Trial Outcomes & Findings for AeroVanc in the Treatment of Methicillin-resistant Staphylococcus Aureus Infection in Patients With Cystic Fibrosis (NCT NCT03181932)

NCT ID: NCT03181932

Last Updated: 2022-12-16

Results Overview

The mean absolute change from baseline in FEV1 percent predicted was analyzed sequentially at Week 4 (end of Cycle 1), Week 12 (end of Cycle 2) and at Week 20 (end of Cycle 3).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 188 participants
• Primary outcome timeframe: Baseline and Week 4, 12 and 20
• Results posted on: 2022-12-16

Participant Flow

76 sites in Canada (2 clinics) and US (74 clinics) enrolled participants in the trial. First participant was enrolled on 20 September 2017 and last subject completed the study on 15 January 2021.

A total of 353 participants were screened, and 188 were randomized in Period 1. In total, 165 participants were screen failures and the reasons for screen failure were ineligibility (n=157), exacerbation (n=6), lost to follow-up (n=1) and other reason (n=1).

Participant milestones

Measure	Double-blind Vancomycin Inhalation Powder Vancomycin inhalation powder 30 mg is administered twice daily (BID) during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Vancomycin inhalation powder: 100 participants are to be treated with double-blind vancomycin inhalation powder (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.	Double-blind Placebo Inhalation Powder Matching placebo is administered BID during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Placebo inhalation powder: 100 participants are to be treated with double-blind placebo (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.
Period 1 (Double-blind Period) STARTED	90	98
Period 1 (Double-blind Period) COMPLETED	79	85
Period 1 (Double-blind Period) NOT COMPLETED	11	13
Period 2 (Open-label Period) STARTED	75	83
Period 2 (Open-label Period) COMPLETED	67	70
Period 2 (Open-label Period) NOT COMPLETED	8	13

Reasons for withdrawal

Measure	Double-blind Vancomycin Inhalation Powder Vancomycin inhalation powder 30 mg is administered twice daily (BID) during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Vancomycin inhalation powder: 100 participants are to be treated with double-blind vancomycin inhalation powder (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.	Double-blind Placebo Inhalation Powder Matching placebo is administered BID during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Placebo inhalation powder: 100 participants are to be treated with double-blind placebo (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.
Period 1 (Double-blind Period) Adverse Event	5	1
Period 1 (Double-blind Period) Lost to Follow-up	0	1
Period 1 (Double-blind Period) Protocol Violation	1	2
Period 1 (Double-blind Period) Withdrawal by Subject	5	9
Period 2 (Open-label Period) Adverse Event	1	6
Period 2 (Open-label Period) Lost to Follow-up	0	1
Period 2 (Open-label Period) Protocol Violation	3	1
Period 2 (Open-label Period) Withdrawal by Subject	2	5
Period 2 (Open-label Period) Reason missing	2	0

Baseline Characteristics

AeroVanc in the Treatment of Methicillin-resistant Staphylococcus Aureus Infection in Patients With Cystic Fibrosis

Baseline characteristics by cohort

Measure	Double-blind Vancomycin Inhalation Powder n=90 Participants Vancomycin inhalation powder 30 mg is administered twice daily (BID) during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Vancomycin inhalation powder: 100 participants are to be treated with double-blind vancomycin inhalation powder (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.	Double-blind Placebo Inhalation Powder n=98 Participants Matching placebo is administered BID during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Placebo inhalation powder: 100 participants are to be treated with double-blind placebo (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.	Total n=188 Participants Total of all reporting groups
Age, Continuous	20.2 years STANDARD_DEVIATION 12.52 • n=5 Participants	18.2 years STANDARD_DEVIATION 8.70 • n=7 Participants	19.2 years STANDARD_DEVIATION 10.71 • n=5 Participants
Age, Customized 6-21 years	64 Participants n=5 Participants	69 Participants n=7 Participants	133 Participants n=5 Participants
Age, Customized >21 years	26 Participants n=5 Participants	29 Participants n=7 Participants	55 Participants n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	50 Participants n=7 Participants	95 Participants n=5 Participants
Sex: Female, Male Male	45 Participants n=5 Participants	48 Participants n=7 Participants	93 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	86 Participants n=5 Participants	92 Participants n=7 Participants	178 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	85 Participants n=5 Participants	94 Participants n=7 Participants	179 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Pseudomonas Aeruginosa Infection Present at Screening (Yes/No?) Yes	51 Participants n=5 Participants	45 Participants n=7 Participants	96 Participants n=5 Participants
Pseudomonas Aeruginosa Infection Present at Screening (Yes/No?) No	39 Participants n=5 Participants	53 Participants n=7 Participants	92 Participants n=5 Participants
Number of Pulmonary Infections in the Previous Year	2.6 infections STANDARD_DEVIATION 1.53 • n=5 Participants	2.6 infections STANDARD_DEVIATION 1.44 • n=7 Participants	2.6 infections STANDARD_DEVIATION 1.48 • n=5 Participants
Baseline Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted	65.25 percent predicted STANDARD_DEVIATION 16.193 • n=5 Participants	66.32 percent predicted STANDARD_DEVIATION 16.939 • n=7 Participants	65.81 percent predicted STANDARD_DEVIATION 16.550 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 4, 12 and 20

Population: Intention-to-treat (ITT) population (defined as all randomized participants). Participants were analyzed according to randomized treatment. The ITT population was also split out by age (≤21 years, \>21 years). The population of participants ≤21 years was used for all main analyses of efficacy endpoints.

The mean absolute change from baseline in FEV1 percent predicted was analyzed sequentially at Week 4 (end of Cycle 1), Week 12 (end of Cycle 2) and at Week 20 (end of Cycle 3).

Outcome measures

Measure	Double-blind Vancomycin Inhalation Powder n=64 Participants Vancomycin inhalation powder 30 mg is administered twice daily (BID) during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Vancomycin inhalation powder: 100 participants are to be treated with double-blind vancomycin inhalation powder (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.	Double-blind Placebo Inhalation Powder n=69 Participants Matching placebo is administered BID during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Placebo inhalation powder: 100 participants are to be treated with double-blind placebo (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.
Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted Week 4	2.39 Percent predicted Standard Deviation 8.078	1.18 Percent predicted Standard Deviation 8.581
Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted Week 12	1.52 Percent predicted Standard Deviation 8.414	0.13 Percent predicted Standard Deviation 8.056
Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted Week 20	1.61 Percent predicted Standard Deviation 9.967	-1.94 Percent predicted Standard Deviation 8.924

SECONDARY outcome

Timeframe: Week 20

Population: ITT population (6-21 years).

The number of pulmonary exacerbations during Period 1 adjusted for the length of follow-up.

Outcome measures

Measure	Double-blind Vancomycin Inhalation Powder n=64 Participants Vancomycin inhalation powder 30 mg is administered twice daily (BID) during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Vancomycin inhalation powder: 100 participants are to be treated with double-blind vancomycin inhalation powder (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.	Double-blind Placebo Inhalation Powder n=69 Participants Matching placebo is administered BID during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Placebo inhalation powder: 100 participants are to be treated with double-blind placebo (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.
Frequency of Pulmonary Exacerbations	0.9 exacerbations Standard Deviation 1.03	0.9 exacerbations Standard Deviation 1.02

SECONDARY outcome

Timeframe: Week 20

Population: ITT population (6-21 years).

Time to first pulmonary exacerbation requiring use of another antibiotic medication (oral, IV, and/or inhaled). The Outcome Measure Data presented are the median percentiles and 95% confidence intervals from Kaplan-Meier estimates.

Outcome measures

Measure	Double-blind Vancomycin Inhalation Powder n=64 Participants Vancomycin inhalation powder 30 mg is administered twice daily (BID) during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Vancomycin inhalation powder: 100 participants are to be treated with double-blind vancomycin inhalation powder (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.	Double-blind Placebo Inhalation Powder n=69 Participants Matching placebo is administered BID during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Placebo inhalation powder: 100 participants are to be treated with double-blind placebo (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.
Time to First Pulmonary Exacerbation	38 days Interval 18.0 to 49.0	48 days Interval 29.0 to 59.0

SECONDARY outcome

Timeframe: Baseline and Week 4, 12, and 20

Population: ITT population (6-21 years).

The CFQ-R was administered every two weeks using a hand-held e-Diary. CFQ-R scores range between 0 and 100, where higher scores indicate a better outcome. The CFQ-R measures functioning in a variety of domains, including Physical Functioning, Vitality, Health Perceptions, Respiratory Symptoms, Treatment Burden, Role Functioning, Emotional Functioning and Social Functioning. The Outcome Measure Data presented are the Respiratory Symptoms Scores.

Outcome measures

Measure	Double-blind Vancomycin Inhalation Powder n=64 Participants Vancomycin inhalation powder 30 mg is administered twice daily (BID) during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Vancomycin inhalation powder: 100 participants are to be treated with double-blind vancomycin inhalation powder (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.	Double-blind Placebo Inhalation Powder n=69 Participants Matching placebo is administered BID during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Placebo inhalation powder: 100 participants are to be treated with double-blind placebo (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Scores Week 4	8.4 score on a scale Interval 4.2 to 12.7	3.0 score on a scale Interval -1.0 to 7.0
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Scores Week 12	6.0 score on a scale Interval 1.4 to 10.6	4.3 score on a scale Interval -0.2 to 8.9
Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Scores Week 20	4.6 score on a scale Interval -0.8 to 10.1	6.3 score on a scale Interval 1.2 to 11.4

SECONDARY outcome

Timeframe: Baseline and Week 4, 12 and 20

Population: ITT population (6-21 years).

The CFRSD-CRISS was administered every two weeks using a hand-held e-Diary. Scores range between 0 and 100, where higher scores indicate a worse outcome.

Outcome measures

Measure	Double-blind Vancomycin Inhalation Powder n=64 Participants Vancomycin inhalation powder 30 mg is administered twice daily (BID) during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Vancomycin inhalation powder: 100 participants are to be treated with double-blind vancomycin inhalation powder (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.	Double-blind Placebo Inhalation Powder n=69 Participants Matching placebo is administered BID during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Placebo inhalation powder: 100 participants are to be treated with double-blind placebo (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.
Change From Baseline in Cystic Fibrosis Respiratory Symptom Diary-Chronic Respiratory Symptom Score (CFRSD-CRISS) Scores Week 4	-3.2 score on a scale Interval -7.3 to 0.9	-5.1 score on a scale Interval -9.1 to -1.1
Change From Baseline in Cystic Fibrosis Respiratory Symptom Diary-Chronic Respiratory Symptom Score (CFRSD-CRISS) Scores Week 12	-4.7 score on a scale Interval -10.1 to 0.6	-8.0 score on a scale Interval -13.3 to -2.8
Change From Baseline in Cystic Fibrosis Respiratory Symptom Diary-Chronic Respiratory Symptom Score (CFRSD-CRISS) Scores Week 20	-7.3 score on a scale Interval -12.5 to -2.0	-5.3 score on a scale Interval -10.3 to -0.4

SECONDARY outcome

Timeframe: Baseline and Week 4, 12 and 20

Population: ITT population (6-21 years).

The mean relative change from Baseline in FEV1 percent predicted

Outcome measures

Measure	Double-blind Vancomycin Inhalation Powder n=64 Participants Vancomycin inhalation powder 30 mg is administered twice daily (BID) during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Vancomycin inhalation powder: 100 participants are to be treated with double-blind vancomycin inhalation powder (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.	Double-blind Placebo Inhalation Powder n=69 Participants Matching placebo is administered BID during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Placebo inhalation powder: 100 participants are to be treated with double-blind placebo (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.
Relative Change in FEV1 Percent Predicted Week 4	2.9 percent predicted Interval -1.0 to 6.8	1.5 percent predicted Interval -2.1 to 5.1
Relative Change in FEV1 Percent Predicted Week 12	1.2 percent predicted Interval -2.8 to 5.2	-0.3 percent predicted Interval -4.1 to 3.5
Relative Change in FEV1 Percent Predicted Week 20	1.7 percent predicted Interval -2.7 to 6.1	-2.2 percent predicted Interval -6.4 to 2.0

SECONDARY outcome

Timeframe: Week 20

Population: ITT population (6-21 years).

The number of successful response cycles a participant achieves over Period 1. A response in a cycle is defined by at least a 5 % relative improvement in FEV1 percent predicted at the end of each the respective cycle.

Outcome measures

Measure	Double-blind Vancomycin Inhalation Powder n=62 Participants Vancomycin inhalation powder 30 mg is administered twice daily (BID) during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Vancomycin inhalation powder: 100 participants are to be treated with double-blind vancomycin inhalation powder (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.	Double-blind Placebo Inhalation Powder n=66 Participants Matching placebo is administered BID during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Placebo inhalation powder: 100 participants are to be treated with double-blind placebo (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.
Number of Successful Response Cycles 1 successful response cycle	18 Participants	27 Participants
Number of Successful Response Cycles 0 successful response cycles	20 Participants	24 Participants
Number of Successful Response Cycles 2 successful response cycles	15 Participants	9 Participants
Number of Successful Response Cycles 3 successful response cycles	9 Participants	6 Participants

SECONDARY outcome

Timeframe: Week 20

Population: ITT population (6-21 years).

The mean treatment difference in FEV1 across all post-baseline visits

Outcome measures

Measure	Double-blind Vancomycin Inhalation Powder n=64 Participants Vancomycin inhalation powder 30 mg is administered twice daily (BID) during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Vancomycin inhalation powder: 100 participants are to be treated with double-blind vancomycin inhalation powder (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.	Double-blind Placebo Inhalation Powder n=69 Participants Matching placebo is administered BID during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Placebo inhalation powder: 100 participants are to be treated with double-blind placebo (75 subjects ≤21 years old, 25 subjects \>21 years old) for 24 weeks during Period 1.
Area Under the FEV1-time Profile	609.7 percent predicted*hour/liter Interval 520.8 to 698.7	583.1 percent predicted*hour/liter Interval 499.8 to 666.5

Adverse Events

Double-blind Vancomycin Inhalation Powder

Serious events: 24 serious events

Other events: 85 other events

Deaths: 0 deaths

Double-blind Placebo Inhalation Powder

Serious events: 35 serious events

Other events: 93 other events

Deaths: 0 deaths

Open-label Vancomycin Inhalation Powder

Serious events: 50 serious events

Other events: 139 other events

Deaths: 0 deaths

Serious adverse events

Measure	Double-blind Vancomycin Inhalation Powder n=90 participants at risk Vancomycin inhalation powder 30 mg is administered twice daily (BID) during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Vancomycin inhalation powder: 100 participants are to be treated with double-blind vancomycin inhalation powder (75 participants ≤21 years old, 25 participants \>21 years old) for 24 weeks during Period 1.	Double-blind Placebo Inhalation Powder n=98 participants at risk Matching placebo is administered BID during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Placebo inhalation powder: 100 participants are to be treated with double-blind placebo (75 participants ≤21 years old, 25 participants \>21 years old) for 24 weeks during Period 1.	Open-label Vancomycin Inhalation Powder n=158 participants at risk In the 24-week Period 2, all participants receive vancomycin inhalation powder 30 mg BID by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Vancomycin inhalation powder: In the 24-week Period 2, all participants are to be treated with open-label vancomycin inhalation powder.
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	21.1% 19/90 • Number of events 24 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	29.6% 29/98 • Number of events 33 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	24.1% 38/158 • Number of events 43 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Infections and infestations Bronchitis	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/98 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.9% 3/158 • Number of events 3 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Infections and infestations Pneumonia	2.2% 2/90 • Number of events 3 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	3.1% 3/98 • Number of events 3 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.9% 3/158 • Number of events 3 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Infections and infestations Pneumonia staphylococcal	1.1% 1/90 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.0% 1/98 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Infections and infestations Appendicitis perforated	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.0% 1/98 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Infections and infestations Influenza	1.1% 1/90 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/98 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Infections and infestations Peritoneal abscess	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.0% 1/98 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Infections and infestations Peritonitis	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.0% 1/98 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Infections and infestations Pneumonia bacterial	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.0% 1/98 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Infections and infestations Sepsis	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.0% 1/98 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Infections and infestations Staphylococcal infection	1.1% 1/90 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/98 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Infections and infestations Systemic viral infection	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.0% 1/98 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Gastrointestinal disorders Constipation	2.2% 2/90 • Number of events 3 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	4.1% 4/98 • Number of events 6 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.3% 2/158 • Number of events 2 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Gastrointestinal disorders Abdominal pain	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.0% 1/98 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Gastrointestinal disorders Distal intestinal obstruction syndrome	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.0% 1/98 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.0% 1/98 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Hepatobiliary disorders Bile duct obstruction	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.0% 1/98 • Number of events 4 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.1% 1/90 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	2.0% 2/98 • Number of events 2 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.3% 2/158 • Number of events 2 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Respiratory, thoracic and mediastinal disorders Asthma	1.1% 1/90 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/98 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.0% 1/98 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Congenital, familial and genetic disorders Cystic fibrosis related diabetes	1.1% 1/90 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/98 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
General disorders Pyrexia	1.1% 1/90 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/98 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Injury, poisoning and procedural complications Overdose	1.1% 1/90 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/98 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Investigations Pulmonary function test decreased	1.1% 1/90 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/98 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Renal and urinary disorders Nephrolithiasis	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.0% 1/98 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Reproductive system and breast disorders Testicular torsion	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.0% 1/98 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Vascular disorders Venous thrombosis	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.0% 1/98 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Infections and infestations Mycobacterial infection	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/98 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.63% 1/158 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Infections and infestations Pneumonia pseudomonal	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/98 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.63% 1/158 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Infections and infestations Pseudomonas infection	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/98 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.63% 1/158 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/98 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.63% 1/158 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/98 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.63% 1/158 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/98 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.63% 1/158 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/98 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.63% 1/158 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Injury, poisoning and procedural complications Concussion	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/98 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.63% 1/158 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Nervous system disorders Loss of consciousness	0.00% 0/90 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/98 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.63% 1/158 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.

Other adverse events

Measure	Double-blind Vancomycin Inhalation Powder n=90 participants at risk Vancomycin inhalation powder 30 mg is administered twice daily (BID) during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Vancomycin inhalation powder: 100 participants are to be treated with double-blind vancomycin inhalation powder (75 participants ≤21 years old, 25 participants \>21 years old) for 24 weeks during Period 1.	Double-blind Placebo Inhalation Powder n=98 participants at risk Matching placebo is administered BID during the 24-week double-blind period (Period 1) by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Placebo inhalation powder: 100 participants are to be treated with double-blind placebo (75 participants ≤21 years old, 25 participants \>21 years old) for 24 weeks during Period 1.	Open-label Vancomycin Inhalation Powder n=158 participants at risk In the 24-week Period 2, all participants receive vancomycin inhalation powder 30 mg BID by inhalation during three dosing cycles, each cycle being 28 days of treatment followed by 28 days of observation. Vancomycin inhalation powder: In the 24-week Period 2, all participants are to be treated with open-label vancomycin inhalation powder.
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	56.7% 51/90 • Number of events 109 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	60.2% 59/98 • Number of events 116 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	49.4% 78/158 • Number of events 140 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Infections and infestations Upper respiratory tract infection	6.7% 6/90 • Number of events 7 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	4.1% 4/98 • Number of events 5 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	7.6% 12/158 • Number of events 15 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Infections and infestations Pneumonia	5.6% 5/90 • Number of events 7 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	4.1% 4/98 • Number of events 4 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Infections and infestations Sinusitis	5.6% 5/90 • Number of events 5 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	6.1% 6/98 • Number of events 6 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	5.7% 9/158 • Number of events 9 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Respiratory, thoracic and mediastinal disorders Cough	46.7% 42/90 • Number of events 62 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	36.7% 36/98 • Number of events 53 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	25.3% 40/158 • Number of events 50 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Respiratory, thoracic and mediastinal disorders Nasal congestion	7.8% 7/90 • Number of events 9 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	10.2% 10/98 • Number of events 15 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	5.1% 8/158 • Number of events 10 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.9% 8/90 • Number of events 8 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	12.2% 12/98 • Number of events 16 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	5.7% 9/158 • Number of events 9 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Respiratory, thoracic and mediastinal disorders Sputum increased	7.8% 7/90 • Number of events 9 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	7.1% 7/98 • Number of events 10 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	5.7% 9/158 • Number of events 11 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.6% 5/90 • Number of events 5 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	6.1% 6/98 • Number of events 9 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	5.1% 8/158 • Number of events 9 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Respiratory, thoracic and mediastinal disorders Wheezing	3.3% 3/90 • Number of events 4 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	8.2% 8/98 • Number of events 8 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	4.4% 7/158 • Number of events 8 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.6% 5/90 • Number of events 5 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	4.1% 4/98 • Number of events 5 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	5.1% 8/158 • Number of events 8 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.6% 5/90 • Number of events 7 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	2.0% 2/98 • Number of events 3 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Gastrointestinal disorders Vomiting	10.0% 9/90 • Number of events 10 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	11.2% 11/98 • Number of events 14 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Gastrointestinal disorders Constipation	3.3% 3/90 • Number of events 6 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	7.1% 7/98 • Number of events 13 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Gastrointestinal disorders Nausea	4.4% 4/90 • Number of events 5 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	10.2% 10/98 • Number of events 11 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	5.1% 8/158 • Number of events 8 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Gastrointestinal disorders Abdominal pain	4.4% 4/90 • Number of events 4 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	7.1% 7/98 • Number of events 11 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Gastrointestinal disorders Diarrhoea	6.7% 6/90 • Number of events 6 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	7.1% 7/98 • Number of events 9 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Investigations Blood glucose increased	1.1% 1/90 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	7.1% 7/98 • Number of events 8 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Investigations Forced expiratory volume decreased	1.1% 1/90 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	6.1% 6/98 • Number of events 6 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Investigations Glucose urine present	2.2% 2/90 • Number of events 2 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	5.1% 5/98 • Number of events 5 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
General disorders Pyrexia	12.2% 11/90 • Number of events 12 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	8.2% 8/98 • Number of events 10 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	5.1% 8/158 • Number of events 9 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
General disorders Chest discomfort	10.0% 9/90 • Number of events 10 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	8.2% 8/98 • Number of events 8 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
General disorders Fatigue	3.3% 3/90 • Number of events 5 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	5.1% 5/98 • Number of events 5 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Nervous system disorders Headache	10.0% 9/90 • Number of events 13 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	12.2% 12/98 • Number of events 14 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	7.6% 12/158 • Number of events 15 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Musculoskeletal and connective tissue disorders Back pain	6.7% 6/90 • Number of events 7 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	1.0% 1/98 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.
Metabolism and nutrition disorders Decreased appetite	1.1% 1/90 • Number of events 1 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	5.1% 5/98 • Number of events 5 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.	0.00% 0/158 • Treatment-emergent adverse events (AEs) were assessed on or after the first dose of trial drug to 28 days after last dose. For all safety analyses, a single set of results was produced including all participants (6-21 and >21 years combined). For the double-blind Period 1, AE data are presented for the vancomycin and placebo groups whereas for the open-label Period 2, AE data for only one combined group is presented.

Additional Information

Raymond D Pratt, Chief Medical Officer

Savara Inc

Phone: +1 512 784 8757

Email: ray.pratt@savarapharma.com

Results disclosure agreements

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