Extension Study of Ataluren in Participants With Nonsense Mutation Cystic Fibrosis

• Sponsor: PTC Therapeutics (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02456103
• Collaborator: (none)
• Enrollment: 246
• Locations: 70
• Arm: 1
• Actual Duration (Months): 21.1
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is an open-label extension study for participants who completed a Phase 3, placebo-controlled study of ataluren in participants with nonsense mutation cystic fibrosis (nmCF) not receiving chronic inhaled aminoglycosides.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: Ataluren	Phase 3

Detailed Description

The primary objective of this Phase 3 extension study will be to obtain long-term safety data to augment the overall safety database. The secondary objectives will be to augment the efficacy data collected in the double-blind study (PTC124-GD-021-CF; NCT02139306).

Study Design

• Study Type: Interventional
• Actual Enrollment: 246 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 3 Extension Study of Ataluren (PTC124) in Patients With Nonsense Mutation Cystic Fibrosis
• Actual Study Start Date: Aug 31, 2015
• Actual Primary Completion Date: Jun 2, 2017
• Actual Study Completion Date: Jun 2, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ataluren Participants will be administered ataluren orally at a dose of 10 milligrams/grams (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.	Drug: Ataluren; Ataluren will be provided as a vanilla-flavored powder to be mixed with water or milk.; Other Names: PTC124 Translarna

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment Emergent Adverse Events (TEAEs) [Baseline up to Week 100]

   TEAE: any untoward medical occurrence or undesirable event that begins or worsens following administration of study drug, whether or not considered related to study drug by Investigator. Serious adverse event (SAE): an adverse event (AE) resulting in any of following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying) or persistent or significant disability/incapacity. Except for cystic fibrosis (CF) pulmonary exacerbations, an event wasn't reported as an SAE, if event was exclusively a relapse or an expected change or progression of baseline CF. AEs included both SAEs and nonserious AEs. AEs classified according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 and coded using Medical Dictionary for Regulatory Activities. A summary of SAEs and all nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.

2. Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Serum Biochemistry, Hematology, and Urinalysis) Parameter [Baseline up to Week 100]

   Clinical laboratory results considered clinically meaningful were determined by Investigator. Serum biochemistry parameters: sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, magnesium, calcium, phosphorus, uric acid, glucose, total protein, albumin, globulin, bilirubin, creatine kinase, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, and cystatin C. Hematology parameters: white blood cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, red cell count with morphology, and platelet count. Urinalysis parameters: pH, specific gravity, glucose, ketones, blood, protein, creatinine, urobilinogen, bilirubin, nitrite, and leukocyte esterase. A summary of all SAEs/nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.

Secondary Outcome Measures

1. Change From Baseline in Percent-Predicted Forced Expiratory Volume in 1 Second (FEV1) as Measured by Spirometry at Week 24 [Baseline, Week 24]

   Pulmonary function of percent-predicted FEV1 was measured using a spirometer. FEV1 is the volume of air that can forcibly be blown out in 1 second. Each percent-predicted FEV1 was based gender, age, and the height value obtained at the same study visit. 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.

2. Change From Baseline in Percent-Predicted of Forced Vital Capacity (FVC) as Measured by Spirometry at Week 24 [Baseline, Week 24]

   Pulmonary function of FVC was measured using a spirometer. FVC is the volume of air that can forcibly be blown out. Each percent-predicted FVC was based gender, age, and the height value obtained at the same study visit. 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.

3. Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Expiration (FEF25-75) as Measured by Spirometry at Week 24 [Baseline, Week 24]

   Pulmonary function of FEF25-75 was measured using a spirometer. FEF25-75 is the forced expiratory flow between 25% and 75% of vital capacity. Each percent-predicted FEF25-75 was based gender, age, and the height value obtained at the same study visit. 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.

4. Rate of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Over 48 Weeks [Baseline up to Week 48]

   A modified Fuchs' exacerbation was defined as an event requiring treatment with or without intravenous antibiotics for any 4 of the following 12 symptoms: 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 percent or more from a previously recorded value; or radiographic changes indicative of pulmonary function. The 48-week rate = (the total number of events/ treatment duration by week)*48.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Completion of study treatment (placebo or active) in the previous Phase 3, double-blind study protocol (Protocol PTC124-GD-021-CF)

• Evidence of signed and dated informed consent/assent document(s) indicating that the participant (and/or the participant's parent/legal guardian) has been informed of all pertinent aspects of the trial.

Exclusion Criteria:

• Known hypersensitivity to any of the ingredients or excipients of the study drug.

• Ongoing participation in any other therapeutic clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Miller Children's Hospital Long Beach	Long Beach	California	United States	90806
3	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
4	Children's Hospital and Research Center at Oakland	Oakland	California	United States	94609
5	Stanford University-Children's Hospital	Palo Alto	California	United States	94304
6	Children's Hospital Colorado	Aurora	Colorado	United States	80045
7	Nemours Children's Clinic	Jacksonville	Florida	United States	32207
8	University of Miami	Miami	Florida	United States	33136
9	Miami Children's Hospital	Miami	Florida	United States	33155
10	All Children's Hospital	Saint Petersburg	Florida	United States	33701
11	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
12	Indiana University	Indianapolis	Indiana	United States	46202
13	Children's Hospital Boston	Boston	Massachusetts	United States	02115
14	Washington University	Saint Louis	Missouri	United States	63110
15	Morristown Medical Center	Morristown	New Jersey	United States	07960
16	Beth Israel Medical Center	New York	New York	United States	10011
17	New York University Langone Medical Center	New York	New York	United States	10016
18	Columbia University Medical Center	New York	New York	United States	10032
19	University of Cincinnati	Cincinnati	Ohio	United States	45221
20	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
21	Drexel University College of Medicine	Philadelphia	Pennsylvania	United States	19129
22	Texas Children's Hospital	Houston	Texas	United States	77094
23	University of Texas Health Science Center	Tyler	Texas	United States	75708
24	Childrens Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226
25	Hospital de Ninos Ricardo Gutierrez	Buenos Aires		Argentina	1330
26	Hospital Universitario Austral	Buenos Aires		Argentina
27	Royal Adelaide Hospital	Adelaide		Australia	5000
28	Prince Charles Hospital	Chermside		Australia	4032
29	Princess Margaret Hospital	Perth		Australia	6840
30	University Hospital Brussels	Brussels		Belgium	1090
31	Hopital Universitaire des Enfants Reine Fabiola	Brussels		Belgium	15
32	University Hospital Leuven	Leuven		Belgium	3000
33	Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul	Porto Alegre		Brazil
34	University Mulitiprofile Hospital for Active Treatment Sveti Georgi EAD	Plovdiv		Bulgaria
35	University Multiprofile Hospital for Active Treatment Aleksandrovska EAD	Sofia		Bulgaria
36	Clinical Research Institute of Montreal	Montreal		Canada	H2W 1R7
37	University of Toronto Hospital for Sick Children	Toronto		Canada	M5G 1X8
38	British Columbia Children's Hospital	Vancouver		Canada	V6H 3V4
39	Hoptial Arnaud de Villeneuve	Montpellier		France	34295
40	Hopital Necker - Enfants Malades	Paris		France	75015
41	Centre de Perharidy	Roscoff		France	29684
42	Centre Hospitalier Regional Sud Reunion	Saint-Pierre		France	97448
43	Charite-Universitatsmedizin Berlin	Berlin		Germany	10117
44	St. Josef Hospital GmbH	Bochum		Germany	44791
45	University of Cologne Children's Hospital	Cologne		Germany	50937
46	Christiane Herzog CF-Zentrum	Frankfurt am Main		Germany	60590
47	Universitatsklinikum Jena	Jena		Germany	1
48	Dr. Von Haunersches Kinderspital	Munchen		Germany	80337
49	LMU Klinikum der Universitat Muchen	Munich		Germany	80539
50	Ippokratio General Hospital Of Thessaloniki	Thessaloniki		Greece	541
51	Meyer Children's Hospital	Haifa		Israel	31096
52	Hadassah University Hospital	Jerusalem		Israel	91240
53	Azienda Ospedaliero Universitaria Ospedall Riuniti di Acona-Umberto I G.M. Lancisi G. Salesi	Ancona		Italy	71
54	Azienda Ospedaliera A Meyer	Firenze		Italy	50139
55	Lombardia Cystic Fibrosis Center	Milan		Italy	20122
56	Azienda Policlinico Umberto I	Rome		Italy	00161
57	Ospedale Pediatrico Bambino Gesu	Rome		Italy	4
58	Azienda Ospedaliera di Verona	Verona		Italy
59	Hagaziekenhuis	s-Gravenweg	Zuid-Holland	Netherlands	2545 CH
60	Radboud University	Nijmegen		Netherlands	6525 GA
61	Szpital Dzieciecy Polanki im Macieja Plazynskiego w Gdansku	Gdansk		Poland
62	Institute of Mother and Child	Warsaw		Poland	01-211
63	Hospital Universitario Vall d'Hebron	Barcelona		Spain	08035
64	Hospital University	Barcelona		Spain	08035
65	Hospital San Juan	Esplugues De Llobregat		Spain	08950
66	Hospital Regional Universitario de Malaga	Malaga		Spain	29001
67	Hospital de Sabadell, Consorci Sanitari Parc Tauli	Sabadell		Spain	08208
68	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
69	St James University Hospital	Leeds		United Kingdom	LS9 7TF
70	Royal Brompton Hospital	London		United Kingdom	SW3 6NP

Sponsors and Collaborators

• PTC Therapeutics

Investigators

• Study Director: Joseph McIntosh, MD, PTC Therapeutics

Study Documents (Full-Text)

• Study Protocol - Mar 27, 2015
• Statistical Analysis Plan - Jul 14, 2017

More Information

Publications

None provided.

• Responsible Party: PTC Therapeutics
• ClinicalTrials.gov Identifier: NCT02456103
• Other Study ID Numbers: PTC124-GD-021e-CF
• First Posted: May 28, 2015
• Last Update Posted: Apr 27, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis

Study Results

Participant Flow

Pre-assignment Detail	All eligible participants, including those who received placebo in the double-blind study (PTC124-GD-021-CF; NCT02139306), were enrolled to this open-label extension study. To avoid interruption in treatment, when possible, Screening/Baseline for this extension study was to occur on the same day as the End-of-Study visit for the double-blind study.

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 milligrams/grams (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.
Period Title: Overall Study
STARTED	246
As-Treated Population	245
Intent-to-treat (ITT) Population	244
COMPLETED	0
NOT COMPLETED	246

Baseline Characteristics

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.
Overall Participants	245
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	23.1 (10.88)
Sex: Female, Male (Count of Participants)
Female	113 46.1%
Male	132 53.9%
Race/Ethnicity, Customized (participants) [Number]
Asian	4 1.6%
White	235 95.9%
White-Arabic/North African Heritage	1 0.4%
Non-White	5 2%
Hispanic or Latino	16 6.5%
Not Hispanic or Latino	229 93.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Description	TEAE: any untoward medical occurrence or undesirable event that begins or worsens following administration of study drug, whether or not considered related to study drug by Investigator. Serious adverse event (SAE): an adverse event (AE) resulting in any of following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying) or persistent or significant disability/incapacity. Except for cystic fibrosis (CF) pulmonary exacerbations, an event wasn't reported as an SAE, if event was exclusively a relapse or an expected change or progression of baseline CF. AEs included both SAEs and nonserious AEs. AEs classified according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 and coded using Medical Dictionary for Regulatory Activities. A summary of SAEs and all nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.
Time Frame	Baseline up to Week 100

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of ataluren (As-Treated Population).

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.
Measure Participants	245
At least 1 TEAE	222 90.6%
Mild TEAE	28 11.4%
Moderate TEAE	147 60%
Severe TEAE	46 18.8%
Life-Threatening TEAE	1 0.4%
Fatal TEAE	0 0%
Serious TEAE	89 36.3%
TEAE Unrelated to Study Drug	140 57.1%
TEAE Unlikely Related to Study Drug	55 22.4%
TEAE Possibly Related to Study Drug	23 9.4%
TEAE Probably Related to Study Drug	4 1.6%

2. Primary Outcome

Title	Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Serum Biochemistry, Hematology, and Urinalysis) Parameter
Description	Clinical laboratory results considered clinically meaningful were determined by Investigator. Serum biochemistry parameters: sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, magnesium, calcium, phosphorus, uric acid, glucose, total protein, albumin, globulin, bilirubin, creatine kinase, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, and cystatin C. Hematology parameters: white blood cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, red cell count with morphology, and platelet count. Urinalysis parameters: pH, specific gravity, glucose, ketones, blood, protein, creatinine, urobilinogen, bilirubin, nitrite, and leukocyte esterase. A summary of all SAEs/nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.
Time Frame	Baseline up to Week 100

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of ataluren (As-Treated Population).

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.
Measure Participants	245
Count of Participants [Participants]	0 0%

3. Secondary Outcome

Title	Change From Baseline in Percent-Predicted Forced Expiratory Volume in 1 Second (FEV1) as Measured by Spirometry at Week 24
Description	Pulmonary function of percent-predicted FEV1 was measured using a spirometer. FEV1 is the volume of air that can forcibly be blown out in 1 second. Each percent-predicted FEV1 was based gender, age, and the height value obtained at the same study visit. 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.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of ataluren and have at least 1 postbaseline efficacy assessment (ITT Population) and had evaluable FEV1 data.

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.
Measure Participants	233
Baseline	60.219 (17.6163)
Change from Baseline at Week 24	0.015 (6.7180)

4. Secondary Outcome

Title	Change From Baseline in Percent-Predicted of Forced Vital Capacity (FVC) as Measured by Spirometry at Week 24
Description	Pulmonary function of FVC was measured using a spirometer. FVC is the volume of air that can forcibly be blown out. Each percent-predicted FVC was based gender, age, and the height value obtained at the same study visit. 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.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of ataluren and have at least 1 postbaseline efficacy assessment (ITT Population) and had evaluable FVC data.

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.
Measure Participants	233
Baseline	75.249 (15.8508)
Change from Baseline at Week 24	0.166 (6.5276)

5. Secondary Outcome

Title	Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Expiration (FEF25-75) as Measured by Spirometry at Week 24
Description	Pulmonary function of FEF25-75 was measured using a spirometer. FEF25-75 is the forced expiratory flow between 25% and 75% of vital capacity. Each percent-predicted FEF25-75 was based gender, age, and the height value obtained at the same study visit. 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.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of ataluren and have at least 1 postbaseline efficacy assessment (ITT Population) and had evaluable FEF25-75 data.

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.
Measure Participants	233
Baseline	38.099 (22.0980)
Change from Baseline at Week 24	0.698 (13.1241)

6. Secondary Outcome

Title	Rate of Pulmonary Exacerbations as Defined by Modified Fuch's Criteria Over 48 Weeks
Description	A modified Fuchs' exacerbation was defined as an event requiring treatment with or without intravenous antibiotics for any 4 of the following 12 symptoms: 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 percent or more from a previously recorded value; or radiographic changes indicative of pulmonary function. The 48-week rate = (the total number of events/ treatment duration by week)*48.
Time Frame	Baseline up to Week 48

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of ataluren and have at least 1 postbaseline efficacy assessment (ITT Population).

Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.
Measure Participants	244
Mean (Standard Deviation) [exacerbations]	1.051 (2.1654)

Adverse Events

Time Frame	Baseline up to Week 100
Adverse Event Reporting Description	Adverse events collected from participants who received at least 1 dose of ataluren (As-Treated Population).
Arm/Group Title	Ataluren
Arm/Group Description	Participants were administered ataluren orally at a dose of 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for up to 96 weeks.
All Cause Mortality
	Ataluren
	Affected / at Risk (%)	# Events
Total	1/245 (0.4%)
Serious Adverse Events
	Ataluren
	Affected / at Risk (%)	# Events
Total	89/245 (36.3%)
Congenital, familial and genetic disorders
Cystic fibrosis lung	1/245 (0.4%)
Gastrointestinal disorders
Abdominal pain lower	1/245 (0.4%)
Distal intestinal obstruction syndrome	1/245 (0.4%)
Duodenal ulcer	1/245 (0.4%)
Enteritis	1/245 (0.4%)
Intestinal obstruction	3/245 (1.2%)
Pancreatitis	1/245 (0.4%)
Infections and infestations
Bronchopulmonary aspergillosis allergic	1/245 (0.4%)
Device related infection	1/245 (0.4%)
Gastroenteritis viral	1/245 (0.4%)
Infective pulmonary exacerbation of cystic fibrosis	63/245 (25.7%)
Mycobacterium abscessus infection	1/245 (0.4%)
Peritonitis	1/245 (0.4%)
Pneumonia	1/245 (0.4%)
Pseudomonas infection	1/245 (0.4%)
Respiratory syncytial virus infection	1/245 (0.4%)
Sinusitis	1/245 (0.4%)
Viral pericarditis	1/245 (0.4%)
Appendicitis	1/245 (0.4%)
Investigations
Forced expiratory volume decreased	2/245 (0.8%)
Protein urine present	1/245 (0.4%)
Pseudomonas test positive	1/245 (0.4%)
Pulmonary function test decreased	1/245 (0.4%)
Metabolism and nutrition disorders
Dehydration	1/245 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of the cervix	1/113 (0.9%)
Nervous system disorders
Depressed level of consciousness	1/245 (0.4%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	1/113 (0.9%)
Renal and urinary disorders
Nephrolithiasis	2/245 (0.8%)
Renal colic	2/245 (0.8%)
Renal failure acute	1/245 (0.4%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/245 (0.4%)
Aspiration	1/245 (0.4%)
Asthma	1/245 (0.4%)
Dyspnoea exertional	1/245 (0.4%)
Haemoptysis	4/245 (1.6%)
Other (Not Including Serious) Adverse Events
	Ataluren
	Affected / at Risk (%)	# Events
Total	191/245 (78%)
Gastrointestinal disorders
Nausea	14/245 (5.7%)
General disorders
Pyrexia	13/245 (5.3%)
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis	136/245 (55.5%)
Influenza	13/245 (5.3%)
Sinusitis	25/245 (10.2%)
Upper respiratory tract infection	21/245 (8.6%)
Viral upper respiratory tract infection	30/245 (12.2%)
Investigations
Forced expiratory volume decreased	16/245 (6.5%)
Nervous system disorders
Headache	16/245 (6.5%)
Respiratory, thoracic and mediastinal disorders
Cough	32/245 (13.1%)
Haemoptysis	14/245 (5.7%)

Limitations/Caveats

This study was terminated early because the CF data from the double-blind CF Study PTC124-GD-021-CF (NCT02139306) did not meet endpoints.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.