Trial Outcomes & Findings for Extension Study of Ataluren (PTC124) in Cystic Fibrosis (NCT NCT01140451)

Last Updated: 2020-10-19

Results Overview

A TEAE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship that occurred or worsened in the period extending from the first dose of study drug to 6 weeks after the last dose of study drug. A serious adverse event (SAE) was an adverse event (AE) resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. AE severity was graded as follows: Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening; Grade 5: fatal. A TEAE was considered related if in the opinion of the Investigator it was possibly or probably caused by the study drug. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the Adverse Events module.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

191 participants

Primary outcome timeframe

Baseline (Week 1 [Total Study Week 48]) up to 4 Weeks Post-Treatment (Week 100 [Total Study Week 148]) or Premature Discontinuation (PD) (whichever occurred first)

Results posted on

2020-10-19

Participant Flow

This was a multicenter, open-label extension study of the safety and efficacy of ataluren in male and female participants with nonsense mutation cystic fibrosis (nmCF) aged ≥6 years who successfully completed Study PTC124-GD-009-CF (NCT00803205 \[Study 009\]).

Participants began the open-label extension study immediately after completing end-of-study visit (Week 48) in Study 009 to avoid interruption in treatment. Most assessments performed at Study 009's final visit were used as Baseline assessments in Study PTC124-GD-009e-CF (009e). Investigators and participants remained blinded to Study 009 dosing.

Participant milestones

Participant milestones
Measure	Ataluren/Ataluren Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Overall Study STARTED	95	96
Overall Study Completed 24 Weeks	89	86
Overall Study Completed 48 Weeks	78	70
Overall Study Completed 72 Weeks	63	62
Overall Study Completed 96 Weeks	57	54
Overall Study As-Treated Population	95	96
Overall Study 96-Week Completer Population	78	70
Overall Study 144-Week Completer Population	57	54
Overall Study COMPLETED	57	54
Overall Study NOT COMPLETED	38	42

Reasons for withdrawal

Reasons for withdrawal
Measure	Ataluren/Ataluren Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Overall Study Withdrawal by Subject	26	33
Overall Study Adverse Event	2	6
Overall Study Physician Decision	5	3
Overall Study Lost to Follow-up	2	0
Overall Study Participants Planning Pregnancy	3	0

Baseline Characteristics

Extension Study of Ataluren (PTC124) in Cystic Fibrosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Total n=191 Participants Total of all reporting groups
Age, Continuous	22.9 years STANDARD_DEVIATION 10.04 • n=93 Participants	24.9 years STANDARD_DEVIATION 9.29 • n=4 Participants	23.9 years STANDARD_DEVIATION 9.70 • n=27 Participants
Sex: Female, Male Female	48 Participants n=93 Participants	49 Participants n=4 Participants	97 Participants n=27 Participants
Sex: Female, Male Male	47 Participants n=93 Participants	47 Participants n=4 Participants	94 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline (Week 1 [Total Study Week 48]) up to 4 Weeks Post-Treatment (Week 100 [Total Study Week 148]) or Premature Discontinuation (PD) (whichever occurred first)

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) At least 1 TEAE	100 percent of participants	97.9 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Grade 1 TEAE	14.7 percent of participants	18.8 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Grade 2 TEAE	62.1 percent of participants	51.0 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Grade 3 TEAE	23.2 percent of participants	26.0 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Grade 4 TEAE	0 percent of participants	1.0 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Grade 5 TEAE	0 percent of participants	1.0 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Unrelated TEAE	29.5 percent of participants	26.0 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Unlikely related TEAE	37.9 percent of participants	33.3 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Possibly related TEAE	28.4 percent of participants	31.3 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Probably related TEAE	4.2 percent of participants	7.3 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Discontinued due to TEAE	2.1 percent of participants	6.3 percent of participants
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Serious TEAE	50.5 percent of participants	57.3 percent of participants

PRIMARY outcome

Timeframe: Baseline (Week 1 [Total Study Week 48]) up to 4 Weeks Post-Treatment (Week 100 [Total Study Week 148]) or PD (whichever occurred first)

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug.

A TELA is any abnormal laboratory value that started or worsened after administration of study drug. Abnormal values were defined as values outside normal range. Values considered abnormal included -Hepatic: Serum total bilirubin ≥1.5\*upper limit of normal (ULN); serum gamma glutamyl transferase \>2.5\*ULN; serum alanine aminotransferase increase of \>150 units/liter (U/L) without increased creatine kinase; -Adrenal: plasma adrenocorticotropic hormone \>ULN (normal cortisol); -Renal: serum cystatin C \>1.33 milligrams (mg)/L; serum creatinine \>ULN-1.5\*ULN for age; serum blood urea nitrogen ≥1.5\*ULN; urine protein:creatinine \>0.40 mg/deciliter (dL):mg/dL; urine protein:osmolality \>0.30 mg/L:milliosmoles/kilogram; urine blood 2+; - Serum Electrolytes: serum sodium \>150 millimoles (mmol)/L, \<130 mmol/L; serum potassium \>5.5, \<3.0 mmol/L; serum magnesium \>1.23 mmol/L, \<0.5 mmol/L; total serum calcium \>2.9 mmol/L, \<2.0 mmol/L; serum phosphorous \<0.8 mmol/L; serum biocarbonate- \<16 mmol/L.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Number of Participants With Any Treatment-Emergent Laboratory Abnormality (TELA) Renal laboratory abnormality	13 Participants	18 Participants
Number of Participants With Any Treatment-Emergent Laboratory Abnormality (TELA) Serum electrolyte laboratory abnormality	39 Participants	47 Participants
Number of Participants With Any Treatment-Emergent Laboratory Abnormality (TELA) Hepatic laboratory abnormality	44 Participants	49 Participants
Number of Participants With Any Treatment-Emergent Laboratory Abnormality (TELA) Adrenal laboratory abnormality	5 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline (Week 1 [Total Study Week 48])

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug. Here, 'Number Analyzed' signifies participants evaluable for the specified week.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Percentage of Predicted Function (Percent-Predicted) of Forced Expiratory Volume in 1 Second (FEV1) at Baseline	60.61 percentage of predicted FEV1 Standard Deviation 17.075	56.49 percentage of predicted FEV1 Standard Deviation 15.954

SECONDARY outcome

Timeframe: Week 48 (Total Study Week 96), End of Treatment (EOT) (Week 96 [Total Study Week 144])

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug. Here, 'Number Analyzed' signifies participants evaluable for the specified week.

Spirometry was used to assess pulmonary function by measuring the percent-predicted, which was determined on the basis of the height value obtained at the same study visit, for FEV1 (the amount of air that can be exhaled in 1 second). Spirometry was validated by using current guidelines of the American Thoracic Society (ATS) and European Respiratory Society (ERS). The percentage of change in percent-predicted of FEV1 was calculated as follows: ((percent-predicted FEV1-Baseline percent-predicted FEV1)/Baseline percent-predicted FEV1)\*100. Baseline was defined as Week 1 or the most recent value of percent-predicted FEV1 prior to the first dose of open-label treatment in Study 009e. A positive change from Baseline indicates that FEV1 improved.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Percentage Change From Baseline in Percent-Predicted of FEV1 at Weeks 48 and 96 Change From Baseline at Week 48	-0.73 percent change Standard Deviation 12.170	1.09 percent change Standard Deviation 23.025
Percentage Change From Baseline in Percent-Predicted of FEV1 at Weeks 48 and 96 Change From Baseline at Week 96	-3.09 percent change Standard Deviation 12.304	-2.12 percent change Standard Deviation 16.893

SECONDARY outcome

Timeframe: Baseline (Week 1 [Total Study Week 48])

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug. Here, 'Number Analyzed' signifies participants evaluable for the specified week.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Percent-Predicted of Forced Vital Capacity (FVC) at Baseline	76.37 percentage of predicted FVC Standard Deviation 15.254	73.26 percentage of predicted FVC Standard Deviation 14.133

SECONDARY outcome

Timeframe: Week 48 (Total Study Week 96), EOT (Week 96 [Total Study Week 144])

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug. Here, 'Number Analyzed' signifies participants evaluable for the specified week.

Spirometry was used to assess pulmonary function by measuring the percent-predicted, which was determined on the basis of the height value obtained at the same study visit, for FVC (the amount of air that can be exhaled after taking a deep breath). Spirometry was validated by using current guidelines of the ATS and ERS. The percentage of change in percent-predicted of FVC was calculated as follows: ((percent-predicted FVC-Baseline percent-predicted FVC)/Baseline percent-predicted FVC)\*100. Baseline was defined as Week 1 or the most recent value of percent-predicted FVC prior to the first dose of open-label treatment in Study 009e. A positive change from Baseline indicates that FVC improved.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Percentage Change From Baseline in Percent-Predicted of FVC at Weeks 48 and 96 Change From Baseline at Week 48	0.05 percent change Standard Deviation 10.690	0.69 percent change Standard Deviation 15.658
Percentage Change From Baseline in Percent-Predicted of FVC at Weeks 48 and 96 Change From Baseline at Week 96	-1.48 percent change Standard Deviation 11.080	-1.17 percent change Standard Deviation 13.940

SECONDARY outcome

Timeframe: Baseline (Week 1 [Total Study Week 48])

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug. Here, 'Number Analyzed' signifies participants evaluable for the specified week.

Spirometry was used to assess pulmonary function by measuring the percent-predicted, which was determined on the basis of the height value obtained at the same study visit, for FEF25-75 (the rate of air flow during the middle part of an exhalation). Spirometry was validated by using current guidelines of the ATS and ERS. Baseline was defined as Week 1 or the most recent value of percent-predicted FEF25-75 prior to the first dose of open-label treatment in Study 009e.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Percent-Predicted of Forced Expiratory Flow Between 25% and 75% of Expiration (FEF25-75) at Baseline	38.16 percentage of predicted FEF25-75 Standard Deviation 24.594	33.11 percentage of predicted FEF25-75 Standard Deviation 23.775

SECONDARY outcome

Timeframe: Week 48 (Total Study Week 96), EOT (Week 96 [Total Study Week 144])

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug. Here, 'Number Analyzed' signifies participants evaluable for the specified week.

Spirometry was used to assess pulmonary function by measuring the percent-predicted, which was determined on the basis of the height value obtained at the same study visit, for FEF25-75 (the rate of air flow during the middle part of an exhalation). Spirometry was validated by using current guidelines of the ATS and ERS. The percentage of change in percent-predicted of FEF25-75 was calculated as follows: ((percent-predicted FEF25-75-Baseline percent-predicted FEF25-75)/Baseline percent-predicted FEF25-75)\*100. Baseline was defined as Week 1 or the most recent value of percent-predicted FEF25-75 prior to the first dose of open-label treatment in Study 009e. A positive change from Baseline indicates that FEF25-75 improved.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Percentage Change From Baseline in Percent-Predicted of FEF25-75 at Weeks 48 and 96 Change From Baseline at Week 48	-0.55 percent change Standard Deviation 22.447	7.89 percent change Standard Deviation 58.780
Percentage Change From Baseline in Percent-Predicted of FEF25-75 at Weeks 48 and 96 Change From Baseline at Week 96	-5.55 percent change Standard Deviation 24.043	-3.29 percent change Standard Deviation 25.283

SECONDARY outcome

Timeframe: Baseline (Week 1 [Total Study Week 48]) up to Week 48 and EOT (Week 96) (Total Study Weeks 96 and 144)

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug.

A Respiratory Event Form (REF), which collected data on various signs, symptoms, and effects for each event, was completed by the Investigator when informed by the participant of a respiratory event. Pulmonary exacerbations were assessed by using the modified Fuchs' criteria, which defines an exacerbation as a respiratory event requiring treatment with parenteral antibiotics for any 4 of the following 12 symptoms with or without intravenous (IV) antibiotics: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; fatigue; temperature \>38°C; anorexia; sinus pain; change in sinus discharge; change in physical examination of the chest; or decrease in pulmonary function by 10% or more from a previously recorded value; or radiographic changes indicative of pulmonary function.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Number of Participants With Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Week 1 up to Week 48	50 Participants	56 Participants
Number of Participants With Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Week 1 up to Week 96	57 Participants	68 Participants

SECONDARY outcome

Timeframe: Baseline (Week 1 [Total Study Week 48]) up to Week 48 (Total Study Week 96)

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug.

A REF, which collected data on various signs, symptoms, and effects for each event, was completed by the Investigator when informed by the participant of a respiratory event. Pulmonary function was assessed by using the modified Fuchs' criteria, which defines an exacerbation as a respiratory event requiring treatment with parenteral antibiotics for any 4 of the following 12 symptoms with or without treatment with IV antibiotics: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; fatigue; temperature \>38°C; anorexia; sinus pain; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10% or more from a previously recorded value; or radiographic changes indicative of pulmonary function. The 48-week exacerbation rate was determined by adding the weekly rates for each arm for each 48-week period and dividing the sum by 48.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Rate of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Over 48 Weeks	1.150 exacerbations Interval 0.843 to 1.457	1.614 exacerbations Interval 1.163 to 2.064

SECONDARY outcome

Timeframe: Weeks 43 up to 48 and Weeks 91 up to 96 (Total Study Weeks 91 up to 96 and Weeks 139 up to 144)

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug. Here, 'Number Analyzed' signifies participants evaluable for the specified week.

A REF, which collected data on various signs, symptoms, and effects for each event, was completed by the Investigator when informed by the participant of a respiratory event. Pulmonary function was assessed by using the modified Fuchs' criteria, which defines an exacerbation as a respiratory event requiring treatment with parenteral antibiotics for any 4 of the following 12 symptoms with or without treatment with IV antibiotics: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; fatigue; temperature \>38°C; anorexia; sinus pain; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10% or more from a previously recorded value; or radiographic changes indicative of pulmonary function. Duration over a 5-week interval is presented. The duration was calculated as follows: estimated date of return to a stable state (as determined by the Investigator) - estimated date of onset of symptoms.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Duration of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Week 43 up to Week 48	3.675 days Interval 1.394 to 5.956	4.734 days Interval 2.258 to 7.21
Duration of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Week 91 up to Week 96	3.567 days Interval 1.124 to 6.01	3.912 days Interval 1.742 to 6.083

SECONDARY outcome

Timeframe: Weeks 43 up to 48 and Weeks 91 up to 96 (Total Study Weeks 91 up to 96 and Weeks 139 up to 144)

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug. Here, 'Number Analyzed' signifies participants evaluable for the specified week.

A REF, which collected data on various signs, symptoms, and effects for each event, was completed by the Investigator when informed by the participant of a respiratory event. Pulmonary function was assessed by using the modified Fuchs' criteria, which defines an exacerbation as a respiratory event requiring treatment with parenteral antibiotics for any 4 of the following 12 symptoms with or without treatment with IV antibiotics: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; fatigue; temperature \>38°C; anorexia; sinus pain; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10% or more from a previously recorded value; or radiographic changes indicative of pulmonary function. Severity of pulmonary exacerbations over a 5-week interval is presented. The severity of pulmonary exacerbations were graded as mild, moderate, or severe.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Number of Participants With Severe Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Week 43 up to Week 48	1 Participants	1 Participants
Number of Participants With Severe Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Week 91 up to Week 96	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline (Week 1 [Total Study Week 48]), Week 48 (Total Study Week 96), EOT (Week 96 [Total Study Week 144])

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug. Here, 'Number Analyzed' signifies participants evaluable for specified categories.

The CFQ-R consists of 44 items, including generic scales of physical functioning, role functioning, vitality, health perceptions, emotional functioning, and social functioning, and CF-specific scales of respiratory and digestive symptoms, body image, eating disturbances, and treatment burden. Questions are scored on a scale from 1 to 4, with higher scores indicating better quality of life (QOL). For some questions, the scale was reversed, so that 1 indicated better QOL. Domain scores were linearly transformed to a 0-100 scale, so that higher scores indicate better QOL. Domain scores were calculated by using the following formula: 100 \* (sum of responses - minimum possible sum)/ (maximum possible sum - minimum possible sum). The minimum possible sum = number of questions \* 1; the maximum possible = the number of questions \* 4. Baseline was Week 1. A negative change from Baseline indicates that health has worsened. Participants may have switched age groups during the study.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Change From Baseline for the Respiratory Domain Score of the Cystic Fibrosis (CF) Questionnaire-Revised (CFQ-R) at Weeks 48 and 96 Aged 6-11 years, Baseline	83.333 units on a scale Standard Deviation 8.9087	86.111 units on a scale Standard Deviation 17.3472
Change From Baseline for the Respiratory Domain Score of the Cystic Fibrosis (CF) Questionnaire-Revised (CFQ-R) at Weeks 48 and 96 Aged 6-11 years, Change From Baseline at Week 48	-13.095 units on a scale Standard Deviation 19.7538	-0 units on a scale Standard Deviation 0
Change From Baseline for the Respiratory Domain Score of the Cystic Fibrosis (CF) Questionnaire-Revised (CFQ-R) at Weeks 48 and 96 Aged 6-11 years, Change From Baseline at Week 96	-5.556 units on a scale Standard Deviation 10.0922	0 units on a scale Standard Deviation NA Standard deviation cannot be calculated with an N of 1.
Change From Baseline for the Respiratory Domain Score of the Cystic Fibrosis (CF) Questionnaire-Revised (CFQ-R) at Weeks 48 and 96 Aged 12-13 years, Baseline	75.000 units on a scale Standard Deviation 16.6667	63.889 units on a scale Standard Deviation 4.8113
Change From Baseline for the Respiratory Domain Score of the Cystic Fibrosis (CF) Questionnaire-Revised (CFQ-R) at Weeks 48 and 96 Aged 12-13 years, Change From Baseline at Week 48	0 units on a scale Standard Deviation 11.7851	16.667 units on a scale Standard Deviation 0
Change From Baseline for the Respiratory Domain Score of the Cystic Fibrosis (CF) Questionnaire-Revised (CFQ-R) at Weeks 48 and 96 Age ≥14 years, Baseline	66.181 units on a scale Standard Deviation 20.5449	65.123 units on a scale Standard Deviation 18.1322
Change From Baseline for the Respiratory Domain Score of the Cystic Fibrosis (CF) Questionnaire-Revised (CFQ-R) at Weeks 48 and 96 Age ≥14 years, Change From Baseline at Week 48	2.691 units on a scale Standard Deviation 17.4280	3.819 units on a scale Standard Deviation 16.2311
Change From Baseline for the Respiratory Domain Score of the Cystic Fibrosis (CF) Questionnaire-Revised (CFQ-R) at Weeks 48 and 96 Age ≥14 years, Change From Baseline at Week 96	5.039 units on a scale Standard Deviation 16.4811	1.307 units on a scale Standard Deviation 20.9228
Change From Baseline for the Respiratory Domain Score of the Cystic Fibrosis (CF) Questionnaire-Revised (CFQ-R) at Weeks 48 and 96 All participants, Baseline	68.203 units on a scale Standard Deviation 20.1408	65.567 units on a scale Standard Deviation 18.1927
Change From Baseline for the Respiratory Domain Score of the Cystic Fibrosis (CF) Questionnaire-Revised (CFQ-R) at Weeks 48 and 96 All participants, Change From Baseline at Week 48	0.722 units on a scale Standard Deviation 17.7087	4.365 units on a scale Standard Deviation 16.0206
Change From Baseline for the Respiratory Domain Score of the Cystic Fibrosis (CF) Questionnaire-Revised (CFQ-R) at Weeks 48 and 96 All participants, Change From Baseline at Week 96	3.274 units on a scale Standard Deviation 16.5408	1.625 units on a scale Standard Deviation 20.6684

SECONDARY outcome

Timeframe: Baseline (Week 1 [Total Study Week 48]) up to EOT (Week 96 [Total Study Week 144])

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug. Here, 'Number Analyzed' signifies participants evaluable for specified categories.

The rate of compliance was defined as the number of actual doses taken divided by the number of planned doses \* 100. Participant-reported data were obtained from the participant's compliance log, which was completed by the participant or the caregiver. The participant or caregiver reported how many doses were taken. Compliance by drug accountability was determined by counting used and unused study drug sachets. All calculations were based on the records of the first dose date to the last dose date.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Rate of Study Drug Compliance By drug accountability	86.057 percent of doses taken Interval 27.03 to 106.06	80.118 percent of doses taken Interval 0.0 to 100.74
Rate of Study Drug Compliance By participant-reported data	81.50 percent of doses taken Interval 0.0 to 99.9	78.59 percent of doses taken Interval 0.0 to 99.7

SECONDARY outcome

Timeframe: Predose at Weeks 1, 16, 32, 48, 64, 80 and EOT (Week 96) (Total Study Weeks 48, 64, 80 96, 112, 128, and 144, respectively)

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug. Here, 'Number Analyzed' signifies participants evaluable for the specified week.

Blood samples were drawn immediately before administration of the first daily dose (dose taken with breakfast) of ataluren. Whenever possible, the predose sample was to be obtained within 15 minutes of study ataluren administration.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Predose Concentration of Ataluren Week 1	1.668 micrograms/milliliter Standard Deviation 3.6279	0 micrograms/milliliter Standard Deviation 0
Predose Concentration of Ataluren Week 16	5.744 micrograms/milliliter Standard Deviation 5.7198	7.552 micrograms/milliliter Standard Deviation 8.3963
Predose Concentration of Ataluren Week 32	6.298 micrograms/milliliter Standard Deviation 7.1222	7.694 micrograms/milliliter Standard Deviation 7.9796
Predose Concentration of Ataluren Week 48	5.874 micrograms/milliliter Standard Deviation 6.8533	6.981 micrograms/milliliter Standard Deviation 6.8874
Predose Concentration of Ataluren Week 64	5.227 micrograms/milliliter Standard Deviation 4.7054	5.703 micrograms/milliliter Standard Deviation 6.2718
Predose Concentration of Ataluren Week 80	6.126 micrograms/milliliter Standard Deviation 6.4939	4.902 micrograms/milliliter Standard Deviation 5.9218
Predose Concentration of Ataluren Week 96	6.390 micrograms/milliliter Standard Deviation 6.8861	5.435 micrograms/milliliter Standard Deviation 6.5315

SECONDARY outcome

Timeframe: Baseline (Week 1 [Total Study Week 48]) up to EOT (Week 96 [Total Study Week 144])

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug.

During treatment, any interventions including hospitalization or use of oral, inhaled, or IV antibiotics was documented if it was due to an exacerbation-like episode. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the Adverse Events module.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Number of Participants Who Required Interventions for Pulmonary Symptoms Hospitalization	44 Participants	49 Participants
Number of Participants Who Required Interventions for Pulmonary Symptoms Use of Inhaled Antibiotics	10 Participants	18 Participants
Number of Participants Who Required Interventions for Pulmonary Symptoms Use of Intravenous Antibiotics	80 Participants	80 Participants

SECONDARY outcome

Timeframe: Baseline (Week 1 [Total Study Week 48]) up to EOT (Week 96 [Total Study Week 144])

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug.

During treatment, participants reported when they missed school or work because of pulmonary symptoms. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the Adverse Events module.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Number of Participants With Disruptions in Activities of Daily Living Because of Pulmonary Symptoms Missed at Least 1 Day of School	23 Participants	25 Participants
Number of Participants With Disruptions in Activities of Daily Living Because of Pulmonary Symptoms Missed at Least 1 Day of Work	27 Participants	25 Participants

SECONDARY outcome

Timeframe: Baseline (Week 1 [Total Study Week 48]) up to EOT (Week 96 [Total Study Week 144])

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug.

During treatment, participants reported when they missed school or work because of pulmonary symptoms. If Event Date was before Day 1 (Baseline) Date, Study Day = Event Date - First Dose Date. If Event Date was on or after Day 1 Date, Study Day = Event Date - First Dose Date + 1. The Duration = Return to Stable Date - Onset Date. Participants with a respiratory event that was ongoing when the participant was discontinued from the study were considered as not evaluable. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the Adverse Events module.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Duration of Disruptions in Activities of Daily Living Because of Pulmonary Symptoms Missed at Least 1 Day of School	25.0 days Interval 7.0 to 187.0	21.5 days Interval 4.0 to 112.0
Duration of Disruptions in Activities of Daily Living Because of Pulmonary Symptoms Missed at Least 1 Day of Work	25.0 days Interval 1.0 to 161.0	22.0 days Interval 1.0 to 131.0

SECONDARY outcome

Timeframe: Baseline (Week 1 [Total Study Week 48]), Week 48 (Total Study Week 96), EOT (Week 96 [Total Study Week 144])

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug. Here, 'Number Analyzed' signifies participants evaluable for the specified week.

Participants were weighed, and the weight was recorded at Baseline and then every 8 weeks during the treatment period. Baseline was Week 1. A positive change from Baseline indicates that weight increased.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Change From Baseline in Body Weight at Weeks 48 and 96 Baseline	53.354 kilograms (kg) Standard Deviation 13.5601	57.444 kilograms (kg) Standard Deviation 11.7890
Change From Baseline in Body Weight at Weeks 48 and 96 Change From Baseline at Week 48	1.232 kilograms (kg) Standard Deviation 2.8322	0.540 kilograms (kg) Standard Deviation 2.8287
Change From Baseline in Body Weight at Weeks 48 and 96 Change From Baseline at Week 96	2.149 kilograms (kg) Standard Deviation 5.0803	0.830 kilograms (kg) Standard Deviation 3.6440

SECONDARY outcome

Timeframe: Baseline (Week 1 [Total Study Week 48]), Week 48 (Total Study Week 96), EOT (Week 96 [Total Study Week 144])

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug. Here, 'Number Analyzed' signifies participants evaluable for the specified week.

Participants were weighed and measured and the weight and height were recorded at each visit. The BMI was determined by dividing the participant's weight by his or her height. Baseline was Week 1. A positive change from Baseline indicates that BMI increased.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=95 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=96 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Change From Baseline in Body Mass Index (BMI) at Weeks 48 and 96 Change From Baseline at Week 96	0.144 kg/square meter (kg/m^2) Standard Deviation 1.1404	0.105 kg/square meter (kg/m^2) Standard Deviation 1.1885
Change From Baseline in Body Mass Index (BMI) at Weeks 48 and 96 Baseline	20.023 kg/square meter (kg/m^2) Standard Deviation 3.3136	21.044 kg/square meter (kg/m^2) Standard Deviation 2.7735
Change From Baseline in Body Mass Index (BMI) at Weeks 48 and 96 Change From Baseline at Week 48	0.179 kg/square meter (kg/m^2) Standard Deviation 0.8323	0.102 kg/square meter (kg/m^2) Standard Deviation 0.9179

SECONDARY outcome

Timeframe: Week 48 (Total Study Week 96) and EOT (Week 96 [Total Study Week 144])

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug. Here, 'Number analyzed' signifies the number of participants analyzed for the specified weeks for this Outcome Measure.

Lungs were imaged by using non-contrast, spiral CT. The administration of CT scans was discontinued for this study via a memorandum sent to all Investigators, based on the results of Study 009, which showed that this exploratory endpoint failed to discriminate active treatment from placebo over the 48-week study period. Therefore, this Outcome Measure was removed from the study as a Secondary Outcome Measure and the CT scans that were administered for this study were not reviewed or analyzed for this Outcome Measure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (Week 1 [Total Study Week 48]) and Week 48 (Total Study Week 96)

TEPD was to be assessed in each nostril by using standardized equipment, techniques, and solutions. Collection of nasal TEPD tracings was discontinued for this study via a memorandum sent to all Investigators, based on the results of Study 009, which showed that this biomarker failed to discriminate active treatment from placebo over the 48-week study period. Therefore, this Outcome Measure was removed from the study as a Secondary Outcome Measure and none of the nasal TEPD tracings were reviewed or analyzed for this Outcome Measure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (Week 1 [Total Study Week 48]), Week 48 (Total Study Week 96)

Population: The Study 009e As-Treated Population: participants who received at least 1 dose of study drug. Here, 'Number Analyzed' signifies participants evaluable for the specified week. One and 4 participants in the ataluren/ataluren and placebo/ataluren groups, respectively, were not evaluable.

Sweat was collected, from each arm, by using pilocarpine iontophoresis. The chloride concentration in the sweat was quantified for each arm by using standard laboratory methods. Tests were considered valid if the sweat collection time was ≤35 minutes; tests with longer collection times were also considered valid if extra time was needed to obtain sufficient volume (≥15uL) for analysis. For analysis purposes, the average of the values from each arm were computed. If the assessment was valid and/or available in only 1 arm, this value was used as if it were the average of both arms. The method used was consistent with the guidelines of the Cystic Fibrosis Foundation Therapeutics - Therapeutic Development Network. Baseline was the most recent value of sweat chloride prior to treatment in Study 009e. A positive change from Baseline indicates that sweat chloride concentration increased.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=94 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=92 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Change From Baseline in the Concentration of Sweat Chloride at Week 48 Baseline	100.26 millimoles/liter Standard Deviation 13.602	97.88 millimoles/liter Standard Deviation 16.444
Change From Baseline in the Concentration of Sweat Chloride at Week 48 Change From Baseline at Week 48	5.34 millimoles/liter Standard Deviation 10.062	3.60 millimoles/liter Standard Deviation 14.422

POST_HOC outcome

Timeframe: Baseline (Week 1 [Total Study Week 48])

Population: Study 009/009e 96-Week Completer Population: participants who completed 48 weeks of treatment with ataluren or placebo in Study 009 and at least 48 weeks of treatment with ataluren in Study 009e. Here, 'Number Analyzed' signifies participants evaluable for the specified week.

Spirometry was used to assess pulmonary function by measuring the percent-predicted, which was determined on the basis of the height value obtained at the same study visit, for FEV1 (the amount of air that can be exhaled in 1 second). Spirometry was validated by using current guidelines of the ATS and ERS. Analyses with the Completer populations were performed to complement the analyses of the Study 009e As-Treated population. Baseline was defined as Week 1 or the most recent value of percent-predicted FEV1 prior to the first dose of open-label treatment in Study 009e.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=78 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=70 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Percent-Predicted of FEV1 in the 96-Week Completer Population at Baseline	60.89 percentage of predicted FEV1 Standard Deviation 13.320	59.50 percentage of predicted FEV1 Standard Deviation 15.622

POST_HOC outcome

Timeframe: Week 48 (Total Study Week 96)

Spirometry was used to assess pulmonary function by measuring the percent-predicted, which was determined on the basis of the height value obtained at the same study visit, for FEV1 (the amount of air that can be exhaled in 1 second). Spirometry was validated by using current guidelines of the ATS and ERS. The percentage of change in percent-predicted of FEV1 was calculated as follows: ((percent-predicted FEV1-Baseline percent-predicted FEV1)/Baseline percent-predicted FEV1)\*100. Analyses with the Completer populations were performed to complement the analyses of the Study 009e As-Treated population. Baseline was defined as Week 1 or the most recent value of percent-predicted FEV1 prior to the first dose of open-label treatment in Study 009e. A positive change from Baseline indicates that FEV1 improved.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=78 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=70 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Percentage Change From Baseline in Percent-Predicted of FEV1 in the 96-Week Completer Population Over a Total of 96 Weeks of Treatment	-1.63 percent change Standard Deviation 13.239	-5.13 percent change Standard Deviation 12.061

POST_HOC outcome

Timeframe: Baseline (Week 1 [Total Study Week 48])

Population: Study 009/009e 144-Week Completer Population: participants who completed 48 weeks of treatment with ataluren or placebo in Study 009 and at least 96 weeks of treatment with ataluren in Study 009e. Here, 'Number Analyzed' signifies participants evaluable for the specified week.

Spirometry was used to assess pulmonary function by measuring the percent-predicted, which was determined on the basis of the height value obtained at the same study visit, for FEV1 (the amount of air that can be exhaled in 1 second). Spirometry was validated by using current guidelines of the ATS and ERS. Analyses with the Completer populations were performed to complement the analyses of the Study 009e As-Treated population. Baseline was defined as Week 1 or the most recent value of percent-predicted FEV1 prior to the first dose of open-label treatment in Study 009e.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=57 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=54 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Percent-Predicted of FEV1 in the 144-Week Completer Population at Baseline	61.68 percentage of predicted FEV1 Standard Deviation 13.790	60.28 percentage of predicted FEV1 Standard Deviation 16.202

POST_HOC outcome

Timeframe: EOT (Week 96 [Total Study Week 144])

Spirometry was used to assess pulmonary function by measuring the percent-predicted, which was determined on the basis of the height value obtained at the same study visit, for FEV1 (the amount of air that can be exhaled in 1 second). Spirometry was validated by using current guidelines of the ATS and ERS. The percentage of change in percent-predicted of FEV1 was calculated as follows: ((percent-predicted FEV1-Baseline percent-predicted FEV1)/Baseline percent-predicted FEV1)\*100. Analyses with the Completer populations were performed to complement the analyses of the Study 009e As-Treated population. Baseline was defined as Week 1 or the most recent value of percent-predicted FEV1 prior to the first dose of open-label treatment in Study 009e. A positive change from Baseline indicates that FEV1 improved.

Outcome measures

Outcome measures
Measure	Ataluren/Ataluren n=57 Participants Participants who received double-blind ataluren during Study 009 continued to receive open-label ataluren taken 3 times per day (TID): 10 milligram (mg)/kilogram (kg) of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.	Placebo/Ataluren n=54 Participants Participants who received double-blind placebo during Study 009 received open-label ataluren TID: 10 mg/kg of body weight with breakfast, 10 mg/kg with lunch, and 20 mg/kg with dinner (total dose 40 mg/kg/day), for up to 96 weeks. Participants were followed for 4 weeks after treatment.
Percentage Change From Baseline in Percent-Predicted of FEV1 in the 144-Week Completer Population Over a Total of 144 Weeks of Treatment	-3.69 percent change Standard Deviation 16.068	-5.89 percent change Standard Deviation 14.854

Adverse Events

Ataluren/Ataluren

Serious events: 48 serious events

Other events: 95 other events

Deaths: 0 deaths

Placebo/Ataluren

Serious events: 57 serious events

Other events: 94 other events

Deaths: 0 deaths

Overall Population

Serious events: 105 serious events

Other events: 189 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Patient Advocacy

PTC Therapeutics, Inc.

Phone: 1-866-562-4620

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor can review results and/or communications prior to public release and can embargo communications regarding trial results for a period that is up to 180 days from the time submitted to the sponsor for review. The sponsor may consult with the PI to require changes to the communication or extend the embargo.
Publication restrictions are in place

Restriction type: OTHER