Trial Outcomes & Findings for International Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis Patients With P. Aeruginosa (NCT NCT00112359)

Last Updated: 2011-04-21

Results Overview

The CFQ-R was administered at baseline and every visit thereafter. The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R respiratory symptoms scale (RSS; range of scores: 0-100; higher scores indicate fewer symptoms).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

166 participants

Primary outcome timeframe

Day 0 to Day 28

Results posted on

2011-04-21

Participant Flow

Phase 3, double-blind, multicenter, multinational, randomized, placebo-controlled trial evaluating AZLI in patients with CF and PA. Participants were enrolled at 53 sites total: 40 in United States, 5 in Canada, 7 in Australia, and 1 in New Zealand. Date of first enrollment was 10 Jun 2005, and date of last participant follow-up was 3 Apr 2007.

Planned study size was 140 participants to be randomized in a 1:1 ratio to AZLI or placebo TID, with 166 actually randomized (83 AZLI, 83 placebo). However, two participants did not receive a dose of drug, and one participant randomized to receive AZLI received placebo in error. Thus, 80 participants received AZLI and 84 received placebo.

Participant milestones

Participant milestones
Measure	Placebo TID Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered three times a day by inhalation using the investigational nebulizer.	75 mg AZLI TID AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day using the investigational nebulizer.
Overall Study STARTED	84	80
Overall Study COMPLETED	57	67
Overall Study NOT COMPLETED	27	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo TID Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered three times a day by inhalation using the investigational nebulizer.	75 mg AZLI TID AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day using the investigational nebulizer.
Overall Study Unrelated adverse event	16	8
Overall Study Trial drug intolerance (adverse event)	2	0
Overall Study Related adverse event	5	3
Overall Study Lost to Follow-up	0	1
Overall Study Personal/administrative	1	1
Overall Study Other	3	0

Baseline Characteristics

International Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Cystic Fibrosis Patients With P. Aeruginosa

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo TID n=84 Participants Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered three times a day by inhalation using the investigational nebulizer.	75 mg AZLI TID n=80 Participants AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day using the investigational nebulizer.	Total n=164 Participants Total of all reporting groups
Age, Categorical <=18 years	16 Participants n=5 Participants	21 Participants n=7 Participants	37 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	66 Participants n=5 Participants	59 Participants n=7 Participants	125 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Age Continuous	31.7 years STANDARD_DEVIATION 14.8 • n=5 Participants	27.4 years STANDARD_DEVIATION 12.8 • n=7 Participants	29.6 years STANDARD_DEVIATION 14.0 • n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants	32 Participants n=7 Participants	71 Participants n=5 Participants
Sex: Female, Male Male	45 Participants n=5 Participants	48 Participants n=7 Participants	93 Participants n=5 Participants
Region of Enrollment North America	63 participants n=5 Participants	62 participants n=7 Participants	125 participants n=5 Participants
Region of Enrollment Australia	21 participants n=5 Participants	18 participants n=7 Participants	39 participants n=5 Participants
Disease severity based on forced expiratory volume in 1 second (FEV1) % predicted Disease severity: FEV1 > 50% predicted	54 participants n=5 Participants	50 participants n=7 Participants	104 participants n=5 Participants
Disease severity based on forced expiratory volume in 1 second (FEV1) % predicted Disease severity: FEV1 <= 50% predicted	30 participants n=5 Participants	30 participants n=7 Participants	60 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 0 to Day 28

Population: ITT population: participants randomized to treatment who received at least part of 1 dose of study drug. Participants summarized by actual treatment received. Missing baseline data not imputed. Missing post-baseline data imputed using worst-case value for withdrawals due to AE or study drug intolerance. All other missing data: LOCF method used.

Outcome measures

Outcome measures
Measure	Placebo TID n=83 Participants Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered three times a day by inhalation using the investigational nebulizer.	75 mg AZLI TID n=80 Participants AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day using the investigational nebulizer.
Change in CFQ-R Respiratory Symptoms Scale (RSS) Score	-2.63 units on a scale Standard Error 1.95	7.08 units on a scale Standard Error 1.98

SECONDARY outcome

Timeframe: Day 0 to Day 14

The CFQ-R was administered at baseline and every visit thereafter. The endpoint was change in respiratory symptoms from baseline, assessed with the CFQ-R RSS (range of scores: 0-100; higher scores indicate fewer symptoms).

Outcome measures

Outcome measures
Measure	Placebo TID n=83 Participants Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered three times a day by inhalation using the investigational nebulizer.	75 mg AZLI TID n=80 Participants AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day using the investigational nebulizer.
Change in CFQ-R RSS Score	0.976 units on a scale Standard Error 1.624	7.007 units on a scale Standard Error 1.647

SECONDARY outcome

Timeframe: Day 0 to Day 42

Outcome measures

Outcome measures
Measure	Placebo TID n=83 Participants Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered three times a day by inhalation using the investigational nebulizer.	75 mg AZLI TID n=80 Participants AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day using the investigational nebulizer.
Change in CFQ-R RSS Score	-5.711 units on a scale Standard Error 1.849	0.618 units on a scale Standard Error 1.875

SECONDARY outcome

Timeframe: Day 0 to Day 28

Spirometry was performed according to American Thoracic Society (ATS) guidelines at each visit. The percent change from baseline in forced expiratory volume (liters) in one second (FEV1) was determined at Day 28.

Outcome measures

Outcome measures
Measure	Placebo TID n=84 Participants Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered three times a day by inhalation using the investigational nebulizer.	75 mg AZLI TID n=80 Participants AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day using the investigational nebulizer.
Percent Change in FEV1 (L)	-2.408 Percent change in FEV1 (L) Standard Error 1.466	7.886 Percent change in FEV1 (L) Standard Error 1.481

SECONDARY outcome

Timeframe: Day 0 to Day 28

Population: Analysis based on ITT population (all participants randomized to treatment who received at least part of 1 dose of study drug). Participants were summarized by the actual treatment received. No imputation methods were used for the analysis.

Sputum samples were collected at all participant visits of the study for analysis of microbiology endpoints. Sputum samples were processed for qualitative and quantitative culture of PA (each morphotype). Due to the skewness of the distribution of CFU data, the data were transformed using the base 10 logarithm, in an attempt to normalize the data and allow for parametric tests, before calculating changes. To account for zero values, 1 was added to each CFU measurement before being transformed. Any CFU data values where PA was not isolated from a valid culture were set to zero.

Outcome measures

Outcome measures
Measure	Placebo TID n=61 Participants Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered three times a day by inhalation using the investigational nebulizer.	75 mg AZLI TID n=53 Participants AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day using the investigational nebulizer.
Change From Baseline in Pseudomonas Aeruginosa (PA) Log10 Colony Forming Units (CFU) Per Gram of Sputum	0.069 Log10 PA CFUs/gram of sputum Standard Error 0.231	-1.384 Log10 PA CFUs/gram of sputum Standard Error 0.247

SECONDARY outcome

Timeframe: Day 0 to Day 42

Population: Analysis based on ITT population (all participants randomized to treatment who received at least part of one dose of study drug). Participants were summarized by the actual treatment received.

Use of IV and inhaled antipseudomonal antibiotics was compiled from data recorded on the Concomitant Medications eCRF.

Outcome measures

Outcome measures
Measure	Placebo TID n=84 Participants Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered three times a day by inhalation using the investigational nebulizer.	75 mg AZLI TID n=80 Participants AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day using the investigational nebulizer.
Number of Participants Receiving Intravenous (IV) or Inhaled Antipseudomonal Antibiotics Other Than Trial Drug	19 participants	12 participants

SECONDARY outcome

Timeframe: Day 0 to Day 42

Details of all hospitalizations, including the dates of admission and discharge, were recorded on the SAE eCRF.

Outcome measures

Outcome measures
Measure	Placebo TID n=84 Participants Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered three times a day by inhalation using the investigational nebulizer.	75 mg AZLI TID n=80 Participants AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day using the investigational nebulizer.
Number of Participants Hospitalized at Least Once Between Day 0 and Day 42	12 participants	4 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 0 to Day 28

Sputum samples were collected at all visits for quantitative and qualitative culture for Staphylococcus aureus, Burkholderia cepacia, Stenotrophomonas maltophilia, Achromobacter xylosoxidans.

Outcome measures

Outcome measures
Measure	Placebo TID n=81 Participants Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered three times a day by inhalation using the investigational nebulizer.	75 mg AZLI TID n=74 Participants AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day using the investigational nebulizer.
Number of Participants With Other Pathogens Present Staphylococcus aureus - Day 0	30 participants	37 participants
Number of Participants With Other Pathogens Present Staphylococcus aureus - Day 28	31 participants	35 participants
Number of Participants With Other Pathogens Present Burkholderia cepacia - Day 0	0 participants	1 participants
Number of Participants With Other Pathogens Present Burkholderia cepacia - Day 28	0 participants	0 participants
Number of Participants With Other Pathogens Present Stenotrophomonas maltophilia - Day 0	4 participants	1 participants
Number of Participants With Other Pathogens Present Stenotrophomonas maltophilia - Day 28	2 participants	2 participants
Number of Participants With Other Pathogens Present Achromobacter xylosoxidans - Day 0	5 participants	1 participants
Number of Participants With Other Pathogens Present Achromobacter xylosoxidans - Day 28	7 participants	1 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 0

PA isolates from sputum samples (collected at all visits) were assessed for their susceptibility to aztreonam. MIC50 = minimum inhibitory concentration (minimum concentration of an agent that inhibits 50% of isolates from a particular organism). MIC90 = minimum inhibitory concentration (minimum concentration of an agent that inhibits 90% of isolates from a particular organism). MIC50 and MIC90 values are single measurements for the entire population and not measured on a per-participant basis.

Outcome measures

Outcome measures
Measure	Placebo TID n=140 PA isolates Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered three times a day by inhalation using the investigational nebulizer.	75 mg AZLI TID n=128 PA isolates AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day using the investigational nebulizer.
Minimum Inhibitory Concentration of Aztreonam Inhibiting 50% (MIC50) and 90% (MIC90) of All PA Isolates (μg/mL) Day 0 MIC50	2 μg/mL	4 μg/mL
Minimum Inhibitory Concentration of Aztreonam Inhibiting 50% (MIC50) and 90% (MIC90) of All PA Isolates (μg/mL) Day 0 MIC90	64 μg/mL	128 μg/mL

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 28

Outcome measures

Outcome measures
Measure	Placebo TID n=116 PA isolates Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered three times a day by inhalation using the investigational nebulizer.	75 mg AZLI TID n=102 PA isolates AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day using the investigational nebulizer.
Minimum Inhibitory Concentration of Aztreonam Inhibiting 50% (MIC50) and 90% (MIC90) of All PA Isolates (μg/mL) Day 28 MIC50	2 μg/mL	8 μg/mL
Minimum Inhibitory Concentration of Aztreonam Inhibiting 50% (MIC50) and 90% (MIC90) of All PA Isolates (μg/mL) Day 28 MIC90	64 μg/mL	128 μg/mL

Adverse Events

Placebo TID

Serious events: 12 serious events

Other events: 67 other events

Deaths: 0 deaths

75 mg AZLI TID

Serious events: 5 serious events

Other events: 63 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Mark Bresnik, MD, Director, Clinical Research

Gilead Sciences, Inc.

Phone: (650) 522-5934

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institution and investigator may publish or present the results of the trial generated there with prior written consent of Gilead; or 2 years after the trial has ended at all institutions. Proposed publications/target venue must go to Gilead 30 days (manuscripts) or 15 days (abstracts/presentations) prior. Any Gilead confidential information in the document(s) must be deleted, or if requested publication delayed for up to 45 days to permit Gilead to obtain intellectual property protection.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo TID n=84 participants at risk Placebo (5 mg/mL lactose when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.5, and osmolality 200 to 400 mOsmol/kg). Placebo was self-administered three times a day by inhalation using the investigational nebulizer.	75 mg AZLI TID n=80 participants at risk AZLI (75 mg/mL aztreonam lysine when reconstituted in diluent \[0.17% saline\]; sterile, pH 4.2 to 7.0, and osmolality 300 to 550 mOsmol/kg). AZLI was self-administered by inhalation three times a day using the investigational nebulizer.
Gastrointestinal disorders Abdominal pain	7.1% 6/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	7.5% 6/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.
Musculoskeletal and connective tissue disorders Arthralgia	6.0% 5/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	0.00% 0/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Chest discomfort	4.8% 4/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	6.2% 5/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Cough	32.1% 27/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	47.5% 38/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Crackles lung	7.1% 6/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	11.2% 9/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.3% 7/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	7.5% 6/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Dyspnoea exacerbated	8.3% 7/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	6.2% 5/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.
General disorders Fatigue	7.1% 6/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	6.2% 5/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Haemoptysis	6.0% 5/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	3.8% 3/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.
Nervous system disorders Headache	11.9% 10/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	7.5% 6/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Nasal congestion	9.5% 8/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	13.8% 11/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	9.5% 8/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	12.5% 10/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Productive cough	27.4% 23/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	15.0% 12/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.
Investigations Pulmonary function test decreased	6.0% 5/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	3.8% 3/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.
General disorders Pyrexia	7.1% 6/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	10.0% 8/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	8.3% 7/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	3.8% 3/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Sinus congestion	2.4% 2/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	5.0% 4/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Throat irritation	2.4% 2/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	6.2% 5/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.
Respiratory, thoracic and mediastinal disorders Wheezing	8.3% 7/84 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.	10.0% 8/80 • AEs that first occurred or worsened after the first dose of study drug through 30 days after the last dose are summarized. An AE was any physical or clinical worsening in symptoms or disease (including clinically significant change in lab values) experienced by participant at any time during the study, whether or not the event was considered related to study participation or study procedures. Participants were only counted once within an SOC and preferred term.