A Safety and Efficacy Trial of Inhaled Mannitol in Adult... | NCT02134353

Status Module

Description Module

Label	Type	Description	Intervention Names
Experimental arm A	Experimental	Active treatment. Inhaled Mannitol	Drug: Inhaled mannitol
Arm B - Control	Placebo Comparator	Arm B	Drug: Placebo Comparator: Arm B - Control

Name	Type	Description	Arm Group Labels	Other Names
Inhaled mannitol	Drug	Inhaled mannitol 400 mg BD for 26 weeks	Experimental arm A

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mean Change in FEV1 (mL) From Baseline (Visit 1) Over the 26-week Treatment Period (to Visit 4).	The mean absolute change from baseline FEV1 (mL) over 26 weeks (measured at week 6, 14 and 26) will be compared between the two treatment groups with a REML (restricted maximum likelihood) based repeated measures approach. Least square means presented are for the average change over the 6, 14, and 26 week visits. Missing values due to withdrawal for reasons related to safety or efficacy were imputed using a baseline observation carried forward approach (BOCF).	26 weeks

Secondary Outcomes

Measure	Description	Time Frame
Mean Change From Baseline FVC (mL) Over the 26-week Treatment Period	To determine whether inhaled mannitol (400 mg b.i.d.) is superior to control for improving lung function as measured by mean change from baseline forced vital capacity (FVC) (mL) over the 26-week treatment period in adult subjects with cystic fibrosis (CF). The mean absolute change from baseline FVC (mL) over 26 weeks will be compared between the two treatment groups with a REML (restricted maximum likelihood) based repeated measures approach. Least square means presented are for the change from baseline averaged over the treatment period (ie the average of the changes at 6 weeks, 14 weeks and 26 weeks). Missing values due to withdrawal for reasons related to safety or efficacy were imputed using a baseline observation carried forward approach (BOCF).

Other Outcomes

Measure	Description	Time Frame
Time to First Pulmonary Exacerbation Over the 26-week Treatment Period	To determine whether inhaled mannitol (400 mg b.i.d.) is superior to control in increasing the time to first protocol defined pulmonary exacerbation over the 26-week treatment period in adult subjects with CF. Protocol defined pulmonary exacerbations are those where 4 or more symptoms are recorded and are treated with IV antibiotics

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Have given written informed consent to participate in this trial in accordance with local regulations;
Have a confirmed diagnosis of cystic fibrosis (positive sweat chloride value ≥ 60 mEq/L) and/or genotype with two identifiable mutations consistent with CF, accompanied by one or more clinical features consistent with the CF phenotype);
Be aged at least 18 years old;
Have FEV1 > 40 % and < 90% predicted (using NHanes III [1]);
Be able to perform all the techniques necessary to measure lung function;
Be adherent with maintenance therapies (antibiotics and or rhDNase), if used, for at least 80% of the time in the two weeks prior to visit 1 and
If rhDNase and/or maintenance antibiotic are being used treatment must have been established at least 1 month prior to screening (Visit 0). The subject should remain on the rhDNase and / or maintenance antibiotics for the duration of the trial. The subject should not commence treatment with rhDNase or maintenance antibiotics during the trial

Exclusion Criteria:

Be investigators, site personnel directly affiliated with this trial, or their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biologically or legally adopted;
Be considered "terminally ill" or eligible for lung transplantation;
Have had a lung transplant;
Be using maintenance nebulized hypertonic saline in the 2 weeks prior to visit 1;
Have had a significant episode of hemoptysis (> 60 mL) in the three months prior to Visit 0;
Have had a myocardial infarction in the three months prior to Visit 0;
Have had a cerebral vascular accident in the three months prior to Visit 0;
Have had major ocular surgery in the three months prior to Visit 0;
Have had major abdominal, chest or brain surgery in the three months prior to Visit 0;
Have a known cerebral, aortic or abdominal aneurysm;
Be breast feeding or pregnant, or plan to become pregnant while in the trial;
Be using an unreliable form of contraception (female subjects at risk of pregnancy only);
Be participating in another investigative drug trial, parallel to, or within 4 weeks of screening (Visit 0);
Have a known allergy to mannitol;
Be using non-selective oral beta blockers;
Have uncontrolled hypertension -i.e. systolic BP > 190 and / or diastolic BP > 100;
Have a condition or be in a situation which in the Investigator's opinion may put the subject at significant risk, may confound results or may interfere significantly with the subject's participation in the trial;or
Have a failed or incomplete MTT at trial entry (as evaluated in Section 8.1.1.1).
The subject must not commence treatment with rhDNase or maintenance antibiotics during the trial.

Name	Affiliation	Role
Moira Aitken, MD		Principal Investigator
Brett Charlton, MD	Medical Director	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Dr Lawrence Sinde		Mobile	Alabama	36608	United States
University of Arizona

PubMed Identifier	Type	Citation	Retractions
33715994	Derived	Flume PA, Amelina E, Daines CL, Charlton B, Leadbetter J, Guasconi A, Aitken ML. Efficacy and safety of inhaled dry-powder mannitol in adults with cystic fibrosis: An international, randomized controlled study. J Cyst Fibros. 2021 Nov;20(6):1003-1009. doi: 10.1016/j.jcf.2021.02.011. Epub 2021 Mar 11.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Experimental Arm A	Active treatment. Inhaled Mannitol Inhaled mannitol: Inhaled mannitol 400 mg twice a day (BD) for 26 weeks
FG001	Arm B - Control	Arm B Control (mannitol 50mg) twice a day (BD) for 26 weeks

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 13, 2014	Aug 3, 2020

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00026.8± 7.63 BG00128.6± 10.75 BG00227.7± 9.37

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00092 BG001107 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00014 BG0017 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Argentina

Title	Measurements
	BG0004 BG0012 BG002

%Predicted FEV1 at Screening

FEV1 (forced expiratory volume at one second)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
>80% to <=90%	BG00031 BG00127 BG002

CFTR Mutation

CFTR (cystic fibrosis transmembrane conductance regulator) Mutation

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Both deltaF508	BG00055 BG00148 BG002

Hospitalisations due to exacerbations in 12 months prior to screening

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
0	BG000121 BG001135 BG002

Exacerbations treated with IV antibiotics in 12 months before screening

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
0	BG000109 BG001120 BG002

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

Mean Change in FEV1 (mL) From Baseline (Visit 1) Over the 26-week Treatment Period (to Visit 4).

The mean absolute change from baseline FEV1 (mL) over 26 weeks (measured at week 6, 14 and 26) will be compared between the two treatment groups with a REML (restricted maximum likelihood) based repeated measures approach.

Least square means presented are for the average change over the 6, 14, and 26 week visits.

Missing values due to withdrawal for reasons related to safety or efficacy were imputed using a baseline observation carried forward approach (BOCF).

Posted

Least Squares Mean

95% Confidence Interval

26 weeks

ID	Title	Description
OG000	Experimental Arm A	Active treatment. Inhaled Mannitol Inhaled mannitol: Inhaled mannitol 400 mg BD for 26 weeks
OG001	Arm B - Control	Arm B Control BD (mannitol 50mg) for 26 weeks

Units	Counts
Participants	OG000209 OG001214

Title

Denominators

Categories

Title	Measurements
	OG00063(25 to 100) OG0018(-27 to 44)

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		Mixed Models Analysis		0.020		Mean Difference (Net)	54			2-Sided	95	8	100			Missing data for withdrawals related to safety or efficacy imputed using BOCF (baseline observation carried forward). Data collected at 6, 14 and 26 weeks.		Superiority

Secondary

Mean Change From Baseline FVC (mL) Over the 26-week Treatment Period

To determine whether inhaled mannitol (400 mg b.i.d.) is superior to control for improving lung function as measured by mean change from baseline forced vital capacity (FVC) (mL) over the 26-week treatment period in adult subjects with cystic fibrosis (CF).

The mean absolute change from baseline FVC (mL) over 26 weeks will be compared between the two treatment groups with a REML (restricted maximum likelihood) based repeated measures approach.

Least square means presented are for the change from baseline averaged over the treatment period (ie the average of the changes at 6 weeks, 14 weeks and 26 weeks).

Missing values due to withdrawal for reasons related to safety or efficacy were imputed using a baseline observation carried forward approach (BOCF).

Posted

Least Squares Mean

95% Confidence Interval

26 weeks

ID	Title	Description
OG000	Experimental Arm A	Active treatment. Inhaled Mannitol Inhaled mannitol: Inhaled mannitol 400 mg BD for 26 weeks
OG001	Arm B - Control	Arm B Control BD (mannitol 50mg) for 26 weeks

Units	Counts
Participants

Other Pre-specified

Time to First Pulmonary Exacerbation Over the 26-week Treatment Period

To determine whether inhaled mannitol (400 mg b.i.d.) is superior to control in increasing the time to first protocol defined pulmonary exacerbation over the 26-week treatment period in adult subjects with CF.

Protocol defined pulmonary exacerbations are those where 4 or more symptoms are recorded and are treated with IV antibiotics

Posted

Median

95% Confidence Interval

days

26 weeks

ID	Title	Description
OG000	Experimental Arm A	Active treatment. Inhaled Mannitol Inhaled mannitol: Inhaled mannitol 400 mg BD for 26 weeks
OG001	Arm B - Control	Arm B Control BD (mannitol 50mg) for 26 weeks

Units	Counts
Participants	OG000

Other Pre-specified

Number of Days on Antibiotics (Oral, Inhaled or IV) Due to Pulmonary Exacerbation

To determine whether in adult subjects with CF, inhaled mannitol (400 mg b.i.d.) is superior to control for decreasing the number of days on antibiotics due to protocol defined pulmonary exacerbations.

Overlapping antibiotics are counted separately.

Posted

Mean

Standard Deviation

days

26 weeks

ID	Title	Description
OG000	Experimental Arm A	Active treatment. Inhaled Mannitol Inhaled mannitol: Inhaled mannitol 400 mg BD for 26 weeks
OG001	Arm B - Control	Arm B Control BD (mannitol 50mg) for 26 weeks

Units	Counts
Participants	OG000

Other Pre-specified

Number of Days in Hospital Due to Pulmonary Exacerbation

To determine whether in adult subjects with CF, inhaled mannitol (400 mg b.i.d.) is superior to control for decreasing the number of days in hospital due to protocol defined pulmonary exacerbation.

Posted

Count of Participants

Participants

26 weeks

ID	Title	Description
OG000	Experimental Arm A	Active treatment. Inhaled Mannitol Inhaled mannitol: Inhaled mannitol 400 mg BD for 26 weeks
OG001	Arm B - Control	Arm B Control BD (mannitol 50mg) for 26 weeks

Units	Counts
Participants	OG000

Other Pre-specified

Rate of Pulmonary Exacerbations Over the 26-week Treatment Period

To determine whether inhaled mannitol (400 mg b.i.d.) decreases the rate of protocol defined pulmonary exacerbations over the 26-week treatment period compared to control in adult subjects with CF.

Protocol defined pulmonary exacerbations defined by having 4 or more symptoms and treated with IV antibiotics.

Posted

Count of Participants

Participants

26 weeks

ID	Title	Description
OG000	Experimental Arm A	Active treatment. Inhaled Mannitol Inhaled mannitol: Inhaled mannitol 400 mg BD for 26 weeks
OG001	Arm B - Control	Arm B Control BD (mannitol 50mg) for 26 weeks

Units	Counts
Participants	OG000

Other Pre-specified

The Incidence of Pulmonary Exacerbations

To determine whether in adult subjects with CF, inhaled mannitol (400 mg b.i.d.) is superior to control for decreasing incidence of protocol defined pulmonary exacerbations, where incidence is defined as the proportion of subjects with 1 or more exacerbation during the 26 week period.

Posted

Count of Participants

Participants

26 weeks

ID	Title	Description
OG000	Experimental Arm A	Active treatment. Inhaled Mannitol Inhaled mannitol: Inhaled mannitol 400 mg BD for 26 weeks
OG001	Arm B - Control	Arm B Control BD (mannitol 50mg) for 26 weeks

Units	Counts
Participants	OG000

Other Pre-specified

Mean Change From Baseline in Ease of Expectoration Measured Using a Visual Analogue Scale (VAS) Over 26 Weeks

To determine whether in adult subjects with CF, inhaled mannitol (400 mg b.i.d.) is superior to control for improving ease of expectoration.

The visual analogue scale (VAS) was 10cm. The position marked by the subject was converted into a score from 0 to 100 where 0 was the worst possible outcome and 100 was the best possible outcome.

The VAS was completed at baseline, 6, 14 and 26 weeks. The mean absolute change from baseline over 26 weeks (ie the average of the changes at 6,14 and 26 weeks) is the outcome measure and will be compared between the two treatment groups with a REML based repeated measures approach.

Least square means presented are for the change from baseline averaged over the treatment period (ie the average of the changes at 6 weeks, 14 weeks and 26 weeks).

Missing values due to withdrawal for reasons related to safety or efficacy were imputed using a baseline observation carried forward approach (BOCF).

Posted

Least Squares Mean

95% Confidence Interval

26 weeks

ID	Title	Description
OG000	Experimental Arm A	Active treatment. Inhaled Mannitol Inhaled mannitol: Inhaled mannitol 400 mg BD for 26 weeks
OG001	Arm B - Control	Arm B Control BD (mannitol 50mg) for 26 weeks

Other Pre-specified

Change From Baseline Over 26 Weeks in CFQ-R Respiratory Domain Score

To determine whether in adult subjects with CF, inhaled mannitol (400 mg b.i.d.) is superior to control for improving respiratory symptoms measured by Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain.

The CFQ-R respiratory domain score is a scale from 0 to 100. Higher scores are a more favourable response.

The mean absolute change from baseline over 26 weeks (measured at week 6, 14 and 26) will be compared between the two treatment groups with a REML (restricted maximum likelihood) based repeated measures approach.

Least square means presented are for the change from baseline averaged over the treatment period (ie the average of the changes at 6 weeks, 14 weeks and 26 weeks).

Missing values due to withdrawal for reasons related to safety or efficacy were imputed using a baseline observation carried forward approach (BOCF).

Intent to Treat (ITT) - All patients randomised.

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

26 weeks

ID	Title	Description
OG000	Experimental Arm A	Active treatment. Inhaled Mannitol Inhaled mannitol: Inhaled mannitol 400 mg BD for 26 weeks
OG001	Arm B - Control	Arm B Control BD (mannitol 50mg) for 26 weeks

Post-Hoc

Absolute Change in Forced Expiratory Flow From 25% to 75% of Vital Capacity (FEF25-75) Over the 26-week Treatment Period.

The mean absolute change from baseline FEF25-75 (mL/s) over weeks 6, 14 and 26 will be compared between the two treatment groups with a REML based repeated measures approach

Least square means presented are for the change from baseline averaged over the treatment period (ie the average of the changes at 6 weeks, 14 weeks and 26 weeks).

Missing values due to withdrawal for reasons related to safety or efficacy were imputed using a baseline observation carried forward approach (BOCF).

Posted

Least Squares Mean

95% Confidence Interval

mL/s

26 weeks

ID	Title	Description
OG000	Experimental Arm A	Active treatment. Inhaled Mannitol Inhaled mannitol: Inhaled mannitol 400 mg BD for 26 weeks
OG001	Arm B - Control	Arm B Control BD (mannitol 50mg) for 26 weeks

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Experimental Arm A	Active treatment. Inhaled Mannitol Inhaled mannitol: Inhaled mannitol 400 mg BD for 26 weeks Subjects randomised and treated.	0	207	31	207	144	207
EG001	Arm B - Control	Arm B Control BD (mannitol 50mg) for 26 weeks Subjects randomised and treated.	1	213	29	213	140	213

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Condition Aggravated	General disorders	MedDRA (11.1)	Non-systematic Assessment	Pulmonary exacerbations were coded to condition aggravated	EG00025 events20 affected207 at risk EG00115 events15 affected213 at risk
Lung Infection	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment		EG0001 events1 affected207 at risk EG0012 events2 affected213 at risk
Pneumonia	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment		EG0001 events1 affected207 at risk EG0012 events2 affected213 at risk
Lobar pneumonia	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment		EG0000 events0 affected207 at risk EG0011 events1 affected213 at risk
Bronchitis	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment		EG0000 events0 affected207 at risk EG0011 events1 affected213 at risk
Lower Respiratory Tract Infection	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment		EG0001 events1 affected207 at risk EG0010 events0 affected213 at risk
Lung infection pseudomonal	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment		EG0001 events1 affected207 at risk EG0010 events0 affected213 at risk
Meningitis bacterial	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment		EG0001 events1 affected207 at risk EG0010 events0 affected213 at risk
Pneumonia bacterial	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment		EG0000 events0 affected207 at risk EG0011 events1 affected213 at risk
Pneumonia viral	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment		EG0000 events0 affected207 at risk EG0011 events1 affected213 at risk
Sepsis	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment		EG0000 events0 affected207 at risk EG0011 events1 affected213 at risk
Staphylococcal bacteraemia	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment		EG0001 events1 affected207 at risk EG0010 events0 affected213 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment		EG0001 events1 affected207 at risk EG0010 events0 affected213 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (11.1)	Non-systematic Assessment		EG0001 events1 affected207 at risk EG0013 events3 affected213 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (11.1)	Non-systematic Assessment		EG0001 events1 affected207 at risk EG0010 events0 affected213 at risk
Pneumomediastinum	Respiratory, thoracic and mediastinal disorders	MedDRA (11.1)	Non-systematic Assessment		EG0000 events0 affected207 at risk EG0011 events1 affected213 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (11.1)	Non-systematic Assessment		EG0000 events0 affected207 at risk EG0011 events1 affected213 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (11.1)	Non-systematic Assessment		EG0000 events0 affected207 at risk EG0011 events1 affected213 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA (11.1)	Non-systematic Assessment		EG0001 events1 affected207 at risk EG0012 events2 affected213 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (11.1)	Non-systematic Assessment		EG0001 events1 affected207 at risk EG0011 events1 affected213 at risk
Distal intestinal obstruction syndrome	Gastrointestinal disorders	MedDRA (11.1)	Non-systematic Assessment		EG0001 events1 affected207 at risk EG0010 events0 affected213 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (11.1)	Non-systematic Assessment		EG0000 events0 affected207 at risk EG0012 events2 affected213 at risk
Depression	Psychiatric disorders	MedDRA (11.1)	Non-systematic Assessment		EG0000 events0 affected207 at risk EG0011 events1 affected213 at risk
Drug abuse	Psychiatric disorders	MedDRA (11.1)	Non-systematic Assessment		EG0000 events0 affected207 at risk EG0011 events1 affected213 at risk
Intentional overdose	Injury, poisoning and procedural complications	MedDRA (11.1)	Non-systematic Assessment		EG0001 events1 affected207 at risk EG0010 events0 affected213 at risk
Guillain-Barre syndrome	Nervous system disorders	MedDRA (11.1)	Non-systematic Assessment		EG0000 events0 affected207 at risk EG0011 events1 affected213 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA (11.1)	Non-systematic Assessment		EG0001 events1 affected207 at risk EG0010 events0 affected213 at risk
Subcutaneous emphysema	Skin and subcutaneous tissue disorders	MedDRA (11.1)	Non-systematic Assessment		EG0000 events0 affected207 at risk EG0011 events1 affected213 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Condition Aggravated	General disorders	MedDRA (11.1)	Non-systematic Assessment	Pulmonary Exacerbations coded as condition aggravated Includes both serious and non-serious AEs (separate summaries of non-serious AEs not available)	EG00084 events56 affected207 at risk EG00175 events59 affected213 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (11.1)	Non-systematic Assessment		EG00025 events23 affected207 at risk EG00125 events21 affected213 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (11.1)	Non-systematic Assessment		EG00027 events20 affected207 at risk EG00133 events20 affected213 at risk
Headache	Nervous system disorders	MedDRA (11.1)	Non-systematic Assessment		EG00041 events12 affected207 at risk EG00147 events22 affected213 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment		EG00017 events14 affected207 at risk EG00112 events11 affected213 at risk
Pyrexia	General disorders	MedDRA (11.1)	Non-systematic Assessment		EG00018 events13 affected207 at risk EG0019 events8 affected213 at risk
Nasopharyngitis	Infections and infestations	MedDRA (11.1)	Non-systematic Assessment		EG00017 events12 affected207 at risk EG00111 events10 affected213 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	Title	Description
BG000	Experimental Arm A	Active treatment. Inhaled Mannitol Inhaled mannitol: Inhaled mannitol 400 mg BD for 26 weeks
BG001	Arm B - Control	Arm B Control BD (mannitol 50mg) for 26 weeks
BG002	Total	Total of all reporting groups