Trial Outcomes & Findings for STOP-COVID19: Superiority Trial Of Protease Inhibition in COVID-19 (NCT NCT04817332)

NCT ID: NCT04817332

Last Updated: 2023-08-22

Results Overview

To determine the participant clinical status on a 7-point ordinal scale, minimum value 1, maximum value 7. Higher values indicate a worse outcome: 1. Not hospitalised, no limitations on activities 2. Not hospitalised, limitation on activities; 3. Hospitalised, not requiring supplemental oxygen; 4. Hospitalised, requiring supplemental oxygen; 5. Hospitalised, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalised, on invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO) 7. Death.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 406 participants
• Primary outcome timeframe: Up to 29 days
• Results posted on: 2023-08-22

Participant Flow

This double-blind, randomized, parallel-group, placebo-controlled trial was conducted at 14 secondary care sites in the United Kingdom Between 05th June 2020 and 28 February 2021

There were two post-randomisation exclusions due to ineligibility in the Brensocatib arm (one was admitted to hospital as an in-patient more than 96 hours prior to randomisation and another was receiving a prohibited medication). These two patients were included in the safety analysis. Four hundred and four participants (190 Brensocatib and 214 placebo) were included in the intention-to-treat analysis.

Participant milestones

Measure	Brensocatib Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of Dipeptidyl peptidase-1 (DPP1)	Placebo Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Overall Study STARTED	192	214
Overall Study COMPLETED	187	211
Overall Study NOT COMPLETED	5	3

Reasons for withdrawal

Measure	Brensocatib Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of Dipeptidyl peptidase-1 (DPP1)	Placebo Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Overall Study Lost to Follow-up	3	3
Overall Study Protocol Violation	2	0

Baseline Characteristics

STOP-COVID19: Superiority Trial Of Protease Inhibition in COVID-19

Baseline characteristics by cohort

Measure	Brensocatib n=190 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=214 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo	Total n=404 Participants Total of all reporting groups
Age, Continuous	62.3 years STANDARD_DEVIATION 12.5 • n=5 Participants	62.0 years STANDARD_DEVIATION 14.9 • n=7 Participants	62.2 years STANDARD_DEVIATION 13.9 • n=5 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	87 Participants n=7 Participants	152 Participants n=5 Participants
Sex: Female, Male Male	125 Participants n=5 Participants	127 Participants n=7 Participants	252 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	9 Participants n=5 Participants	11 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	175 Participants n=5 Participants	195 Participants n=7 Participants	370 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Chronic cardiac disease	34 Participants n=5 Participants	37 Participants n=7 Participants	71 Participants n=5 Participants
COPD	29 Participants n=5 Participants	22 Participants n=7 Participants	51 Participants n=5 Participants
Obesity	41 Participants n=5 Participants	48 Participants n=7 Participants	89 Participants n=5 Participants
Diabetes without complications	29 Participants n=5 Participants	33 Participants n=7 Participants	62 Participants n=5 Participants
Hospitalized, not requiring supplemental oxygen	42 Participants n=5 Participants	50 Participants n=7 Participants	92 Participants n=5 Participants
Hospitalized, requiring supplemental oxygen	128 Participants n=5 Participants	140 Participants n=7 Participants	268 Participants n=5 Participants
Hospitalized, on non-invasive ventilation or high flow oxygen devices	20 Participants n=5 Participants	24 Participants n=7 Participants	44 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 29 days

Population: Intention to treat

To determine the participant clinical status on a 7-point ordinal scale, minimum value 1, maximum value 7. Higher values indicate a worse outcome:

1. Not hospitalised, no limitations on activities

2. Not hospitalised, limitation on activities;

3. Hospitalised, not requiring supplemental oxygen;

4. Hospitalised, requiring supplemental oxygen;

5. Hospitalised, on non-invasive ventilation or high flow oxygen devices;

6. Hospitalised, on invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO)

7. Death.

Outcome measures

Measure	Brensocatib n=187 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=211 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Comparison of Participant Clinical Status Between Treatment Arms Not hospitalized, no limitations on activities	28 participants	40 participants
Comparison of Participant Clinical Status Between Treatment Arms Not hospitalized, limitations on activities	112 participants	129 participants
Comparison of Participant Clinical Status Between Treatment Arms Hospitalized, not requiring supplemental oxygen	7 participants	11 participants
Comparison of Participant Clinical Status Between Treatment Arms Hospitalized, requiring supplemental oxygen	6 participants	1 participants
Comparison of Participant Clinical Status Between Treatment Arms Hospitalized, on non-invasive ventilation or high flow oxygen devices	0 participants	1 participants
Comparison of Participant Clinical Status Between Treatment Arms Hospitalized, on invasive mechanical ventilation or ECMO	5 participants	6 participants
Comparison of Participant Clinical Status Between Treatment Arms Death	29 participants	23 participants

SECONDARY outcome

Timeframe: Day 29

Population: ITT. Days to improvement was derived as 1. days from randomization to date of first follow-up day where there was an improvement in CSTAT 2. those who died before improvement were censored at date of death. 3. those who withdrew or were loss to follow-up before improvement, if their day 29 status was unknown, they were censored at the date of loss to follow-up/withdrawal 4. other participants were censored at day 29 from randomisation in study time if there were no improvement.

Evaluation of the clinical efficacy of Brensocatib relative to standard care: 7-point ordinal scale, minimum value 1, maximum value 7. Higher values indicate a worse outcome:

1. Not hospitalised, no limitations on activities

2. Not hospitalised, limitations on activities

3. Hospitalised, not requiring supplemental oxygen

4. Hospitalised, requiring supplemental oxygen

5. Hospitalised, on non-invasive ventilation or high flow oxygen devices

6. Hospitalised, on invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO)

7. Death

Outcome measures

Measure	Brensocatib n=190 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=214 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Improvement of One Category From Admission Using 7-point Ordinal Scale.	159 Participants	186 Participants

SECONDARY outcome

Timeframe: Day 15

Population: ITT

Evaluation of the clinical efficacy of Brensocatib relative to standard care: 7-point ordinal scale, minimum value 1, maximum value 7. Higher values indicate a worse outcome:

1. Not hospitalised, no limitations on activities

2. Not hospitalised, limitations on activities

3. Hospitalised, not requiring supplemental oxygen

4. Hospitalised, requiring supplemental oxygen

5. Hospitalised, on non-invasive ventilation or high flow oxygen devices

6. Hospitalised, on invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO)

7. Death

Outcome measures

Measure	Brensocatib n=190 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=214 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Participant Clinical Status on 7-point Ordinal Scale Death	20 Participants	18 Participants
Participant Clinical Status on 7-point Ordinal Scale Missing	5 Participants	3 Participants
Participant Clinical Status on 7-point Ordinal Scale Not hospitalised, no limitations on activities	22 Participants	26 Participants
Participant Clinical Status on 7-point Ordinal Scale Not hospitalised, limitations on activities	103 Participants	124 Participants
Participant Clinical Status on 7-point Ordinal Scale Hospitalised, not requiring supplemental oxygen	12 Participants	19 Participants
Participant Clinical Status on 7-point Ordinal Scale Hospitalised, requiring supplemental oxygen	16 Participants	13 Participants
Participant Clinical Status on 7-point Ordinal Scale Hospitalised, on non-invasive ventilation or high flow oxygen devices	3 Participants	5 Participants
Participant Clinical Status on 7-point Ordinal Scale Hospitalised, on invasive mechanical ventilation or ECMO	9 Participants	6 Participants

SECONDARY outcome

Timeframe: Baseline to days 3, 5, 8, 11 and 29

Population: ITT

Evaluation of the clinical efficacy of Brensocatib relative to standard care: 7-point ordinal scale, minimum value 1, maximum value 7. Higher values indicate a worse outcome:

1. Not hospitalised, no limitations on activities

2. Not hospitalised, limitations on activities

3. Hospitalised, not requiring supplemental oxygen

4. Hospitalised, requiring supplemental oxygen

5. Hospitalised, on non-invasive ventilation or high flow oxygen devices

6. Hospitalised, on invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO)

7. Death

Outcome measures

Measure	Brensocatib n=190 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=214 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Mean Change in the 7-point Ordinal Scale Baseline to day 8	0.7 Units on WHO scale Standard Deviation 1.5	0.9 Units on WHO scale Standard Deviation 1.0
Mean Change in the 7-point Ordinal Scale Baseline to day 5	0.5 Units on WHO scale Standard Deviation 1.1	0.5 Units on WHO scale Standard Deviation 1.1
Mean Change in the 7-point Ordinal Scale Baseline to day 29	1.0 Units on WHO scale Standard Deviation 2.0	1.3 Units on WHO scale Standard Deviation 2.0
Mean Change in the 7-point Ordinal Scale Baseline to day 15	1.0 Units on WHO scale Standard Deviation 1.8	1.2 Units on WHO scale Standard Deviation 1.6
Mean Change in the 7-point Ordinal Scale Baseline to day 11	0.9 Units on WHO scale Standard Deviation 1.6	1.1 Units on WHO scale Standard Deviation 1.5
Mean Change in the 7-point Ordinal Scale Baseline to day 3	0.2 Units on WHO scale Standard Deviation 0.8	0.2 Units on WHO scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: Up to 29 days

Population: ITT. Those who died before being discharged or having a NEWS of ≤ 2 were censored at date of death. For those who withdrew or were loss to follow-up before being discharged or having a NEWS of ≤ 2, if their day 29 status was unknown, they were censored at the date of loss to follow-up/withdrawal. Other participants were censored at day 29 or 28 days from randomisation in study time if they were still in hospital and never had a NEWS of ≤ 2.

Evaluation of the clinical efficacy of Brensocatib relative to standard care: National Early Warning Score (NEWS). NEWS is a system that scores 6 physiological parameters (respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness or new-onset confusion, temperature) to give an aggerate score. Minimum score is 1, maximum score is 20.. Higher scores indicate worsening clinical outcomes.

Outcome measures

Measure	Brensocatib n=190 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=214 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Number of Participants Discharged or to a National Early Warning Score (NEWS) of Equal or Less Than 2 and Maintained for 24 Hours, Whichever Occurs First.	172 Participants	195 Participants

SECONDARY outcome

Timeframe: Baseline to day 15

Evaluation of the clinical efficacy of Brensocatib relative to standard care: National Early Warning Score. NEWS is a system that scores 6 physiological parameters (respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness or new-onset confusion, temperature) to give an aggerate score. Minimum score is 1, maximum score is 20.. Higher scores indicate worsening clinical outcomes.

Outcome measures

Measure	Brensocatib n=190 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=214 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Change From Baseline of National Early Warning Score (NEWS). -9	2 Participants	0 Participants
Change From Baseline of National Early Warning Score (NEWS). -8	0 Participants	1 Participants
Change From Baseline of National Early Warning Score (NEWS). -7	1 Participants	0 Participants
Change From Baseline of National Early Warning Score (NEWS). -6	0 Participants	2 Participants
Change From Baseline of National Early Warning Score (NEWS). -5	1 Participants	0 Participants
Change From Baseline of National Early Warning Score (NEWS). -4	1 Participants	3 Participants
Change From Baseline of National Early Warning Score (NEWS). -3	4 Participants	1 Participants
Change From Baseline of National Early Warning Score (NEWS). -2	1 Participants	1 Participants
Change From Baseline of National Early Warning Score (NEWS). -1	3 Participants	3 Participants
Change From Baseline of National Early Warning Score (NEWS). 0	15 Participants	24 Participants
Change From Baseline of National Early Warning Score (NEWS). 1	22 Participants	24 Participants
Change From Baseline of National Early Warning Score (NEWS). 2	36 Participants	34 Participants
Change From Baseline of National Early Warning Score (NEWS). 7	3 Participants	4 Participants
Change From Baseline of National Early Warning Score (NEWS). 3	28 Participants	36 Participants
Change From Baseline of National Early Warning Score (NEWS). -11	1 Participants	0 Participants
Change From Baseline of National Early Warning Score (NEWS). 4	21 Participants	28 Participants
Change From Baseline of National Early Warning Score (NEWS). 5	10 Participants	14 Participants
Change From Baseline of National Early Warning Score (NEWS). 6	11 Participants	6 Participants
Change From Baseline of National Early Warning Score (NEWS). 8	1 Participants	4 Participants
Change From Baseline of National Early Warning Score (NEWS). 9	0 Participants	2 Participants
Change From Baseline of National Early Warning Score (NEWS). 10	0 Participants	1 Participants
Change From Baseline of National Early Warning Score (NEWS). missing	29 Participants	26 Participants

SECONDARY outcome

Timeframe: 1-29 days

Population: ITT.

Evaluation of the clinical efficacy of Brensocatib relative to standard care: oxygenation

Outcome measures

Measure	Brensocatib n=190 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=214 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Number of Oxygen Therapy Free Days	24 days Interval 11.0 to 27.0	24.5 days Interval 17.0 to 27.0

SECONDARY outcome

Timeframe: 0-29 days

Population: For the duration of new oxygen use analysis, only participants who were hospitalised but not requiring supplemental oxygen (CSTAT = 3) at baseline were included

Evaluation of the clinical efficacy of Brensocatib relative to standard care: oxygenation

Outcome measures

Measure	Brensocatib n=39 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=42 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Incidence and Duration of New Oxygen Therapy Use During the Trial	0 days Interval 0.0 to 2.0	0 days Interval 0.0 to 1.0

SECONDARY outcome

Timeframe: 1-29 days

Population: ITT

Evaluation of the clinical efficacy of Brensocatib relative to standard care: Mechanical ventilation

Outcome measures

Measure	Brensocatib n=190 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=214 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Number of Mechanical Ventilator Free Days	28 days Interval 22.0 to 28.0	28 days Interval 26.0 to 28.0

SECONDARY outcome

Timeframe: 1-29 days

Evaluation of the clinical efficacy of Brensocatib relative to standard care: Mechanical ventilation

Outcome measures

Measure	Brensocatib n=190 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=214 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Incidence and Duration of New Mechanical Ventilation Use During the Trial.	0 days Interval 0.0 to 0.0	0 days Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Duration between date of admission and discharge assessed up to 29 days.

Evaluation of the clinical efficacy of Brensocatib relative to standard care: hospitalisation

Outcome measures

Measure	Brensocatib n=190 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=214 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Duration of Hospitalisation (Days).	8.4 days Standard Deviation 8.3	8.2 days Standard Deviation 8.3

SECONDARY outcome

Timeframe: Day 1 to 29

Population: ITT

Evaluation of the clinical efficacy of Brensocatib relative to standard care: mortality. Survival analysis was used to compare 28-day mortality between the treatment arms. Participants who did not die were censored on the last study day. Those who withdrew or were loss to follow-up and their day 29 status was unknown were censored at the date of loss to follow-up/withdrawal. Other participants were censored 28 days from randomisation in study time.

Outcome measures

Measure	Brensocatib n=190 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=214 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
28-day Mortality	29 Participants	23 Participants

SECONDARY outcome

Timeframe: 1-29 days

Population: There were two post-randomisation exclusions due to ineligibility in the brensocatib group (one patient was admitted to hospital as an inpatient more than 96 h before randomisation and another was receiving a prohibited medication). These 2 excluded patients were included with the ITT population in the safety analysis

Evaluation of the safety of the intervention through 29 days of follow-up as compared to the control arm

Outcome measures

Measure	Brensocatib n=192 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=214 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Cumulative Incidence of Serious Adverse Events (SAEs)	40 Participants	35 Participants

SECONDARY outcome

Timeframe: 1-29 days

Population: Safety

Evaluation of the safety of the intervention through 28 days of follow-up as compared to the control arm

Outcome measures

Measure	Brensocatib n=192 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=214 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Discontinuation or Temporary Suspension of Treatment	13 Participants	12 Participants

SECONDARY outcome

Timeframe: Day 29

Population: Hospitalised participants only

Evaluation of the safety of the intervention through 28 days of follow-up as compared to the control arm

Outcome measures

Measure	Brensocatib n=14 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=18 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Changes in White Cell Count (x10^9/L) Over Time (Hospitalised Participants Only)	8.9 10^9cells/L Standard Deviation 4.7	8.5 10^9cells/L Standard Deviation 3.1

SECONDARY outcome

Timeframe: Day 29

Population: Hospitalised participants only

Evaluation of the safety of the intervention through 28 days of follow-up as compared to the control arm

Outcome measures

Measure	Brensocatib n=14 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=18 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Changes in Haemoglobin (g/L) Over Time (Hospitalised Participants Only)	195.4 g/l Standard Deviation 264	105.5 g/l Standard Deviation 21.7

SECONDARY outcome

Timeframe: Day 29

Population: Safety

Evaluation of the safety of the intervention through 28 days of follow-up as compared to the control arm

Outcome measures

Measure	Brensocatib n=14 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=18 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Changes in Platelets (x10^9/L) Over Time (Hospitalised Participants Only)	270 10^9cells/L Standard Deviation 94.3	269 10^9cells/L Standard Deviation 117

SECONDARY outcome

Timeframe: Day 29

Population: Hospitalised patients only

Evaluation of the safety of the intervention through 28 days of follow-up as compared to the control arm

Outcome measures

Measure	Brensocatib n=14 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=19 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Changes in Creatinine (Umol/L) Over Time (Hospitalised Participants Only)	84.9 umol/L Standard Deviation 39	84.1 umol/L Standard Deviation 52

SECONDARY outcome

Timeframe: Day 29

Population: Safety

Evaluation of the safety of the intervention through 28 days of follow-up as compared to the control arm

Outcome measures

Measure	Brensocatib n=14 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=16 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Changes in Total Bilirubin (Umol/L) Over Time (Hospitalised Participants Only)	8.4 umol/L Standard Deviation 3.9	9.3 umol/L Standard Deviation 9.8

SECONDARY outcome

Timeframe: Day 29

Population: safety

Evaluation of the safety of the intervention through 28 days of follow-up as compared to the control arm

Outcome measures

Measure	Brensocatib n=14 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=15 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Changes in Alanine Aminotransferase (U/L) Over Time (Hospitalised Participants Only)	62.8 U/L Standard Deviation 43.2	52.3 U/L Standard Deviation 92.8

SECONDARY outcome

Timeframe: Day 29

Population: Safety

Evaluation of the safety of the intervention through 28 days of follow-up as compared to the control arm

Outcome measures

Measure	Brensocatib n=3 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=4 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Changes in Aspartate Aminotransferase U/L Over Time (Hospitalised Participants Only)	22 U/L Standard Deviation 11.4	28.8 U/L Standard Deviation 14.9

SECONDARY outcome

Timeframe: 1-29 days

Population: Safety

Evaluation of the safety of the intervention through 29 days of follow-up as compared to the control arm

Outcome measures

Measure	Brensocatib n=192 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=214 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Adverse Events of Special Interest- Hyperkeratosis, Infections and Dental Complications Hyperkeratosis	0 Participants	0 Participants
Adverse Events of Special Interest- Hyperkeratosis, Infections and Dental Complications Dental complications	0 Participants	1 Participants
Adverse Events of Special Interest- Hyperkeratosis, Infections and Dental Complications Secondary infections	6 Participants	7 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 15 and day 29

Evaluation of the virologic efficacy of Brensocatib by assessing percent of participants with SARS-CoV-2 detectable in nasopharyngeal sample

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 15 and day 29

Evaluation of the virologic efficacy of Brensocatib by assessing presence of SARS-CoV-2 virus in nasopharyngeal samples

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Days 1, 8, 15, 29

Evaluation of the virologic efficacy of Brensocatib by measuring neutrophil elastase and heparin binding protein measurement in blood

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 29

Population: Substudy

Neutrophil elastase activity was measure as follows: whole blood samples were treated with either 10mg/mL zymosan to stimulate neutrophil degranulation or with hanks' balanced salt solution (HBSS) at 37°C for 30 minutes. Following incubation, samples were centrifuged, and blood plasma frozen at -80°C for analysis. Neutrophil elastase activity was subsequently measured by cleavage of the specific fluorogenic substrate MeOSuc-AAPV-AMC. The stimulated elastase activity was calculated by subtracting the plasma elastase activity following incubation with zymosan stimulation from the elastase activity after incubation with buffer alone. Results presents arbitrary fluorescence intensity units (units/mL) as no reference standard is included in the assay. This outcome was included to assess the inhibition of neutrophil serine proteases by DPP1 treatment. Lower values indicate reduced elastase activity.

Outcome measures

Measure	Brensocatib n=50 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=48 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Blood Neutrophil Elastase Activity	103 Units/ml Standard Deviation 65	166 Units/ml Standard Deviation 97

OTHER_PRE_SPECIFIED outcome

Timeframe: Days 1, 15, 29

Evaluation of the virologic efficacy of Brensocatib

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Days 1, 15, 29

Evaluation of the virologic efficacy of Brensocatib by flow cytometry- CD88, CXCR2, CD66b, CD11b, CD63)

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Days 1, 15, 29

Evaluation of the virologic efficacy of Brensocatib by flow cytometry

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 29

Population: ITT

To evaluate patient reported outcome measures between the groups using EQ-5D-5L questionnaire. EQ-5D-5L comprises of five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression and each dimension has 5 levels. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The total EQ-5D-5L score ranges from -0.594 to 1. A higher total score indicates better outcome.

Outcome measures

Measure	Brensocatib n=190 Participants Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=214 Participants Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Quality of Life Measured by EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)	0.67 units on a scale Standard Deviation 0.29	0.67 units on a scale Standard Deviation 0.25

Adverse Events

Brensocatib

Serious events: 40 serious events

Other events: 86 other events

Deaths: 29 deaths

Placebo

Serious events: 35 serious events

Other events: 99 other events

Deaths: 23 deaths

Serious adverse events

Measure	Brensocatib n=192 participants at risk Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=214 participants at risk Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Cardiac disorders Cardiac disorders	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Gastrointestinal disorders	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	1.4% 3/214 • Number of events 3 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
General disorders General disorders	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Infections and infestations Infections	13.5% 26/192 • Number of events 26 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	10.7% 23/214 • Number of events 23 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Nervous system disorders Nervous system disorders	2.1% 4/192 • Number of events 4 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.93% 2/214 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Psychiatric disorders Psychiatric disorders	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.93% 2/214 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Renal and urinary disorders Renal and urinary disorders	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Respiratory, thoracic and mediastinal disorders Respiratory disorders	3.6% 7/192 • Number of events 7 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	2.3% 5/214 • Number of events 5 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Skin and subcutaneous tissue disorders Skin disorders	1.0% 2/192 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Vascular disorders Vascular disorders	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs

Other adverse events

Measure	Brensocatib n=192 participants at risk Brensocatib oral tablet, 25mg once per day for 28 days Brensocatib: Selective, competitive, and reversible inhibitor of DPP1	Placebo n=214 participants at risk Placebo oral tablet, 25mg once per day for 28 days Placebo: Matched placebo
Metabolism and nutrition disorders Steroid diabetes	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Metabolism and nutrition disorders Hypokalaemia	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Vascular disorders Peripheral ischaemia	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
General disorders Chest pain	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	1.9% 4/214 • Number of events 4 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
General disorders Cold sweat	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
General disorders Chest discomfort	1.0% 2/192 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
General disorders Swelling face	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
General disorders Oedema peripheral	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
General disorders Extravasation	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
General disorders Malaise	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
General disorders Feeling hot	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
General disorders Peripheral swelling	1.0% 2/192 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	1.9% 4/214 • Number of events 4 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Respiratory, thoracic and mediastinal disorders Hiccups	1.0% 2/192 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Respiratory, thoracic and mediastinal disorders Epistaxis	1.6% 3/192 • Number of events 3 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	1.4% 3/214 • Number of events 3 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Psychiatric disorders Hallucination, visual	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Psychiatric disorders Insomnia	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.93% 2/214 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Psychiatric disorders Delirium	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Psychiatric disorders Nightmare	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Psychiatric disorders Suicidal ideation	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Investigations Electrocardiogram abnormal	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Investigations Alanine aminotransferase increased	1.0% 2/192 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.93% 2/214 • Number of events 4 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Investigations Liver function test abnormal	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Investigations Glycosylated haemoglobin increased	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Investigations Blood glucose abnormal	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Investigations Blood glucose increased	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Investigations Transaminases increased	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Injury, poisoning and procedural complications Fall	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Cardiac disorders Bradycardia	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Cardiac disorders Palpitations	1.0% 2/192 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Cardiac disorders Atrial fibrillation	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.93% 2/214 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Cardiac disorders Tachyarrhythmia	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Cardiac disorders Acute coronary syndrome	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Cardiac disorders Supraventricular tachycardia	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Cardiac disorders Sinus bradycardia	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Nervous system disorders Dizziness	1.6% 3/192 • Number of events 3 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	2.3% 5/214 • Number of events 5 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Nervous system disorders Headache	1.0% 2/192 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.93% 2/214 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Nervous system disorders Memory impairment	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Nervous system disorders Syncope	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Nervous system disorders Hypoaesthesia	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Nervous system disorders Dysarthria	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Nervous system disorders Paraesthesia	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Blood and lymphatic system disorders Anaemia	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Eye disorders Vision blurred	1.0% 2/192 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Eye disorders Eye pruritus	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Abdominal pain	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	1.9% 4/214 • Number of events 4 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Dyspepsia	1.6% 3/192 • Number of events 3 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	1.9% 4/214 • Number of events 4 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Diarrhoea	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.93% 2/214 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Dry mouth	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.93% 2/214 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Nausea	1.6% 3/192 • Number of events 3 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	1.4% 3/214 • Number of events 3 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Vomiting	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	1.9% 4/214 • Number of events 4 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Constipation	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	1.9% 4/214 • Number of events 4 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Flatulence	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Gastritis erosive	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Gastrooesophageal reflux disease	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Oral mucosal eruption	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Gingival bleeding	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Glossodynia	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Tongue blistering	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Oral mucosal blistering	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Swollen tongue	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Oral pain	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Hypoaesthesia oral	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Gingival pain	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Lip pain	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Lip swelling	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Paraesthesia oral	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Tongue erythema	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Toothache	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Tongue discolouration	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Hepatobiliary disorders Hepatic function abnormal	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Skin and subcutaneous tissue disorders Pruritus	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Skin and subcutaneous tissue disorders Rash pustular	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Skin and subcutaneous tissue disorders Rash	2.6% 5/192 • Number of events 5 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	3.3% 7/214 • Number of events 7 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Skin and subcutaneous tissue disorders Eczema	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Skin and subcutaneous tissue disorders Mouth ulceration	1.0% 2/192 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Skin and subcutaneous tissue disorders Subcutaneous emphysema	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Skin and subcutaneous tissue disorders Dry skin	1.0% 2/192 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Skin and subcutaneous tissue disorders Rash pruritic	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Skin and subcutaneous tissue disorders Acne	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Gastrointestinal disorders Hyperhidrosis	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Renal and urinary disorders Acute kidney injury	1.0% 2/192 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Renal and urinary disorders Cholelithiasis	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Renal and urinary disorders Pollakiuria	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.93% 2/214 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Renal and urinary disorders Dysuria	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Musculoskeletal and connective tissue disorders Arthralgia	1.0% 2/192 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	1.9% 4/214 • Number of events 4 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Musculoskeletal and connective tissue disorders Plantar fasciitis	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Musculoskeletal and connective tissue disorders Back pain	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Musculoskeletal and connective tissue disorders Muscle spasms	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Infections and infestations Clostridium difficile colitis	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Infections and infestations Respiratory tract infection	1.0% 2/192 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.93% 2/214 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Infections and infestations Oral candidiasis	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	1.4% 3/214 • Number of events 3 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Musculoskeletal and connective tissue disorders Candida infection	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Infections and infestations Vulvovaginal candidiasis	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.93% 2/214 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Infections and infestations Pneumonia	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Infections and infestations Urinary tract infection	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Infections and infestations Pharyngitis	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Infections and infestations Staphylococcal bacteraemia	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Infections and infestations Serratia infection	0.52% 1/192 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.00% 0/214 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Metabolism and nutrition disorders Hyperglycaemia	2.1% 4/192 • Number of events 4 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.93% 2/214 • Number of events 2 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs
Metabolism and nutrition disorders Gout	0.00% 0/192 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs	0.47% 1/214 • Number of events 1 • 29 days Adverse events were reported by the participant, site principal investigators or delegated staff responsible for detecting documenting and recording events that met the definition of an adverse event. Participants discharged from hospital before the end of the trial were given a diary to record adverse events up to day 28. Site principal investigators were responsible for assigning seriousness and causality of AEs

Additional Information

Professor James D Chalmers

University of Dundee, UK

Phone: 01382660111

Email: jchalmers@dundee.ac.uk

Results disclosure agreements

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

Restriction type: LTE60