Trial Outcomes & Findings for Inhaled Vancomycin Tolerability, Safety and Pharmacokinetics (NCT NCT01537666)

NCT ID: NCT01537666

Last Updated: 2014-03-31

Results Overview

Each participant was monitored regularly for Adverse Events (AEs) throughout the study. The Investigator or designee enquired about AEs by asking participants non-leading questions such as: "How do you feel?" or "Have you had any (other) medical problems since your last visit/assessment?" Additionally, several safety procedures (physical examinations, vital signs, safety laboratory tests, 12-lead ECGs, and spirometry) were conducted on participants at regular intervals. All AEs reported spontaneously by participants or in response to questioning or observation by the Investigator, including those related to safety procedures, were recorded. For each AE, the Investigator recorded the following assessments: seriousness, severity (Mild, Moderate, or Severe), and relationship to study drug (Not Related, Remote, Possible, Probable, or Highly Probable). AEs were considered drug-related if given a relationship of Possible, Probable, or Highly Probable.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 25 participants
• Primary outcome timeframe: Healthy volunteers = 2 weeks; CF Patients = 1 week
• Results posted on: 2014-03-31

Participant Flow

Participant milestones

Measure	Aerovanc 16 mg (Subset IV Vancomycin) in Healthy Volunteers AeroVanc : Vancomycin hydrochloride dry powder for inhalation (N=6)/ Subset received IV vancomycin hydrochloride : Vancomycin hydrochloride solution for intravenous administration (N=2 from this group, 6 overall)	AeroVanc 32 mg (Subset IV Vancomycin) in Healthy Volunteers AeroVanc : Vancomycin hydrochloride dry powder for inhalation (N=6)/ Subset received IV vancomycin hydrochloride : Vancomycin hydrochloride solution for intravenous administration (N=2 from this group, 6 overall)	AeroVanc 80 mg (Subset IV Vancomycin) in Healthy Volunteers AeroVanc : Vancomycin hydrochloride dry powder for inhalation (N=6)/ Subset received IV vancomycin hydrochloride : Vancomycin hydrochloride solution for intravenous administration (N=2 from this group, 6 overall)	AeroVanc 32 and 80 mg in CF Patients AeroVanc : Vancomycin hydrochloride dry powder for inhalation
Overall Study STARTED	6	6	6	7
Overall Study COMPLETED	6	6	6	7
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Inhaled Vancomycin Tolerability, Safety and Pharmacokinetics

Baseline characteristics by cohort

Measure	Aerovanc 16 mg (Subset IV Vancomycin) in Healthy Volunteers n=6 Participants AeroVanc : Vancomycin hydrochloride dry powder for inhalation (N=6)/ Subset received IV vancomycin hydrochloride : Vancomycin hydrochloride solution for intravenous administration (N=2 from this group, 6 overall)	AeroVanc 32 mg (Subset IV Vancomycin) in Healthy Volunteers n=6 Participants AeroVanc : Vancomycin hydrochloride dry powder for inhalation (N=6)/ Subset received IV vancomycin hydrochloride : Vancomycin hydrochloride solution for intravenous administration (N=2 from this group, 6 overall)	AeroVanc 80 mg (Subset IV Vancomycin) in Healthy Volunteers n=6 Participants AeroVanc : Vancomycin hydrochloride dry powder for inhalation (N=6)/ Subset received IV vancomycin hydrochloride : Vancomycin hydrochloride solution for intravenous administration (N=2 from this group, 6 overall)	AeroVanc 32 and 80 mg in CF Patients n=7 Participants AeroVanc : Vancomycin hydrochloride dry powder for inhalation	Total n=25 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	7 Participants n=4 Participants	25 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Continuous	28.2 years STANDARD_DEVIATION 10.5 • n=5 Participants	24.7 years STANDARD_DEVIATION 3.7 • n=7 Participants	22.2 years STANDARD_DEVIATION 2.8 • n=5 Participants	29.7 years STANDARD_DEVIATION 7.8 • n=4 Participants	26.3 years STANDARD_DEVIATION 7.2 • n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	4 Participants n=4 Participants	22 Participants n=21 Participants
Region of Enrollment Australia	6 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	7 participants n=4 Participants	25 participants n=21 Participants

PRIMARY outcome

Timeframe: Healthy volunteers = 2 weeks; CF Patients = 1 week

Population: All 18 healthy volunteers who received single doses of AeroVanc, 6 of which also received a single dose of IV vancomycin. All 7 Cystic Fibrosis patients who received at least one single dose of AeroVanc.

Each participant was monitored regularly for Adverse Events (AEs) throughout the study. The Investigator or designee enquired about AEs by asking participants non-leading questions such as: "How do you feel?" or "Have you had any (other) medical problems since your last visit/assessment?" Additionally, several safety procedures (physical examinations, vital signs, safety laboratory tests, 12-lead ECGs, and spirometry) were conducted on participants at regular intervals. All AEs reported spontaneously by participants or in response to questioning or observation by the Investigator, including those related to safety procedures, were recorded. For each AE, the Investigator recorded the following assessments: seriousness, severity (Mild, Moderate, or Severe), and relationship to study drug (Not Related, Remote, Possible, Probable, or Highly Probable). AEs were considered drug-related if given a relationship of Possible, Probable, or Highly Probable.

Outcome measures

Measure	AeroVanc 16 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 16 mg AeroVanc in health volunteers.	AeroVanc 32 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 32 mg AeroVanc in health volunteers.	AeroVanc 80 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 80 mg AeroVanc in health volunteers.	IV Vancomycin 250 mg in Healthy Volunteers n=6 Participants Single IV dose of Vancomycin 250 mg in Healthy Volunteers. Group comprised of 2 subjects from each of the AeroVanc in Healthy Volunteers groups.	AeroVanc 32 mg in Cystic Fibrosis Patients n=6 Participants Single inhaled dose of 32 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.	AeroVanc 80 mg in Cystic Fibrosis Patients n=6 Participants Single inhaled dose of 80 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.
Safety and Tolerability - Number of Participants With Treatment Emergent Adverse Events (TEAEs = Adverse Events That Started During or After the First Dose of Study Drug) Total with at least one TEAE	2 participants	5 participants	2 participants	2 participants	6 participants	5 participants
Safety and Tolerability - Number of Participants With Treatment Emergent Adverse Events (TEAEs = Adverse Events That Started During or After the First Dose of Study Drug) Subset of total with drug-related TEAEs	2 participants	3 participants	2 participants	1 participants	4 participants	4 participants
Safety and Tolerability - Number of Participants With Treatment Emergent Adverse Events (TEAEs = Adverse Events That Started During or After the First Dose of Study Drug) Subset of total with severe TEAEs	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants
Safety and Tolerability - Number of Participants With Treatment Emergent Adverse Events (TEAEs = Adverse Events That Started During or After the First Dose of Study Drug) Subset of total with severe, drug-related TEAEs	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Safety and Tolerability - Number of Participants With Treatment Emergent Adverse Events (TEAEs = Adverse Events That Started During or After the First Dose of Study Drug) Subset of total with serious TEAEs	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants
Safety and Tolerability - Number of Participants With Treatment Emergent Adverse Events (TEAEs = Adverse Events That Started During or After the First Dose of Study Drug) Subset of total with serious, drug-related TEAEs	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose

Population: All healthy volunteers (N=18) who received a single 16, 32, or 80 mg inhaled dose of AeroVanc. Subset (N=6 comprised of 2 patients from each of the AeroVanc groups) who received a single 250 mg IV dose of vancomycin.

Blood samples were obtained from the healthy volunteers to evaluate systemic pharmacokinetics of vancomycin after a single dose administration of AeroVanc or a single dose of IV vancomycin.

Half-life is the time it takes for the concentration of drug to decline by 50%.

Outcome measures

Measure	AeroVanc 16 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 16 mg AeroVanc in health volunteers.	AeroVanc 32 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 32 mg AeroVanc in health volunteers.	AeroVanc 80 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 80 mg AeroVanc in health volunteers.	IV Vancomycin 250 mg in Healthy Volunteers n=6 Participants Single IV dose of Vancomycin 250 mg in Healthy Volunteers. Group comprised of 2 subjects from each of the AeroVanc in Healthy Volunteers groups.	AeroVanc 32 mg in Cystic Fibrosis Patients Single inhaled dose of 32 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.	AeroVanc 80 mg in Cystic Fibrosis Patients Single inhaled dose of 80 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.
Plasma Pharmacokinetics - Elimination Half Life (t½)	8.454 Hours Standard Deviation 2.017	8.648 Hours Standard Deviation 0.530	8.044 Hours Standard Deviation 1.296	7.226 Hours Standard Deviation 1.128	—	—

SECONDARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose

Population: All healthy volunteers (N=18) who received a single 16, 32, or 80 mg inhaled dose of AeroVanc. Subset (N=6 comprised of 2 patients from each of the AeroVanc groups) who received a single 250 mg IV dose of vancomycin.

Blood samples were obtained from the healthy volunteers to evaluate systemic pharmacokinetics of vancomycin after a single dose administration of AeroVanc or a single dose of IV vancomycin.

Tmax is the time it takes to reach the maximum plasma concentration of a drug.

Outcome measures

Measure	AeroVanc 16 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 16 mg AeroVanc in health volunteers.	AeroVanc 32 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 32 mg AeroVanc in health volunteers.	AeroVanc 80 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 80 mg AeroVanc in health volunteers.	IV Vancomycin 250 mg in Healthy Volunteers n=6 Participants Single IV dose of Vancomycin 250 mg in Healthy Volunteers. Group comprised of 2 subjects from each of the AeroVanc in Healthy Volunteers groups.	AeroVanc 32 mg in Cystic Fibrosis Patients Single inhaled dose of 32 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.	AeroVanc 80 mg in Cystic Fibrosis Patients Single inhaled dose of 80 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.
Plasma Pharmacokinetics - Time to Reach the Maximum Plasma Concentration (Tmax)	2.083 Hours Standard Deviation 0.801	1.833 Hours Standard Deviation 0.606	1.333 Hours Standard Deviation 0.408	0.917 Hours Standard Deviation 0.204	—	—

SECONDARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose

Population: All healthy volunteers (N=18) who received a single 16, 32, or 80 mg inhaled dose of AeroVanc. Subset (N=6 comprised of 2 patients from each of the AeroVanc groups) who received a single 250 mg IV dose of vancomycin.

Blood samples were obtained from the healthy volunteers to evaluate systemic pharmacokinetics of vancomycin after a single dose administration of AeroVanc or a single dose of IV vancomycin.

Cmax is the maximum observed concentration of a drug.

Outcome measures

Measure	AeroVanc 16 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 16 mg AeroVanc in health volunteers.	AeroVanc 32 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 32 mg AeroVanc in health volunteers.	AeroVanc 80 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 80 mg AeroVanc in health volunteers.	IV Vancomycin 250 mg in Healthy Volunteers n=6 Participants Single IV dose of Vancomycin 250 mg in Healthy Volunteers. Group comprised of 2 subjects from each of the AeroVanc in Healthy Volunteers groups.	AeroVanc 32 mg in Cystic Fibrosis Patients Single inhaled dose of 32 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.	AeroVanc 80 mg in Cystic Fibrosis Patients Single inhaled dose of 80 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.
Plasma Pharmacokinetics - Maximum Plasma Concentration (Cmax)	108.82 ng/ml Standard Deviation 33.16	231.50 ng/ml Standard Deviation 89.64	617.83 ng/ml Standard Deviation 230.03	10028.33 ng/ml Standard Deviation 1767.69	—	—

SECONDARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose

Population: All healthy volunteers (N=18) who received a single 16, 32, or 80 mg inhaled dose of AeroVanc. Subset (N=6 comprised of 2 patients from each of the AeroVanc groups) who received a single 250 mg IV dose of vancomycin.

Blood samples were obtained from the healthy volunteers to evaluate systemic pharmacokinetics of vancomycin after a single dose administration of AeroVanc or a single dose of IV vancomycin.

AUCt is a way of expressing the total amount of drug exposure over a specified time period.

Outcome measures

Measure	AeroVanc 16 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 16 mg AeroVanc in health volunteers.	AeroVanc 32 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 32 mg AeroVanc in health volunteers.	AeroVanc 80 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 80 mg AeroVanc in health volunteers.	IV Vancomycin 250 mg in Healthy Volunteers n=6 Participants Single IV dose of Vancomycin 250 mg in Healthy Volunteers. Group comprised of 2 subjects from each of the AeroVanc in Healthy Volunteers groups.	AeroVanc 32 mg in Cystic Fibrosis Patients Single inhaled dose of 32 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.	AeroVanc 80 mg in Cystic Fibrosis Patients Single inhaled dose of 80 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.
Plasma Pharmacokinetics - Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUCt)	1209.644 h*ng/ml Standard Deviation 237.696	2379.790 h*ng/ml Standard Deviation 975.410	6257.858 h*ng/ml Standard Deviation 1506.939	41027.792 h*ng/ml Standard Deviation 2696.013	—	—

SECONDARY outcome

Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose

Population: All healthy volunteers (N=18) who received a single 16, 32, or 80 mg inhaled dose of AeroVanc. Subset (N=6 comprised of 2 patients from each of the AeroVanc groups) who received a single 250 mg IV dose of vancomycin.

Blood samples were obtained from the healthy volunteers to evaluate systemic pharmacokinetics of vancomycin after a single dose administration of AeroVanc or a single dose of IV vancomycin.

AUCinf is a way of estimating the total amount of drug exposure over an infinite time period.

Outcome measures

Measure	AeroVanc 16 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 16 mg AeroVanc in health volunteers.	AeroVanc 32 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 32 mg AeroVanc in health volunteers.	AeroVanc 80 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 80 mg AeroVanc in health volunteers.	IV Vancomycin 250 mg in Healthy Volunteers n=6 Participants Single IV dose of Vancomycin 250 mg in Healthy Volunteers. Group comprised of 2 subjects from each of the AeroVanc in Healthy Volunteers groups.	AeroVanc 32 mg in Cystic Fibrosis Patients Single inhaled dose of 32 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.	AeroVanc 80 mg in Cystic Fibrosis Patients Single inhaled dose of 80 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.
Plasma Pharmacokinetics - Area Under the Plasma Concentration-time Curve From Time 0 to Infinite Time (AUCinf)	1461.407 h*ng/ml Standard Deviation 257.189	3051.12 h*ng/ml Standard Deviation 959.14	7135.735 h*ng/ml Standard Deviation 1457.921	44356.356 h*ng/ml Standard Deviation 3623.420	—	—

SECONDARY outcome

Timeframe: 1, 8 and 24 hours post-dose

Population: All CF patients who received a 32 mg dose of AeroVanc followed at least one week later by an 80 mg dose of AeroVanc (N=5). One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.

Sputum samples were obtained from the patients with cystic fibrosis to evaluate lung pharmacokinetics of vancomycin after a single dose administration of AeroVanc.

Cmax is the maximum observed concentration of a drug.

Outcome measures

Measure	AeroVanc 16 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 16 mg AeroVanc in health volunteers.	AeroVanc 32 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 32 mg AeroVanc in health volunteers.	AeroVanc 80 mg in Healthy Volunteers Single inhaled dose of 80 mg AeroVanc in health volunteers.	IV Vancomycin 250 mg in Healthy Volunteers Single IV dose of Vancomycin 250 mg in Healthy Volunteers. Group comprised of 2 subjects from each of the AeroVanc in Healthy Volunteers groups.	AeroVanc 32 mg in Cystic Fibrosis Patients Single inhaled dose of 32 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.	AeroVanc 80 mg in Cystic Fibrosis Patients Single inhaled dose of 80 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.
Lung Pharmacokinetics - Maximum Sputum Concentration (Cmax)	95.775 µg/ml Standard Deviation 171.544	269.17 µg/ml Standard Deviation 510.98	—	—	—	—

SECONDARY outcome

Timeframe: 1, 8 and 24 hours post-dose

Population: All CF patients who received a 32 mg dose of AeroVanc followed at least one week later by an 80 mg dose of AeroVanc (N=5). One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.

Sputum samples were obtained from the patients with cystic fibrosis to evaluate lung pharmacokinetics of vancomycin after a single dose administration of AeroVanc.

Cmin is the minimum observed concentration of a drug.

Outcome measures

Measure	AeroVanc 16 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 16 mg AeroVanc in health volunteers.	AeroVanc 32 mg in Healthy Volunteers n=6 Participants Single inhaled dose of 32 mg AeroVanc in health volunteers.	AeroVanc 80 mg in Healthy Volunteers Single inhaled dose of 80 mg AeroVanc in health volunteers.	IV Vancomycin 250 mg in Healthy Volunteers Single IV dose of Vancomycin 250 mg in Healthy Volunteers. Group comprised of 2 subjects from each of the AeroVanc in Healthy Volunteers groups.	AeroVanc 32 mg in Cystic Fibrosis Patients Single inhaled dose of 32 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.	AeroVanc 80 mg in Cystic Fibrosis Patients Single inhaled dose of 80 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.
Lung Pharmacokinetics - Minimum Sputum Concentration (Cmin)	3.050 µg/ml Standard Deviation 3.679	7.990 µg/ml Standard Deviation 8.066	—	—	—	—

Adverse Events

AeroVanc 16 mg in Healthy Volunteers

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

AeroVanc 32 mg in Healthy Volunteers

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

AeroVanc 80 mg in Healthy Volunteers

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

AeroVanc 32 mg in Cystic Fibrosis Patients

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

AeroVanc 80 mg in Cystic Fibrosis Patients

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

IV Vancomycin 250 mg in Healthy Volunteers

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	AeroVanc 16 mg in Healthy Volunteers n=6 participants at risk Single inhaled dose of 16 mg AeroVanc in health volunteers.	AeroVanc 32 mg in Healthy Volunteers n=6 participants at risk Single inhaled dose of 32 mg AeroVanc in health volunteers.	AeroVanc 80 mg in Healthy Volunteers n=6 participants at risk Single inhaled dose of 80 mg AeroVanc in health volunteers.	AeroVanc 32 mg in Cystic Fibrosis Patients n=6 participants at risk Single inhaled dose of 32 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.	AeroVanc 80 mg in Cystic Fibrosis Patients n=6 participants at risk Single inhaled dose of 80 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.	IV Vancomycin 250 mg in Healthy Volunteers n=6 participants at risk Comprised of 2 patients from each of the AeroVanc in Healthy Volunteer groups.
Renal and urinary disorders AGGRAVATED RENAL COLIC	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.

Other adverse events

Measure	AeroVanc 16 mg in Healthy Volunteers n=6 participants at risk Single inhaled dose of 16 mg AeroVanc in health volunteers.	AeroVanc 32 mg in Healthy Volunteers n=6 participants at risk Single inhaled dose of 32 mg AeroVanc in health volunteers.	AeroVanc 80 mg in Healthy Volunteers n=6 participants at risk Single inhaled dose of 80 mg AeroVanc in health volunteers.	AeroVanc 32 mg in Cystic Fibrosis Patients n=6 participants at risk Single inhaled dose of 32 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.	AeroVanc 80 mg in Cystic Fibrosis Patients n=6 participants at risk Single inhaled dose of 80 mg AeroVanc. One patient withdrew after receiving a 32 mg dose and was replaced with a patient who only received an 80 mg dose.	IV Vancomycin 250 mg in Healthy Volunteers n=6 participants at risk Comprised of 2 patients from each of the AeroVanc in Healthy Volunteer groups.
Gastrointestinal disorders Diarrhoea	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.
Gastrointestinal disorders Nausea	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	16.7% 1/6 • Number of events 2 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.
Gastrointestinal disorders Oral discomfort	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.
General disorders Chest discomfort	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.
General disorders Feeling hot	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.
Infections and infestations Upper respiratory tract infection	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	33.3% 2/6 • Number of events 3 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.
Injury, poisoning and procedural complications Excoriation	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.
Investigations Forced expiratory volume decreased	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	33.3% 2/6 • Number of events 2 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.
Investigations Liver function test abnormal	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.
Nervous system disorders Dizziness	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.
Nervous system disorders Headache	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	33.3% 2/6 • Number of events 2 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	33.3% 2/6 • Number of events 2 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	33.3% 2/6 • Number of events 2 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	50.0% 3/6 • Number of events 3 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.
Skin and subcutaneous tissue disorders Drug eruption	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	16.7% 1/6 • Number of events 1 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.	0.00% 0/6 • All 25 subjects enrolled received at least part of their allocated study treatments and are included in the safety population. All subjects received their allocated dose, and in Part 2 of the study, 5 subjects received both the 32 mg and 80 mg doses. AEs were grouped by system organ class and summarized by dose level at the time of onset of the AE. All AE summaries are restricted to TEAEs, defined as AEs that began on or after the start of study drug. AEs without an onset date or time were excluded from the summary tables as it was not possible to allocate to a particular treatment.

Additional Information

Taneli Jouhikainen, MD, MBA; Chief Operating Officer

Savara Inc.

Phone: (888) 302-4876

Email: info@savarapharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee The PI cannot at any time during or after the Study make any announcement, oral presentation or publication relating to the Study, or any of the methods, results of, or conclusions from, the Study without the prior written consent of the Sponsor.
• Publication restrictions are in place

Restriction type: OTHER