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Sponsor decision due to commercial availability of ataluren.
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The primary objective of this study is to obtain long term safety data of ataluren in male participants with nonsense mutation dystrophinopathy (who participated and completed a previous Phase 3 study of ataluren [PTC124-GD-020-DMD {NCT01826487}]) to augment the overall safety database. Screening and baseline procedures are structured to avoid a gap in treatment between the double-blind study (PTC124-GD-020-DMD) and this extension study.
This study may be further extended by amendment until either ataluren becomes commercially available or the clinical development of ataluren in duchenne muscular dystrophy (DMD) is discontinued.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ataluren | Experimental | 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 up to 144 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ataluren | Drug | Ataluren will be administered per the dose and schedule specified in the arm. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE): any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of AEs: graded per Common Terminology Criteria for AEs (CTCAE), Version 3.0 as Grade 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). Drug-related AEs: AEs with possible, probable, unlikely relationship, or unrelated to study drug. Serious AEs (SAEs): 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: an AE that occurred or worsened in the period extending from first dose of study drug in this study to 6 weeks after last dose of study drug in this study. A summary of other non-serious AEs and all SAEs, regardless of causality is located in Reported AE section. | Baseline (Day 1) up to 6 weeks post-treatment (Week 150) |
| Number of Participants With Abnormalities in Clinical Laboratory Parameters | Abnormalities in laboratory variables as pre-defined in protocol for safety-monitoring were: Hepatic (Serum alanine aminotransferase [ALT]: increase of greater than [>] 150 units/liter [U/L] with stable or decrease of creatinine kinese [CK]; Serum glutamyl amino transferase [GGT] [U/L]: Grade 2 [>2.5 - 5.0 * upper limit of normal {ULN}]), renal (Serum cystatin C miiligrams/liter [mg/L] >1.33 - 2.00 mg/L; Serum blood urea nitrogen [UREAN] [millimoles/liter {mmol/L}] greater than or equal to [≥]1.5 - 3.0 * ULN; Urine occult blood: 2+ [Small], 3+ [Moderate], 4+ [Large]), and electrolytes (Serum sodium: low [mmol/L], Grade 3-4 [less than {<}130 mmol/L]; serum potassium: high [mmol/L], Grade 3-4 [>6.0 mmol/L]; and Serum bicarbonate [mmol/L]: Grade 2 [<16 - 11 mmol/L]). | Baseline (Day 1) up to 6 weeks post-treatment (Week 150) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in 6MWD at Week 144 | The 6MWD test was performed in a 30 meters long flat corridor, where the participant was instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. Ambulation was assessed via the 6MWD test following standardized procedures by measuring the 6MWD in meters. Participants were not permitted to use assistive devices (walker, long leg braces, or short leg braces) during the 6MWD test. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Francesco Bibbiani, M.D. | PTC Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, Los Angeles | Los Angeles | California | 90095 | United States | ||
| UC Davis Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30135256 | Derived | Thangarajh M, Elfring GL, Trifillis P, McIntosh J, Peltz SW; Ataluren Phase 2b Study Group. The relationship between deficit in digit span and genotype in nonsense mutation Duchenne muscular dystrophy. Neurology. 2018 Sep 25;91(13):e1215-e1219. doi: 10.1212/WNL.0000000000006245. Epub 2018 Aug 22. |
| Label | URL |
|---|---|
| Related Info | View source |
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A total of 221 participants completed the double-blind Phase 3 Study PTC124-GD-020-DMD. Of the 221 participants who completed Study PTC124-GD-020-DMD, 219 participants were enrolled in this open-label extension study and 218 were treated.
All participants who successfully completed the double-blind, placebo-controlled Phase 3 study (PTC124-GD-020-DMD [NCT01826487]) were screened for this open-label extension study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ataluren | 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 up to 144 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 19, 2015 | Jul 17, 2020 |
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| Baseline, Week 144 |
| Change From Baseline in Time to Stand From Supine Position at Week 144 | If the time taken to perform this test exceeded 30 seconds or if a participant could not perform this test due to disease progression, a value of 30 seconds was used. | Baseline, Week 144 |
| Change From Baseline in Time to Walk/Run 10 Meters at Week 144 | If the time taken to perform this test exceeded 30 seconds or if a participant could not perform this test due to disease progression, a value of 30 seconds was used. | Baseline, Week 144 |
| Change From Baseline in Time to Climb 4 Stairs at Week 144 | If the time taken to perform this test exceeded 30 seconds or if a participant could not perform this test due to disease progression, a value of 30 seconds was used. | Baseline, Week 144 |
| Change From Baseline in Time to Descend 4 Stairs at Week 144 | If the time taken to perform this test exceeded 30 seconds or if a participant could not perform this test due to disease progression, a value of 30 seconds was used. | Baseline, Week 144 |
| Change From Baseline in Physical Function Total Score as Measured by NSAA at Week 144 | Physical function was assessed via the NSAA, a functional scale specifically designed for ambulant Duchenne muscular dystrophy (DMD) participants. The assessment comprised tests for 17 abilities of a participant, such as ability to stand, rise from the floor, get from lying to sitting, get from sitting to standing, raise one's head, stand on one's heels, hop, jump, and run. For each activity, a score of 0, 1, or 2 was recorded, with 0 = "unable to achieve independently," 1 = "modified method but achieves goal independent of physical assistance from another," or 2 = "normal- achieves goal without any assistance." The sum of these scores (except for 'raise one's head' activity score) was reported as the ordinal total score, which was transformed to a linear total score ranging from 0 (worst) to 100 (best). Participants with confirmed loss of ambulation at a particular visit were assigned a score of 0. | Baseline, Week 144 |
| Change From Baseline in PUL Total Score at Week 144 | The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into shoulder level (4 items), elbow level (9 items), and distal level (8 items) dimensions. Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. Each dimension was scored separately with a maximum score of 16 for shoulder level, 34 for elbow level, and 24 for distal level. Total score was calculated by adding the 3 level scores, with a maximum global score of 74 (total score range = 0-74). Higher score = better outcome. | Baseline, Week 144 |
| Change From Baseline in Percent Predicted FVC as Measured by Spirometry at Week 144 | FVC is a standard pulmonary function test. FVC was defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Percent predicted FVC (in %) = [(observed FVC)/(predicted FVC)]*100. | Baseline, Week 144 |
| Change From Baseline in Percent Predicted FEV1 as Measured by Spirometry at Week 144 | FEV1 is a standard pulmonary function test. FEV1 was defined as the volume of air that can forcibly be blown out in 1 second, after full inspiration in the upright position, measured in liters. Percent predicted FEV1 (in %) = [(observed FEV1)/(predicted FEV1)]*100. | Baseline, Week 144 |
| Change From Baseline in PEF as Measured by Spirometry at Week 144 | PEF was defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. | Baseline, Week 144 |
| Change From Baseline in PCF as Measured by Spirometry at Week 144 | PCF measures an individual's maximum speed of expiration during cough. | Baseline, Week 144 |
| Change From Baseline in PODCI Transfers/Basic Mobility Score at Week 144 | Changes in health-related quality of life (HRQL) were measured via the PODCI questionnaire that has been shown to correlate with disease progression and clinical outcome measures in DMD. PODCI includes a Global Functioning Scale and 5 core scales: Upper Extremity and Physical Function,Transfer/Basic Mobility, Sports/Physical Functioning, Pain/Comfort,and Happiness. The following PODCI domain was prespecified in the protocol for analysis:Transfers/Basic Mobility domain assesses difficulty experienced in performing routine motor activities in daily life. Each domain was scored from 0 to 100, with 0 representing a poor outcome/worse health, while 100 representing the highest level of functioning and least pain. | Baseline, Week 144 |
| Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel | Changes in activities of daily living and disease symptoms were captured via a DMD-specific survey administered by Site personnel. At screening or baseline, the participant and/or parent/caregiver were asked to identify any activities of daily living (for example, ambulation, balance, personal hygiene/grooming, dressing and undressing, self-feeding, using the bathroom, handwriting, school performance, behavior or energy level) or symptoms that were affected by the participant's DMD. At post-baseline visit (Week 144), the same participant and/or parent/caregiver was asked to describe any changes from baseline in those activities of daily living/symptoms, within the following categories: physical functioning; general energy level; cognition/school function; emotional/social functioning; and sleep. Changes from baseline were reported on a 5-point Likert scale: 1 (much better), 2 (slightly better), 3 (unchanged), 4 (slightly worse), or 5 (much worse). | Baseline, Week 144 |
| Ataluren Plasma Concentration | Pre-dose ataluren plasma concentrations prior to morning ataluren administration at each clinic visit was assessed using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC/MS-MS) method. | Pre-dose at Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 144 |
| Change From Baseline in Systolic and Diastolic Blood Pressure at Week 144 | Blood pressure determination was performed with the participant in a sitting position after a 5-minute rest. | Baseline, Week 144 |
| Change From Baseline in Pulse Rate at Week 144 | Pulse rate determination was performed with the participant in a sitting position after a 5-minute rest. | Baseline, Week 144 |
| Change From Baseline in Body Temperature at Week 144 | Baseline, Week 144 |
| Sacramento |
| California |
| 95817 |
| United States |
| Stanford University Medical Center | Stanford | California | 94305 | United States |
| Children's Hospital Colorado - Center for Cancer and Blood Disorders | Aurora | Colorado | 80045 | United States |
| Child Neurology Center of Northwest Florida | Gulf Breeze | Florida | 32561 | United States |
| Rush University Medical Center | Chicago | Illinois | 60612 | United States |
| University of Iowa | Iowa City | Iowa | 52242 | United States |
| University of Kansas Medical Center | Kansas City | Kansas | 66160 | United States |
| Children's Hospital Boston | Boston | Massachusetts | 02115 | United States |
| University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| Washington University School of Medicine, Division of Endocrinology, Metabolism and Lipid Research | St Louis | Missouri | 63110 | United States |
| Columbia University College of Physicians & Surgeons | New York | New York | 10032 | United States |
| Children's Hospital Cincinnati | Cincinnati | Ohio | 45229 | United States |
| Nationwide Children's Hospital | Columbus | Ohio | 43209 | United States |
| Oregon Health & Science University | Portland | Oregon | 97239 | United States |
| The Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania | 15224 | United States |
| Childrens Medical Center Dallas, Texas | Dallas | Texas | 75207 | United States |
| Texas Children's Hospital | Houston | Texas | 77030 | United States |
| University of Utah | Salt Lake City | Utah | 84112 | United States |
| Seattle Children's Hospital - Childhood Cancer and Blood Disorders | Seattle | Washington | 98105 | United States |
| The Children's Hospital at Westmead | Westmead | New South Wales | 2145 | Australia |
| The Royal Children's Hospital | Parkville | Victoria | 3052 | Australia |
| UZ Leuven | Leuven | 3000 | Belgium |
| Universidade Federal do Rio de Janeiro - Instituto de Puericultura e Pediatria Martagao Gesteira | Rio de Janeiro | 21.941-912 | Brazil |
| Sao Paulo University -HC/FMUSP | São Paulo | 05403-900 | Brazil |
| Aleksandrovska Hospital | Sofia | 1431 | Bulgaria |
| Alberta Children's Hospital | Calgary | Alberta | T3B 6A8 | Canada |
| British Columbia Children's Hospital | Vancouver | British Columbia | V6H 3V4 | Canada |
| Children's Hospital of Western Ontario | London | Ontario | N6C 2RC | Canada |
| Hospital Luis Calvo Mackenna | Santiago | Santiago Metropolitan | Chile |
| Hospital Clinico Universidad Catolica | Santiago | 8330073 | Chile |
| University Hospital Brno | Brno | 635 00 | Czechia |
| Motol University Hospital | Prague | 150 06 | Czechia |
| Hospital de la Timone | Marseille | 13385 | France |
| CHU de Nantes | Nantes | 44093 | France |
| Hopital Necker - Enfants Malades | Paris | 75015 | France |
| Groupe Hospitalier Pitie-Salpetriere | Paris | 75651 | France |
| Universitaetsklinikum Essen | Essen | 45122 | Germany |
| University Medical Center Freiburg | Freiburg im Breisgau | 79106 | Germany |
| Universitat Munchen - von Haunersche Kinder Clinic | München | 80337 | Germany |
| Hadassah University Hospital | Jerusalem | 91240 | Israel |
| Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano | Milan | 20122 | Italy |
| Bambino Gesu Hospital | Rome | 00165 | Italy |
| U.O. Complessa di Neuropsichiatria Infantile | Rome | 00168 | Italy |
| Policlinico Universitario G. Martino | Sicily | 98125 | Italy |
| Medical University of Warsaw | Warsaw | 502-097 | Poland |
| Seoul National University Hospital | Seoul | 110-744 | South Korea |
| Hospital Sant Joan de Deu | Barcelona | 08950 | Spain |
| Hospital Universitari i Politecnic la Fe | Valencia | 46026 | Spain |
| Queen Silvia Children's Hospital | Gothenburg | SE-416 85 | Sweden |
| Astrid Lindgren Childrens Hospital | Stockholm | 17176 | Sweden |
| CHUV Lausanne | Lausanne | 1011 | Switzerland |
| Hacettepe Childrens Hospital | Ankara | 06100 | Turkey (Türkiye) |
| Erciyes University Faculty of Medicine | Talas/Kayseri | 38039 | Turkey (Türkiye) |
| University College London Institute of Child Health | London | WC1N 3JH | United Kingdom |
| Royal Manchester Children's Hospital | Manchester | M13 9WL | United Kingdom |
| The Newcastle upon Tyne Hospitals, NHS Foundation Trust | Newcastle upon Tyne | NE1 3BZ | United Kingdom |
| As-treated Population | All participants who received at least 1 dose of study drug. |
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| COMPLETED |
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| NOT COMPLETED |
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|
As Treated (AT) population included all participants who received at least 1 dose of ataluren treatment in this extension study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Ataluren | 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 up to 144 weeks. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||||
| 6 Minute Walk Distance (6MWD) | The 6MWD test was performed in a 30 meters long flat corridor, where the participant was instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. Ambulation was assessed via the 6MWD test following standardized procedures by measuring the 6MWD in meters. Participants were not permitted to use assistive devices (walker, long leg braces, or short leg braces) during the 6MWD test. | This baseline characteristic was analyzed on ambulatory participants only. | Mean | Standard Deviation | meters |
| |||||||||||||||
| Time to Stand From Supine Position | 'Number analyzed' signifies participants of as-treated population analyzed for this parameter. | Mean | Standard Deviation | seconds |
| ||||||||||||||||
| Time to Walk/Run 10 Meters | 'Number analyzed' signifies participants of as-treated population analyzed for this parameter. | Mean | Standard Deviation | seconds |
| ||||||||||||||||
| Time to Climb 4 Stairs | 'Number analyzed' signifies participants of as-treated population analyzed for this parameter. | Mean | Standard Deviation | seconds |
| ||||||||||||||||
| Time to Descend 4 Stairs | 'Number analyzed' signifies participants of as-treated population analyzed for this parameter. | Mean | Standard Deviation | seconds |
| ||||||||||||||||
| North Star Ambulatory Assessment (NSAA) Total Score | NSAA comprised tests of 17 abilities, such as ability to stand, rise from floor, get from lying to sitting, get from sitting to standing, raise one's head, stand on one's heels, hop, jump, and run. For each activity, a score of 0, 1, or 2 was recorded, with 0 = "unable to achieve independently," 1 = "modified method but achieves goal independent of physical assistance from another," or 2 = "normal- achieves goal without any assistance." Sum of these 17 scores was reported as ordinal total score, which can be transformed to a linear total score from 0 (worst) to 100 (best). | This baseline parameter was analyzed on ambulatory participants with a baseline value. | Mean | Standard Deviation | units on a scale |
| |||||||||||||||
| Performance Upper Limb (PUL) Total Score | PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into shoulder (4 items), elbow (9 items), and distal (8 items) level dimensions. Scoring options per item may vary from 0-1 and 0-6, according to performance, with higher values corresponding to better performance. Each dimension was scored separately with a maximum score of 16 for shoulder level, 34 for elbow level, and 24 for distal level. Total score was calculated by adding 3 level scores, with a maximum global score of 74 (total score range = 0-74). Higher score = better outcome. | 'Number analyzed' signifies participants of as-treated population analyzed for this parameter. | Mean | Standard Deviation | units on a scale |
| |||||||||||||||
| Percent Predicted Forced Vital Capacity (FVC) | FVC is a standard pulmonary function test. FVC was defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Percent predicted FVC (in %) = [(observed FVC)/(predicted FVC)]*100. | 'Number analyzed' signifies participants of as-treated population analyzed for this parameter. | Mean | Standard Deviation | percent predicted FVC |
| |||||||||||||||
| Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) | FEV1 is a standard pulmonary function test. FEV1 was defined as the volume of air that can forcibly be blown out in 1 second, after full inspiration in the upright position, measured in liters. Percent predicted FEV1 (in %) = [(observed FEV1)/(predicted FEV1)]*100. | 'Number analyzed' signifies participants of as-treated population analyzed for this parameter. | Mean | Standard Deviation | percent predicted FEV1 |
| |||||||||||||||
| Peak Expiratory Flow (PEF) | PEF was defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. | 'Number analyzed' signifies participants of as-treated population analyzed for this parameter. | Mean | Standard Deviation | liters/second (L/sec) |
| |||||||||||||||
| Peak Cough Flow (PCF) | PCF measures an individual's maximum speed of expiration during cough. | 'Number analyzed' signifies participants of as-treated population analyzed for this parameter. | Mean | Standard Deviation | L/sec |
| |||||||||||||||
| Pediatric Outcomes Data Collection Instrument (PODCI) Transfers/Basic Mobility Score | PODCI includes a Global Functioning Scale and 5 core scales: Upper Extremity & Physical Function,Transfer/Basic Mobility, Sports/Physical Functioning, Pain/Comfort,and Happiness. Following PODCI domains were prespecified in protocol for analysis:Transfers/Basic Mobility domain assesses difficulty experienced in performing routine motor activities in daily life. Each domain was scored from 0 (poor outcome/worse health) to 100 (the highest level of functioning & least pain). | 'Number analyzed' signifies participants of as-treated population analyzed for this parameter. | Mean | Standard Deviation | units on a scale |
| |||||||||||||||
| Blood Pressure | 'Number analyzed' signifies participants of as-treated population analyzed for this parameter. | Mean | Standard Deviation | millimeters of mercury (mm Hg) |
| ||||||||||||||||
| Pulse Rate | 'Number analyzed' signifies participants of as-treated population analyzed for this parameter. | Mean | Standard Deviation | beats/minute |
| ||||||||||||||||
| Body Temperature | 'Number analyzed' signifies participants of as-treated population analyzed for this parameter. | Mean | Standard Deviation | degrees centigrade |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE): any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of AEs: graded per Common Terminology Criteria for AEs (CTCAE), Version 3.0 as Grade 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). Drug-related AEs: AEs with possible, probable, unlikely relationship, or unrelated to study drug. Serious AEs (SAEs): 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: an AE that occurred or worsened in the period extending from first dose of study drug in this study to 6 weeks after last dose of study drug in this study. A summary of other non-serious AEs and all SAEs, regardless of causality is located in Reported AE section. | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. | Posted | Count of Participants | Participants | Baseline (Day 1) up to 6 weeks post-treatment (Week 150) |
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| Primary | Number of Participants With Abnormalities in Clinical Laboratory Parameters | Abnormalities in laboratory variables as pre-defined in protocol for safety-monitoring were: Hepatic (Serum alanine aminotransferase [ALT]: increase of greater than [>] 150 units/liter [U/L] with stable or decrease of creatinine kinese [CK]; Serum glutamyl amino transferase [GGT] [U/L]: Grade 2 [>2.5 - 5.0 * upper limit of normal {ULN}]), renal (Serum cystatin C miiligrams/liter [mg/L] >1.33 - 2.00 mg/L; Serum blood urea nitrogen [UREAN] [millimoles/liter {mmol/L}] greater than or equal to [≥]1.5 - 3.0 * ULN; Urine occult blood: 2+ [Small], 3+ [Moderate], 4+ [Large]), and electrolytes (Serum sodium: low [mmol/L], Grade 3-4 [less than {<}130 mmol/L]; serum potassium: high [mmol/L], Grade 3-4 [>6.0 mmol/L]; and Serum bicarbonate [mmol/L]: Grade 2 [<16 - 11 mmol/L]). | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. | Posted | Count of Participants | Participants | Baseline (Day 1) up to 6 weeks post-treatment (Week 150) |
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| Secondary | Change From Baseline in 6MWD at Week 144 | The 6MWD test was performed in a 30 meters long flat corridor, where the participant was instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. Ambulation was assessed via the 6MWD test following standardized procedures by measuring the 6MWD in meters. Participants were not permitted to use assistive devices (walker, long leg braces, or short leg braces) during the 6MWD test. | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Overall number of participants analyzed' = participants who had both baseline and post-baseline 6MWD value at specified timepoint. | Posted | Mean | Standard Deviation | meters | Baseline, Week 144 |
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| Secondary | Change From Baseline in Time to Stand From Supine Position at Week 144 | If the time taken to perform this test exceeded 30 seconds or if a participant could not perform this test due to disease progression, a value of 30 seconds was used. | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Overall number of participants analyzed' = participants who had both baseline and post-baseline value of this parameter at specified timepoint. | Posted | Mean | Standard Deviation | seconds | Baseline, Week 144 |
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| Secondary | Change From Baseline in Time to Walk/Run 10 Meters at Week 144 | If the time taken to perform this test exceeded 30 seconds or if a participant could not perform this test due to disease progression, a value of 30 seconds was used. | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Overall number of participants analyzed' = participants who had both baseline and post-baseline value of this parameter at specified timepoint. | Posted | Mean | Standard Deviation | seconds | Baseline, Week 144 |
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| Secondary | Change From Baseline in Time to Climb 4 Stairs at Week 144 | If the time taken to perform this test exceeded 30 seconds or if a participant could not perform this test due to disease progression, a value of 30 seconds was used. | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Overall number of participants analyzed' = participants who had both baseline and post-baseline value of this parameter at specified timepoint. | Posted | Mean | Standard Deviation | seconds | Baseline, Week 144 |
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| Secondary | Change From Baseline in Time to Descend 4 Stairs at Week 144 | If the time taken to perform this test exceeded 30 seconds or if a participant could not perform this test due to disease progression, a value of 30 seconds was used. | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Overall number of participants analyzed' = participants who had both baseline and post-baseline value of this parameter at specified timepoint. | Posted | Mean | Standard Deviation | seconds | Baseline, Week 144 |
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| Secondary | Change From Baseline in Physical Function Total Score as Measured by NSAA at Week 144 | Physical function was assessed via the NSAA, a functional scale specifically designed for ambulant Duchenne muscular dystrophy (DMD) participants. The assessment comprised tests for 17 abilities of a participant, such as ability to stand, rise from the floor, get from lying to sitting, get from sitting to standing, raise one's head, stand on one's heels, hop, jump, and run. For each activity, a score of 0, 1, or 2 was recorded, with 0 = "unable to achieve independently," 1 = "modified method but achieves goal independent of physical assistance from another," or 2 = "normal- achieves goal without any assistance." The sum of these scores (except for 'raise one's head' activity score) was reported as the ordinal total score, which was transformed to a linear total score ranging from 0 (worst) to 100 (best). Participants with confirmed loss of ambulation at a particular visit were assigned a score of 0. | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Overall number of participants analyzed' = participants who had both baseline and post-baseline value of this parameter at specified timepoint. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 144 |
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| Secondary | Change From Baseline in PUL Total Score at Week 144 | The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into shoulder level (4 items), elbow level (9 items), and distal level (8 items) dimensions. Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. Each dimension was scored separately with a maximum score of 16 for shoulder level, 34 for elbow level, and 24 for distal level. Total score was calculated by adding the 3 level scores, with a maximum global score of 74 (total score range = 0-74). Higher score = better outcome. | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Overall number of participants analyzed' = participants who had both baseline and post-baseline value of this parameter at specified timepoint. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 144 |
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| Secondary | Change From Baseline in Percent Predicted FVC as Measured by Spirometry at Week 144 | FVC is a standard pulmonary function test. FVC was defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Percent predicted FVC (in %) = [(observed FVC)/(predicted FVC)]*100. | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Overall number of participants analyzed' = participants who had both baseline and post-baseline value of this parameter at specified timepoint. | Posted | Mean | Standard Deviation | percent predicted FVC | Baseline, Week 144 |
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| Secondary | Change From Baseline in Percent Predicted FEV1 as Measured by Spirometry at Week 144 | FEV1 is a standard pulmonary function test. FEV1 was defined as the volume of air that can forcibly be blown out in 1 second, after full inspiration in the upright position, measured in liters. Percent predicted FEV1 (in %) = [(observed FEV1)/(predicted FEV1)]*100. | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Overall number of participants analyzed' = participants who had both baseline and post-baseline value of this parameter at specified timepoint. | Posted | Mean | Standard Deviation | percent predicted FEV1 | Baseline, Week 144 |
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| Secondary | Change From Baseline in PEF as Measured by Spirometry at Week 144 | PEF was defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Overall number of participants analyzed' = participants who had both baseline and post-baseline value of this parameter at specified timepoint. | Posted | Mean | Standard Deviation | L/sec | Baseline, Week 144 |
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| Secondary | Change From Baseline in PCF as Measured by Spirometry at Week 144 | PCF measures an individual's maximum speed of expiration during cough. | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Overall number of participants analyzed' = participants who had both baseline and post-baseline value of this parameter at specified timepoint. | Posted | Mean | Standard Deviation | L/sec | Baseline, Week 144 |
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| Secondary | Change From Baseline in PODCI Transfers/Basic Mobility Score at Week 144 | Changes in health-related quality of life (HRQL) were measured via the PODCI questionnaire that has been shown to correlate with disease progression and clinical outcome measures in DMD. PODCI includes a Global Functioning Scale and 5 core scales: Upper Extremity and Physical Function,Transfer/Basic Mobility, Sports/Physical Functioning, Pain/Comfort,and Happiness. The following PODCI domain was prespecified in the protocol for analysis:Transfers/Basic Mobility domain assesses difficulty experienced in performing routine motor activities in daily life. Each domain was scored from 0 to 100, with 0 representing a poor outcome/worse health, while 100 representing the highest level of functioning and least pain. | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Overall number of participants analyzed' = participants who had both baseline and post-baseline value of this parameter at specified timepoint. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 144 |
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| Secondary | Number of Participants With Change From Baseline in Activities of Daily Living and Disease Status at Week 144, as Assessed by a Standardized Survey Administered by Site Personnel | Changes in activities of daily living and disease symptoms were captured via a DMD-specific survey administered by Site personnel. At screening or baseline, the participant and/or parent/caregiver were asked to identify any activities of daily living (for example, ambulation, balance, personal hygiene/grooming, dressing and undressing, self-feeding, using the bathroom, handwriting, school performance, behavior or energy level) or symptoms that were affected by the participant's DMD. At post-baseline visit (Week 144), the same participant and/or parent/caregiver was asked to describe any changes from baseline in those activities of daily living/symptoms, within the following categories: physical functioning; general energy level; cognition/school function; emotional/social functioning; and sleep. Changes from baseline were reported on a 5-point Likert scale: 1 (much better), 2 (slightly better), 3 (unchanged), 4 (slightly worse), or 5 (much worse). | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Number analyzed 'signifies participants evaluable for specified categories. | Posted | Count of Participants | Participants | Baseline, Week 144 |
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| Secondary | Ataluren Plasma Concentration | Pre-dose ataluren plasma concentrations prior to morning ataluren administration at each clinic visit was assessed using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC/MS-MS) method. | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoints. | Posted | Mean | Standard Deviation | micrograms/milliliter (μg/mL) | Pre-dose at Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 144 |
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| Secondary | Change From Baseline in Systolic and Diastolic Blood Pressure at Week 144 | Blood pressure determination was performed with the participant in a sitting position after a 5-minute rest. | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Overall number of participants analyzed' = participants who had both baseline and post-baseline value of this parameter at specified timepoint. | Posted | Mean | Standard Deviation | mmHg | Baseline, Week 144 |
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| Secondary | Change From Baseline in Pulse Rate at Week 144 | Pulse rate determination was performed with the participant in a sitting position after a 5-minute rest. | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Overall number of participants analyzed' = participants who had both baseline and post-baseline value of this parameter at specified timepoint. | Posted | Mean | Standard Deviation | beats/minute | Baseline, Week 144 |
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| Secondary | Change From Baseline in Body Temperature at Week 144 | AT population included all participants who received at least 1 dose of ataluren treatment in this extension study. Here, 'Overall number of participants analyzed' = participants who had both baseline and post-baseline value of this parameter at specified timepoint. | Posted | Mean | Standard Deviation | degrees centigrade | Baseline, Week 144 |
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Baseline (Day 1) up to 6 weeks post-treatment (Week 150)
AT population included all participants who received at least 1 dose of ataluren treatment in this extension study.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ataluren | Participants received ataluren 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 up to 144 weeks. | 0 | 218 | 24 | 218 | 201 | 218 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Exposure to communicable disease | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
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| Femur fracture | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
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| Hip fracture | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
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| Laceration | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Adenoiditis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Chronic sinusitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Varicella | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Colitis ulcerative | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Intussusception | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Joint contracture | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Tendinous contracture | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Pulmonary artery stenosis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Bradycardia | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
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| Transposition of the great vessels | Congenital, familial and genetic disorders | MedDRA 20.1 | Systematic Assessment |
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| Ventricular septal defect | Congenital, familial and genetic disorders | MedDRA 20.1 | Systematic Assessment |
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| Cataract | Eye disorders | MedDRA 20.1 | Systematic Assessment |
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| Drug hypersensitivity | Immune system disorders | MedDRA 20.1 | Systematic Assessment |
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| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
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| Nephrolithiasis | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ear infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
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| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
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| Disease progression | General disorders | MedDRA 20.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 20.1 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
The study was terminated early per Sponsor decision due to commercial availability of ataluren.
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Patient Advocacy | PTC Therapeutics, Inc. | 1-866-562-4620 | medinfo@ptcbio.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 23, 2019 | Jul 17, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D020388 | Muscular Dystrophy, Duchenne |
| D009136 | Muscular Dystrophies |
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| ID | Term |
|---|---|
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
Not provided
Not provided
| ID | Term |
|---|---|
| C515878 | ataluren |
Not provided
Not provided
Not provided
| Asian |
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| Hispanic |
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| Other |
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| Missing |
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| Diastolic blood pressure |
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| Title | Measurements |
|---|---|
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| AEs Leading to Withdrawal From Study |
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| Mild AEs |
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| Moderate AEs |
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| Severe AEs |
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| Life-threatening AEs |
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| Units | Counts |
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| Participants |
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| Slightly worse |
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| Much worse |
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| Slightly worse |
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| Much worse |
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| Slightly worse |
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| Much worse |
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| Slightly worse |
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| Much worse |
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| Slightly worse |
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| Much worse |
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| Slightly worse |
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| Much worse |
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| Slightly worse |
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| Much worse |
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| Slightly worse |
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| Much worse |
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