Phase 2B Extension Study of Ataluren (PTC124) in Duchenne/Becker Muscular Dystrophy (DMD/BMD)
Sponsor
PTC Therapeutics (Industry)
Overall Status
Terminated
CT.gov ID
NCT00847379
Collaborator
Genzyme, a Sanofi Company (Industry)
173
37
1
15.7
4.7
0.3
Study Details
Study Description
Brief Summary
Duchenne/Becker muscular dystrophy (DMD/BMD) is a genetic disorder that develops in boys. It is caused by a mutation in the gene for dystrophin, a protein that is important for maintaining normal muscle structure and function. Loss of dystrophin causes muscle fragility that leads to weakness and loss of walking ability during childhood and teenage years. A specific type of mutation, called a nonsense (premature stop codon) mutation is the cause of DMD/BMD in approximately 10-15% of boys with the disease. Ataluren (PTC124) is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 2b extension trial that will evaluate the long-term safety of ataluren (PTC124) in boys with nonsense mutation DMD/BMD, as determined by adverse events and laboratory abnormalities. The study will also assess changes in walking, muscle function, and other important clinical and laboratory measures.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This is a Phase 2b, international, multicenter, open-label extension study for participants who successfully completed blinded study drug in Study 007. This extension study will evaluate the long-term administration of ataluren administered 3 times per day (TID) at morning, midday, and evening doses of 20, 20, and 40 milligrams/kilogram (mg/kg), respectively, in participants with nonsense mutation Duchenne/Becker muscular dystrophy (nmDBMD).
Study Design
Study Type:
Interventional
Actual Enrollment
:
173 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2B Extension Study of PTC124 in Subjects With Nonsense-Mutation-Mediated Duchenne and Becker Muscular Dystrophy
Actual Study Start Date
:
Jan 31, 2009
Actual Primary Completion Date
:
May 24, 2010
Actual Study Completion Date
:
May 24, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Overall Participants: High-Dose Ataluren All participants will receive ataluren suspension orally three times a day (TID), 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, will be initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose will be increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level is well tolerated. |
Drug: Ataluren
Ataluren oral powder for suspension will be administered as per dose and schedule specified in the arm.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Treatment-Emergent Adverse Events (AEs) [Baseline (Week 48 of Study 007) up to Week 102]
An AE was 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) and severe (interferes significantly with usual function). 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 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 serious AEs, regardless of causality is located in Reported AE section.
- Number of Participants With Clinically Significant Abnormal Laboratory Parameters [Baseline (Week 48 of Study 007) up to Week 102]
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
- Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 60 [Baseline (Week 48 of Study 007), Week 60]
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.
- Change From Baseline in Mean Activity Period/Day/Visit at Week 60, as Assessed by Step Activity Monitoring (SAM) [Baseline (Week 48 of Study 007), Week 60]
The SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). Mean activity period/day/visit was computed for each participant. For each day, an active period was defined as the first time after 3:00 AM that greater than (>) 2 strides/minute were recorded to the last time prior to midnight that >2 strides/minute were recorded. Days were deleted on which such an active period was less than (<) 50 percent (%) of the mean active period across all days for that participant's visit.
- Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 60, as Assessed by SAM [Baseline (Week 48 of Study 007), Week 60]
The SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). Mean total step count/day/visit during the active periods was computed for each participant. For each day, an active period was defined as the first time after 3:00 AM that >2 strides/minute were recorded to the last time prior to midnight that >2 strides/minute were recorded. Days were deleted on which such an active period was <50% of the mean active period across all days for that participant's visit.
- Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 60, as Assessed by SAM [Baseline (Week 48 of Study 007), Week 60]
The SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). Mean total step count/hour during the active periods for the days in a visit was computed for each participant. For each day, an active period was defined as the first time after 3:00 AM that >2 strides/minute were recorded to the last time prior to midnight that >2 strides/minute were recorded. Days were deleted on which such an active period was <50% of the mean active period across all days for that participant's visit.
- Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM [Baseline (Week 48 of Study 007), Week 60]
SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). The maximum continuous 10-minute, 20-minute, 30-minute, and 60-minute total step counts were computed for each participant. For each day, an active period was defined as the first time after 3:00 AM that >2 strides/minute were recorded to the last time prior to midnight that >2 strides/minute were recorded. Days were deleted on which such an active period was <50% of the mean active period across all days for that participant's visit.
- Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 [Baseline (Week 48 of Study 007), Week 60]
SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear SAM for at least 9 consecutive days. SAM was used to record number of strides/minute following each visit. A stride is leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again. Percentage of time during active periods spent at no activity (0 steps/min), low activity (≤15 steps/min), medium activity (16-30 steps/min), and high activity (>30 steps/min) were computed for each participant. For each day, an active period was defined as first time after 3:00 AM that >2 strides/minute were recorded to the last time prior to midnight that >2 strides/minute were recorded. Days were deleted on which such an active period was <50% of the mean active period across all days for that participant's visit.
- Change From Baseline in Time to Stand From Supine Position at Week 60 [Baseline (Week 48 of Study 007), Week 60]
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. Change from baseline data has been reported.
- Change From Baseline in Time to Walk/Run 10 Meters at Week 60 [Baseline (Week 48 of Study 007), Week 60]
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. Change from baseline data has been reported.
- Change From Baseline in Time to Climb 4 Stairs at Week 60 [Baseline (Week 48 of Study 007), Week 60]
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. Change from baseline data has been reported.
- Change From Baseline in Time to Descend 4 Stairs at Week 60 [Baseline (Week 48 of Study 007), Week 60]
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. Change from baseline data has been reported.
- Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 [Baseline (Week 48 of Study 007), Week 60]
The heart rate was measured with a Polar RS400 heart rate monitor, which consists of a transmitter strap worn around the chest and a wristwatch receiver. The monitor produces a digital text file with 1 value per minute that represents the mean heart rate for that minute. Mean heart rates values were collected prior to, during, and after the 6MWT. The participant rested for 5 minutes in a sitting position prior to the 6MWT, and the mean heart rate for the last minute of this rest period was collected and documented as the resting heart rate. During the 6MWT, the mean heart rate was collected and documented as the active heart rate. After completing the 6MWT and resting for 3 minutes, the mean heart rate for 1 minute was collected and documented as the recovery heart rate.
- Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 [Baseline (Week 48 of Study 007), Week 60]
Basic attention and working memory was measured using the digit span task. A series of digits (0-9) were presented to the child in an auditory format only. The task had 2 parts; in the forward condition, the child was requested to repeat back the digits in the order they were presented and in the backward condition, he was requested to reverse the order of presentation. A raw score of the total number of correct responses was converted to an age-scaled-score (z-score) by subtracting the corresponding mean and dividing by the corresponding standard deviation of a reference population for that age.
- Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 60 [Baseline (Week 48 of Study 007), Week 60]
HRQL was measured via the PedsQL. The generic core module (including physical, emotional, social and school functioning scales) comprises 23 questions and the fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. The PedsQL was completed by both the participant and/or a parent/caregiver. Examples of items in each of the generic core module scales include: "It is hard for me to run"; "I feel sad or blue"; "I cannot do things that other kids my age can do;" and "It is hard to pay attention in class." Each of the generic core module items was scored on a 5-point Likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating better health-related quality of life. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 60.
- Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 60 [Baseline (Week 48 of Study 007), Week 60]
HRQL was measured via the PedsQL. The generic core module (including physical, emotional, social and school functioning scales) comprises 23 questions and the fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. The PedsQL was completed by both the participant and/or a parent/caregiver. Examples of items in each of the generic core module scales include: "It is hard for me to run"; "I feel sad or blue"; "I cannot do things that other kids my age can do;" and "It is hard to pay attention in class." Each of the generic core module items was scored on a 5-point likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating better health-related quality of life. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.
- Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 [Baseline (Week 48 of Study 007), Week 60]
HRQL was measured via the PedsQL. The fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. PedsQL was completed by both the participant and/or a parent/caregiver. Fatigue-specific module obtains information relating to items such as: "I feel too tired to do things that I like to do"; "I spend a lot of time in bed"; and "I have trouble remembering more than one thing at a time;" Each of the fatigue-specific module items was scored on a 5-point Likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating less fatigue. Total score was the sum of all items over the number of items answered on all scales. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 60.
- Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 [Baseline (Week 48 of Study 007), Week 60]
HRQL was measured via the PedsQL. The fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. The PedsQL was completed by both the participant and/or a parent/caregiver. Fatigue-specific module obtains information relating to items such as: "I feel too tired to do things that I like to do"; "I spend a lot of time in bed"; and "I have trouble remembering more than one thing at a time;" Each of the fatigue-specific module items was scored on a 5-point likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating less fatigue. Total score was the sum of all items over the number of items answered on all scales. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 60.
- Change From Baseline in Participant and Parent/Caregiver Reported Activities of Daily Living of Participants Who Were Unable to Complete the 6MWT (Nonambulatory Participants), as Measured by the Egen Klassifikation (EK) Scale at Week 60 [Baseline (Week 48 of Study 007), Week 60]
Activities of daily living were measured using the EK scale in all participants who were unable to complete the 6MWT at Screening/Baseline on Day 1. The EK scale is an ordinal scale ranging from 0 to 30 points where 0 represents the highest level of independent function and 30 the lowest. The scale consists of 10 categories (each scored 0 to 3), involving different functional domains including 1) ability to use wheelchair, 2) ability to transfer from wheelchair, 3) ability to stand, 4) ability to balance in the wheelchair, 5) ability to move the arms, 6) ability to use the hands and arms when eating, 7) ability to turn in bed, 8) ability to cough, 9) ability to speak, and 10) physical well-being. The administration of the EK scale consisted of an interview of the participant to capture how he performed the tasks of daily life (as described by Categories 1 to 9) and how he perceived his well-being (as described by Category 10).
- Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 [Baseline (Week 48 of Study 007), Week 60]
TSQM consisted of 14 questions about treatment satisfaction with drug in 4 domains: Effectiveness (Questions 1-3 scored as 1 [extremely dissatisfied] to 7 [extremely satisfied]), Side Effects (question 4 scored as 0 [no] or 1 [yes]; question 5 scored as 1 [extremely bothersome] to 5 [not at all bothersome]; questions 6 - 8 scored as 1 [a great deal] to 5 [not at all]), Convenience (questions 9 and 10 scored as 1 [extremely difficult] to 7 [extremely easy]; question 11 scored as 1 [extremely inconvenient] to 5 [extremely convenient]) and Global Satisfaction (question 12 scored as 1 [not at all confident] to 7 [extremely confident]; question 13 scored as 1 [not at all certain] to 5 [extremely certain]; question 14 scored as 1 [extremely dissatisfied] to 5 [extremely satisfied]). The scores of each of the domains were added together and an algorithm was used to create a score of 0 to 100, with higher scores indicating better treatment satisfaction.
- Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 60 [Baseline (Week 48 of Study 007), Week 60]
Blood samples collected for chemistry assays were used to quantify serum CK concentrations. Serum CK was assessed as a potential biomarker for muscle fragility, with a reduction in serum CK considered to be a positive outcome.
- Study Drug Compliance [Baseline (Week 48 of Study 007) to Week 96]
Study drug compliance was assessed by participant daily diary and quantification of used and unused study drug. Compliance was assessed in terms of the percentage of drug actually taken relative to the amount that should have been taken during the study.
- Trough Ataluren Plasma Concentration [Pre-morning dose (0 hour) at Baseline (Week 48 of 007 study), Weeks 54, 60, 72, 84, and 96]
Plasma samples for the determination of ataluren concentrations were analyzed at the bioanalytical laboratory for ataluren parent drug using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC/MS-MS) method with a lower limit of quantitation (LLOQ) of 0.5 micrograms/millilitre (mcg/mL). Values below the LLOQ were set to 0.
Eligibility Criteria
Criteria
Ages Eligible for Study:
5 Years
and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Completion of blinded study drug treatment in the previous Phase 2b study (PTC124-GD-007-DMD).
-
Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if less than [<]18 years of age).
-
In participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during PTC124 administration and the 6-week follow up period.
-
Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.
Exclusion Criteria:
-
Known hypersensitivity to any of the ingredients or excipients of the study drug (Litesse® UltraTM [refined polydextrose], polyethylene glycol 3350, Lutrol® micro F127 [poloxamer 407], mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, Cab-O-Sil® M5P [colloidal silica], magnesium stearate).
-
Ongoing participation in any other therapeutic clinical trial.
-
Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the subject, makes it unlikely that the course of treatment or follow up would be completed, or could impair the assessment of study results.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California - Davis | Sacramento | California | United States | 95817 |
| 2 | Department of Rehabilitation, The Children's Hospital | Aurora | Colorado | United States | 80045 |
| 3 | Child Neurology Center of NW Florida | Gulf Breeze | Florida | United States | 32561 |
| 4 | University of Iowa Children's Hospital, Division of Child Neurology | Iowa City | Iowa | United States | 52242 |
| 5 | University of Kansas Medical Center | Kansas City | Kansas | United States | 66160 |
| 6 | Children's Hospital of Boston | Boston | Massachusetts | United States | 02115 |
| 7 | University of Minnesota | Minneapolis | Minnesota | United States | 55414 |
| 8 | Washington University Medical School | Saint Louis | Missouri | United States | 63110 |
| 9 | Columbia University | New York | New York | United States | 10032 |
| 10 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 11 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
| 12 | Shriners Hospital for Children-Portland | Portland | Oregon | United States | 97239 |
| 13 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
| 14 | Southwestern University | Dallas | Texas | United States | 75207 |
| 15 | University of Utah | Salt Lake City | Utah | United States | 84112 |
| 16 | The Royal Children's Hospital | Parkville | Victoria | Australia | 3052 |
| 17 | The Children's Hospital at Westmead | Westmead | Australia | 2145 | |
| 18 | UZ Leuven | Leuven | Belgium | ||
| 19 | Alberta Children's Hospital | London | Ontario | Canada | |
| 20 | Children's Hospital of Western Ontario | London | Ontario | Canada | |
| 21 | British Colombia Children's Hopsital | Vancouver | Canada | ||
| 22 | Hopital d'Enfants CHU Timone | Marseille cedex 20 | France | 13385 | |
| 23 | Laboratoire d'Exploration Fonctionnelles | Nantes cedex 1 | France | ||
| 24 | Groupe Hospitalier Pitie-Salpetriere, Institut de Myologie | Paris | France | ||
| 25 | University of Essen - Clinic for Children | Essen | Germany | ||
| 26 | University Hospital | Freiburg | Germany | ||
| 27 | Hadassah University Hopspital | Jerusalem | Israel | ||
| 28 | Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena | Milano | Italy | 20122 | |
| 29 | Ospedale Pediatrico Bambino Gesu | Roma | Italy | 00165 | |
| 30 | U.O. Complessa di Neuropsichiatria Infantile-Policlinico A. Gemelli-Universita Cattolica | Roma | Italy | 00168 | |
| 31 | Hospital Sant Joan de Deu | Barcelona | Spain | ||
| 32 | Hospital Universitario La Fe | Valencia | Spain | ||
| 33 | Queen Silvia Children's Hospital | Goteborg | Sweden | S-416 85 | |
| 34 | Astrid Lindgren Pediatric Hospital | Stockholm | Sweden | ||
| 35 | UCL Instititute of Child Health, Dubowitz | London | United Kingdom | ||
| 36 | University of Newcastle | Newcastle Upon Tyne | United Kingdom | ||
| 37 | Robert Jones & Agnes Hunt Orthopaedic Hospital | Oswestry | United Kingdom |
Sponsors and Collaborators
- PTC Therapeutics
- Genzyme, a Sanofi Company
Investigators
- Study Director: Leone Atkinson, M.D., Ph.D., PTC Therapeutics
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Hirawat S, Welch EM, Elfring GL, Northcutt VJ, Paushkin S, Hwang S, Leonard EM, Almstead NG, Ju W, Peltz SW, Miller LL. Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single- and multiple-dose administration to healthy male and female adult volunteers. J Clin Pharmacol. 2007 Apr;47(4):430-44.
- Welch EM, Barton ER, Zhuo J, Tomizawa Y, Friesen WJ, Trifillis P, Paushkin S, Patel M, Trotta CR, Hwang S, Wilde RG, Karp G, Takasugi J, Chen G, Jones S, Ren H, Moon YC, Corson D, Turpoff AA, Campbell JA, Conn MM, Khan A, Almstead NG, Hedrick J, Mollin A, Risher N, Weetall M, Yeh S, Branstrom AA, Colacino JM, Babiak J, Ju WD, Hirawat S, Northcutt VJ, Miller LL, Spatrick P, He F, Kawana M, Feng H, Jacobson A, Peltz SW, Sweeney HL. PTC124 targets genetic disorders caused by nonsense mutations. Nature. 2007 May 3;447(7140):87-91. Epub 2007 Apr 22.
Responsible Party:
PTC Therapeutics
ClinicalTrials.gov Identifier:
NCT00847379
Other Study ID Numbers:
- PTC124-GD-007e-DMD
First Posted:
Feb 19, 2009
Last Update Posted:
Jul 15, 2020
Last Verified:
Jun 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by PTC Therapeutics
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | A total of 173 participants were screened for eligibility to enter this extension study after completing the 48-week double-blind study PTC124-GD-007-DMD (NCT00592553). All participants met entry criteria and enrolled in this study. |
|---|---|
| Pre-assignment Detail | Participants were categorized by the treatment group to which they had been randomly assigned in Study PTC124-GD-007-DMD (NCT00592553). |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren |
|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally 3 times a day (TID), 20 milligrams/kilogram (mg/kg) at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit (Week 48) in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Period Title: Overall Study | |||
| STARTED | 59 | 57 | 57 |
| As-treated Population | 59 | 57 | 57 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 59 | 57 | 57 |
Baseline Characteristics
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Total of all reporting groups |
| Overall Participants | 59 | 57 | 57 | 173 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
9.4
(2.53)
|
9.7
(2.89)
|
9.3
(2.28)
|
9.5
(2.57)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Male |
59
100%
|
57
100%
|
57
100%
|
173
100%
|
Outcome Measures
| Title | Number of Participants With Treatment-Emergent Adverse Events (AEs) |
|---|---|
| Description | An AE was 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) and severe (interferes significantly with usual function). 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 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 serious AEs, regardless of causality is located in Reported AE section. |
| Time Frame | Baseline (Week 48 of Study 007) up to Week 102 |
Outcome Measure Data
| Analysis Population Description |
|---|
| As-treated population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 59 | 57 | 57 | 173 |
| Any AEs |
52
88.1%
|
49
86%
|
48
84.2%
|
149
86.1%
|
| Drug-related AEs |
10
16.9%
|
10
17.5%
|
22
38.6%
|
42
24.3%
|
| Serious AEs |
0
0%
|
1
1.8%
|
2
3.5%
|
3
1.7%
|
| Mild AEs |
34
57.6%
|
23
40.4%
|
26
45.6%
|
83
48%
|
| Moderate AEs |
13
22%
|
22
38.6%
|
19
33.3%
|
54
31.2%
|
| Severe AEs |
5
8.5%
|
4
7%
|
3
5.3%
|
12
6.9%
|
| Title | Number of Participants With Clinically Significant Abnormal Laboratory Parameters |
|---|---|
| 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 (Week 48 of Study 007) up to Week 102 |
Outcome Measure Data
| Analysis Population Description |
|---|
| As-treated population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 59 | 57 | 57 | 173 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Change From Baseline in 6-Minute Walk Distance (6MWD) at Week 60 |
|---|---|
| Description | 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. |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable at specified timepoints. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 53 | 50 | 49 | 152 |
| Baseline |
351.60
(130.312)
|
375.95
(98.976)
|
356.25
(109.369)
|
361.11
(113.760)
|
| Change at Week 60 |
-17.23
(39.608)
|
-10.50
(41.390)
|
-7.06
(50.121)
|
-11.56
(43.881)
|
| Title | Change From Baseline in Mean Activity Period/Day/Visit at Week 60, as Assessed by Step Activity Monitoring (SAM) |
|---|---|
| Description | The SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). Mean activity period/day/visit was computed for each participant. For each day, an active period was defined as the first time after 3:00 AM that greater than (>) 2 strides/minute were recorded to the last time prior to midnight that >2 strides/minute were recorded. Days were deleted on which such an active period was less than (<) 50 percent (%) of the mean active period across all days for that participant's visit. |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable at specified timepoints. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 53 | 50 | 49 | 152 |
| Baseline |
759.715
(77.5210)
|
742.223
(107.7264)
|
747.464
(102.6531)
|
750.016
(96.1057)
|
| Change at Week 60 |
1.946
(61.2247)
|
34.283
(88.1587)
|
-1.866
(93.0531)
|
10.991
(82.6356)
|
| Title | Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 60, as Assessed by SAM |
|---|---|
| Description | The SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). Mean total step count/day/visit during the active periods was computed for each participant. For each day, an active period was defined as the first time after 3:00 AM that >2 strides/minute were recorded to the last time prior to midnight that >2 strides/minute were recorded. Days were deleted on which such an active period was <50% of the mean active period across all days for that participant's visit. |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable at specified timepoints. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 53 | 50 | 49 | 152 |
| Baseline |
4934.575
(2433.230)
|
4543.766
(2051.300)
|
5175.330
(2307.436)
|
4883.613
(2272.108)
|
| Change at Week 60 |
-357.679
(1232.109)
|
-215.062
(1761.773)
|
-647.504
(1680.522)
|
-409.558
(1566.386)
|
| Title | Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 60, as Assessed by SAM |
|---|---|
| Description | The SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). Mean total step count/hour during the active periods for the days in a visit was computed for each participant. For each day, an active period was defined as the first time after 3:00 AM that >2 strides/minute were recorded to the last time prior to midnight that >2 strides/minute were recorded. Days were deleted on which such an active period was <50% of the mean active period across all days for that participant's visit. |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable at specified timepoints. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 53 | 50 | 49 | 152 |
| Baseline |
395.491
(200.7671)
|
368.672
(155.6648)
|
420.684
(188.9124)
|
394.787
(183.0994)
|
| Change at Week 60 |
-27.650
(87.8797)
|
-34.693
(128.0609)
|
-54.755
(122.4142)
|
-39.010
(113.3481)
|
| Title | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 60, as Assessed by SAM |
|---|---|
| Description | SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear the SAM for at least 9 consecutive days. SAM was used to record the number of strides/minute following each visit. A stride is the leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again (that is, a stride generally equals 2 steps). The maximum continuous 10-minute, 20-minute, 30-minute, and 60-minute total step counts were computed for each participant. For each day, an active period was defined as the first time after 3:00 AM that >2 strides/minute were recorded to the last time prior to midnight that >2 strides/minute were recorded. Days were deleted on which such an active period was <50% of the mean active period across all days for that participant's visit. |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable for specified categories. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 53 | 50 | 49 | 152 |
| Baseline: 10-minute total step count |
34.603
(12.4886)
|
32.863
(8.8533)
|
35.256
(10.0379)
|
34.241
(10.5911)
|
| Change at Week 60: 10-minute total step count |
-1.140
(6.9584)
|
-0.607
(7.2946)
|
-2.372
(7.1735)
|
-1.384
(7.1170)
|
| Baseline: 20-minute total step count |
28.138
(11.0629)
|
26.096
(7.9168)
|
28.323
(9.3133)
|
27.526
(9.5426)
|
| Change at Week 60: 20-minute total step count |
-1.459
(6.7165)
|
-0.662
(6.2171)
|
-2.510
(6.4346)
|
-1.558
(6.4549)
|
| Baseline: 30-minute total step count |
24.222
(9.9576)
|
22.205
(7.1045)
|
24.498
(8.4938)
|
23.648
(8.6306)
|
| Change at Week 60: 30-minute total step count |
-1.400
(5.7605)
|
-0.450
(5.6811)
|
-2.457
(5.9579)
|
-1.452
(5.8110)
|
| Baseline: 60-minute total step count |
18.019
(7.8145)
|
16.453
(5.6625)
|
18.599
(6.9509)
|
17.691
(6.8991)
|
| Change at Week 60: 60-minute total step count |
-0.977
(3.7328)
|
-0.210
(4.7035)
|
-2.257
(5.1038)
|
-1.162
(4.5803)
|
| Title | Change From Baseline in Percentage of Time During Active Period Spent at No Activity (0 Steps/Minute[Min]), Low Activity (Less Than or Equal to [≤]15 Steps/Min), Medium Activity (16-30 Steps/Min), and High Activity (Greater Than[>]30 Steps/Min) at Week 60 |
|---|---|
| Description | SAM is a pedometer (worn on the ankle) that continuously records the number of steps per time interval. Participants were instructed to continue to wear SAM for at least 9 consecutive days. SAM was used to record number of strides/minute following each visit. A stride is leg motion that begins when the foot with SAM leaves the floor and ends when the same foot touches the floor again. Percentage of time during active periods spent at no activity (0 steps/min), low activity (≤15 steps/min), medium activity (16-30 steps/min), and high activity (>30 steps/min) were computed for each participant. For each day, an active period was defined as first time after 3:00 AM that >2 strides/minute were recorded to the last time prior to midnight that >2 strides/minute were recorded. Days were deleted on which such an active period was <50% of the mean active period across all days for that participant's visit. |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable for specified categories. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 53 | 50 | 49 | 152 |
| Baseline: Time spent at no activity |
52.818
(14.4129)
|
53.372
(12.2352)
|
50.006
(12.5263)
|
52.094
(13.1188)
|
| Change at Week 60: Time spent at no activity |
-0.051
(8.1776)
|
0.830
(11.2481)
|
2.194
(7.8652)
|
0.985
(9.1467)
|
| Baseline: Time spent at low activity |
30.677
(7.8531)
|
31.170
(7.2431)
|
32.393
(7.2426)
|
31.392
(7.4462)
|
| Change at Week 60: Time spent at low activity |
1.270
(5.8178)
|
1.172
(8.3050)
|
0.252
(5.5885)
|
0.896
(6.6058)
|
| Baseline: Time spent at medium activity |
10.248
(4.7620)
|
10.119
(4.4344)
|
10.983
(4.6049)
|
10.442
(4.5901)
|
| Change at Week 60: Time spent at medium activity |
-0.542
(2.0960)
|
-1.356
(3.7830)
|
-0.965
(3.3763)
|
-0.944
(3.1392)
|
| Baseline: Time spent at high activity |
6.404
(4.5938)
|
5.370
(3.4243)
|
6.673
(4.5847)
|
6.149
(4.2476)
|
| Change at Week 60: Time spent at high activity |
-0.643
(2.2656)
|
-0.520
(2.7196)
|
-1.506
(2.9904)
|
-0.898
(2.6913)
|
| Title | Change From Baseline in Time to Stand From Supine Position at Week 60 |
|---|---|
| Description | 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. Change from baseline data has been reported. |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable at specified timepoints. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 53 | 50 | 49 | 152 |
| Baseline |
13.736
(11.3353)
|
11.796
(10.3544)
|
12.398
(11.6010)
|
12.666
(11.0678)
|
| Change at Week 60 |
0.665
(3.0080)
|
-0.187
(4.6289)
|
0.002
(4.6322)
|
0.166
(4.1373)
|
| Title | Change From Baseline in Time to Walk/Run 10 Meters at Week 60 |
|---|---|
| Description | 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. Change from baseline data has been reported. |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable at specified timepoints. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 53 | 50 | 49 | 152 |
| Baseline |
8.143
(5.1475)
|
6.986
(2.9995)
|
6.967
(3.5789)
|
7.384
(4.0530)
|
| Change at Week 60 |
1.441
(4.4822)
|
0.547
(2.2058)
|
0.758
(2.6862)
|
0.922
(3.2905)
|
| Title | Change From Baseline in Time to Climb 4 Stairs at Week 60 |
|---|---|
| Description | 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. Change from baseline data has been reported. |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable at specified timepoints. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 53 | 50 | 49 | 152 |
| Baseline |
9.077
(9.2543)
|
6.738
(6.4069)
|
8.071
(9.2057)
|
7.984
(8.4076)
|
| Change at Week 60 |
0.831
(2.4664)
|
0.696
(4.0707)
|
0.194
(2.5268)
|
0.574
(3.0898)
|
| Title | Change From Baseline in Time to Descend 4 Stairs at Week 60 |
|---|---|
| Description | 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. Change from baseline data has been reported. |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable at specified timepoints. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 53 | 50 | 49 | 152 |
| Baseline |
7.685
(8.9934)
|
5.638
(5.5635)
|
6.641
(7.8591)
|
6.675
(7.6319)
|
| Change at Week 60 |
1.167
(4.7624)
|
0.626
(5.2567)
|
-0.648
(4.9202)
|
0.385
(5.0045)
|
| Title | Change From Baseline in Heart Rate Before, During, and After Each 6MWD Test at Week 60, as Assessed by Heart Rate Monitoring With the Polar® RS400 |
|---|---|
| Description | The heart rate was measured with a Polar RS400 heart rate monitor, which consists of a transmitter strap worn around the chest and a wristwatch receiver. The monitor produces a digital text file with 1 value per minute that represents the mean heart rate for that minute. Mean heart rates values were collected prior to, during, and after the 6MWT. The participant rested for 5 minutes in a sitting position prior to the 6MWT, and the mean heart rate for the last minute of this rest period was collected and documented as the resting heart rate. During the 6MWT, the mean heart rate was collected and documented as the active heart rate. After completing the 6MWT and resting for 3 minutes, the mean heart rate for 1 minute was collected and documented as the recovery heart rate. |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and had sufficient baseline and on-treatment data in Study 007e to assess measure of interest, excluding participants who had lost all independent ambulation. 'Number analyzed'=participants evaluable for specified categories. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 53 | 50 | 49 | 152 |
| Baseline: Resting heart rate |
105.3
(13.29)
|
108.8
(10.71)
|
103.7
(12.98)
|
105.9
(12.48)
|
| Change at Week 60: Resting heart rate |
4.0
(13.91)
|
3.7
(10.11)
|
4.8
(10.82)
|
4.2
(11.65)
|
| Baseline: Active heart rate |
138.7
(21.45)
|
144.8
(14.55)
|
138.6
(20.87)
|
140.6
(19.36)
|
| Change at Week 60: Active heart rate |
1.6
(17.65)
|
6.1
(15.45)
|
2.4
(14.87)
|
3.4
(16.07)
|
| Baseline: Recovery heart rate |
110.0
(13.32)
|
112.0
(12.17)
|
109.4
(13.21)
|
110.4
(12.88)
|
| Change at Week 60: Recovery heart rate |
2.1
(12.82)
|
4.6
(12.57)
|
2.3
(11.29)
|
3.0
(12.20)
|
| Title | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 60 |
|---|---|
| Description | Basic attention and working memory was measured using the digit span task. A series of digits (0-9) were presented to the child in an auditory format only. The task had 2 parts; in the forward condition, the child was requested to repeat back the digits in the order they were presented and in the backward condition, he was requested to reverse the order of presentation. A raw score of the total number of correct responses was converted to an age-scaled-score (z-score) by subtracting the corresponding mean and dividing by the corresponding standard deviation of a reference population for that age. |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, who had sufficient baseline and on-treatment data in Study 007e to assess the measure of interest. 'Number analyzed'=participants evaluable for specified categories. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 58 | 56 | 56 | 170 |
| Baseline: Forward condition |
4.1
(2.97)
|
3.6
(2.54)
|
3.2
(2.21)
|
3.6
(2.61)
|
| Change at Week 60: Forward condition |
0.0
(1.53)
|
0.0
(1.19)
|
0.0
(1.22)
|
0.0
(1.32)
|
| Baseline: Backward condition |
1.4
(0.98)
|
1.3
(0.82)
|
1.2
(0.66)
|
1.3
(0.84)
|
| Change at Week 60: Backward condition |
0.1
(0.86)
|
-0.1
(0.66)
|
0.0
(0.58)
|
0.0
(0.71)
|
| Title | Change From Baseline in Participant- Reported Health-Related Quality of Life (HRQL) as Measured by the Pediatric Quality of Life Inventory (PedsQL) Physical, Emotional, Social, and School Functioning Domain Scores at Week 60 |
|---|---|
| Description | HRQL was measured via the PedsQL. The generic core module (including physical, emotional, social and school functioning scales) comprises 23 questions and the fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. The PedsQL was completed by both the participant and/or a parent/caregiver. Examples of items in each of the generic core module scales include: "It is hard for me to run"; "I feel sad or blue"; "I cannot do things that other kids my age can do;" and "It is hard to pay attention in class." Each of the generic core module items was scored on a 5-point Likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating better health-related quality of life. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 60. |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, who had sufficient baseline and on-treatment data in Study 007e to assess the measure of interest. 'Number analyzed'=participants evaluable for specified categories. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 58 | 56 | 56 | 170 |
| Baseline: Physical functioning score |
63.8145
(24.46918)
|
63.3019
(22.72039)
|
60.4865
(22.33484)
|
62.5995
(23.11654)
|
| Change at Week 60: Physical functioning score |
-0.5982
(14.91137)
|
-1.2538
(14.60384)
|
1.2755
(19.01169)
|
-0.1804
(16.23570)
|
| Baseline: Emotional functioning score |
76.852
(21.1530)
|
73.241
(20.1681)
|
73.265
(22.2568)
|
74.490
(21.1086)
|
| Change at Week 60: Emotional functioning score |
-1.675
(13.6361)
|
2.128
(14.9181)
|
-0.995
(13.1621)
|
-0.223
(13.9106)
|
| Baseline: Social functioning score |
72.5000
(21.60429)
|
68.6111
(21.37748)
|
71.3000
(21.32858)
|
70.7911
(21.36670)
|
| Change at Week 60: Social functioning score |
-2.2000
(13.48317)
|
0.8511
(17.36185)
|
0.3500
(15.15237)
|
-0.3571
(15.32468)
|
| Baseline: School functioning score |
72.019
(20.7756)
|
71.111
(18.2918)
|
69.063
(20.3861)
|
70.779
(19.7213)
|
| Change at Week 60: School functioning score |
-1.064
(16.5153)
|
-1.630
(17.7029)
|
1.809
(16.9214)
|
-0.286
(16.9931)
|
| Title | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 60 |
|---|---|
| Description | HRQL was measured via the PedsQL. The generic core module (including physical, emotional, social and school functioning scales) comprises 23 questions and the fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. The PedsQL was completed by both the participant and/or a parent/caregiver. Examples of items in each of the generic core module scales include: "It is hard for me to run"; "I feel sad or blue"; "I cannot do things that other kids my age can do;" and "It is hard to pay attention in class." Each of the generic core module items was scored on a 5-point likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating better health-related quality of life. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48. |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, who had sufficient baseline and on-treatment data in Study 007e to assess the measure of interest. 'Number analyzed'=participants evaluable for specified categories. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 58 | 56 | 56 | 170 |
| Baseline: Physical functioning score |
56.8217
(23.80718)
|
52.5162
(20.02845)
|
52.6307
(24.35727)
|
54.0152
(22.78661)
|
| Change at Week 60: Physical functioning score |
-0.8499
(12.75478)
|
-1.1662
(13.27447)
|
-0.1736
(14.75049)
|
-0.7143
(13.55924)
|
| Baseline: Emotional functioning score |
74.7368
(17.73870)
|
72.5455
(16.04025)
|
68.2813
(22.05309)
|
71.8676
(18.87211)
|
| Change at Week 60: Emotional functioning score |
-1.9231
(11.11289)
|
-0.3061
(13.32323)
|
-1.9213
(16.86642)
|
-1.4113
(13.95342)
|
| Baseline: Social functioning score |
61.9518
(19.07606)
|
61.6136
(15.44605)
|
59.7545
(21.34593)
|
61.1086
(18.71300)
|
| Change at Week 60: Social functioning score |
1.5144
(13.03356)
|
-0.7908
(11.34994)
|
0.3472
(12.76238)
|
0.3790
(12.38287)
|
| Baseline: School functioning score |
68.6607
(16.05363)
|
64.0000
(15.07389)
|
65.9091
(18.20894)
|
66.2048
(16.50694)
|
| Change at Week 60: School functioning score |
0.8000
(9.60230)
|
1.6667
(10.93177)
|
-1.0377
(12.60946)
|
0.4305
(11.13464)
|
| Title | Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 |
|---|---|
| Description | HRQL was measured via the PedsQL. The fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. PedsQL was completed by both the participant and/or a parent/caregiver. Fatigue-specific module obtains information relating to items such as: "I feel too tired to do things that I like to do"; "I spend a lot of time in bed"; and "I have trouble remembering more than one thing at a time;" Each of the fatigue-specific module items was scored on a 5-point Likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating less fatigue. Total score was the sum of all items over the number of items answered on all scales. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 60. |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, who had sufficient baseline and on-treatment data in Study 007e to assess the measure of interest. 'Number analyzed'=participants evaluable at specified timepoints. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 58 | 56 | 56 | 170 |
| Baseline |
76.7968
(18.31310)
|
72.7833
(20.95237)
|
72.5947
(17.32956)
|
74.1111
(18.92041)
|
| Change at Week 60 |
-2.0484
(9.77928)
|
0.3650
(15.94374)
|
-1.8049
(11.12724)
|
-1.2005
(12.42615)
|
| Title | Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 60 |
|---|---|
| Description | HRQL was measured via the PedsQL. The fatigue-specific module (including general fatigue, sleep/rest fatigue, and cognitive fatigue scales) comprises an additional 18 questions. The PedsQL was completed by both the participant and/or a parent/caregiver. Fatigue-specific module obtains information relating to items such as: "I feel too tired to do things that I like to do"; "I spend a lot of time in bed"; and "I have trouble remembering more than one thing at a time;" Each of the fatigue-specific module items was scored on a 5-point likert response scale from 0 (never a problem) to 4 (almost always a problem). Scores were transformed on a scale from 0 to 100 (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating less fatigue. Total score was the sum of all items over the number of items answered on all scales. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 60. |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, who had sufficient baseline and on-treatment data in Study 007e to assess the measure of interest. 'Number analyzed'=participants evaluable at specified timepoints. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 58 | 56 | 56 | 170 |
| Baseline |
75.7864
(13.88014)
|
71.6596
(12.78488)
|
71.1062
(13.62739)
|
72.8724
(13.53355)
|
| Change at Week 60 |
-0.3272
(6.64218)
|
1.2219
(10.11693)
|
0.2269
(8.55130)
|
0.3341
(8.44319)
|
| Title | Change From Baseline in Participant and Parent/Caregiver Reported Activities of Daily Living of Participants Who Were Unable to Complete the 6MWT (Nonambulatory Participants), as Measured by the Egen Klassifikation (EK) Scale at Week 60 |
|---|---|
| Description | Activities of daily living were measured using the EK scale in all participants who were unable to complete the 6MWT at Screening/Baseline on Day 1. The EK scale is an ordinal scale ranging from 0 to 30 points where 0 represents the highest level of independent function and 30 the lowest. The scale consists of 10 categories (each scored 0 to 3), involving different functional domains including 1) ability to use wheelchair, 2) ability to transfer from wheelchair, 3) ability to stand, 4) ability to balance in the wheelchair, 5) ability to move the arms, 6) ability to use the hands and arms when eating, 7) ability to turn in bed, 8) ability to cough, 9) ability to speak, and 10) physical well-being. The administration of the EK scale consisted of an interview of the participant to capture how he performed the tasks of daily life (as described by Categories 1 to 9) and how he perceived his well-being (as described by Category 10). |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Non-Ambulatory 007e population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, and who had lost all independent ambulation prior to entering Study 007e. 'Number analyzed'=participants evaluable at specified timepoints. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 5 | 4 | 6 | 15 |
| Baseline |
3.0
(2.00)
|
4.3
(0.50)
|
3.2
(1.92)
|
3.5
(1.61)
|
| Change at Week 60 |
1.5
(0.58)
|
0.8
(1.26)
|
-0.8
(1.48)
|
0.4
(1.50)
|
| Title | Change From Baseline in Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score at Week 60 |
|---|---|
| Description | TSQM consisted of 14 questions about treatment satisfaction with drug in 4 domains: Effectiveness (Questions 1-3 scored as 1 [extremely dissatisfied] to 7 [extremely satisfied]), Side Effects (question 4 scored as 0 [no] or 1 [yes]; question 5 scored as 1 [extremely bothersome] to 5 [not at all bothersome]; questions 6 - 8 scored as 1 [a great deal] to 5 [not at all]), Convenience (questions 9 and 10 scored as 1 [extremely difficult] to 7 [extremely easy]; question 11 scored as 1 [extremely inconvenient] to 5 [extremely convenient]) and Global Satisfaction (question 12 scored as 1 [not at all confident] to 7 [extremely confident]; question 13 scored as 1 [not at all certain] to 5 [extremely certain]; question 14 scored as 1 [extremely dissatisfied] to 5 [extremely satisfied]). The scores of each of the domains were added together and an algorithm was used to create a score of 0 to 100, with higher scores indicating better treatment satisfaction. |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, who had sufficient baseline and on-treatment data in Study 007e to assess the measure of interest. 'Number analyzed'=participants evaluable for specified categories. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 58 | 56 | 56 | 170 |
| Baseline: Effectiveness score |
56.8134
(26.72451)
|
53.8580
(21.53292)
|
50.4274
(22.96804)
|
53.7212
(23.82541)
|
| Change at Week 60: Effectiveness score |
2.7778
(15.52191)
|
5.6159
(19.53233)
|
1.7778
(14.99307)
|
3.3295
(16.68460)
|
| Baseline: Side-effects score |
96.8182
(10.81681)
|
97.7273
(7.64176)
|
96.8364
(8.94695)
|
97.1291
(9.18246)
|
| Change at Week 60: Side-effects score |
0.7353
(12.16084)
|
-1.0638
(7.74500)
|
-1.2587
(10.84441)
|
-0.4994
(10.43907)
|
| Baseline: Convenience score |
57.4074
(16.10609)
|
57.9798
(19.05889)
|
60.5967
(16.65858)
|
58.6345
(17.26216)
|
| Change at Week 60: Convenience score |
0.8386
(12.39372)
|
-1.6548
(11.75175)
|
1.3333
(9.80472)
|
0.2222
(11.38059)
|
| Baseline: Global satisfaction score |
61.4286
(25.95857)
|
60.4870
(23.30835)
|
56.7791
(21.25768)
|
59.5819
(23.54109)
|
| Change at Week 60: Global satisfaction score |
-0.2695
(13.57882)
|
1.2538
(15.30213)
|
-0.4643
(14.78188)
|
0.1429
(14.45922)
|
| Title | Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 60 |
|---|---|
| Description | Blood samples collected for chemistry assays were used to quantify serum CK concentrations. Serum CK was assessed as a potential biomarker for muscle fragility, with a reduction in serum CK considered to be a positive outcome. |
| Time Frame | Baseline (Week 48 of Study 007), Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e, who had sufficient baseline and on-treatment data in Study 007e to assess the measure of interest. 'Number analyzed'=participants evaluable at specified timepoints. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 58 | 56 | 56 | 170 |
| Baseline |
9163.1
(5542.80)
|
10009.1
(5828.26)
|
9150.7
(5657.67)
|
9442.8
(5656.99)
|
| Change at Week 60 |
-455.1
(4962.00)
|
-520.5
(6164.96)
|
-334.3
(4810.45)
|
-435.1
(5310.37)
|
| Title | Study Drug Compliance |
|---|---|
| Description | Study drug compliance was assessed by participant daily diary and quantification of used and unused study drug. Compliance was assessed in terms of the percentage of drug actually taken relative to the amount that should have been taken during the study. |
| Time Frame | Baseline (Week 48 of Study 007) to Week 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| As-treated population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 59 | 57 | 57 | 173 |
| Median (Full Range) [percentage of drug] |
0.00
|
0.00
|
0.00
|
0.00
|
| Title | Trough Ataluren Plasma Concentration |
|---|---|
| Description | Plasma samples for the determination of ataluren concentrations were analyzed at the bioanalytical laboratory for ataluren parent drug using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC/MS-MS) method with a lower limit of quantitation (LLOQ) of 0.5 micrograms/millilitre (mcg/mL). Values below the LLOQ were set to 0. |
| Time Frame | Pre-morning dose (0 hour) at Baseline (Week 48 of 007 study), Weeks 54, 60, 72, 84, and 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| As-treated population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e. 'Number analyzed'=participants evaluable at specified timepoints. |
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren |
|---|---|---|---|---|
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. |
| Measure Participants | 59 | 57 | 57 | 173 |
| Week 48 |
12.656
(10.8951)
|
4.541
(3.4381)
|
0.000
(0.0000)
|
5.773
(8.4333)
|
| Week 54 |
10.801
(8.4858)
|
13.941
(14.5222)
|
11.564
(9.3312)
|
12.097
(11.1172)
|
| Week 60 |
11.547
(9.6034)
|
13.830
(11.9096)
|
13.302
(9.4765)
|
12.890
(10.3574)
|
| Week 72 |
12.279
(10.5894)
|
13.930
(10.6393)
|
10.948
(6.3465)
|
12.424
(9.4948)
|
| Week 84 |
15.232
(8.8909)
|
14.773
(10.4404)
|
11.082
(14.6331)
|
13.901
(10.7415)
|
| Week 96 |
8.430
|
5.685
(2.7648)
|
6.600
(2.5167)
|
Adverse Events
| Time Frame | Baseline (Week 48 of Study 007) up to Week 102 | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | As-treated population included all participants who completed Study 007 and received ≥1 dose of ataluren in Study 007e. | |||||||
| Arm/Group Title | High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren | ||||
| Arm/Group Description | Participants who were randomized to receive high-dose ataluren in study PTC124-GD-007-DMD, continued to receive ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive low-dose ataluren in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | Participants who were randomized to receive placebo in study PTC124-GD-007-DMD, received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of placebo at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | All participants received ataluren suspension orally TID, 20 mg/kg at morning, 20 mg/kg at midday, and 40 mg/kg at evening (total daily dose 80 mg/kg) for up to 96 weeks in this study. Any participant who was receiving a reduced dose of ataluren at the end of treatment visit in study PTC124-GD-007-DMD, was initiated ataluren therapy in this extension study at the 5-, 5-, and 10-mg/kg dose level; dose was increased to 10, 10, and 20 mg/kg at Week 6 and to 20, 20, and 40 mg/kg at Week 12, if the preceding dose level was well tolerated. | ||||
All Cause Mortality |
||||||||
| High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/59 (0%) | 1/57 (1.8%) | 2/57 (3.5%) | 3/173 (1.7%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Femur fracture | 0/59 (0%) | 1/57 (1.8%) | 1/57 (1.8%) | 2/173 (1.2%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 0/59 (0%) | 0/57 (0%) | 1/57 (1.8%) | 1/173 (0.6%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| High-Dose Ataluren/High-Dose Ataluren | Low-Dose Ataluren/High-Dose Ataluren | Placebo/High-Dose Ataluren | Overall Participants: High-Dose Ataluren | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 53/59 (89.8%) | 51/57 (89.5%) | 51/57 (89.5%) | 155/173 (89.6%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Lymphadenopathy | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 2/57 (3.5%) | 2 | 3/173 (1.7%) | 3 |
| Anaemia | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Microcytic anaemia | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Neutropenia | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Cardiac disorders | ||||||||
| Dilatation ventricular | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 | 2/173 (1.2%) | 2 |
| Arrhythmia | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Cardiomyopathy | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Left ventricular hypertrophy | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Tachycardia | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Congenital, familial and genetic disorders | ||||||||
| Kidney malformation | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Ear and labyrinth disorders | ||||||||
| Deafness | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Ear pain | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Tympanic membrane hyperaemia | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Vertigo | 1/59 (1.7%) | 5 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 5 |
| Endocrine disorders | ||||||||
| Cushingoid | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Eye disorders | ||||||||
| Cataract | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 2/173 (1.2%) | 2 |
| Myopia | 1/59 (1.7%) | 1 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 2/173 (1.2%) | 2 |
| Abnormal sensation in eye | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Conjunctivitis | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Hypermetropia | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Photophobia | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Strabismus | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Vision blurred | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Gastrointestinal disorders | ||||||||
| Vomiting | 11/59 (18.6%) | 16 | 12/57 (21.1%) | 23 | 20/57 (35.1%) | 33 | 43/173 (24.9%) | 72 |
| Diarrhoea | 3/59 (5.1%) | 4 | 11/57 (19.3%) | 13 | 6/57 (10.5%) | 8 | 20/173 (11.6%) | 25 |
| Abdominal pain | 6/59 (10.2%) | 10 | 4/57 (7%) | 4 | 6/57 (10.5%) | 7 | 16/173 (9.2%) | 21 |
| Abdominal pain upper | 2/59 (3.4%) | 2 | 9/57 (15.8%) | 11 | 4/57 (7%) | 5 | 15/173 (8.7%) | 18 |
| Flatulence | 7/59 (11.9%) | 7 | 4/57 (7%) | 4 | 3/57 (5.3%) | 3 | 14/173 (8.1%) | 14 |
| Nausea | 5/59 (8.5%) | 5 | 3/57 (5.3%) | 4 | 3/57 (5.3%) | 3 | 11/173 (6.4%) | 12 |
| Dyspepsia | 1/59 (1.7%) | 1 | 2/57 (3.5%) | 2 | 2/57 (3.5%) | 2 | 5/173 (2.9%) | 5 |
| Constipation | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 3/57 (5.3%) | 3 | 4/173 (2.3%) | 4 |
| Stomach discomfort | 1/59 (1.7%) | 1 | 2/57 (3.5%) | 3 | 1/57 (1.8%) | 1 | 4/173 (2.3%) | 5 |
| Aerophagia | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 2/57 (3.5%) | 2 | 3/173 (1.7%) | 3 |
| Gastrooesophageal reflux disease | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 2/173 (1.2%) | 2 |
| Abdominal discomfort | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 2 | 1/173 (0.6%) | 2 |
| Abdominal pain lower | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Abdominal tenderness | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Abnormal faeces | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Aphthous stomatitis | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Chapped lips | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Duodenogastric reflux | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Eructation | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Faecal incontinence | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Gastritis | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Gastrointestinal sounds abnormal | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Gingivitis | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Oral pain | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Tongue disorder | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| General disorders | ||||||||
| Disease progression | 9/59 (15.3%) | 9 | 7/57 (12.3%) | 7 | 3/57 (5.3%) | 3 | 19/173 (11%) | 19 |
| Asthenia | 2/59 (3.4%) | 3 | 5/57 (8.8%) | 5 | 2/57 (3.5%) | 2 | 9/173 (5.2%) | 10 |
| Gait disturbance | 4/59 (6.8%) | 4 | 3/57 (5.3%) | 3 | 2/57 (3.5%) | 2 | 9/173 (5.2%) | 9 |
| Pyrexia | 4/59 (6.8%) | 4 | 2/57 (3.5%) | 3 | 3/57 (5.3%) | 4 | 9/173 (5.2%) | 11 |
| Fatigue | 3/59 (5.1%) | 3 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 | 5/173 (2.9%) | 5 |
| Malaise | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Oedema peripheral | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Immune system disorders | ||||||||
| Hypersensitivity | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 | 2/173 (1.2%) | 2 |
| Infections and infestations | ||||||||
| Influenza | 7/59 (11.9%) | 7 | 5/57 (8.8%) | 5 | 6/57 (10.5%) | 6 | 18/173 (10.4%) | 18 |
| Nasopharyngitis | 3/59 (5.1%) | 4 | 8/57 (14%) | 10 | 5/57 (8.8%) | 5 | 16/173 (9.2%) | 19 |
| Upper respiratory tract infection | 6/59 (10.2%) | 8 | 3/57 (5.3%) | 4 | 5/57 (8.8%) | 5 | 14/173 (8.1%) | 17 |
| Ear infection | 2/59 (3.4%) | 3 | 2/57 (3.5%) | 2 | 4/57 (7%) | 5 | 8/173 (4.6%) | 10 |
| Gastroenteritis viral | 3/59 (5.1%) | 3 | 1/57 (1.8%) | 2 | 3/57 (5.3%) | 3 | 7/173 (4%) | 8 |
| Gastroenteritis | 2/59 (3.4%) | 2 | 0/57 (0%) | 0 | 3/57 (5.3%) | 4 | 5/173 (2.9%) | 6 |
| Otitis media | 2/59 (3.4%) | 2 | 2/57 (3.5%) | 3 | 1/57 (1.8%) | 1 | 5/173 (2.9%) | 6 |
| Rhinitis | 1/59 (1.7%) | 1 | 1/57 (1.8%) | 1 | 2/57 (3.5%) | 2 | 4/173 (2.3%) | 4 |
| Bronchitis | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 2/57 (3.5%) | 2 | 3/173 (1.7%) | 3 |
| Croup infectious | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 2/57 (3.5%) | 2 | 3/173 (1.7%) | 3 |
| Lower respiratory tract infection | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 3/57 (5.3%) | 4 | 3/173 (1.7%) | 4 |
| Paronychia | 1/59 (1.7%) | 1 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 | 3/173 (1.7%) | 3 |
| Sinusitis | 0/59 (0%) | 0 | 2/57 (3.5%) | 2 | 1/57 (1.8%) | 4 | 3/173 (1.7%) | 6 |
| Urinary tract infection | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 2/57 (3.5%) | 2 | 3/173 (1.7%) | 3 |
| Viral infection | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 2/57 (3.5%) | 2 | 3/173 (1.7%) | 3 |
| Enterobiasis | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 | 2/173 (1.2%) | 2 |
| Gastrointestinal infection | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 2 | 2/173 (1.2%) | 3 |
| Molluscum contagiosum | 1/59 (1.7%) | 1 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 2/173 (1.2%) | 2 |
| Pharyngitis | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 2/173 (1.2%) | 2 |
| Pharyngitis streptococcal | 2/59 (3.4%) | 3 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 2/173 (1.2%) | 3 |
| Tinea pedis | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 3 | 2/173 (1.2%) | 4 |
| Conjunctivitis infective | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Helicobacter infection | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Localised infection | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Lung infection | 0/59 (0%) | 0 | 1/57 (1.8%) | 2 | 0/57 (0%) | 0 | 1/173 (0.6%) | 2 |
| Onychomycosis | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Oral herpes | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Otitis externa | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Pneumonia | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Scarlet fever | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Injury, poisoning and procedural complications | ||||||||
| Fall | 5/59 (8.5%) | 6 | 5/57 (8.8%) | 5 | 4/57 (7%) | 4 | 14/173 (8.1%) | 15 |
| Contusion | 2/59 (3.4%) | 3 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 3/173 (1.7%) | 4 |
| Iliotibial band syndrome | 1/59 (1.7%) | 1 | 2/57 (3.5%) | 2 | 0/57 (0%) | 0 | 3/173 (1.7%) | 3 |
| Joint sprain | 1/59 (1.7%) | 1 | 2/57 (3.5%) | 2 | 0/57 (0%) | 0 | 3/173 (1.7%) | 3 |
| Arthropod bite | 2/59 (3.4%) | 2 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 2/173 (1.2%) | 2 |
| Femur fracture | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 2/173 (1.2%) | 2 |
| Limb injury | 1/59 (1.7%) | 1 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 2/173 (1.2%) | 2 |
| Lower limb fracture | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 2/173 (1.2%) | 2 |
| Arthropod sting | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Excoriation | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Facial bones fracture | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Foot fracture | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Head injury | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Humerus fracture | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Incision site erythema | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Lumbar vertebral fracture | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Mouth injury | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Muscle strain | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Overdose | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Procedural pain | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Skin laceration | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Spinal compression fracture | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Wound | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Wound dehiscence | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Investigations | ||||||||
| Blood sodium increased | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 | 2/173 (1.2%) | 2 |
| Weight decreased | 0/59 (0%) | 0 | 2/57 (3.5%) | 2 | 0/57 (0%) | 0 | 2/173 (1.2%) | 2 |
| Blood bicarbonate decreased | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Blood triglycerides increased | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Breath sounds abnormal | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Weight increased | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 2/59 (3.4%) | 2 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 | 4/173 (2.3%) | 4 |
| Dehydration | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Hypovitaminosis | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Insulin resistance | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Iron deficiency | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 4/59 (6.8%) | 11 | 3/57 (5.3%) | 3 | 4/57 (7%) | 7 | 11/173 (6.4%) | 21 |
| Muscular weakness | 5/59 (8.5%) | 6 | 4/57 (7%) | 4 | 2/57 (3.5%) | 2 | 11/173 (6.4%) | 12 |
| Pain in extremity | 5/59 (8.5%) | 8 | 4/57 (7%) | 4 | 1/57 (1.8%) | 1 | 10/173 (5.8%) | 14 |
| Joint contracture | 4/59 (6.8%) | 4 | 4/57 (7%) | 8 | 1/57 (1.8%) | 1 | 9/173 (5.2%) | 13 |
| Arthralgia | 3/59 (5.1%) | 3 | 4/57 (7%) | 4 | 0/57 (0%) | 0 | 7/173 (4%) | 7 |
| Muscle tightness | 2/59 (3.4%) | 2 | 3/57 (5.3%) | 3 | 1/57 (1.8%) | 1 | 6/173 (3.5%) | 6 |
| Lordosis | 2/59 (3.4%) | 2 | 1/57 (1.8%) | 1 | 2/57 (3.5%) | 2 | 5/173 (2.9%) | 5 |
| Musculoskeletal chest pain | 2/59 (3.4%) | 2 | 1/57 (1.8%) | 1 | 2/57 (3.5%) | 2 | 5/173 (2.9%) | 5 |
| Myalgia | 2/59 (3.4%) | 3 | 2/57 (3.5%) | 2 | 1/57 (1.8%) | 1 | 5/173 (2.9%) | 6 |
| Muscle spasms | 1/59 (1.7%) | 1 | 3/57 (5.3%) | 3 | 0/57 (0%) | 0 | 4/173 (2.3%) | 4 |
| Osteoporosis | 3/59 (5.1%) | 3 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 3/173 (1.7%) | 3 |
| Tendinous contracture | 1/59 (1.7%) | 1 | 2/57 (3.5%) | 2 | 0/57 (0%) | 0 | 3/173 (1.7%) | 3 |
| Muscle atrophy | 1/59 (1.7%) | 1 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 2/173 (1.2%) | 2 |
| Scoliosis | 0/59 (0%) | 0 | 2/57 (3.5%) | 2 | 0/57 (0%) | 0 | 2/173 (1.2%) | 2 |
| Tendon disorder | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 | 2/173 (1.2%) | 2 |
| Coccydynia | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Groin pain | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Growth retardation | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Joint instability | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Muscle contracture | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Musculoskeletal pain | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Neck pain | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Musculoskeletal stiffness | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Skin papilloma | 1/59 (1.7%) | 1 | 4/57 (7%) | 5 | 1/57 (1.8%) | 1 | 6/173 (3.5%) | 7 |
| Melanocytic naevus | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Nervous system disorders | ||||||||
| Headache | 5/59 (8.5%) | 48 | 15/57 (26.3%) | 48 | 14/57 (24.6%) | 17 | 34/173 (19.7%) | 113 |
| Migraine | 2/59 (3.4%) | 2 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 | 4/173 (2.3%) | 4 |
| Areflexia | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Dizziness | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Hypertonia | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Hypotonia | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Memory impairment | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Partial seizures | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Sedation | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Sinus headache | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Psychiatric disorders | ||||||||
| Attention deficit/hyperactivity disorder | 2/59 (3.4%) | 2 | 2/57 (3.5%) | 2 | 1/57 (1.8%) | 1 | 5/173 (2.9%) | 5 |
| Abnormal behaviour | 0/59 (0%) | 0 | 3/57 (5.3%) | 3 | 0/57 (0%) | 0 | 3/173 (1.7%) | 3 |
| Aggression | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 2/173 (1.2%) | 2 |
| Obsessive-compulsive disorder | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 2/57 (3.5%) | 2 | 2/173 (1.2%) | 2 |
| Tic | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 2 | 2/173 (1.2%) | 3 |
| Depression | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Frustration | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Oppositional defiant disorder | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Renal and urinary disorders | ||||||||
| Enuresis | 2/59 (3.4%) | 2 | 3/57 (5.3%) | 3 | 1/57 (1.8%) | 1 | 6/173 (3.5%) | 6 |
| Urine abnormality | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 2/57 (3.5%) | 2 | 3/173 (1.7%) | 3 |
| Pollakiuria | 1/59 (1.7%) | 1 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 2/173 (1.2%) | 2 |
| Urinary incontinence | 2/59 (3.4%) | 2 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 2/173 (1.2%) | 2 |
| Dysuria | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Haematuria | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Kidney enlargement | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Micturition urgency | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Pyelocaliectasis | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Renal cyst | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Ureteric dilatation | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 6/59 (10.2%) | 6 | 1/57 (1.8%) | 1 | 6/57 (10.5%) | 6 | 13/173 (7.5%) | 13 |
| Oropharyngeal pain | 4/59 (6.8%) | 6 | 2/57 (3.5%) | 2 | 1/57 (1.8%) | 1 | 7/173 (4%) | 9 |
| Nasal congestion | 2/59 (3.4%) | 2 | 2/57 (3.5%) | 2 | 2/57 (3.5%) | 2 | 6/173 (3.5%) | 6 |
| Epistaxis | 3/59 (5.1%) | 3 | 1/57 (1.8%) | 2 | 0/57 (0%) | 0 | 4/173 (2.3%) | 5 |
| Wheezing | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 2/173 (1.2%) | 2 |
| Asthma | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Dyspnoea | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Pharyngeal erythema | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Postnasal drip | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Productive cough | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Respiratory tract congestion | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Rhinitis allergic | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Sinus congestion | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Snoring | 0/59 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 1/173 (0.6%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||
| Rash | 2/59 (3.4%) | 2 | 1/57 (1.8%) | 1 | 3/57 (5.3%) | 3 | 6/173 (3.5%) | 6 |
| Dry skin | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 2/57 (3.5%) | 2 | 3/173 (1.7%) | 3 |
| Ecchymosis | 2/59 (3.4%) | 2 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 2/173 (1.2%) | 2 |
| Eczema | 1/59 (1.7%) | 2 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 2/173 (1.2%) | 3 |
| Pruritus | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 | 2/173 (1.2%) | 2 |
| Acne | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Cold sweat | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Hyperkeratosis | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Keratosis pilaris | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Petechiae | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Pityriasis rosea | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Rash maculo-papular | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Rash papular | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Skin chapped | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Skin depigmentation | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Skin discolouration | 0/59 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Skin exfoliation | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Skin odour abnormal | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Swelling face | 1/59 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 | 1/173 (0.6%) | 1 |
| Vascular disorders | ||||||||
| Hot flush | 0/59 (0%) | 0 | 1/57 (1.8%) | 2 | 0/57 (0%) | 0 | 1/173 (0.6%) | 2 |
| Hypertension | 0/59 (0%) | 0 | 2/57 (3.5%) | 2 | 2/57 (3.5%) | 2 | 4/173 (2.3%) | 4 |
Limitations/Caveats
This study was prematurely terminated by Sponsor per Data Monitoring Committee (DMC) recommendation to discontinue ongoing studies of high-dose ataluren in nmDBMD due to lack of efficacy for the high-dose ataluren.
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.
Results Point of Contact
| Name/Title | Patient Advocacy |
|---|---|
| Organization | PTC Therapeutics, Inc. |
| Phone | 1-866-562-4620 |
| medinfo@ptcbio.com |
Responsible Party:
PTC Therapeutics
ClinicalTrials.gov Identifier:
NCT00847379
Other Study ID Numbers:
- PTC124-GD-007e-DMD
First Posted:
Feb 19, 2009
Last Update Posted:
Jul 15, 2020
Last Verified:
Jun 1, 2020