Safety of Tobramycin Inhalation Powder (TIP) vs Tobramyci... | NCT00388505

Label	Type	Description	Intervention Names
Tobramycin inhalation powder (TIP)	Experimental	Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.	Drug: Tobramycin Inhalation Powder
Tobramycin solution for inhalation (TOBI)	Active Comparator	Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.	Drug: Tobramycin Solution for Inhalation

Name	Type	Description	Arm Group Labels	Other Names
Tobramycin Inhalation Powder	Drug	Tobramycin Inhalation Powder (TIP) capsules for inhalation.	Tobramycin inhalation powder (TIP)

Measure	Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events	An adverse event (AE) is any untoward medical occurrence, including any unfavorable and unintended sign, symptom or disease temporally associated with the use of the study medication that does not necessarily have a causal relationship with study medication. A serious AE (SAE) is an event that results in death, is life-threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability, is a congenital anomaly or defect, or is a significant medical event that may jeopardize the patient or require intervention to prevent one of the outcomes listed above.	25 weeks

Measure	Description	Time Frame
Serum Tobramycin Concentrations	Serum tobramycin concentrations were measured in a subset of participants at Week 1 (start of cycle 1), Week 5 (End of Cycle 1), Week 17 (start of cycle 3) and Week 21 (end of cycle 3). Serum samples were collected at pre-dose and post-dose at specified intervals; one specimen between 0 to 2 hours; two additional specimens between 2 and 5 hours (sample times must have been a minimum of 2 hours apart).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Confirmed diagnosis of cystic fibrosis
Male and female patients at least 6 years of age at the time of screening.
Forced expiratory volume in one second (FEV1) at screening must be at least 25% and less than or equal to 75% of normal predicted values for age, sex, and height based on Knudson criteria.
Pseudomonas aeruginosa, a type of bacteria, must be present in a sputum/deep-throat cough swab culture (or bronchoalveolar lavage [BAL]) within 6 months prior to screening and in the sputum/ deep-throat cough swab culture at the screening visit.
Able to comply with all protocol requirements.
Clinically stable in the opinion of the investigator.
Use of an effective means of contraception in females of childbearing potential.
Provide written informed consent, Health Authority Portability and Accountability Act (HIPAA) authorization (where applicable), and assent (as appropriate) prior to the performance of any study-related procedure.

Exclusion Criteria:

History of sputum culture or deep-throat cough swab (or BAL) culture yielding Burkholderia cepacia (B cepacia), a type of bacteria, within 2 years prior to screening and/or sputum culture yielding B cepacia at screening.
Coughing up more than 60 cc of blood from the respiratory tract at any time within 30 days prior to study drug administration.
Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics.
Females who are pregnant (positive pregnancy test), lactating, or are planning to become pregnant during the study.
History of hearing loss or chronic ringing in the ears deemed clinically significant by the investigator.
Use of systemic or inhaled antipseudomonal antibiotics within 28 days prior to study drug administration.
Use of loop diuretics within 7 days prior to study drug administration.
Use of any investigational treatment within 28 days prior to study drug administration.
Initiation of treatment with chronic macrolide therapy, dornase alpha treatment or inhaled corticosteroids within 28 days prior to study drug administration (patients may be taking these therapies at the time of enrollment, but they must have initiated treatment more than 28 days prior to study drug administration).

Other protocol-defined inclusion/exclusion criteria may apply

Name	Affiliation	Role
Michael Konstan, MD	University Hospitals Cleveland Medical Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Hartford	Connecticut	06102	United States
Emory University CF Center

Label	URL
Related Info	View source

ID	Title	Description
FG000	Tobramycin Inhalation Powder (TIP)	Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
FG001	Tobramycin Solution for Inhalation (TOBI)

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

Number of Participants With Treatment-emergent Adverse Events

An adverse event (AE) is any untoward medical occurrence, including any unfavorable and unintended sign, symptom or disease temporally associated with the use of the study medication that does not necessarily have a causal relationship with study medication. A serious AE (SAE) is an event that results in death, is life-threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability, is a congenital anomaly or defect, or is a significant medical event that may jeopardize the patient or require intervention to prevent one of the outcomes listed above.

All Randomized Safety population.

Posted

Number

participants

25 weeks

ID	Title	Description
OG000	Tobramycin Inhalation Powder (TIP)	Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
OG001	Tobramycin Solution for Inhalation (TOBI)	Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.

Units	Counts
Participants	OG000308 OG001209

Title

Denominators

Categories

Any adverse event

Title	Measurements
	OG000278 OG001176

Serious adverse event

Title	Measurements
	OG000

Secondary

Serum Tobramycin Concentrations

Serum tobramycin concentrations were measured in a subset of participants at Week 1 (start of cycle 1), Week 5 (End of Cycle 1), Week 17 (start of cycle 3) and Week 21 (end of cycle 3). Serum samples were collected at pre-dose and post-dose at specified intervals; one specimen between 0 to 2 hours; two additional specimens between 2 and 5 hours (sample times must have been a minimum of 2 hours apart).

Pharmacokinetic subpopulation

Posted

Mean

Standard Deviation

μg/mL

Weeks 1, 5, 17 and 21

ID	Title	Description
OG000	Tobramycin Inhalation Powder (TIP)	Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
OG001	Tobramycin Solution for Inhalation (TOBI)	Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.

Units	Counts
Participants

Secondary

Percentage of Participants With a Decrease From Baseline in Auditory Acuity

Audiology testing was performed only at selected centers. Auditory acuity was measured from 250 to 8000 Hertz using a standard dual-channel audiometer.

Audiology subpopulation

Posted

Number

percentage of participants

Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21)

ID	Title	Description
OG000	Tobramycin Inhalation Powder (TIP)	Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
OG001	Tobramycin Solution for Inhalation (TOBI)	Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.

Units	Counts
Participants

Secondary

Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in One Second (%FEV1)

Forced expiratory volume in one second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 is then converted to a percentage of normal (percent predicted) based on height, weight, and race. FEV1 was measured at Baseline (prior to beginning study treatment) and predose on Day 28 of Cycles 1, 2 and 3 and at the follow-up visit.

Relative change = 100 * ((Day 28 of Cycle 3 value - Baseline value)/ Baseline value).

Intent to treat population for patients with available data. For Final Visit, the last available post-baseline measurement is reported.

Posted

Mean

Standard Deviation

percent of predicted

Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25)

ID	Title	Description
OG000	Tobramycin Inhalation Powder (TIP)	Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
OG001	Tobramycin Solution for Inhalation (TOBI)	Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.

Secondary

Patient Satisfaction Assessed Using the Treatment Satisfaction Questionnaire for Medication

Patient's self-reported treatment satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM, a validated instrument) which was modified by adding four study-specific questions; the standard fourteen questions of the TSQM were not altered. Responses to nearly all items are rated on a five-point or seven-point rating scale and the items are factored into 4 domains. The TSQM domain scores range from 0 to 100 with higher scores representing higher satisfaction for that domain.

Intent-to-treat population for whom data were available.

Posted

Mean

Standard Deviation

Scores on a scale

Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21).

ID	Title	Description
OG000	Tobramycin Inhalation Powder (TIP)	Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
OG001	Tobramycin Solution for Inhalation (TOBI)	Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.

Secondary

Change From Baseline in Pseudomonas Aeruginosa Sputum Density

Three Pseudomonas aeruginosa biotypes were assessed in patient's sputum; mucoid, dry and small colony variant. Overall density is defined as the sum of all bio-types in Pseudomonas aeruginosa density.

Intent to treat population for patients with available data. For Final Visit, the last available post-baseline measurement is reported.

Posted

Mean

Standard Deviation

log10 Colony forming units/g

Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25).

ID	Title	Description
OG000	Tobramycin Inhalation Powder (TIP)	Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
OG001	Tobramycin Solution for Inhalation (TOBI)	Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.

Units	Counts
Participants

Secondary

Change From Baseline in Tobramycin Minimum Inhibitory Concentration

The minimum inhibitory concentration (MIC) is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation. The MIC of tobramycin against total Pseudomonas aeruginosa colonization was assessed over the course of the study.

Intent to treat population for patients with available data. For Final Visit, the last available post-baseline measurement is reported.

Posted

Mean

Standard Deviation

μg/mL

Baseline and Day 28 of Cycles 1, 2 and 3 (Weeks 5, 13 and 21) and Final Visit (Week 25)

ID	Title	Description
OG000	Tobramycin Inhalation Powder (TIP)	Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
OG001	Tobramycin Solution for Inhalation (TOBI)	Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.

Units	Counts

Secondary

Antipseudomonal Antibiotic Usage During the Study

The average number of days patients required antipseudomonal antibiotics during the course of the study.

Patients in the intent-to-treat population who required antipseudomonal antibiotics.

Posted

Mean

Standard Deviation

days

25 Weeks

ID	Title	Description
OG000	Tobramycin Inhalation Powder (TIP)	Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
OG001	Tobramycin Solution for Inhalation (TOBI)	Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.

Units	Counts
Participants	OG000

Secondary

Hospitalization Due to Respiratory Events During the Study

The average number of days patients were hospitalized due to respiratory events during the course of the study.

Patients in the intent-to-treat population who were hospitalized due to respiratory events.

Posted

Mean

Standard Deviation

days

25 Weeks

ID	Title	Description
OG000	Tobramycin Inhalation Powder (TIP)	Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
OG001	Tobramycin Solution for Inhalation (TOBI)	Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cystic fibrosis lung	Congenital, familial and genetic disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected308 at risk EG0012 affected209 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0011 affected209 at risk
Crohn's disease	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0011 affected209 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Distal ileal obstruction syndrome	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Distal intestinal obstruction syndrome	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0011 affected209 at risk
Frequent bowel movements	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0011 affected209 at risk
Pancreatic insufficiency	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0011 affected209 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0011 affected209 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0011 affected209 at risk
Chest pain	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Fatigue	General disorders	MedDRA 14.0	Systematic Assessment	EG0003 affected308 at risk EG0010 affected209 at risk
Pyrexia	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0012 affected209 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0011 affected209 at risk
Hepatosplenomegaly	Hepatobiliary disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Appendicitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Bronchitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0006 affected308 at risk EG0011 affected209 at risk
Bronchopneumonia	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0012 affected209 at risk
Bronchopulmonary aspergillosis allergic	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0011 affected209 at risk
Influenza	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0002 affected308 at risk EG0012 affected209 at risk
Lung abscess	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0011 affected209 at risk
Lung infection pseudomonal	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0002 affected308 at risk EG0011 affected209 at risk
Pneumonia	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0002 affected308 at risk EG0012 affected209 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0002 affected308 at risk EG0012 affected209 at risk
Pseudomonas bronchitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Pseudomonas infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0012 affected209 at risk
Respiratory tract infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0011 affected209 at risk
Sinusitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0002 affected308 at risk EG0011 affected209 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Urinary tract infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Ulna fracture	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0011 affected209 at risk
Blood glucose increased	Investigations	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Chest X-ray abnormal	Investigations	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0011 affected209 at risk
Forced expiratory volume decreased	Investigations	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0011 affected209 at risk
Oxygen saturation	Investigations	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Pulmonary function test decreased	Investigations	MedDRA 14.0	Systematic Assessment	EG0004 affected308 at risk EG0013 affected209 at risk
Weight decreased	Investigations	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0013 affected209 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0011 affected209 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0011 affected209 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0011 affected209 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Benign lung neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0011 affected209 at risk
Cervicobrachial syndrome	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Headache	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Sinus headache	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Depression	Psychiatric disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0011 affected209 at risk
Panic attack	Psychiatric disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Bronchiectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0012 affected209 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0007 affected308 at risk EG0015 affected209 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0005 affected308 at risk EG0014 affected209 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected308 at risk EG0010 affected209 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected308 at risk EG0011 affected209 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0008 affected308 at risk EG0014 affected209 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0012 affected209 at risk
Increased bronchial secretion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Lung consolidation	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG00060 affected308 at risk EG00139 affected209 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0011 affected209 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0011 affected209 at risk
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0011 affected209 at risk
Rales	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Sputum discoloured	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected308 at risk EG0010 affected209 at risk
Sputum increased	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0005 affected308 at risk EG0011 affected209 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected308 at risk EG0011 affected209 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00012 affected308 at risk EG00117 affected209 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00023 affected308 at risk EG00119 affected209 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00019 affected308 at risk EG00111 affected209 at risk
Chest discomfort	General disorders	MedDRA 14.0	Systematic Assessment	EG00020 affected308 at risk EG0016 affected209 at risk
Fatigue	General disorders	MedDRA 14.0	Systematic Assessment	EG00018 affected308 at risk EG00110 affected209 at risk
Pyrexia	General disorders	MedDRA 14.0	Systematic Assessment	EG00047 affected308 at risk EG00125 affected209 at risk
Sinusitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG00017 affected308 at risk EG00115 affected209 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG00021 affected308 at risk EG00118 affected209 at risk
Pulmonary function test decreased	Investigations	MedDRA 14.0	Systematic Assessment	EG00018 affected308 at risk EG00114 affected209 at risk
Headache	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG00034 affected308 at risk EG00125 affected209 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG000145 affected308 at risk EG00163 affected209 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG00042 affected308 at risk EG0018 affected209 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG00044 affected308 at risk EG00122 affected209 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG00035 affected308 at risk EG00123 affected209 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG00057 affected308 at risk EG00133 affected209 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG00025 affected308 at risk EG00115 affected209 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG00043 affected308 at risk EG00122 affected209 at risk
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG00017 affected308 at risk EG0018 affected209 at risk
Rales	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG00021 affected308 at risk EG00113 affected209 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG00022 affected308 at risk EG00115 affected209 at risk
Sputum increased	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG00049 affected308 at risk EG00135 affected209 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG00021 affected308 at risk EG00113 affected209 at risk

ID	Term
D010182	Pancreatic Diseases
D004066	Digestive System Diseases
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D007232	Infant, Newborn, Diseases

ID	Term
D015656	Respiratory Mechanics
D012119	Respiration
D012143	Respiratory Physiological Phenomena
D002943	Circulatory and Respiratory Physiological Phenomena

ID	Title	Description
BG000	Tobramycin Inhalation Powder (TIP)	Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
BG001	Tobramycin Solution for Inhalation (TOBI)	Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Tobramycin Inhalation Powder (TIP)	Participants received four 28 mg capsules of tobramycin inhalation powder (TIP) delivered with the T-326 inhaler twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.			85	308	241	308
EG001	Tobramycin Solution for Inhalation (TOBI)	Participants received one 300 mg (in 5 mL) ampoule of tobramycin solution for inhalation (TOBI) delivered with a nebulizer twice daily for 28 days followed by 28 days off therapy (one cycle) for a total of three cycles.			61	209	148	209