Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Investigation of GSK3335065 Intravenous (IV) Infusion in Healthy Adults (NCT NCT03245619)

Results Overview

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. All Subject Population comprised of all participants randomized to treatment who received at least one dose of study treatment. AEs and SAEs were collected from admission until follow-up. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

18 participants

Primary outcome timeframe

Up to Day 22

Results posted on

2020-06-16

Participant Flow

This was planned to be a 3 part, dose escalation study; however, the study was terminated during Part A (Cohort 3) because a relationship between GSK3335065 and ventricular tachycardia in a participant could not be excluded. Hence, participants were not recruited in Cohorts 4 to 8 of Part A; Part B and Part C were not initiated.

A total of 55 participants were screened of which 33 failed screening and 4 were kept in reserve but not used. A total of 18 participants were enrolled in the study. The study was conducted in the United Kingdom. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Participant milestones

Participant milestones
Measure	Part A: Placebo Healthy male participants were administered a single intravenous (IV) bolus dose of GSK3335065 matching placebo on Day 1.	Part A-Cohort 1: GSK3335065 0.1 mg Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.	Part A-Cohort 2: GSK3335065 0.25 mg Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.	Part A-Cohort 3: GSK3335065 1.3 mg Healthy male participants were administered a single IV bolus dose of GSK3335065 1.3 mg on Day 1.
Part A (Up to Day 22) STARTED	5	6	6	1
Part A (Up to Day 22) COMPLETED	1	0	0	1
Part A (Up to Day 22) NOT COMPLETED	4	6	6	0
Part B (Up to 34 Days) STARTED	0	0	0	0
Part B (Up to 34 Days) COMPLETED	0	0	0	0
Part B (Up to 34 Days) NOT COMPLETED	0	0	0	0
Part C (Up to 34 Days) STARTED	0	0	0	0
Part C (Up to 34 Days) COMPLETED	0	0	0	0
Part C (Up to 34 Days) NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: Placebo Healthy male participants were administered a single intravenous (IV) bolus dose of GSK3335065 matching placebo on Day 1.	Part A-Cohort 1: GSK3335065 0.1 mg Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.	Part A-Cohort 2: GSK3335065 0.25 mg Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.	Part A-Cohort 3: GSK3335065 1.3 mg Healthy male participants were administered a single IV bolus dose of GSK3335065 1.3 mg on Day 1.	Part A-Cohort 4: GSK335065 2.6 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 2.6 mg.	Part A-Cohort 5: GSK335065 5.5 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 5.5 mg.	Part A-Cohort 6: GSK335065 12 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 12 mg.	Part A-Cohort 7: GSK335065 35 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 35 mg.	Part A-Cohort 8: GSK335065 54 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 54 mg.	Part B: Placebo Healthy male participants were planned to be administered IV bolus dose of placebo on Day 1 followed by continuous IV infusion of placebo for 7 days.	Part B-Cohort 9: 0.14 mg IV Bolus+0.012 mg/Hour IV Infusion Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.012 mg/hour for 7 days.	Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.	Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.	Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.	Part C: Placebo Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered either a single intravenous dose of placebo or repeat doses of placebo as continuous infusion over 7 days.	Part C-Cohort 13: GSK3335065 Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.	Part C-Cohort 14: GSK3335065 Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
Part A (Up to Day 22) Physician Decision	4	6	6	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Investigation of GSK3335065 Intravenous (IV) Infusion in Healthy Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: Placebo n=5 Participants Healthy male participants were administered a single intravenous (IV) bolus dose of GSK3335065 matching placebo on Day 1.	Part A-Cohort 1: GSK3335065 0.1 mg n=6 Participants Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.	Part A-Cohort 2: GSK3335065 0.25 mg n=6 Participants Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.	Part A-Cohort 3: GSK3335065 1.3 mg n=1 Participants Healthy male participants were administered a single IV bolus dose of GSK3335065 1.3 mg on Day 1.	Part A-Cohort 4: GSK335065 2.6 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 2.6 mg.	Part A-Cohort 5: GSK335065 5.5 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 5.5 mg.	Part A-Cohort 6: GSK335065 12 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 12 mg.	Part A-Cohort 7: GSK335065 35 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 35 mg.	Part A-Cohort 8: GSK335065 54 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 54 mg.	Part B: Placebo Healthy male participants were planned to be administered IV bolus dose of placebo on Day 1 followed by continuous IV infusion of placebo for 7 days.	Part B-Cohort 9: 0.14 mg IV Bolus+0.012 mg/Hour IV Infusion Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.012 mg/hour for 7 days.	Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.	Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.	Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.	Part C: Placebo Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered either a single intravenous dose of placebo or repeat doses of placebo as continuous infusion over 7 days.	Part C-Cohort 13: GSK3335065 Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.	Part C-Cohort 14: GSK3335065 Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.	Total n=18 Participants Total of all reporting groups
Age, Continuous	41.8 Years STANDARD_DEVIATION 5.97 • n=5 Participants	35.8 Years STANDARD_DEVIATION 11.81 • n=7 Participants	43.2 Years STANDARD_DEVIATION 7.57 • n=5 Participants	47.0 Years STANDARD_DEVIATION NA • n=4 Participants	—	—	—	—	—	—	—	—	—	—	—	—	—	40.6 Years STANDARD_DEVIATION 8.91 • n=44 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=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	0 Participants n=135 Participants	0 Participants n=136 Participants	0 Participants n=44 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	0 Participants n=135 Participants	0 Participants n=136 Participants	18 Participants n=44 Participants
Race/Ethnicity, Customized African American/African Heritage	1 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=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	0 Participants n=135 Participants	0 Participants n=136 Participants	1 Participants n=44 Participants
Race/Ethnicity, Customized White-White/Caucasian/European Heritage	4 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	0 Participants n=135 Participants	0 Participants n=136 Participants	17 Participants n=44 Participants

PRIMARY outcome

Timeframe: Up to Day 22

Population: All Subject Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. All Subject Population comprised of all participants randomized to treatment who received at least one dose of study treatment. AEs and SAEs were collected from admission until follow-up. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Outcome measures

Outcome measures
Measure	Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion n=6 Participants Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.	Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion n=6 Participants Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.	Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion n=1 Participants Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.	Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.	Part C: Placebo n=5 Participants Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered either a single intravenous dose of placebo or repeat doses of placebo as continuous infusion over 7 days.	Part A-Cohort 5: GSK335065 5.5 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 5.5 mg.	Part A-Cohort 6: GSK335065 12 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 12 mg.	Part A-Cohort 7: GSK335065 35 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 35 mg.	Part A-Cohort 8: GSK335065 54 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 54 mg.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part A Any AE	4 Participants	3 Participants	1 Participants	—	3 Participants	—	—	—	—
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part A Any SAE	0 Participants	0 Participants	1 Participants	—	0 Participants	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60 and 72 hours post-dose

Population: PK Parameter Population. Only participants with PK parameters that could be derived are summarized.

Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis. Data for Cohort 1 is derived only from time points up to 3 hours as later data in this participant was below limit of quantification.

Outcome measures

Outcome measures
Measure	Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion n=4 Participants Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.	Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.	Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.	Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.	Part C: Placebo n=1 Participants Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered either a single intravenous dose of placebo or repeat doses of placebo as continuous infusion over 7 days.	Part A-Cohort 5: GSK335065 5.5 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 5.5 mg.	Part A-Cohort 6: GSK335065 12 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 12 mg.	Part A-Cohort 7: GSK335065 35 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 35 mg.	Part A-Cohort 8: GSK335065 54 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 54 mg.
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC[0-Inf]) for GSK3335065-Part A (Cohorts 1 and 2)	310.46 Hours*nanograms per milliliter Geometric Coefficient of Variation 26.2	—	—	—	51.68 Hours*nanograms per milliliter Geometric Coefficient of Variation NA Geometric coefficient of variation could not be calculated as only one participant was analyzed at the specified time point.	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour pre-dose, 6, 12, 15, 20, and 30 minutes, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156 and 168 hours post-dose

Population: PK Parameter Population. Data was not collected for Cohorts 4 to 8 as no participants were enrolled.

Blood samples for PK analysis of GSK3335065 were collected at the indicated time points. PK parameters were calculated using standard non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.	Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.	Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.	Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.	Part C: Placebo n=1 Participants Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered either a single intravenous dose of placebo or repeat doses of placebo as continuous infusion over 7 days.	Part A-Cohort 5: GSK335065 5.5 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 5.5 mg.	Part A-Cohort 6: GSK335065 12 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 12 mg.	Part A-Cohort 7: GSK335065 35 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 35 mg.	Part A-Cohort 8: GSK335065 54 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 54 mg.
AUC(0-Inf) for GSK3335065-Part A (Cohorts 3 to 8)	—	—	—	—	2811.51 Hours*nanograms per milliliter Geometric Coefficient of Variation NA Geometric coefficient of variation could not be calculated as only one participant was analyzed.	—	—	—	—

Other events: 0 other events

Deaths: 0 deaths

Part C-Cohort 14: GSK3335065

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part A: Placebo n=5 participants at risk Healthy male participants were administered a single intravenous (IV) bolus dose of GSK3335065 matching placebo on Day 1.	Part A-Cohort 1: GSK3335065 0.1 mg n=6 participants at risk Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.	Part A-Cohort 2: GSK3335065 0.25 mg n=6 participants at risk Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.	Part A-Cohort 3: GSK3335065 1.3 mg n=1 participants at risk Healthy male participants were administered a single IV bolus dose of GSK3335065 1.3 mg on Day 1.	Part A-Cohort 4: GSK335065 2.6 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 2.6 mg.	Part A-Cohort 5: GSK335065 5.5 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 5.5 mg.	Part A-Cohort 6: GSK335065 12 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 12 mg.	Part A-Cohort 7: GSK335065 35 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 35 mg.	Part A-Cohort 8: GSK335065 54 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 54 mg.	Part B: Placebo Healthy male participants were planned to be administered IV bolus dose of placebo on Day 1 followed by continuous IV infusion of placebo for 7 days.	Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.	Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.	Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.	Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.	Part C: Placebo Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered either a single intravenous dose of placebo or repeat doses of placebo as continuous infusion over 7 days.	Part C-Cohort 13: GSK3335065 Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.	Part C-Cohort 14: GSK3335065 Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
Cardiac disorders Tachycardia	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	100.0% 1/1 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Other adverse events

Other adverse events
Measure	Part A: Placebo n=5 participants at risk Healthy male participants were administered a single intravenous (IV) bolus dose of GSK3335065 matching placebo on Day 1.	Part A-Cohort 1: GSK3335065 0.1 mg n=6 participants at risk Healthy male participants were administered a single IV bolus dose of GSK3335065 0.1 milligram (mg) on Day 1.	Part A-Cohort 2: GSK3335065 0.25 mg n=6 participants at risk Healthy male participants were administered a single IV bolus dose of GSK3335065 0.25 mg on Day 1.	Part A-Cohort 3: GSK3335065 1.3 mg n=1 participants at risk Healthy male participants were administered a single IV bolus dose of GSK3335065 1.3 mg on Day 1.	Part A-Cohort 4: GSK335065 2.6 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 2.6 mg.	Part A-Cohort 5: GSK335065 5.5 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 5.5 mg.	Part A-Cohort 6: GSK335065 12 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 12 mg.	Part A-Cohort 7: GSK335065 35 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 35 mg.	Part A-Cohort 8: GSK335065 54 mg Healthy male participants were planned to be administered a single IV bolus dose of GSK335065 54 mg.	Part B: Placebo Healthy male participants were planned to be administered IV bolus dose of placebo on Day 1 followed by continuous IV infusion of placebo for 7 days.	Part B-Cohort 9: 0.14mg IV Bolus+0.012 mg/Hour IV Infusion Participants were planned to be administered an IV bolus dose of GSK3335065 0.14 mg on Day 1 followed by continuous IV infusion of GSK3335065 0.012 mg/ hour for 7 days.	Part B-Cohort 10: 7.5 mg IV Bolus+0.63 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 7.5 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 0.63 mg/hour for 7 days.	Part B-Cohort 11: 12 mg IV Bolus+1.1 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 12 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 1.1 mg/hour for 7 days.	Part B-Cohort 12: 23 mg IV Bolus Dose+2.1 mg/Hour IV Infusion Participants were planned to be administered IV bolus dose of GSK3335065 23 mg on Day 1 followed by continuous IV infusion of GSK3335065 at a dose of 2.1 mg/hour for 7 days.	Part C: Placebo Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered either a single intravenous dose of placebo or repeat doses of placebo as continuous infusion over 7 days.	Part C-Cohort 13: GSK3335065 Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered a single intravenous dose of GSK3335065.	Part C-Cohort 14: GSK3335065 Part C was planned to be conducted in women of non-child bearing potential. Participants were planned to be administered repeat doses of GSK3335065 as continuous IV infusion over 7 days.
Nervous system disorders Headache	40.0% 2/5 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	16.7% 1/6 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Nervous system disorders Dizziness	20.0% 1/5 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Infections and infestations Nasopharyngitis	20.0% 1/5 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Cardiac disorders Tachycardia	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	16.7% 1/6 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
General disorders Infusion site erythema	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	16.7% 1/6 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Injury, poisoning and procedural complications Contusion	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	16.7% 1/6 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	16.7% 1/6 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	16.7% 1/6 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	16.7% 1/6 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
General disorders Vessel puncture site bruise	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	16.7% 1/6 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	16.7% 1/6 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	16.7% 1/6 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Infections and infestations Abscess oral	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	100.0% 1/1 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Infections and infestations Gingival abscess	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	100.0% 1/1 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Nervous system disorders Lethargy	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	0.00% 0/6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	100.0% 1/1 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.	— 0/0 • Adverse events (AEs) and serious adverse events (SAEs) were collected from admission until follow-up (Up to Day 22) for Part A (Cohorts 1 to 3). AEs and SAEs were not collected for Part A (Cohorts 4 to 8) and Parts B and C as no participants were enrolled due to termination of the study during Part A-Cohort 3. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place