Study of Ataluren in Nonsense Mutation Cystic Fibrosis (A... | NCT02139306

ID	Type	Description	Link
2013-004581-34	EudraCT Number

Name	Class
Cystic Fibrosis Foundation	OTHER
ECFS-Clinical Trial Network (ECFS-CTN)	UNKNOWN

Label	Type	Description	Intervention Names
Ataluren (PTC124®)	Experimental	Participants received ataluren as oral powder for suspension at the dosages of 10, 10, and 20-mg/kg at morning, midday and evening, respectively for 48 weeks of treatment duration or until treatment discontinuation.	Drug: Ataluren (PTC124®)
Placebo	Placebo Comparator	Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Ataluren (PTC124®)	Drug	Oral Ataluren TID	Ataluren (PTC124®)
Placebo

Measure	Description	Time Frame
Absolute Change From Baseline in Percent-predicted Forced Expiratory Volume in One Second (ppFEV1) at Week 48	The FEV1 is the volume of air forcibly exhaled in one second and is measured using forced expiratory air spirometry. Change in ppFEV1 at Week 48 was defined as the average between the change from baseline at Week 40 and that at Week 48. Baseline for ppFEV1 was defined as an average of ppFEV1 at Screening (Weeks -4 to -1) and Baseline (Day 1) visits.	From Baseline to Week 48

Measure	Description	Time Frame
48-week Rate of Pulmonary Exacerbations	Pulmonary exacerbations were assessed using expanded Fuchs criteria. The expanded Fuchs exacerbation is defined as the presence of at least 4 of 12 Fuchs' signs and symptoms requiring treatment with any form of antibiotic treatment (inhaled, oral, or intravenous). Fuchs' signs and symptoms included increased cough; change in sputum volume, color, or consistency; new or increased hemoptysis; increased dyspnea during moderate or mild exertion, or at rest; sinus pain or tenderness; change in sinus discharge; malaise, fatigue, or lethargy; anorexia or weight loss; temperature above 38 degrees Celsius; change in findings on chest examination; relative 10% decrease in ppFEV1, and chest radiography results consistent with pulmonary infection. The 48-week rate was calculated as: 48-week rate = total number of events /treatment duration by week*48.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Evidence of signed and dated informed consent/assent document(s) indicating that the subject (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial
Age >=6 years.
Body weight >=16 kg.
Sweat chloride >60 milliequivalent per liter (mEq/L)
Documentation of the presence of a nonsense mutation in at least 1 allele of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, as determined by genotyping performed at a laboratory certified by the College of American Pathologists (CAP), or under the Clinical Laboratory Improvement Act/Amendment (CLIA), or by an equivalent organization
Verification that a blood sample has been drawn for sequencing of the CFTR gene
Ability to perform a valid, reproducible spirometry test using the study-specific spirometer with demonstration of an FEV1 >=40% and <=90% of predicted
Demonstration at Visit 2 of a valid %-predicted FEV1 within 15% of the Screening % predicted FEV1 value
Resting oxygen saturation (as measured by pulse oximetry) >=92% on room air.
Confirmed screening laboratory values within pre-specified ranges
In subjects who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and 60-day follow-up period
Willingness and ability to comply with all study procedures and assessments, including scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions

Exclusion Criteria:

Known hypersensitivity to any of the ingredients or excipients of the study drug
Previous participation in the Phase 3 trial of ataluren (PTC124-GD-009-CF).
Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or re-initiation) in a chronic treatment/prophylaxis regimen for Cystic Fibrosis (CF) or for CF-related conditions within 4 weeks prior to screening
Chronic use of inhaled aminoglycosides (eg, tobramycin) or use of inhaled aminoglycosides within 4 weeks prior to screening.
Exposure to another investigational drug within 4 weeks prior to screening
Ongoing participation in any other therapeutic clinical trial
Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection (including viral illnesses) within 3 weeks prior to screening
Treatment with intravenous antibiotics within 3 weeks prior to screening
Ongoing immunosuppressive therapy (other than corticosteroids)
Ongoing warfarin, phenytoin, or tolbutamide therapy
History of solid organ or hematological transplantation
Major complications of lung disease (including massive hemoptysis, pneumothorax, or pleural effusion) within 8 weeks prior to screening
Known portal hypertension
Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test
Pregnancy or breast-feeding
Current smoker or a smoking history of >=10 pack-years (number of cigarette packs/day x number of years smoked).
Prior or ongoing medical condition (eg, concomitant illness, alcoholism, drug abuse, psychiatric condition), medical history, physical findings, electrocardiogram (ECG) findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the subject, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results

Name	Affiliation	Role
Joseph McIntosh, MD	PTC Therapeutics	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35233	United States
Pulmonary Associates of Mobile PC

PubMed Identifier	Type	Citation	Retractions
36866921	Derived	Aslam AA, Sinha IP, Southern KW. Ataluren and similar compounds (specific therapies for premature termination codon class I mutations) for cystic fibrosis. Cochrane Database Syst Rev. 2023 Mar 3;3(3):CD012040. doi: 10.1002/14651858.CD012040.pub3.
32682670	Derived	VanDevanter DR, Hamblett NM, Simon N, McIntosh J, Konstan MW. Evaluating assumptions of definition-based pulmonary exacerbation endpoints in cystic fibrosis clinical trials. J Cyst Fibros. 2021 Jan;20(1):39-45. doi: 10.1016/j.jcf.2020.07.008. Epub 2020 Jul 15.

Label	URL
Related Info	View source

ID	Title	Description
FG000	Ataluren	Participants received ataluren as oral powder for suspension at the dosages of 10, 10, and 20-mg/kg at morning, midday and evening, respectively for 48 weeks of treatment duration or until treatment discontinuation.
FG001	Placebo

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

Absolute Change From Baseline in Percent-predicted Forced Expiratory Volume in One Second (ppFEV1) at Week 48

The FEV1 is the volume of air forcibly exhaled in one second and is measured using forced expiratory air spirometry. Change in ppFEV1 at Week 48 was defined as the average between the change from baseline at Week 40 and that at Week 48. Baseline for ppFEV1 was defined as an average of ppFEV1 at Screening (Weeks -4 to -1) and Baseline (Day 1) visits.

The intent-to-treat (ITT) population included all randomized participants who had FEV1 data available at Baseline and at least one post-baseline visit.

Posted

Least Squares Mean

95% Confidence Interval

Percentage of predicted FEV1

From Baseline to Week 48

ID	Title	Description
OG000	Ataluren	Participants received ataluren as oral powder for suspension at the dosages of 10, 10, and 20-mg/kg at morning, midday and evening, respectively for 48 weeks of treatment duration or until treatment discontinuation
OG001	Placebo	Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.

Units	Counts
Participants	OG000138 OG001136

Title

Denominators

Categories

Title	Measurements
	OG000-1.396(-2.7735 to -0.0180) OG001-1.992(-3.3271 to -0.6576)

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-model, repeated-measures		0.5336		Mean Difference (Net)	0.597	Standard Error of the Mean	0.9570	2-Sided	95	-1.2881	2.4813					Superiority

Secondary

48-week Rate of Pulmonary Exacerbations

Pulmonary exacerbations were assessed using expanded Fuchs criteria. The expanded Fuchs exacerbation is defined as the presence of at least 4 of 12 Fuchs' signs and symptoms requiring treatment with any form of antibiotic treatment (inhaled, oral, or intravenous). Fuchs' signs and symptoms included increased cough; change in sputum volume, color, or consistency; new or increased hemoptysis; increased dyspnea during moderate or mild exertion, or at rest; sinus pain or tenderness; change in sinus discharge; malaise, fatigue, or lethargy; anorexia or weight loss; temperature above 38 degrees Celsius; change in findings on chest examination; relative 10% decrease in ppFEV1, and chest radiography results consistent with pulmonary infection. The 48-week rate was calculated as: 48-week rate = total number of events /treatment duration by week*48.

The ITT population included all randomized participants who had FEV1 data available at Baseline and at least one post-baseline visit.

Posted

Mean

Standard Deviation

number of exacerbations per 48 weeks

Week 48

ID	Title	Description
OG000	Ataluren	Participants received ataluren as oral powder for suspension at the dosages of 10, 10, and 20-mg/kg at morning, midday and evening, respectively for 48 weeks of treatment duration or until treatment discontinuation.
OG001	Placebo	Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.

Secondary

Change From Baseline in the Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Domain at Week 48

The teen/adult CFQ-R was used for this study. It was developed specifically for participants with cystic fibrosis. It is a disease-specific instrument designed to measure impact on overall health, daily life, perceived well-being, and symptoms. The respiratory domain assessed respiratory symptoms like coughing, congestion, wheezing etc. Scaling of each item is done via 4-point Likert scales. Scores for each item are summed up to generate a domain score. Scores ranges from 0 to 100, with higher scores indicating better health and lower scores indicating worse health.

The ITT population included all randomized participants who had FEV1 data available at Baseline and at least one post-baseline visit.

Posted

Least Squares Mean

95% Confidence Interval

units on a scale

Baseline (Day 1) and Week 48

ID	Title	Description
OG000	Ataluren	Participants received ataluren as oral powder for suspension at the dosages of 10, 10, and 20-mg/kg at morning, midday and evening, respectively for 48 weeks of treatment duration or until treatment discontinuation.
OG001	Placebo	Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.

Secondary

Change From Baseline in Body Mass Index (BMI) at Week 48

Malnutrition is common in participants with cystic fibrosis. The BMI is an important clinical measure of nutritional status.

The ITT population included all randomized participants who had FEV1 data available at Baseline and at least one post-baseline visit.

Posted

Least Squares Mean

95% Confidence Interval

kilogram per meter square (kg/m^2)

Baseline (Day 1) and Week 48

ID	Title	Description
OG000	Ataluren	Participants received ataluren as oral powder for suspension at the dosages of 10, 10, and 20-mg/kg at morning, midday and evening, respectively for 48 weeks of treatment duration or until treatment discontinuation.
OG001	Placebo	Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)

An adverse event (AE) is any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A TEAE is defined as an AE that occurs or worsens in the period extending from first dose of study drug to 4 weeks after last dose of study drug. An SAE is an untoward medical occurrence or effect associated with the use of a study drug at any dose, regardless of whether it is considered to be related to the study drug, which results in one of the following: death; inpatient hospitalization or prolongation of existing hospitalization; life threatening adverse event; persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; any other medically important event; or a pregnancy resulting in spontaneous abortion, stillbirth, neonatal death, or congenital anomaly.

The as-treated population included all randomized participants who actually received any study treatment.

Posted

Number

participants

From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)

ID	Title	Description
OG000	Ataluren	Participants received ataluren as oral powder for suspension at the dosages of 10, 10, and 20-mg/kg at morning, midday and evening, respectively for 48 weeks of treatment duration or until treatment discontinuation.
OG001

Secondary

Number of Participants With TEAEs by Severity and Relationship to Study Drugs

The relationship of TEAEs to the study drugs were assessed as: probable related, possibly related, unlikely related, and unrelated. The severity of TEAEs were graded using the Common Terminology Criteria for Adverse Events, Version 3.0 as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal).

The as-treated population included all randomized participants who actually received any study treatment.

Posted

Number

participants

From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)

ID	Title	Description
OG000	Ataluren	Participants received ataluren as oral powder for suspension at the dosages of 10, 10, and 20-mg/kg at morning, midday and evening, respectively for 48 weeks of treatment duration or until treatment discontinuation.
OG001	Placebo	Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.

Units	Counts
Participants

Secondary

Number of Participants With SAEs by Severity and Relationship to Study Drugs

The relationship of SAEs to the study drugs were assessed as: probable related, possibly related, unlikely related, and unrelated. The severity of SAEs were graded using the Common Terminology Criteria for Adverse Events, Version 3.0 as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal).

The as-treated population included all randomized participants who actually received any study treatment.

Posted

Number

participants

From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)

ID	Title	Description
OG000	Ataluren	Participants received ataluren as oral powder for suspension at the dosages of 10, 10, and 20-mg/kg at morning, midday and evening, respectively for 48 weeks of treatment duration or until treatment discontinuation.
OG001	Placebo	Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.

Units	Counts
Participants

Secondary

Number of Participants With Abnormal Vital Signs Reported as TEAEs

Vital signs included systolic and diastolic blood pressure, pulse rate, pulse oximetry, and body temperature. Participants with abnormal vital signs who required clinical intervention or further investigation (beyond ordering a repeat [confirmatory] test) unless they are associated with an already reported clinical event are reported.

The as-treated population included all randomized participants who actually received any study treatment.

Posted

Number

participants

From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)

ID	Title	Description
OG000	Ataluren	Participants received ataluren as oral powder for suspension at the dosages of 10, 10, and 20-mg/kg at morning, midday and evening, respectively for 48 weeks of treatment duration or until treatment discontinuation.
OG001	Placebo	Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.

Units	Counts
Participants

Secondary

Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs

Clinical laboratory tests included haematology, biochemistry, and urinalysis. Participants with abnormal laboratory parameters who required clinical intervention or further investigation (beyond ordering a repeat [confirmatory] test) unless they are associated with an already reported clinical event are reported.

The as-treated population included all randomized participants who actually received any study treatment.

Posted

Number

participants

From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)

ID	Title	Description
OG000	Ataluren	Participants received ataluren as oral powder for suspension at the dosages of 10, 10, and 20-mg/kg at morning, midday and evening, respectively for 48 weeks of treatment duration or until treatment discontinuation.
OG001	Placebo	Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.

Units	Counts
Participants

Secondary

Number of Participants With Abnormal Electrocardiogram Reported as TEAEs

Participants with abnormal electrocardiogram who required clinical intervention or further investigation (beyond ordering a repeat [confirmatory] test) unless they are associated with an already reported clinical event are reported.

The as-treated population included all randomized participants who actually received any study treatment.

Posted

Number

participants

From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)

ID	Title	Description
OG000	Ataluren	Participants received ataluren as oral powder for suspension at the dosages of 10, 10, and 20-mg/kg at morning, midday and evening, respectively for 48 weeks of treatment duration or until treatment discontinuation.
OG001	Placebo	Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Infective pulmonary exacerbation of cystic fibrosis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG00036 events25 affected140 at risk EG00150 events34 affected139 at risk
Pseudomonas infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0002 events2 affected140 at risk EG0010 events0 affected139 at risk
Aspergillus infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected139 at risk
Bronchopneumonia	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected140 at risk EG0012 events1 affected139 at risk
Bronchopulmonary aspergillosis allergic	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected139 at risk
Device related sepsis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected139 at risk
Peritonitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected139 at risk
Pneumonia	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected140 at risk EG0012 events2 affected139 at risk
Pneumonia influenzal	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected139 at risk
Respiratory tract infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0002 events1 affected140 at risk EG0010 events0 affected139 at risk
Gastroenteritis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected139 at risk
Mycobacterium abscessus infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected139 at risk
Pneumonia staphylococcal	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected139 at risk
Respiratory tract infection fungal	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected139 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected139 at risk
Sinusitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected140 at risk EG0012 events2 affected139 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0004 events4 affected140 at risk EG0012 events1 affected139 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected139 at risk
Nasal polyps	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected140 at risk EG0011 events1 affected139 at risk
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected139 at risk
Bronchopneumopathy	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected139 at risk
Pneumothorax spontaneous	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected139 at risk
Constipation	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected139 at risk
Distal intestinal obstruction syndrome	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected139 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected139 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0003 events3 affected140 at risk EG0010 events0 affected139 at risk
Renal failure acute	Renal and urinary disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected139 at risk
Pulmonary function test decreased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0003 events1 affected140 at risk EG0010 events0 affected139 at risk
Forced expiratory volume decreased	Investigations	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected139 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected140 at risk EG0011 events1 affected139 at risk
Headache	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected139 at risk
Syncope	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected139 at risk
Red man syndrome	Skin and subcutaneous tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0001 events1 affected140 at risk EG0010 events0 affected139 at risk
Pseudocholinesterase deficiency	Congenital, familial and genetic disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected139 at risk
Thrombosis in device	General disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected139 at risk
Costochondritis	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected139 at risk
Suicidal ideation	Psychiatric disorders	MedDRA (17.0)	Systematic Assessment	EG0000 events0 affected140 at risk EG0011 events1 affected139 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG00015 events13 affected140 at risk EG00120 events12 affected139 at risk
Nausea	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG00014 events11 affected140 at risk EG00112 events10 affected139 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG00015 events11 affected140 at risk EG0016 events5 affected139 at risk
Vomiting	Gastrointestinal disorders	MedDRA (17.0)	Systematic Assessment	EG0008 events8 affected140 at risk EG0017 events4 affected139 at risk
Pyrexia	General disorders	MedDRA (17.0)	Systematic Assessment	EG00017 events9 affected140 at risk EG00112 events10 affected139 at risk
Infective pulmonary exacerbation of cystic fibrosis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG000142 events75 affected140 at risk EG001145 events78 affected139 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG00043 events27 affected140 at risk EG00125 events21 affected139 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG00025 events21 affected140 at risk EG00126 events21 affected139 at risk
Sinusitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG00020 events16 affected140 at risk EG00111 events11 affected139 at risk
Nasopharyngitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG00013 events10 affected140 at risk EG00110 events8 affected139 at risk
Rhinitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG00012 events10 affected140 at risk EG0019 events8 affected139 at risk
Influenza	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0007 events7 affected140 at risk EG0019 events8 affected139 at risk
Pharyngitis	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0008 events7 affected140 at risk EG0013 events2 affected139 at risk
Pseudomonas infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0004 events4 affected140 at risk EG00110 events9 affected139 at risk
Staphylococcal infection	Infections and infestations	MedDRA (17.0)	Systematic Assessment	EG0004 events4 affected140 at risk EG0019 events8 affected139 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (17.0)	Systematic Assessment	EG0007 events7 affected140 at risk EG0017 events3 affected139 at risk
Headache	Nervous system disorders	MedDRA (17.0)	Systematic Assessment	EG00023 events12 affected140 at risk EG00118 events16 affected139 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG00036 events25 affected140 at risk EG00131 events25 affected139 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (17.0)	Systematic Assessment	EG00017 events12 affected140 at risk EG00122 events10 affected139 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	Ataluren	Participants received ataluren as oral powder for suspension at the dosages of 10, 10, and 20-mg/kg at morning, midday and evening, respectively for 48 weeks of treatment duration or until treatment discontinuation
BG001	Placebo	Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.
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	Ataluren	Participants received ataluren as oral powder for suspension at the dosages of 10, 10, and 20-mg/kg at morning, midday and evening, respectively for 48 weeks of treatment duration or until treatment discontinuation.	0	140	40	140	123	140
EG001	Placebo	Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.	0	139	46	139	120	139