alone	NA L/h Geometric Coefficient of Variation NA AVI not dosed alone	NA L/h Geometric Coefficient of Variation NA AVI not dosed alone	NA L/h Geometric Coefficient of Variation NA AVI not dosed alone	NA L/h Geometric Coefficient of Variation NA AVI not dosed alone	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA AVI not dosed alone	NA L/h Geometric Coefficient of Variation NA AVI not dosed alone	—	—	—
PK- Plasma Pharmacokinetic Parameters CL and CLr for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C CLr (L/h) - ATM alone	NA L/h Geometric Coefficient of Variation NA Not evaluated	3.93 L/h Geometric Coefficient of Variation 19.0	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA ATM not dosed alone	NA L/h Geometric Coefficient of Variation NA ATM not dosed alone	NA L/h Geometric Coefficient of Variation NA ATM not dosed alone	NA L/h Geometric Coefficient of Variation NA ATM not dosed alone	NA L/h Geometric Coefficient of Variation NA ATM not dosed alone	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA ATM not dosed alone	NA L/h Geometric Coefficient of Variation NA ATM not dosed alone	—	—	—
PK- Plasma Pharmacokinetic Parameters CL and CLr for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C CLr (L/h) - AVI alone	NA L/h Geometric Coefficient of Variation NA Not evaluated	9.77 L/h Geometric Coefficient of Variation 21.6	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA AVI not dosed alone	NA L/h Geometric Coefficient of Variation NA AVI not dosed alone	NA L/h Geometric Coefficient of Variation NA AVI not dosed alone	NA L/h Geometric Coefficient of Variation NA AVI not dosed alone	NA L/h Geometric Coefficient of Variation NA AVI not dosed alone	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA AVI not dosed alone	NA L/h Geometric Coefficient of Variation NA AVI not dosed alone	—	—	—
PK- Plasma Pharmacokinetic Parameters CL and CLr for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C CL(L/h) - ATM in combination (Day 1)	NA L/h Geometric Coefficient of Variation NA Not evaluated	5.33 L/h Geometric Coefficient of Variation 12.9	NA L/h Geometric Coefficient of Variation NA Not evaluated	5.79 L/h Geometric Coefficient of Variation 16.3	6.15 L/h Geometric Coefficient of Variation 5.5	5.29 L/h Geometric Coefficient of Variation 17.8	5.56 L/h Geometric Coefficient of Variation 9.9	5.99 L/h Geometric Coefficient of Variation 13.4	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA Not evaluated	—	—	—
PK- Plasma Pharmacokinetic Parameters CL and CLr for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C CLr (L/h) - ATM in comination (Day 1)	NA L/h Geometric Coefficient of Variation NA Not evaluated	3.78 L/h Geometric Coefficient of Variation 17.6	NA L/h Geometric Coefficient of Variation NA Not evaluated	4.04 L/h Geometric Coefficient of Variation 14.4	4.10 L/h Geometric Coefficient of Variation 7.4	4.18 L/h Geometric Coefficient of Variation 14.0	4.09 L/h Geometric Coefficient of Variation 21.5	4.43 L/h Geometric Coefficient of Variation 11.8	NA L/h Geometric Coefficient of Variation NA Not evaluated	4.22 L/h Geometric Coefficient of Variation 17.2	3.41 L/h Geometric Coefficient of Variation 16.9	—	—	—
PK- Plasma Pharmacokinetic Parameters CL and CLr for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C CL(L/h) - AVI in combination (Day 1)	NA L/h Geometric Coefficient of Variation NA Not evaluated	10.3 L/h Geometric Coefficient of Variation 17.7	NA L/h Geometric Coefficient of Variation NA Not evaluated	11.8 L/h Geometric Coefficient of Variation 12.4	12.5 L/h Geometric Coefficient of Variation 12.7	11.3 L/h Geometric Coefficient of Variation 12.8	12.6 L/h Geometric Coefficient of Variation 11.9	13.1 L/h Geometric Coefficient of Variation 14.8	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA Not evaluated	—	—	—
PK- Plasma Pharmacokinetic Parameters CL and CLr for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C CLr (L/h) - AVI in comination (Day 1)	NA L/h Geometric Coefficient of Variation NA Not evaluated	8.71 L/h Geometric Coefficient of Variation 17.1	NA L/h Geometric Coefficient of Variation NA Not evaluated	10.6 L/h Geometric Coefficient of Variation 19.3	10.9 L/h Geometric Coefficient of Variation 12.5	11.1 L/h Geometric Coefficient of Variation 11.7	11.9 L/h Geometric Coefficient of Variation 24.6	12.5 L/h Geometric Coefficient of Variation 15.6	NA L/h Geometric Coefficient of Variation NA Not evaluated	10.8 L/h Geometric Coefficient of Variation 16.3	7.78 L/h Geometric Coefficient of Variation 27.9	—	—	—
PK- Plasma Pharmacokinetic Parameters CL and CLr for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C CL(L/h) - ATM in combination (Steady state)	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA Not evaluated	7.27 L/h Geometric Coefficient of Variation 14.0	NA L/h Geometric Coefficient of Variation NA Not calculated as \<3 patients	6.49 L/h Geometric Coefficient of Variation 15.9	6.72 L/h Geometric Coefficient of Variation 7.9	7.39 L/h Geometric Coefficient of Variation 11.1	NA L/h Geometric Coefficient of Variation NA Not evaluated	7.10 L/h Geometric Coefficient of Variation 15.8	5.79 L/h Geometric Coefficient of Variation 12.2	—	—	—
PK- Plasma Pharmacokinetic Parameters CL and CLr for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C CLr (L/h) - ATM in comination (Steady state)	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA Not evaluated	4.66 L/h Geometric Coefficient of Variation 18.9	NA L/h Geometric Coefficient of Variation NA Not calculated as \<3 patients	4.93 L/h Geometric Coefficient of Variation 15.2	5.07 L/h Geometric Coefficient of Variation 27.8	5.25 L/h Geometric Coefficient of Variation 13.5	NA L/h Geometric Coefficient of Variation NA Not evaluated	4.97 L/h Geometric Coefficient of Variation 19.0	3.99 L/h Geometric Coefficient of Variation 21.0	—	—	—
PK- Plasma Pharmacokinetic Parameters CL and CLr for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C CL(L/h) - AVI in combination (Steady state)	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA Not evaluated	14.3 L/h Geometric Coefficient of Variation 13.1	NA L/h Geometric Coefficient of Variation NA Not calculated as \<3 patients	13.8 L/h Geometric Coefficient of Variation 11.7	15.5 L/h Geometric Coefficient of Variation 10.4	15.4 L/h Geometric Coefficient of Variation 12.7	NA L/h Geometric Coefficient of Variation NA Not evaluated	14.0 L/h Geometric Coefficient of Variation 19.7	10.6 L/h Geometric Coefficient of Variation 14.0	—	—	—
PK- Plasma Pharmacokinetic Parameters CL and CLr for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C CLr (L/h) - AVI in comination (Steady state)	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA Not evaluated	NA L/h Geometric Coefficient of Variation NA Not evaluated	12.4 L/h Geometric Coefficient of Variation 24.8	NA L/h Geometric Coefficient of Variation NA Not calculated as \<3 patients	13.9 L/h Geometric Coefficient of Variation 11.5	14.7 L/h Geometric Coefficient of Variation 24.6	14.5 L/h Geometric Coefficient of Variation 14.6	NA L/h Geometric Coefficient of Variation NA Not evaluated	13.0 L/h Geometric Coefficient of Variation 22.0	9.49 L/h Geometric Coefficient of Variation 18.7	—	—	—

SECONDARY outcome

Volume of distribution at steady state (Vss).

Outcome measures

Outcome measures
Measure	Part A: Placebo n=4 Participants Placebo	Part A: Drug n=8 Participants Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)	Part B: Placebo n=16 Participants Placebo	Part B: Cohort 1 Drug n=8 Participants ATM (2000mg) + AVI (375mg)	Part B: Cohort 2 Drug n=4 Participants ATM (2000mg) + AVI (600mg)	Part B: Cohort 3 Drug n=8 Participants ATM (1500mg) + AVI (600mg)	Part B: Cohort 4 Drug n=10 Participants ATM (1500mg) + AVI (450mg)	Part B: Cohort 5 Drug n=10 Participants ATM (1500mg) + AVI (410mg)	Part C: Placebo n=6 Participants Placebo	Part C: Cohort 1 Drug n=10 Participants Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)	Part C: Cohort 2 Drug n=8 Participants Aged \>65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)	Part A: Aztreonam (ATM) 2000mg Crossover period ATm 2000mg	Part A: Avibactam (AVI) 600mg Crossover period AVI 600mg	Part A: ATM 2000mg + AVI 600mg Crossover period ATM 2000mg + AVI 600mg
PK- Plasma Pharmacokinetic Parameter Vss for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C Vss (L) - ATM alone	NA L Geometric Coefficient of Variation NA Not evaluated	13.4 L Geometric Coefficient of Variation 16.3	NA L Geometric Coefficient of Variation NA Not evaluated	NA L Geometric Coefficient of Variation NA ATM not dosed alone	NA L Geometric Coefficient of Variation NA ATM not dosed alone	NA L Geometric Coefficient of Variation NA ATM not dosed alone	NA L Geometric Coefficient of Variation NA ATM not dosed alone	NA L Geometric Coefficient of Variation NA ATM not dosed alone	NA L Geometric Coefficient of Variation NA Not evaluated	NA L Geometric Coefficient of Variation NA ATM not dosed alone	NA L Geometric Coefficient of Variation NA ATM not dosed alone	—	—	—
PK- Plasma Pharmacokinetic Parameter Vss for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C Vss (L) - AVI alone	NA L Geometric Coefficient of Variation NA Not evaluated	20.1 L Geometric Coefficient of Variation 10.0	NA L Geometric Coefficient of Variation NA Not evaluated	NA L Geometric Coefficient of Variation NA AVI not dosed alone	NA L Geometric Coefficient of Variation NA AVI not dosed alone	NA L Geometric Coefficient of Variation NA AVI not dosed alone	NA L Geometric Coefficient of Variation NA AVI not dosed alone	NA L Geometric Coefficient of Variation NA AVI not dosed alone	NA L Geometric Coefficient of Variation NA Not evaluated	NA L Geometric Coefficient of Variation NA AVI not dosed alone	NA L Geometric Coefficient of Variation NA AVI not dosed alone	—	—	—
PK- Plasma Pharmacokinetic Parameter Vss for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C Vss (L) - ATM in comination	NA L Geometric Coefficient of Variation NA Not evaluated	13.8 L Geometric Coefficient of Variation 10.4	NA L Geometric Coefficient of Variation NA Not evaluated	15.4 L Geometric Coefficient of Variation 13.3	15.1 L Geometric Coefficient of Variation 5.2	12.5 L Geometric Coefficient of Variation 14.9	13.7 L Geometric Coefficient of Variation 11.9	15.6 L Geometric Coefficient of Variation 18.9	NA L Geometric Coefficient of Variation NA Not evaluated	NA L Geometric Coefficient of Variation NA Not evaluated	NA L Geometric Coefficient of Variation NA Not evaluated	—	—	—
PK- Plasma Pharmacokinetic Parameter Vss for Aztreonam (ATM) and Avibactam (AVI) Alone and in Combination (ATM-AVI) in Parts A, B and C Vss (L) - AVI in comination	NA L Geometric Coefficient of Variation NA Not evaluated	19.0 L Geometric Coefficient of Variation 15.3	NA L Geometric Coefficient of Variation NA Not evaluated	22.8 L Geometric Coefficient of Variation 15.6	22.2 L Geometric Coefficient of Variation 10.6	20.0 L Geometric Coefficient of Variation 18.9	23.5 L Geometric Coefficient of Variation 15.5	25.2 L Geometric Coefficient of Variation 26.0	NA L Geometric Coefficient of Variation NA Not evaluated	NA L Geometric Coefficient of Variation NA Not evaluated	NA L Geometric Coefficient of Variation NA Not evaluated	—	—	—

Adverse Events

Part A: Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part A: Drug

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part B: Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part B: Cohort 1 Drug

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part B: Cohort 2 Drug

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part B: Cohort 3 Drug

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Part B: Cohort 4 Drug

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Part B: Cohort 5 Drug

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part C: Placebo

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Part C: Cohort 1 Drug

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Part C: Cohort 2 Drug

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Part A: Aztreonam (ATM) 2000mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part A: Avibactam (AVI) 600mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part A: ATM 2000mg + AVI 600mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part A: Placebo n=4 participants at risk Placebo	Part A: Drug n=8 participants at risk Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)	Part B: Placebo n=16 participants at risk Placebo	Part B: Cohort 1 Drug n=8 participants at risk ATM (2000mg) + AVI (375mg)	Part B: Cohort 2 Drug n=4 participants at risk ATM (2000mg) + AVI (600mg)	Part B: Cohort 3 Drug n=8 participants at risk ATM (1500mg) + AVI (600mg)	Part B: Cohort 4 Drug n=10 participants at risk ATM (1500mg) + AVI (450mg)	Part B: Cohort 5 Drug n=10 participants at risk ATM (1500mg) + AVI (410mg)	Part C: Placebo n=6 participants at risk Placebo	Part C: Cohort 1 Drug n=10 participants at risk Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)	Part C: Cohort 2 Drug n=8 participants at risk Aged \>65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)	Part A: Aztreonam (ATM) 2000mg n=7 participants at risk Crossover period ATM 2000mg	Part A: Avibactam (AVI) 600mg n=8 participants at risk Crossover period AVI 600mg	Part A: ATM 2000mg + AVI 600mg n=7 participants at risk Crossover period ATM 2000mg + AVI 600mg
Infections and infestations Pneumonia	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	16.7% 1/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.

Other adverse events

Other adverse events
Measure	Part A: Placebo n=4 participants at risk Placebo	Part A: Drug n=8 participants at risk Aztreonam (ATM) 2000mg, Avibactam (AVI) 600mg, ATM 2000mg +AVI 600mg (crossover)	Part B: Placebo n=16 participants at risk Placebo	Part B: Cohort 1 Drug n=8 participants at risk ATM (2000mg) + AVI (375mg)	Part B: Cohort 2 Drug n=4 participants at risk ATM (2000mg) + AVI (600mg)	Part B: Cohort 3 Drug n=8 participants at risk ATM (1500mg) + AVI (600mg)	Part B: Cohort 4 Drug n=10 participants at risk ATM (1500mg) + AVI (450mg)	Part B: Cohort 5 Drug n=10 participants at risk ATM (1500mg) + AVI (410mg)	Part C: Placebo n=6 participants at risk Placebo	Part C: Cohort 1 Drug n=10 participants at risk Aged 18-45: ATM (500mg followed by 1500mg) + AVI (136.7mg followed by 410mg)	Part C: Cohort 2 Drug n=8 participants at risk Aged \>65: ATM (500mg followed by 1500mg) + AVI (136.7mg + 410mg)	Part A: Aztreonam (ATM) 2000mg n=7 participants at risk Crossover period ATM 2000mg	Part A: Avibactam (AVI) 600mg n=8 participants at risk Crossover period AVI 600mg	Part A: ATM 2000mg + AVI 600mg n=7 participants at risk Crossover period ATM 2000mg + AVI 600mg
Investigations Transaminases increased	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Gastrointestinal disorders Diarrhoea	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	25.0% 2/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	20.0% 2/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	50.0% 4/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Gastrointestinal disorders Abdominal distension	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	10.0% 1/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	10.0% 1/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	10.0% 1/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Gastrointestinal disorders Abdominal pain	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	10.0% 1/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Gastrointestinal disorders Dry mouth	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Gastrointestinal disorders Frequent bowel movements	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Gastrointestinal disorders Oral pain	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
General disorders Catheter site pain	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	10.0% 1/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	16.7% 1/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
General disorders Fatigue	25.0% 1/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
General disorders Infusion site reaction	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	10.0% 1/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
General disorders Catheter site erythema	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
General disorders Catheter site haematoma	25.0% 1/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
General disorders Catheter site oedema	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
General disorders Infusion site pain	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Immune system disorders Seasonal allergy	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	10.0% 1/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Infections and infestations Candidiasis	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	6.2% 1/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Infections and infestations Otitis externa	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	6.2% 1/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Infections and infestations Rhinitis	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	10.0% 1/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Investigations Liver function test abnormal	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	50.0% 2/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	37.5% 3/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	30.0% 3/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Investigations Neutrophil count decreased	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Metabolism and nutrition disorders Hyperamylasaemia	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	6.2% 1/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	20.0% 2/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	10.0% 1/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	10.0% 1/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	16.7% 1/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Nervous system disorders Headache	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	10.0% 1/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	10.0% 1/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	33.3% 2/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	25.0% 2/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Nervous system disorders Dizziness	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	6.2% 1/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	10.0% 1/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Nervous system disorders Dysgeusia	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Nervous system disorders Paraesthesia	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Renal and urinary disorders Pollakiuria	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	10.0% 1/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Skin and subcutaneous tissue disorders Skin irritation	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	6.2% 1/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	20.0% 2/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Skin and subcutaneous tissue disorders Blister	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	10.0% 1/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Vascular disorders Phlebitis	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	10.0% 1/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	12.5% 1/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.
Vascular disorders Hot flush	25.0% 1/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/16 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/4 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/6 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/10 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/8 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.	0.00% 0/7 • from screening visit (Day -28) to follow up visit (FUP). FUP=3 to 7 days post treatment period 3 (up to Day 22) in Part A, 3 to 7 days after receiving the final dose on Day 11 (days 14 to 18) in Part B, and 3 to 7 days after receiving the final dose on Day 10 (days 13 to 17) in Part C.

Additional Information

Paul Newell, Medical Science Director

AstraZeneca

Phone: +44 1625 515727

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Confidentiality clauses are in place through a Master Services agreement, which limits the discloser of confidential information to what's expressed in 33.2 and 33.3: disclosure to third party only after written consent, or disclosure of confidential information only to the extent necessary to comply with reporting obligations from AZ, CRO or applicable laws.
Publication restrictions are in place

Restriction type: OTHER