Study of Ataluren (PTC124) in Cystic Fibrosis

• Sponsor: PTC Therapeutics (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02107859
• Collaborator: (none)
• Enrollment: 61
• Locations: 17
• Arm: 1
• Actual Duration (Months): 36.4
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of this study is to determine the long-term safety and tolerability of ataluren in participants with nonsense mutation cystic fibrosis (nmCF) who completed participation in the double-blind study PTC124-GD-009-CF (NCT00803205), as assessed by adverse events and laboratory abnormalities. The secondary objective of this study includes the assessment of the efficacy of ataluren, as measured by forced expiratory volume in 1 second (FEV1) and pulmonary exacerbation rate, and other safety parameters (for example, 12-lead electrocardiogram [ECG] measurements, vital signs).

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Safety and Efficacy Study for Patients With Nonsense Mutation Cystic Fibrosis Previously Treated With Ataluren (PTC124)
• Actual Study Start Date: May 23, 2014
• Actual Primary Completion Date: Jun 5, 2017
• Actual Study Completion Date: Jun 5, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ataluren Participants will receive ataluren suspension orally 3 times a day (TID), 10 milligrams/kilogram (mg/kg) at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.	Drug: Ataluren; Ataluren will be administered per dose and schedule specified in the arm.; Other Names: PTC124

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Baseline (Day 1) up to end of study (Week 196)]

   AE: any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of an AE was classified as: mild (does not interfere with usual function), moderate (interferes to some extent with usual function), severe (interferes significantly with usual function), life threatening (results in potential threat to life), and fatal AEs. Drug-related AEs: AEs with a possible or probable relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention. TEAE: AE that occurred or worsened from first dose of study drug to 4 weeks after last dose of study drug. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

2. Number of Participants With Clinically Significant Laboratory Abnormalities [Baseline (Day 1) up to end of study (Week 196)]

   Laboratory parameters tests included hematology, biochemistry assay (hepatic, renal, and serum electrolyte values), adrenal assays, and urinalysis. Clinical significance was defined as per investigator's judgement.

Secondary Outcome Measures

1. Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at the End of Treatment (Week 192), as Assessed by Spirometry [Baseline, Week 192]

   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Percent of predicted FEV1 = (observed value)/(predicted value) * 100%. Change from baseline in percent predicted FEV1 at the end of treatment was reported.

2. Percentage of Participants With Pulmonary Exacerbation, As Assessed by Modified Fuchs Criteria [Baseline up to Week 192]

   The modified Fuchs' criteria defined exacerbation as the presence of at least 4 of the following 12 Fuchs' signs and symptoms without the requirement for treatment with antibiotics: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; fatigue; temperature greater than (>) 38 degrees celsius (°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.

3. Percentage of Participants With Pulmonary Exacerbation, As Assessed by Expanded Fuchs' Criteria [Baseline up to Week 192]

   The expanded Fuchs' criteria defined exacerbation as the presence of at least 4 of the following 12 Fuchs' signs and symptoms requiring any form of antibiotic treatment (inhaled, oral, or intravenous): 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.

4. Percentage of Participants With Pulmonary Exacerbation, As Assessed by Classic Fuchs' Criteria [Baseline up to Week 192]

   The Classic Fuchs' criteria defined exacerbation as the presence of at least 4 of the following 12 Fuchs' signs and symptoms requiring treatment with parenteral 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 percent or more from a previously recorded value; or radiographic changes indicative of pulmonary function.

5. Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters at Final Visit (Week 196) [Baseline, Week 196]

   ECG parameters included RR duration, PR duration, QRS duration, QT duration, QTCB (Bazett's correction formula) duration, QTCF (Fridericia's correction formula) duration.

6. Change From Baseline in Heart Rate at Final Visit (Week 196), as Assessed by 12-Lead ECG [Baseline, Week 196]

   Heart rate was measured using 12-lead ECG.

7. Change From Baseline in Vital Signs at Final Visit (Week 196) [Baseline, Week 196]

   Vital Signs included systolic blood pressure (SBP) and diastolic blood pressure (DBP).

Other Outcome Measures

1. Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at the End of Treatment (Week 192), as Assessed by Spirometry [Baseline, Week 192]

   FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position. Percent of predicted FVC = (observed value)/(predicted value) * 100%. Change from baseline in percent predicted FVC at the end of treatment was reported.

2. Change From Baseline in Percent Predicted Forced Expiratory Flow Between 25% and 75% of Expiration (FEF25-75) at the End of Treatment (Week 192), as Assessed by Spirometry [Baseline, Week 192]

   FEF25-75 is the forced expiratory flow between 25 and 75% of vital capacity.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Ability to provide written informed consent (parental/guardian consent and participant assent if less than [<] 18 years of age).

• Evidence of completed participation in the double-blind study, PTC124-GD-009-CF (Study 009).

• Body weight greater than or equal to (≥) 16 kilograms (kg).

• Performance of a valid, reproducible spirometry test using the study-specific spirometer during the screening period.

• Confirmed laboratory values within the central laboratory ranges at screening.

• In male and female participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and 60-day follow-up period.

• Willingness and ability to comply with all study procedures and assessments, including scheduled visits, drug administration plan, laboratory tests, and study restrictions.

Key Exclusion Criteria:

• Chronic use of systemic tobramycin within 4 weeks prior to screening.

• Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection (including viral illnesses) within 3 weeks prior to screening or between screening and randomization.

• Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or re-initiation) in a chronic treatment/prophylaxis regimen for CF or for CF-related conditions within 4 weeks prior to screening and randomization.

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

• Exposure to another investigational drug within 4 weeks prior to screening.

• Treatment with intravenous antibiotics within 3 weeks prior to screening.

• History of solid organ or hematological transplantation.

• Ongoing immunosuppressive therapy (other than corticosteroids).

• Positive hepatitis B surface antigen, hepatitis C antibody test or human immunodeficiency virus (HIV) test.

• Known portal hypertension.

• Pregnancy or breast-feeding.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama-Birmingham	Birmingham	Alabama	United States	35233
2	Miller Children's Hospital Long Beach	Long Beach	California	United States	90806
3	Denver Children's Hospital	Aurora	Colorado	United States	80045
4	Children's Hospital Chicago	Chicago	Illinois	United States	60614
5	Children's Hospital Boston	Boston	Massachusetts	United States	02115
6	Beth Israel Medical Center	New York	New York	United States	10003
7	Rainbow Babies & Children's Hospital	Cleveland	Ohio	United States	44106
8	Hôpital Universitaire des Enfants Reine Fabiola	Brussels		Belgium
9	University Hospital Brussels	Brussels		Belgium
10	University Hospital Leuven	Leuven		Belgium
11	Hôpital Necker - Enfants Malades	Paris		France
12	Hôpital des Enfants	Toulouse		France	31059
13	Hadassah University Hospital - Mount Scopus	Jerusalem		Israel	91240
14	Università La Sapienza	Roma		Italy
15	Azienda Ospedaliera di Verona	Verona		Italy
16	Hospital Universitario La Paz	Madrid		Spain
17	Karolinska University Hospital, Huddinge	Stockholm		Sweden

Sponsors and Collaborators

• PTC Therapeutics

Investigators

• Study Director: Joseph McIntosh, MD, PTC Therapeutics, Inc.

Study Documents (Full-Text)

• Statistical Analysis Plan - Jul 14, 2017
• Study Protocol - Feb 8, 2016

More Information

Additional Information:

• PTC Therapeutics, Inc. website

Publications

None provided.

• Responsible Party: PTC Therapeutics
• ClinicalTrials.gov Identifier: NCT02107859
• Other Study ID Numbers: PTC124-GD-023-CF; 2013-005449-35
• First Posted: Apr 8, 2014
• Last Update Posted: Mar 25, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by PTC Therapeutics: Cystic fibrosis; Nonsense mutation; Premature stop codon; PTC124; Ataluren
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis

Study Results

Participant Flow

Recruitment Details	Participants with nonsense mutation cystic fibrosis (nmCF) who had completed the double-blind study PTC124-GD-009-CF (NCT00803205) were enrolled and treated in this open-label extension study.
Pre-assignment Detail	On 2 March 2017, it was announced that the Phase 3 double-blind study PTC124-GD-021-CF (NCT02139306) did not achieve its primary or secondary endpoints. Based on these results, clinical development of ataluren in cystic fibrosis was discontinued and this ongoing open-label extension study was closed.

Arm/Group Title	Ataluren
Arm/Group Description	Participants received ataluren suspension orally 3 times a day (TID), 10 milligrams/kilogram (mg/kg) at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Period Title: Overall Study
STARTED	61
As-treated Population	61
Intent-to-treat (ITT) Population	60
COMPLETED	0
NOT COMPLETED	61

Baseline Characteristics

Arm/Group Title	Ataluren
Arm/Group Description	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Overall Participants	61
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	27.5 (10.73)
Sex: Female, Male (Count of Participants)
Female	34 55.7%
Male	27 44.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1.6%
Not Hispanic or Latino	60 98.4%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Count of Participants)
White-White/Caucasian	61 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	AE: any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of an AE was classified as: mild (does not interfere with usual function), moderate (interferes to some extent with usual function), severe (interferes significantly with usual function), life threatening (results in potential threat to life), and fatal AEs. Drug-related AEs: AEs with a possible or probable relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention. TEAE: AE that occurred or worsened from first dose of study drug to 4 weeks after last dose of study drug. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time Frame	Baseline (Day 1) up to end of study (Week 196)

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who received at least 1 dose of ataluren.

Arm/Group Title	Ataluren
Arm/Group Description	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Measure Participants	61
Any TEAEs	61 100%
Mild AEs	4 6.6%
Moderate AEs	26 42.6%
Severe AEs	30 49.2%
Life-threatening AEs	0 0%
Fatal AEs	1 1.6%
AEs unrelated to ataluren	35 57.4%
AEs unlikely related to ataluren	12 19.7%
AEs possible related to ataluren	13 21.3%
AEs probable related to ataluren	1 1.6%
Serious TEAEs	36 59%

2. Primary Outcome

Title	Number of Participants With Clinically Significant Laboratory Abnormalities
Description	Laboratory parameters tests included hematology, biochemistry assay (hepatic, renal, and serum electrolyte values), adrenal assays, and urinalysis. Clinical significance was defined as per investigator's judgement.
Time Frame	Baseline (Day 1) up to end of study (Week 196)

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who received at least 1 dose of ataluren.

Arm/Group Title	Ataluren
Arm/Group Description	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Measure Participants	61
Count of Participants [Participants]	0 0%

3. Secondary Outcome

Title	Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at the End of Treatment (Week 192), as Assessed by Spirometry
Description	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Percent of predicted FEV1 = (observed value)/(predicted value) * 100%. Change from baseline in percent predicted FEV1 at the end of treatment was reported.
Time Frame	Baseline, Week 192

Outcome Measure Data

Analysis Population Description

ITT population included all participants who had at least 1 post-baseline efficacy assessment. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint.

Arm/Group Title	Ataluren
Arm/Group Description	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Measure Participants	59
Baseline	56.203 (17.2964)
Change at Week 192	-1.214 (3.6384)

4. Secondary Outcome

Title	Percentage of Participants With Pulmonary Exacerbation, As Assessed by Modified Fuchs Criteria
Description	The modified Fuchs' criteria defined exacerbation as the presence of at least 4 of the following 12 Fuchs' signs and symptoms without the requirement for treatment with antibiotics: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; fatigue; temperature greater than (>) 38 degrees celsius (°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.
Time Frame	Baseline up to Week 192

Outcome Measure Data

Analysis Population Description

ITT population included all participants who had at least 1 post-baseline efficacy assessment.

Arm/Group Title	Ataluren
Arm/Group Description	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Measure Participants	60
Number [percentage of participants]	68.3 112%

5. Secondary Outcome

Title	Percentage of Participants With Pulmonary Exacerbation, As Assessed by Expanded Fuchs' Criteria
Description	The expanded Fuchs' criteria defined exacerbation as the presence of at least 4 of the following 12 Fuchs' signs and symptoms requiring any form of antibiotic treatment (inhaled, oral, or intravenous): 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.
Time Frame	Baseline up to Week 192

Outcome Measure Data

Analysis Population Description

ITT population included all participants who had at least 1 post-baseline efficacy assessment.

Arm/Group Title	Ataluren
Arm/Group Description	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Measure Participants	60
Number [percentage of participants]	68.3 112%

6. Secondary Outcome

Title	Percentage of Participants With Pulmonary Exacerbation, As Assessed by Classic Fuchs' Criteria
Description	The Classic Fuchs' criteria defined exacerbation as the presence of at least 4 of the following 12 Fuchs' signs and symptoms requiring treatment with parenteral 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 percent or more from a previously recorded value; or radiographic changes indicative of pulmonary function.
Time Frame	Baseline up to Week 192

Outcome Measure Data

Analysis Population Description

ITT population included all participants who had at least 1 post-baseline efficacy assessment.

Arm/Group Title	Ataluren
Arm/Group Description	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Measure Participants	60
Number [percentage of participants]	58.3 95.6%

7. Secondary Outcome

Title	Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters at Final Visit (Week 196)
Description	ECG parameters included RR duration, PR duration, QRS duration, QT duration, QTCB (Bazett's correction formula) duration, QTCF (Fridericia's correction formula) duration.
Time Frame	Baseline, Week 196

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who received at least 1 dose of ataluren. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable for specified categories.

Arm/Group Title	Ataluren
Arm/Group Description	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Measure Participants	59
Baseline: RR duration	828.17 (132.15)
Change at Week 196: RR duration	-14.27 (115.62)
Baseline: PR duration	145.02 (19.29)
Change at Week 196: PR duration	-2.69 (12.25)
Baseline: QRS duration	83.90 (8.00)
Change at Week 196: QRS duration	0.33 (6.12)
Baseline: QT duration	370.71 (28.11)
Change at Week 196: QT duration	-4.38 (25.63)
Baseline: QTCB duration	408.92 (22.05)
Change at Week 196: QTCB duration	-0.71 (17.96)
Baseline: QTCF duration	395.47 (19.23)
Change at Week 196: QTCF duration	-2.27 (17.13)

8. Secondary Outcome

Title	Change From Baseline in Heart Rate at Final Visit (Week 196), as Assessed by 12-Lead ECG
Description	Heart rate was measured using 12-lead ECG.
Time Frame	Baseline, Week 196

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who received at least 1 dose of ataluren. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable for specified categories.

Arm/Group Title	Ataluren
Arm/Group Description	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Measure Participants	59
Baseline	74.31 (12.06)
Change at Week 196	2.04 (10.11)

9. Secondary Outcome

Title	Change From Baseline in Vital Signs at Final Visit (Week 196)
Description	Vital Signs included systolic blood pressure (SBP) and diastolic blood pressure (DBP).
Time Frame	Baseline, Week 196

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who received at least 1 dose of ataluren. Here, 'Number analyzed' signifies participants evaluable for specified categories.

Arm/Group Title	Ataluren
Arm/Group Description	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Measure Participants	61
Baseline: SBP	114.8 (9.10)
Change at Week 196: SBP	0.6 (12.62)
Baseline: DBP	71.2 (8.93)
Change at Week 196: DBP	-0.3 (9.93)

10. Other Pre-specified Outcome

Title	Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at the End of Treatment (Week 192), as Assessed by Spirometry
Description	FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position. Percent of predicted FVC = (observed value)/(predicted value) * 100%. Change from baseline in percent predicted FVC at the end of treatment was reported.
Time Frame	Baseline, Week 192

Outcome Measure Data

Analysis Population Description

ITT population included all participants who had at least 1 post-baseline efficacy assessment. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint.

Arm/Group Title	Ataluren
Arm/Group Description	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Measure Participants	59
Baseline	73.576 (14.6552)
Change at Week 192	-2.286 (4.5722)

11. Other Pre-specified Outcome

Title	Change From Baseline in Percent Predicted Forced Expiratory Flow Between 25% and 75% of Expiration (FEF25-75) at the End of Treatment (Week 192), as Assessed by Spirometry
Description	FEF25-75 is the forced expiratory flow between 25 and 75% of vital capacity.
Time Frame	Baseline, Week 192

Outcome Measure Data

Analysis Population Description

Due to change in planned analysis FEV25-75 was not calculated and summarized.

Arm/Group Title	Ataluren
Arm/Group Description	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
Measure Participants	0

Adverse Events

Time Frame	Baseline up to end of study (Week 196)
Adverse Event Reporting Description	As-treated population included all participants who received at least 1 dose of ataluren.
Arm/Group Title	Ataluren
Arm/Group Description	Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
All Cause Mortality
	Ataluren
	Affected / at Risk (%)	# Events
Total	1/61 (1.6%)
Serious Adverse Events
	Ataluren
	Affected / at Risk (%)	# Events
Total	36/61 (59%)
Congenital, familial and genetic disorders
Cystic fibrosis	1/61 (1.6%)
Gastrointestinal disorders
Constipation	1/61 (1.6%)
Distal ileal obstruction syndrome	1/61 (1.6%)
Distal intestinal obstruction syndrome	3/61 (4.9%)
Intestinal obstruction	1/61 (1.6%)
Hepatobiliary disorders
Gallbladder pain	1/61 (1.6%)
Infections and infestations
Appendicitis	1/61 (1.6%)
Cellulitis	1/61 (1.6%)
Clostridium difficile infection	1/61 (1.6%)
Device related infection	1/61 (1.6%)
Infective pulmonary exacerbation of cystic fibrosis	27/61 (44.3%)
Viral upper respiratory tract infection	1/61 (1.6%)
Injury, poisoning and procedural complications
Femur fracture	1/61 (1.6%)
Investigations
Blood creatine increased	1/61 (1.6%)
Forced expiratory volume decreased	2/61 (3.3%)
Pulmonary function test decreased	1/61 (1.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	1/61 (1.6%)
Renal and urinary disorders
Renal failure	1/61 (1.6%)
Renal failure acute	1/61 (1.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/61 (1.6%)
Haemoptysis	7/61 (11.5%)
Pneumothorax	1/61 (1.6%)
Respiratory failure	1/61 (1.6%)
Vascular disorders
Deep vein thrombosis	1/61 (1.6%)
Other (Not Including Serious) Adverse Events
	Ataluren
	Affected / at Risk (%)	# Events
Total	61/61 (100%)
Gastrointestinal disorders
Abdominal pain	6/61 (9.8%)
Abdominal pain upper	5/61 (8.2%)
Constipation	7/61 (11.5%)
Diarrhoea	8/61 (13.1%)
Haemorrhoids	4/61 (6.6%)
Nausea	6/61 (9.8%)
Vomiting	4/61 (6.6%)
Immune system disorders
Drug hypersensitivity	5/61 (8.2%)
Infections and infestations
Gastroenteritis	5/61 (8.2%)
Infective pulmonary exacerbation of cystic fibrosis	50/61 (82%)
Influenza	4/61 (6.6%)
Nasopharyngitis	5/61 (8.2%)
Oral candidiasis	4/61 (6.6%)
Sinusitis	6/61 (9.8%)
Upper respiratory tract infection	9/61 (14.8%)
Viral upper respiratory tract infection	22/61 (36.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/61 (8.2%)
Back pain	5/61 (8.2%)
Musculoskeletal chest pain	4/61 (6.6%)
Nervous system disorders
Headache	5/61 (8.2%)
Respiratory, thoracic and mediastinal disorders
Cough	9/61 (14.8%)
Haemoptysis	12/61 (19.7%)

Limitations/Caveats

Based on the results of study PTC124-GD-021-CF (NCT02139306) (did not achieve its primary or secondary endpoints), clinical development of ataluren in cystic fibrosis was discontinued and this ongoing open-label extension study was closed.

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.