Cystic Fibrosis
Conditions
Brief summary
Cystic fibrosis (CF) is a genetic disorder caused by a mutation in the gene that makes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. A specific type of mutation called a nonsense (premature stop codon) mutation is the cause of CF in approximately 10% of patients with the disease. Ataluren is an orally delivered investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 3 extension trial that will evaluate the long-term safety of ataluren in adult and pediatric participants with nonsense mutation CF (nmCF), as determined by adverse events and laboratory abnormalities. The study will also assess changes in pulmonary function, CF pulmonary exacerbations, health-related quality of life, antibiotic use for CF-related infections, CF-related disruptions to daily living, body weight, and CF pathophysiology. Funding source for this study is the FDA OOPD.
Detailed description
This Phase 3, open-label, safety and efficacy study will be performed at sites in North America, Europe, and Israel. The study will enroll up to approximately 208 participants with nmCF who participated in a previous Phase 3 study of ataluren (PTC124-GD-009-CF \[Study 009\], NCT00803205). Participants will receive study drug 3 times per day (TID) (at breakfast, lunch, and dinner) for approximately 48 weeks (approximately 1 year). Study assessments will be performed at clinic visits every 8 weeks.
Interventions
DRUGAtaluren
Ataluren will be provided as a vanilla-flavored powder to be mixed with water or milk.
Sponsors
Cystic Fibrosis Foundation
PTC Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This extension study was not blinded. The investigators and participants remained blinded to the Study 009 treatment assignments throughout participation in Study PTC124-GD-009e-CF.
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Completion of blinded study drug treatment in the previous Phase 3 study (PTC124-GD-009-CF). * Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if \<18 years of age). * In participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during ataluren administration and the 4-week follow up period. * Willingness and ability to comply with 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 (list provided at study sites). * Current pregnancy or lactating, or pregnancy or lactating during the previous Phase 3 study. * Ongoing participation in any other therapeutic clinical trial. * Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, ECG findings, or laboratory abnormality that, in the Investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow up would be completed, or could impair the assessment of study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | 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) | 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. |
| Number of Participants With Any Treatment-Emergent Laboratory Abnormality (TELA) | Baseline (Week 1 [Total Study Week 48]) up to 4 Weeks Post-Treatment (Week 100 [Total Study Week 148]) or PD (whichever occurred first) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent-Predicted of Forced Vital Capacity (FVC) at Baseline | Baseline (Week 1 [Total Study Week 48]) | 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. 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. |
| Percentage Change From Baseline in Percent-Predicted of FVC at Weeks 48 and 96 | Week 48 (Total Study Week 96), 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 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. |
| Percent-Predicted of Forced Expiratory Flow Between 25% and 75% of Expiration (FEF25-75) at Baseline | Baseline (Week 1 [Total Study Week 48]) | 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. |
| Percentage Change From Baseline in Percent-Predicted of FEF25-75 at Weeks 48 and 96 | Week 48 (Total Study Week 96), 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 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. |
| Number of Participants With Pulmonary Exacerbations as Defined by Modified Fuch's Criteria | Baseline (Week 1 [Total Study Week 48]) up to Week 48 and EOT (Week 96) (Total Study Weeks 96 and 144) | 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. |
| Rate of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Over 48 Weeks | Baseline (Week 1 [Total Study Week 48]) up to Week 48 (Total Study Week 96) | 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. |
| Duration of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria | Weeks 43 up to 48 and Weeks 91 up to 96 (Total Study Weeks 91 up to 96 and Weeks 139 up to 144) | 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. |
| Number of Participants With Severe Pulmonary Exacerbations as Defined by Modified Fuch's Criteria | Weeks 43 up to 48 and Weeks 91 up to 96 (Total Study Weeks 91 up to 96 and Weeks 139 up to 144) | 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. |
| Change From Baseline for the Respiratory Domain Score of the Cystic Fibrosis (CF) Questionnaire-Revised (CFQ-R) at Weeks 48 and 96 | Baseline (Week 1 [Total Study Week 48]), Week 48 (Total Study Week 96), EOT (Week 96 [Total Study Week 144]) | 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. |
| Percentage of Predicted Function (Percent-Predicted) of Forced Expiratory Volume in 1 Second (FEV1) at Baseline | Baseline (Week 1 [Total Study Week 48]) | 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). 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. |
| Predose Concentration of Ataluren | 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) | 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. |
| Number of Participants Who Required Interventions for Pulmonary Symptoms | Baseline (Week 1 [Total Study Week 48]) up to EOT (Week 96 [Total Study Week 144]) | 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. |
| Number of Participants With Disruptions in Activities of Daily Living Because of Pulmonary Symptoms | Baseline (Week 1 [Total Study Week 48]) up to EOT (Week 96 [Total Study Week 144]) | 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. |
| Duration of Disruptions in Activities of Daily Living Because of Pulmonary Symptoms | Baseline (Week 1 [Total Study Week 48]) up to EOT (Week 96 [Total Study Week 144]) | 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. |
| Change From Baseline in Body Weight at Weeks 48 and 96 | Baseline (Week 1 [Total Study Week 48]), Week 48 (Total Study Week 96), EOT (Week 96 [Total Study Week 144]) | 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. |
| Change From Baseline in Body Mass Index (BMI) at Weeks 48 and 96 | Baseline (Week 1 [Total Study Week 48]), Week 48 (Total Study Week 96), EOT (Week 96 [Total Study Week 144]) | 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. |
| Total Lung Computed Tomography (CT) Score at Weeks 48 and 96 | Week 48 (Total Study Week 96) and EOT (Week 96 [Total Study Week 144]) | 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. |
| Change From Baseline in the Nasal Transepithelial Potential Difference (TEPD) at Week 48 | 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. |
| Change From Baseline in the Concentration of Sweat Chloride at Week 48 | Baseline (Week 1 [Total Study Week 48]), Week 48 (Total Study Week 96) | 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. |
| Rate of Study Drug Compliance | Baseline (Week 1 [Total Study Week 48]) up to EOT (Week 96 [Total Study Week 144]) | 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. |
| Percentage Change From Baseline in Percent-Predicted of FEV1 at Weeks 48 and 96 | Week 48 (Total Study Week 96), End of Treatment (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 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. |
Countries
Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
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 \[Study 009\]).
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 95 |
| 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. | 96 |
| Total | 191 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 6 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Participants Planning Pregnancy | 3 | 0 |
| Overall Study | Physician Decision | 5 | 3 |
| Overall Study | Withdrawal by Subject | 26 | 33 |
Baseline characteristics
| Characteristic | Ataluren/Ataluren | Placebo/Ataluren | Total |
|---|---|---|---|
| Age, Continuous | 22.9 years STANDARD_DEVIATION 10.04 | 24.9 years STANDARD_DEVIATION 9.29 | 23.9 years STANDARD_DEVIATION 9.7 |
| Sex: Female, Male Female | 48 Participants | 49 Participants | 97 Participants |
| Sex: Female, Male Male | 47 Participants | 47 Participants | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 95 / 95 | 94 / 96 | 189 / 191 |
| serious Total, serious adverse events | 48 / 95 | 57 / 96 | 105 / 191 |
Outcome results
Primary
Number of Participants With Any Treatment-Emergent Laboratory Abnormality (TELA)
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ataluren/Ataluren | Number of Participants With Any Treatment-Emergent Laboratory Abnormality (TELA) | Renal laboratory abnormality | 13 Participants |
| Ataluren/Ataluren | Number of Participants With Any Treatment-Emergent Laboratory Abnormality (TELA) | Serum electrolyte laboratory abnormality | 39 Participants |
| Ataluren/Ataluren | Number of Participants With Any Treatment-Emergent Laboratory Abnormality (TELA) | Hepatic laboratory abnormality | 44 Participants |
| Ataluren/Ataluren | Number of Participants With Any Treatment-Emergent Laboratory Abnormality (TELA) | Adrenal laboratory abnormality | 5 Participants |
| Placebo/Ataluren | Number of Participants With Any Treatment-Emergent Laboratory Abnormality (TELA) | Adrenal laboratory abnormality | 3 Participants |
| Placebo/Ataluren | Number of Participants With Any Treatment-Emergent Laboratory Abnormality (TELA) | Renal laboratory abnormality | 18 Participants |
| Placebo/Ataluren | Number of Participants With Any Treatment-Emergent Laboratory Abnormality (TELA) | Hepatic laboratory abnormality | 49 Participants |
| Placebo/Ataluren | Number of Participants With Any Treatment-Emergent Laboratory Abnormality (TELA) | Serum electrolyte laboratory abnormality | 47 Participants |
Primary
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ataluren/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | At least 1 TEAE | 100 percent of participants |
| Ataluren/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 1 TEAE | 14.7 percent of participants |
| Ataluren/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 2 TEAE | 62.1 percent of participants |
| Ataluren/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 3 TEAE | 23.2 percent of participants |
| Ataluren/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 4 TEAE | 0 percent of participants |
| Ataluren/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 5 TEAE | 0 percent of participants |
| Ataluren/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Unrelated TEAE | 29.5 percent of participants |
| Ataluren/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Unlikely related TEAE | 37.9 percent of participants |
| Ataluren/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Possibly related TEAE | 28.4 percent of participants |
| Ataluren/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Probably related TEAE | 4.2 percent of participants |
| Ataluren/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Discontinued due to TEAE | 2.1 percent of participants |
| Ataluren/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 50.5 percent of participants |
| Placebo/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Discontinued due to TEAE | 6.3 percent of participants |
| Placebo/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | At least 1 TEAE | 97.9 percent of participants |
| Placebo/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Unrelated TEAE | 26.0 percent of participants |
| Placebo/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 1 TEAE | 18.8 percent of participants |
| Placebo/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Probably related TEAE | 7.3 percent of participants |
| Placebo/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 2 TEAE | 51.0 percent of participants |
| Placebo/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Unlikely related TEAE | 33.3 percent of participants |
| Placebo/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 3 TEAE | 26.0 percent of participants |
| Placebo/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Serious TEAE | 57.3 percent of participants |
| Placebo/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 4 TEAE | 1.0 percent of participants |
| Placebo/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Possibly related TEAE | 31.3 percent of participants |
| Placebo/Ataluren | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 5 TEAE | 1.0 percent of participants |
Secondary
Change From Baseline for the Respiratory Domain Score of the Cystic Fibrosis (CF) Questionnaire-Revised (CFQ-R) at Weeks 48 and 96
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren/Ataluren | 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 |
| Ataluren/Ataluren | 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 |
| Ataluren/Ataluren | 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 17.428 |
| Ataluren/Ataluren | 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 |
| Ataluren/Ataluren | 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 |
| Ataluren/Ataluren | 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 |
| Ataluren/Ataluren | 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 |
| Ataluren/Ataluren | 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 |
| Ataluren/Ataluren | 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 |
| Ataluren/Ataluren | 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 |
| Ataluren/Ataluren | 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 |
| Placebo/Ataluren | 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 | 1.625 units on a scale | Standard Deviation 20.6684 |
| Placebo/Ataluren | 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 | 3.819 units on a scale | Standard Deviation 16.2311 |
| Placebo/Ataluren | 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 | 86.111 units on a scale | Standard Deviation 17.3472 |
| Placebo/Ataluren | 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 | 0 units on a scale | — |
| Placebo/Ataluren | 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 | 63.889 units on a scale | Standard Deviation 4.8113 |
| Placebo/Ataluren | 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 | 16.667 units on a scale | Standard Deviation 0 |
| Placebo/Ataluren | 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 | 65.123 units on a scale | Standard Deviation 18.1322 |
| Placebo/Ataluren | 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 | 1.307 units on a scale | Standard Deviation 20.9228 |
| Placebo/Ataluren | 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 | 65.567 units on a scale | Standard Deviation 18.1927 |
| Placebo/Ataluren | 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 | 4.365 units on a scale | Standard Deviation 16.0206 |
| Placebo/Ataluren | 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 | -0 units on a scale | Standard Deviation 0 |
Secondary
Change From Baseline in Body Mass Index (BMI) at Weeks 48 and 96
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren/Ataluren | 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 |
| Ataluren/Ataluren | 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 |
| Ataluren/Ataluren | 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 |
| Placebo/Ataluren | Change From Baseline in Body Mass Index (BMI) at Weeks 48 and 96 | Change From Baseline at Week 48 | 0.102 kg/square meter (kg/m^2) | Standard Deviation 0.9179 |
| Placebo/Ataluren | Change From Baseline in Body Mass Index (BMI) at Weeks 48 and 96 | Baseline | 21.044 kg/square meter (kg/m^2) | Standard Deviation 2.7735 |
| Placebo/Ataluren | Change From Baseline in Body Mass Index (BMI) at Weeks 48 and 96 | Change From Baseline at Week 96 | 0.105 kg/square meter (kg/m^2) | Standard Deviation 1.1885 |
Secondary
Change From Baseline in Body Weight at Weeks 48 and 96
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren/Ataluren | Change From Baseline in Body Weight at Weeks 48 and 96 | Baseline | 53.354 kilograms (kg) | Standard Deviation 13.5601 |
| Ataluren/Ataluren | 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 |
| Ataluren/Ataluren | 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 |
| Placebo/Ataluren | Change From Baseline in Body Weight at Weeks 48 and 96 | Baseline | 57.444 kilograms (kg) | Standard Deviation 11.789 |
| Placebo/Ataluren | Change From Baseline in Body Weight at Weeks 48 and 96 | Change From Baseline at Week 48 | 0.540 kilograms (kg) | Standard Deviation 2.8287 |
| Placebo/Ataluren | Change From Baseline in Body Weight at Weeks 48 and 96 | Change From Baseline at Week 96 | 0.830 kilograms (kg) | Standard Deviation 3.644 |
Secondary
Change From Baseline in the Concentration of Sweat Chloride at Week 48
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren/Ataluren | Change From Baseline in the Concentration of Sweat Chloride at Week 48 | Baseline | 100.26 millimoles/liter | Standard Deviation 13.602 |
| Ataluren/Ataluren | 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 |
| Placebo/Ataluren | Change From Baseline in the Concentration of Sweat Chloride at Week 48 | Baseline | 97.88 millimoles/liter | Standard Deviation 16.444 |
| Placebo/Ataluren | Change From Baseline in the Concentration of Sweat Chloride at Week 48 | Change From Baseline at Week 48 | 3.60 millimoles/liter | Standard Deviation 14.422 |
Secondary
Change From Baseline in the Nasal Transepithelial Potential Difference (TEPD) at Week 48
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.
Time frame: Baseline (Week 1 [Total Study Week 48]) and 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 the number of participants analyzed for the specified weeks for this Outcome Measure.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Change From Baseline in the Nasal Transepithelial Potential Difference (TEPD) at Week 48 | Baseline | — |
| Unknown | Change From Baseline in the Nasal Transepithelial Potential Difference (TEPD) at Week 48 | Change From Baseline at Week 48 | — |
Secondary
Duration of Disruptions in Activities of Daily Living Because of Pulmonary Symptoms
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ataluren/Ataluren | Duration of Disruptions in Activities of Daily Living Because of Pulmonary Symptoms | Missed at Least 1 Day of School | 25.0 days |
| Ataluren/Ataluren | Duration of Disruptions in Activities of Daily Living Because of Pulmonary Symptoms | Missed at Least 1 Day of Work | 25.0 days |
| Placebo/Ataluren | Duration of Disruptions in Activities of Daily Living Because of Pulmonary Symptoms | Missed at Least 1 Day of School | 21.5 days |
| Placebo/Ataluren | Duration of Disruptions in Activities of Daily Living Because of Pulmonary Symptoms | Missed at Least 1 Day of Work | 22.0 days |
Secondary
Duration of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Ataluren/Ataluren | Duration of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria | Week 43 up to Week 48 | 3.675 days |
| Ataluren/Ataluren | Duration of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria | Week 91 up to Week 96 | 3.567 days |
| Placebo/Ataluren | Duration of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria | Week 43 up to Week 48 | 4.734 days |
| Placebo/Ataluren | Duration of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria | Week 91 up to Week 96 | 3.912 days |
Secondary
Number of Participants Who Required Interventions for Pulmonary Symptoms
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ataluren/Ataluren | Number of Participants Who Required Interventions for Pulmonary Symptoms | Hospitalization | 44 Participants |
| Ataluren/Ataluren | Number of Participants Who Required Interventions for Pulmonary Symptoms | Use of Inhaled Antibiotics | 10 Participants |
| Ataluren/Ataluren | Number of Participants Who Required Interventions for Pulmonary Symptoms | Use of Intravenous Antibiotics | 80 Participants |
| Placebo/Ataluren | Number of Participants Who Required Interventions for Pulmonary Symptoms | Hospitalization | 49 Participants |
| Placebo/Ataluren | Number of Participants Who Required Interventions for Pulmonary Symptoms | Use of Inhaled Antibiotics | 18 Participants |
| Placebo/Ataluren | Number of Participants Who Required Interventions for Pulmonary Symptoms | Use of Intravenous Antibiotics | 80 Participants |
Secondary
Number of Participants With Disruptions in Activities of Daily Living Because of Pulmonary Symptoms
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ataluren/Ataluren | Number of Participants With Disruptions in Activities of Daily Living Because of Pulmonary Symptoms | Missed at Least 1 Day of Work | 27 Participants |
| Ataluren/Ataluren | Number of Participants With Disruptions in Activities of Daily Living Because of Pulmonary Symptoms | Missed at Least 1 Day of School | 23 Participants |
| Placebo/Ataluren | Number of Participants With Disruptions in Activities of Daily Living Because of Pulmonary Symptoms | Missed at Least 1 Day of School | 25 Participants |
| Placebo/Ataluren | Number of Participants With Disruptions in Activities of Daily Living Because of Pulmonary Symptoms | Missed at Least 1 Day of Work | 25 Participants |
Secondary
Number of Participants With Pulmonary Exacerbations as Defined by Modified Fuch's Criteria
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ataluren/Ataluren | Number of Participants With Pulmonary Exacerbations as Defined by Modified Fuch's Criteria | Week 1 up to Week 48 | 50 Participants |
| Ataluren/Ataluren | Number of Participants With Pulmonary Exacerbations as Defined by Modified Fuch's Criteria | Week 1 up to Week 96 | 57 Participants |
| Placebo/Ataluren | Number of Participants With Pulmonary Exacerbations as Defined by Modified Fuch's Criteria | Week 1 up to Week 48 | 56 Participants |
| Placebo/Ataluren | Number of Participants With Pulmonary Exacerbations as Defined by Modified Fuch's Criteria | Week 1 up to Week 96 | 68 Participants |
Secondary
Number of Participants With Severe Pulmonary Exacerbations as Defined by Modified Fuch's Criteria
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ataluren/Ataluren | Number of Participants With Severe Pulmonary Exacerbations as Defined by Modified Fuch's Criteria | Week 43 up to Week 48 | 1 Participants |
| Ataluren/Ataluren | Number of Participants With Severe Pulmonary Exacerbations as Defined by Modified Fuch's Criteria | Week 91 up to Week 96 | 0 Participants |
| Placebo/Ataluren | Number of Participants With Severe Pulmonary Exacerbations as Defined by Modified Fuch's Criteria | Week 43 up to Week 48 | 1 Participants |
| Placebo/Ataluren | Number of Participants With Severe Pulmonary Exacerbations as Defined by Modified Fuch's Criteria | Week 91 up to Week 96 | 1 Participants |
Secondary
Percentage Change From Baseline in Percent-Predicted of FEF25-75 at Weeks 48 and 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 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren/Ataluren | 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 |
| Ataluren/Ataluren | 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 |
| Placebo/Ataluren | Percentage Change From Baseline in Percent-Predicted of FEF25-75 at Weeks 48 and 96 | Change From Baseline at Week 48 | 7.89 percent change | Standard Deviation 58.78 |
| Placebo/Ataluren | Percentage Change From Baseline in Percent-Predicted of FEF25-75 at Weeks 48 and 96 | Change From Baseline at Week 96 | -3.29 percent change | Standard Deviation 25.283 |
Secondary
Percentage Change From Baseline in Percent-Predicted of FEV1 at Weeks 48 and 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 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren/Ataluren | 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 12.17 |
| Ataluren/Ataluren | 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 |
| Placebo/Ataluren | Percentage Change From Baseline in Percent-Predicted of FEV1 at Weeks 48 and 96 | Change From Baseline at Week 48 | 1.09 percent change | Standard Deviation 23.025 |
| Placebo/Ataluren | Percentage Change From Baseline in Percent-Predicted of FEV1 at Weeks 48 and 96 | Change From Baseline at Week 96 | -2.12 percent change | Standard Deviation 16.893 |
Secondary
Percentage Change From Baseline in Percent-Predicted of FVC at Weeks 48 and 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 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren/Ataluren | 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 10.69 |
| Ataluren/Ataluren | 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 11.08 |
| Placebo/Ataluren | Percentage Change From Baseline in Percent-Predicted of FVC at Weeks 48 and 96 | Change From Baseline at Week 48 | 0.69 percent change | Standard Deviation 15.658 |
| Placebo/Ataluren | Percentage Change From Baseline in Percent-Predicted of FVC at Weeks 48 and 96 | Change From Baseline at Week 96 | -1.17 percent change | Standard Deviation 13.94 |
Secondary
Percentage of Predicted Function (Percent-Predicted) of Forced Expiratory Volume in 1 Second (FEV1) at Baseline
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). 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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ataluren/Ataluren | 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 |
| Placebo/Ataluren | Percentage of Predicted Function (Percent-Predicted) of Forced Expiratory Volume in 1 Second (FEV1) at Baseline | 56.49 percentage of predicted FEV1 | Standard Deviation 15.954 |
Secondary
Percent-Predicted of Forced Expiratory Flow Between 25% and 75% of Expiration (FEF25-75) at Baseline
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ataluren/Ataluren | 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 |
| Placebo/Ataluren | Percent-Predicted of Forced Expiratory Flow Between 25% and 75% of Expiration (FEF25-75) at Baseline | 33.11 percentage of predicted FEF25-75 | Standard Deviation 23.775 |
Secondary
Percent-Predicted of Forced Vital Capacity (FVC) at Baseline
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. 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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ataluren/Ataluren | Percent-Predicted of Forced Vital Capacity (FVC) at Baseline | 76.37 percentage of predicted FVC | Standard Deviation 15.254 |
| Placebo/Ataluren | Percent-Predicted of Forced Vital Capacity (FVC) at Baseline | 73.26 percentage of predicted FVC | Standard Deviation 14.133 |
Secondary
Predose Concentration of Ataluren
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ataluren/Ataluren | Predose Concentration of Ataluren | Week 32 | 6.298 micrograms/milliliter | Standard Deviation 7.1222 |
| Ataluren/Ataluren | Predose Concentration of Ataluren | Week 64 | 5.227 micrograms/milliliter | Standard Deviation 4.7054 |
| Ataluren/Ataluren | Predose Concentration of Ataluren | Week 16 | 5.744 micrograms/milliliter | Standard Deviation 5.7198 |
| Ataluren/Ataluren | Predose Concentration of Ataluren | Week 80 | 6.126 micrograms/milliliter | Standard Deviation 6.4939 |
| Ataluren/Ataluren | Predose Concentration of Ataluren | Week 48 | 5.874 micrograms/milliliter | Standard Deviation 6.8533 |
| Ataluren/Ataluren | Predose Concentration of Ataluren | Week 96 | 6.390 micrograms/milliliter | Standard Deviation 6.8861 |
| Ataluren/Ataluren | Predose Concentration of Ataluren | Week 1 | 1.668 micrograms/milliliter | Standard Deviation 3.6279 |
| Placebo/Ataluren | Predose Concentration of Ataluren | Week 96 | 5.435 micrograms/milliliter | Standard Deviation 6.5315 |
| Placebo/Ataluren | Predose Concentration of Ataluren | Week 1 | 0 micrograms/milliliter | Standard Deviation 0 |
| Placebo/Ataluren | Predose Concentration of Ataluren | Week 16 | 7.552 micrograms/milliliter | Standard Deviation 8.3963 |
| Placebo/Ataluren | Predose Concentration of Ataluren | Week 32 | 7.694 micrograms/milliliter | Standard Deviation 7.9796 |
| Placebo/Ataluren | Predose Concentration of Ataluren | Week 48 | 6.981 micrograms/milliliter | Standard Deviation 6.8874 |
| Placebo/Ataluren | Predose Concentration of Ataluren | Week 64 | 5.703 micrograms/milliliter | Standard Deviation 6.2718 |
| Placebo/Ataluren | Predose Concentration of Ataluren | Week 80 | 4.902 micrograms/milliliter | Standard Deviation 5.9218 |
Secondary
Rate of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Over 48 Weeks
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ataluren/Ataluren | Rate of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Over 48 Weeks | 1.150 exacerbations |
| Placebo/Ataluren | Rate of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Over 48 Weeks | 1.614 exacerbations |
Secondary
Rate of Study Drug Compliance
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ataluren/Ataluren | Rate of Study Drug Compliance | By drug accountability | 86.057 percent of doses taken |
| Ataluren/Ataluren | Rate of Study Drug Compliance | By participant-reported data | 81.50 percent of doses taken |
| Placebo/Ataluren | Rate of Study Drug Compliance | By drug accountability | 80.118 percent of doses taken |
| Placebo/Ataluren | Rate of Study Drug Compliance | By participant-reported data | 78.59 percent of doses taken |
Secondary
Total Lung Computed Tomography (CT) Score at Weeks 48 and 96
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.
Time frame: 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.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Total Lung Computed Tomography (CT) Score at Weeks 48 and 96 | Week 48 | — |
| Unknown | Total Lung Computed Tomography (CT) Score at Weeks 48 and 96 | Week 96 | — |
Post Hoc
Percentage Change From Baseline in Percent-Predicted of FEV1 in the 144-Week Completer Population Over a Total of 144 Weeks of Treatment
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.
Time frame: EOT (Week 96 [Total Study Week 144])
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ataluren/Ataluren | 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 |
| Placebo/Ataluren | Percentage Change From Baseline in Percent-Predicted of FEV1 in the 144-Week Completer Population Over a Total of 144 Weeks of Treatment | -5.89 percent change | Standard Deviation 14.854 |
Post Hoc
Percentage Change From Baseline in Percent-Predicted of FEV1 in the 96-Week Completer Population Over a Total of 96 Weeks of Treatment
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.
Time frame: Week 48 (Total Study Week 96)
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ataluren/Ataluren | 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 |
| Placebo/Ataluren | Percentage Change From Baseline in Percent-Predicted of FEV1 in the 96-Week Completer Population Over a Total of 96 Weeks of Treatment | -5.13 percent change | Standard Deviation 12.061 |
Post Hoc
Percent-Predicted of FEV1 in the 144-Week Completer Population at Baseline
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ataluren/Ataluren | Percent-Predicted of FEV1 in the 144-Week Completer Population at Baseline | 61.68 percentage of predicted FEV1 | Standard Deviation 13.79 |
| Placebo/Ataluren | Percent-Predicted of FEV1 in the 144-Week Completer Population at Baseline | 60.28 percentage of predicted FEV1 | Standard Deviation 16.202 |
Post Hoc
Percent-Predicted of FEV1 in the 96-Week Completer Population at Baseline
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ataluren/Ataluren | Percent-Predicted of FEV1 in the 96-Week Completer Population at Baseline | 60.89 percentage of predicted FEV1 | Standard Deviation 13.32 |
| Placebo/Ataluren | Percent-Predicted of FEV1 in the 96-Week Completer Population at Baseline | 59.50 percentage of predicted FEV1 | Standard Deviation 15.622 |