Safety and Effectiveness of AZLI (an Inhaled Antibiotic)... | NCT01314716

Label	Type	Description	Intervention Names
AZLI-AZLI	Experimental	Participants were randomized to receive blinded AZLI for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI for 28 days plus 56 days of treatment-free follow-up.	Drug: AZLI
Placebo-AZLI	Placebo Comparator	Participants were randomized to receive blinded placebo to match AZLI for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI for 28 days plus 56 days of treatment-free follow-up.	Drug: AZLI Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
AZLI	Drug	AZLI 75 mg reconstituted with diluent and administered via nebulizer three times daily	AZLI-AZLI Placebo-AZLI

Measure	Description	Time Frame
Change in QOL-B Respiratory Symptoms Score at Day 28	The mean (SD) change in the Respiratory Symptoms score on the Quality of Life Questionnaire-Bronchiectasis (QOL-B) was measured from baseline to the end of Course 1 (Day 28). The QOL-B respiratory symptoms score was transformed onto a scale of 0-100, with higher scores representing a better quality of life.	Baseline to Day 28

Measure	Description	Time Frame
Change in QOL-B Respiratory Symptoms Score at Day 84	The mean (SD) change in the Respiratory Symptoms score on the QOL-B was measured from baseline to the end of Course 2 (Day 84). The QOL-B respiratory symptoms score was transformed onto a scale of 0-100, with higher scores representing a better quality of life.	Baseline to Day 84

Name	Affiliation	Role
Anne O'Donnell, MD	Georgetown University Hospital	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Florence Research Associates		Florence	Alabama	35630	United States
Clinical Trials Connection

PubMed Identifier	Type	Citation	Retractions
25154045	Derived	Barker AF, O'Donnell AE, Flume P, Thompson PJ, Ruzi JD, de Gracia J, Boersma WG, De Soyza A, Shao L, Zhang J, Haas L, Lewis SA, Leitzinger S, Montgomery AB, McKevitt MT, Gossage D, Quittner AL, O'Riordan TG. Aztreonam for inhalation solution in patients with non-cystic fibrosis bronchiectasis (AIR-BX1 and AIR-BX2): two randomised double-blind, placebo-controlled phase 3 trials. Lancet Respir Med. 2014 Sep;2(9):738-49. doi: 10.1016/S2213-2600(14)70165-1. Epub 2014 Aug 18.

ID	Title	Description
FG000	AZLI-AZLI	Participants were randomized to receive blinded Aztreonam for Inhalation Solution (AZLI) 75 mg three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 84 days.
FG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change in QOL-B Respiratory Symptoms Score at Day 28

The mean (SD) change in the Respiratory Symptoms score on the Quality of Life Questionnaire-Bronchiectasis (QOL-B) was measured from baseline to the end of Course 1 (Day 28). The QOL-B respiratory symptoms score was transformed onto a scale of 0-100, with higher scores representing a better quality of life.

Participants in the ITT Analysis Set with scores at both baseline and Day 28 were analyzed.

Posted

Mean

Standard Deviation

units on a scale

Baseline to Day 28

ID	Title	Description
OG000	AZLI-AZLI	Participants were randomized to receive blinded AZLI 75 mg three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.
OG001	Placebo-AZLI	Participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.

Units	Counts
Participants	OG000128 OG001132

Title

Denominators

Categories

Title	Measurements
	OG0008.2± 17.13 OG0013.2± 14.67

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		MMRM		0.011	P-value was based on T-test from mixed-effect model repeated measures (MMRM).	Differences in least squares mean	4.6			2-Sided	95	1.1	8.2				No	Superiority or Other

Secondary

Change in QOL-B Respiratory Symptoms Score at Day 84

The mean (SD) change in the Respiratory Symptoms score on the QOL-B was measured from baseline to the end of Course 2 (Day 84). The QOL-B respiratory symptoms score was transformed onto a scale of 0-100, with higher scores representing a better quality of life.

Participants in the ITT Analysis Set with scores at both baseline and Day 84 were analyzed.

Posted

Mean

Standard Deviation

units on a scale

Baseline to Day 84

ID	Title	Description
OG000	AZLI-AZLI	Participants were randomized to receive blinded AZLI 75 mg three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.
OG001	Placebo-AZLI	Participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.

Units	Counts

Secondary

Time to Protocol-Defined Exacerbation (PDE)

Protocol-defined exacerbation was defined as an acute worsening of respiratory disease that triggered the initiation of a non-study antibiotic meeting at least 3 major criteria, or 2 major and at least 2 minor criteria.

Major Criteria: increased sputum production; increased discoloration of sputum; increased dyspnea; increased cough
Minor Criteria: fever (> 38º C) measured during clinic visit; increased malaise or fatigue; forced expiratory volume in 1 second (FEV1) (L) or forced vital capacity (FVC) decreased > 10% from baseline; new or increased hemoptysis

ITT Analysis Set

Posted

Median

95% Confidence Interval

days

Baseline to Day 112

ID	Title	Description
OG000	AZLI-AZLI	Participants were randomized to receive blinded AZLI 75 mg three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.
OG001	Placebo-AZLI	Participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	AZLI-AZLI (Double-Blind)	Adverse events for this reporting group were reported from baseline to Day 112 while participants were receiving double-blind AZLI; participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.	18	135	112	135
EG001	Placebo-AZLI (Double-Blind)	Adverse events for this reporting group were reported from baseline to Day 112 while participants were receiving double-blind placebo; participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.	16	137	101	137
EG002	AZLI-AZLI (Open-Label)	Adverse events for this reporting group were reported from Day 112 to Day 196 plus 30 days while participants were receiving open-label AZLI; participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.	8	112	54	112
EG003	Placebo-AZLI (Open-Label)	Adverse events for this reporting group were reported from Day 112 to Day 196 plus 30 days while participants were receiving open-label AZLI; participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.	9	110	58	110

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Infective exacerbation of bronchiectasis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0004 affected135 at risk EG0012 affected137 at risk EG0020 affected112 at risk EG0033 affected110 at risk
Pneumonia	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0003 affected135 at risk EG0012 affected137 at risk EG0021 affected112 at risk EG003
Bronchitis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0002 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Diverticulitis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Mycobacterium avium complex infection	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0011 affected137 at risk EG0020 affected112 at risk EG003
Fungal oesophagitis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Lung infection pseudomonal	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0011 affected137 at risk EG0020 affected112 at risk EG003
Sinusitis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0011 affected137 at risk EG0020 affected112 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0002 affected135 at risk EG0016 affected137 at risk EG0020 affected112 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0011 affected137 at risk EG0020 affected112 at risk EG003
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0011 affected137 at risk EG0020 affected112 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0011 affected137 at risk EG0020 affected112 at risk EG003
Lung infiltration	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Hip fracture	Injury, poisoning and procedural complications	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Patella fracture	Injury, poisoning and procedural complications	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0011 affected137 at risk EG0020 affected112 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Wrist fracture	Injury, poisoning and procedural complications	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0011 affected137 at risk EG0021 affected112 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0011 affected137 at risk EG0020 affected112 at risk EG003
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0010 affected137 at risk EG0021 affected112 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0011 affected137 at risk EG0020 affected112 at risk EG003
Breast neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Hyperthyroidism	Endocrine disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0011 affected137 at risk EG0020 affected112 at risk EG003
Hypertensive crisis	Vascular disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Lung infection	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0010 affected137 at risk EG0021 affected112 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0010 affected137 at risk EG0021 affected112 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0010 affected137 at risk EG0022 affected112 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0010 affected137 at risk EG0021 affected112 at risk EG003
Foot fracture	Injury, poisoning and procedural complications	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0010 affected137 at risk EG0021 affected112 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Device malfunction	General disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0010 affected137 at risk EG0021 affected112 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003
Oesophageal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0010 affected137 at risk EG0021 affected112 at risk EG003
Depression	Psychiatric disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0010 affected137 at risk EG0020 affected112 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG00066 affected135 at risk EG00165 affected137 at risk EG00227 affected112 at risk EG00338 affected110 at risk
Sputum increased	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG00059 affected135 at risk EG00150 affected137 at risk EG00219 affected112 at risk EG003
Sputum discoloured	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG00048 affected135 at risk EG00138 affected137 at risk EG00221 affected112 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG00050 affected135 at risk EG00147 affected137 at risk EG00226 affected112 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG00018 affected135 at risk EG00113 affected137 at risk EG00211 affected112 at risk EG003
Fatigue	General disorders	MedDRA 15.1	Systematic Assessment	EG00025 affected135 at risk EG00125 affected137 at risk EG00214 affected112 at risk EG003
Malaise	General disorders	MedDRA 15.1	Systematic Assessment	EG00014 affected135 at risk EG00119 affected137 at risk EG0024 affected112 at risk EG003
Pyrexia	General disorders	MedDRA 15.1	Systematic Assessment	EG00030 affected135 at risk EG00121 affected137 at risk EG00212 affected112 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 15.1	Systematic Assessment	EG0009 affected135 at risk EG00113 affected137 at risk EG0025 affected112 at risk EG003
Headache	Nervous system disorders	MedDRA 15.1	Systematic Assessment	EG00017 affected135 at risk EG00114 affected137 at risk EG0027 affected112 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG00012 affected135 at risk EG00111 affected137 at risk EG0020 affected112 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0007 affected135 at risk EG0014 affected137 at risk EG0020 affected112 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG00012 affected135 at risk EG00114 affected137 at risk EG0020 affected112 at risk EG003
Throat irritation	Respiratory, thoracic and mediastinal disorders	MedDRA 15.1	Systematic Assessment	EG0007 affected135 at risk EG0014 affected137 at risk EG0020 affected112 at risk EG003
Chills	General disorders	MedDRA 15.1	Systematic Assessment	EG00010 affected135 at risk EG0013 affected137 at risk EG0020 affected112 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0006 affected135 at risk EG0018 affected137 at risk EG0020 affected112 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 15.1	Systematic Assessment	EG0007 affected135 at risk EG0015 affected137 at risk EG0020 affected112 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 15.1	Systematic Assessment	EG0006 affected135 at risk EG00110 affected137 at risk EG0020 affected112 at risk EG003
Rhinitis	Infections and infestations	MedDRA 15.1	Systematic Assessment	EG0002 affected135 at risk EG0017 affected137 at risk EG0020 affected112 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 15.1	Systematic Assessment	EG0001 affected135 at risk EG0017 affected137 at risk EG0020 affected112 at risk EG003
Pain	General disorders	MedDRA 15.1	Systematic Assessment	EG0000 affected135 at risk EG0010 affected137 at risk EG0027 affected112 at risk EG003

ID	Term
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases

ID	Title	Description
BG000	AZLI-AZLI	Participants were randomized to receive blinded AZLI 75 mg three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.
BG001	Placebo-AZLI	Participants were randomized to receive blinded placebo to match AZLI three times daily via investigational nebulizer for 2 cycles of 28 days on treatment with each cycle followed by 28 days off treatment, followed by open-label AZLI 75 mg three times daily for 28 days plus 56 days of treatment-free follow-up.
BG002	Total	Total of all reporting groups