Phase 2B Study of PTC124 (Ataluren) in Duchenne/Becker Muscular Dystrophy (DMD/BMD)
Study Details
Study Description
Brief Summary
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 13 percent (%) of boys with the disease. Ataluren is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 2b trial that will evaluate the clinical benefit of ataluren in boys with DMD/BMD due to a nonsense mutation. The main goals of the study are to understand whether ataluren can improve walking, activity, muscle function, and strength and whether the drug can safely be given for a long period of time.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This study is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, efficacy and safety study, designed to document the clinical benefit of ataluren when administered as therapy of patients with DMD/BMD due to a nonsense mutation (premature stop codon) in the dystrophin gene.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: High-Dose Ataluren Participants will 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 48 weeks. |
Drug: Ataluren
Ataluren will be administered as per the dose and schedule specified in the respective arms.
Other Names:
|
| Experimental: Low-Dose Ataluren Participants will receive ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. |
Drug: Ataluren
Ataluren will be administered as per the dose and schedule specified in the respective arms.
Other Names:
|
| Placebo Comparator: Placebo Participants will receive placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
Drug: Placebo
Placebo matching to ataluren will be administered as the schedule specified in the respective arm.
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in 6MWD at Week 48 [Baseline, Week 48]
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.
Secondary Outcome Measures
- Change From Baseline in Time to Stand From Supine Position at Week 48 [Baseline, Week 48]
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 48 [Baseline, Week 48]
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 48 [Baseline, Week 48]
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 48 [Baseline, Week 48]
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 Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry [Baseline, Week 48]
Upper and lower extremity myometry was performed using a myometer following standardized procedures. Muscle groups evaluated included knee flexors, knee extensors, elbow flexors, elbow extensors, and shoulder abductors. Bilateral assessments were done and 3 measurements were recorded from each muscle group on each side if possible. Mean values for the left and right sides were calculated.
- Change From Baseline in Mean Activity Period/Day/Visit at Week 48, as Assessed by Step Activity Monitoring (SAM) [Baseline, Week 48]
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. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. 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 48, as Assessed by SAM [Baseline, Week 48]
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. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. 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 48, as Assessed by SAM [Baseline, Week 48]
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. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. 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 48, as Assessed by SAM [Baseline, Week 48]
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. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. 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 the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 [Baseline, Week 48]
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. Proportion of time during active periods spent at low activity(≤15 steps/minute), medium activity(16-30 steps/minute), and high activity(>30 steps/minute) were computed for each participant. Mean obtained during Screening and following Week 1 visit were used as baseline data for analysis. 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 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 48 [Baseline, Week 48]
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 Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 [Baseline, Week 48]
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 48 [Baseline, Week 48]
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 48.
- Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 [Baseline, Week 48]
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 48.
- Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score [Week 48]
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 Participant/Caregiver-Reported Number of Daily Accidental Falls at Week 48 [Baseline, Week 48]
Number of falls was determined by daily diary records maintained by participants and/or parent/caregivers.
- Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 [Baseline, Week 48]
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 Heart Rate Before, During, and After Each 6MWT at Week 48, as Assessed by Heart Rate Monitoring With the Polar® RS400 [Baseline, Week 48]
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 Serum Concentration of Creatine Kinase (CK) at Week 48 [Baseline, Week 48]
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.
- Percent Change From Pre-Treatment Visit (1 Week Prior to Baseline Visit) in Biceps Muscle Dystrophin Expression at Post-Treatment Visit (Week 36), as Determined by Immunofluorescence [Pre-Treatment (1 week prior to baseline), post-treatment (Week 36)]
Immunofluorescence evidence of a change in dystrophin expression on biceps muscle biopsy was defined as an increase in the staining of the sarcolemmal membrane with an antibody to the C-terminal portion of the dystrophin protein (excluding revertant fibers) between the pre-treatment (1 week prior to Baseline visit) and post-treatment (Week 36) biopsies. The biceps muscle was biopsied from one arm for confirmation of the absence or reduced levels of dystrophin prior to treatment initiation and from the other arm to assess for production of dystrophin post-treatment.
Other Outcome Measures
- Percentage of Participants With Treatment-Emergent Adverse Events (AEs) [Baseline up to Week 54]
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. Treatment-emergent adverse event (TEAE) was defined as an adverse event that occurred or worsened in the period extending from first dose of study drug to 6 weeks after the last dose of study drug. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.
- Study Drug Compliance [Baseline to Week 48]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if <18 years of age).
-
Male sex.
-
Age ≥5 years.
-
Phenotypic evidence of DMD/BMD based on the onset of characteristic clinical symptoms or signs (that is, proximal muscle weakness, waddling gait, and Gowers' maneuver) by 9 years of age, an elevated serum CK level, and ongoing difficulty with ambulation.
-
Documentation of the presence of a nonsense point mutation in the dystrophin gene as determined by gene sequencing from a laboratory certified by the College of American Pathologists (CAP), the Clinical Laboratory Improvement Act/Amendment (CLIA), or an equivalent organization.
-
Documentation that a blood sample has been drawn for confirmation of the presence of a nonsense mutation in the dystrophin gene.
-
Ability to walk ≥75 meters unassisted during the screening 6-minute walk test. Note: Other personal assistance or use of assistive devices for ambulation (for example, short leg braces, long leg braces or walkers) were not permitted.
-
Confirmed screening laboratory values within the central laboratory ranges (hepatic, adrenal, renal, and serum electrolytes parameters).
-
In participants who were sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and 6-week follow-up periods.
-
Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions. Note: Psychological, social, familial, or geographical factors that might preclude adequate study participation (in particular, the ability to satisfactorily perform the 6MWT) should have been considered.
Exclusion Criteria:
-
Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of study treatment.
-
Initiation of systemic corticosteroid therapy within 6 months prior to start of study treatment or change in systemic corticosteroid therapy (for example, initiation, change in type of drug, dose modification not related to body weight change, schedule modification, interruption, discontinuation, or reinitiation) within 3 months prior to start of study treatment.
-
Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or reinitiation) in prophylaxis/treatment for congestive heart failure within 3 months prior to start of study treatment.
-
Treatment with warfarin within 1 month prior to start of study treatment.
-
Prior therapy with ataluren.
-
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).
-
Exposure to another investigational drug within 2 months prior to start of study treatment.
-
History of major surgical procedure within 30 days prior to start of study treatment.
-
Ongoing immunosuppressive therapy (other than corticosteroids).
-
Ongoing participation in any other therapeutic clinical trial.
-
Expectation of major surgical procedure (for example, scoliosis surgery) during the 12-month treatment period of the study.
-
Requirement for daytime ventilator assistance.
-
Clinical symptoms and signs of congestive heart failure (American College of Cardiology/American Heart Association Stage C or Stage D) or evidence on echocardiogram of clinically significant myopathy.
-
Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, electrocardiogram findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California-Davis | Sacramento | California | United States | |
| 2 | The Children's Hospital | Aurora | Colorado | United States | |
| 3 | Child Neurology Center of Pensacola | Pensacola | Florida | United States | |
| 4 | University of Iowa Healthcare | Iowa City | Iowa | United States | |
| 5 | University of Kansas Medical Centre | Kansas City | Kansas | United States | |
| 6 | Children's Hospital of Boston/Harvard Medical School | Boston | Massachusetts | United States | |
| 7 | University of Minnesota | Minneapolis | Minnesota | United States | |
| 8 | Washington University School of Medicine | Saint Louis | Missouri | United States | |
| 9 | Columbia University Medical School | New York | New York | United States | |
| 10 | Duke University Medical Center | Durham | North Carolina | United States | |
| 11 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229-3039 |
| 12 | Shriners Hospital for Children | Portland | Oregon | United States | |
| 13 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | |
| 14 | Southwestern University | Dallas | Texas | United States | |
| 15 | University of Utah | Salt Lake City | Utah | United States | |
| 16 | Royal Children's Hospital | Parkville | Victoria | Australia | |
| 17 | Institute For Neuromuscular Research, The Children's Hospital at Westmead | Westmead | Australia | ||
| 18 | University Hospital KU Leuven | Leuven | Belgium | ||
| 19 | Alberta Children's Hospital | Calgary | Alberta | Canada | |
| 20 | British Columbia Children's Hospital | Vancouver | British Columbia | Canada | |
| 21 | London Health Sciences Center | London | Ontario | Canada | |
| 22 | Service de Neuropediatrie, hôpital La Timone | Marseille | France | ||
| 23 | Neuromuscular center of Nantes | Nantes | France | ||
| 24 | Groupe Hospitalier La Pitie-Salpetriere | Paris | France | ||
| 25 | University Clinic for Children, University of Essen | Essen | Germany | ||
| 26 | University Hospital | Freiburg | Germany | ||
| 27 | Hadassah Medical Center, Hebrew University Hospital | Jerusalem | Israel | ||
| 28 | Ospedale Maggiore Policlinico in Milan | Milan | Italy | ||
| 29 | Ospedale Pediatrico Bambino Gesu | Rome | Italy | ||
| 30 | U.O. Complessa di Neuropsichiatria Infantile | Rome | Italy | ||
| 31 | Hospital Sant Joan de déu | Barcelona | Spain | ||
| 32 | Hospital Universitari La Fe | Valencia | Spain | ||
| 33 | Queen Silvia Children's Hospital | Göteborg | Sweden | ||
| 34 | Astrid Lindgren Pediatric Hospital | Stockholm | Sweden | ||
| 35 | Imperial College London, Hammersmith Hospital | London | United Kingdom | ||
| 36 | Univ of Newcastle, Institute of Human Genetics | Newcastle | United Kingdom | ||
| 37 | Robert Jones and Agnes Hunt Orthopaedic NHS Trust | Oswestry | United Kingdom |
Sponsors and Collaborators
- PTC Therapeutics
Investigators
- Study Director: Leone Atkinson, MD, PhD, PTC Therapeutics
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PTC124-GD-007-DMD
- 2007-005478-29
Study Results
Participant Flow
| Recruitment Details | A total of 185 participants were screened for eligibility, of which 11 participants did not meet entry criteria. |
|---|---|
| Pre-assignment Detail | A total of 174 eligible participants were randomized in 1:1:1 ratio to receive either placebo, low-dose ataluren, or high-dose ataluren. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | Participants received 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Period Title: Overall Study | |||
| STARTED | 60 | 57 | 57 |
| As-treated Population | 60 | 57 | 57 |
| ITT Population | 60 | 57 | 57 |
| COMPLETED | 59 | 57 | 57 |
| NOT COMPLETED | 1 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo | Total |
|---|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. | Total of all reporting groups |
| Overall Participants | 60 | 57 | 57 | 174 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
8.4
(2.53)
|
8.8
(2.91)
|
8.3
(2.33)
|
8.5
(2.59)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Male |
60
100%
|
57
100%
|
57
100%
|
174
100%
|
| 6-Minute Walk Distance (6MWD) (meters) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [meters] |
358.2
(103.97)
|
350.0
(97.55)
|
359.6
(87.67)
|
356.0
(96.30)
|
Outcome Measures
| Title | Change From Baseline in 6MWD at Week 48 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 59 | 55 | 55 |
| Mean (Standard Deviation) [meters] |
-41.81
(89.234)
|
-12.86
(72.007)
|
-42.56
(90.046)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | High-Dose Ataluren, Placebo |
|---|---|---|
| Comments | Analysis was performed using mixed model for repeated measures (MMRM) method including rank transformed 6MWD as the dependent variable; and rank transformed baseline 6MWD, treatment, visit, age (less than [<] 9 years versus [vs.] greater than or equal to [>=] 9 years) and corticosteroid use (yes vs. no) stratification factors, and interaction between treatment and visit as independent variables. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4756 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Square (LS) Mean Difference |
| Estimated Value | -30.52 | |
| Confidence Interval |
(2-Sided) 95% -114.8 to 53.75 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 42.68 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Low-Dose Ataluren, Placebo |
|---|---|---|
| Comments | Analysis was performed using MMRM method including rank transformed 6MWD as the dependent variable; and rank transformed baseline 6MWD, treatment, visit, age (< 9 years vs. >= 9 years) and corticosteroid use (yes vs. no) stratification factors, and interaction between treatment and visit as independent variables. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1490 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 62.65 | |
| Confidence Interval |
(2-Sided) 95% -22.66 to 147.96 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 43.21 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Time to Stand From Supine Position at Week 48 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable at specified timepoint. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Baseline |
12.25
(11.191)
|
10.80
(9.924)
|
11.50
(11.440)
|
| Change at Week 48 |
3.00
(5.686)
|
3.23
(5.761)
|
3.24
(7.253)
|
| Title | Change From Baseline in Time to Walk/Run 10 Meters at Week 48 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable at specified timepoint. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Baseline |
7.80
(5.243)
|
7.45
(4.373)
|
6.86
(2.813)
|
| Change at Week 48 |
2.37
(6.149)
|
1.68
(5.617)
|
3.03
(6.691)
|
| Title | Change From Baseline in Time to Climb 4 Stairs at Week 48 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable at specified timepoint. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Baseline |
7.63
(7.522)
|
6.94
(6.474)
|
6.04
(5.661)
|
| Change at Week 48 |
3.51
(6.794)
|
2.39
(4.618)
|
4.79
(7.949)
|
| Title | Change From Baseline in Time to Descend 4 Stairs at Week 48 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable at specified timepoint. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Baseline |
6.75
(7.219)
|
6.08
(5.985)
|
5.52
(5.753)
|
| Change at Week 48 |
2.95
(7.323)
|
2.41
(6.162)
|
4.03
(7.828)
|
| Title | Change From Baseline in Force Exerted During Knee Flexion and Extension, Elbow Flexion and Extension, and Shoulder Abduction at Week 48, as Assessed by Myometry |
|---|---|
| Description | Upper and lower extremity myometry was performed using a myometer following standardized procedures. Muscle groups evaluated included knee flexors, knee extensors, elbow flexors, elbow extensors, and shoulder abductors. Bilateral assessments were done and 3 measurements were recorded from each muscle group on each side if possible. Mean values for the left and right sides were calculated. |
| Time Frame | Baseline, Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable for specified categories. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Baseline: Force during knee flexion |
12.45
(4.684)
|
12.08
(4.217)
|
11.06
(3.494)
|
| Change at Week 48: Force during knee flexion |
0.39
(3.148)
|
-0.07
(3.511)
|
0.38
(2.991)
|
| Baseline: Force during knee extension |
12.71
(7.910)
|
12.81
(5.753)
|
12.96
(6.162)
|
| Change at Week 48: Force during knee extension |
-0.59
(3.511)
|
-0.63
(3.616)
|
-1.85
(3.899)
|
| Baseline: Force exerted during elbow flexion |
8.72
(4.709)
|
7.66
(3.154)
|
8.14
(2.972)
|
| Change at Week 48: Force during elbow flexion |
-0.50
(1.832)
|
-0.10
(1.680)
|
-0.35
(1.807)
|
| Baseline: Force during elbow extension |
6.81
(3.815)
|
6.19
(3.083)
|
6.77
(2.785)
|
| Change at Week 48: Force during elbow extension |
-0.28
(1.473)
|
0.10
(1.493)
|
-0.51
(2.333)
|
| Title | Change From Baseline in Mean Activity Period/Day/Visit at Week 48, 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. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoint. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Baseline |
756.84
(84.612)
|
761.86
(76.984)
|
751.71
(60.513)
|
| Change at Week 48 |
0.87
(57.833)
|
-22.23
(84.759)
|
-19.91
(91.960)
|
| Title | Change From Baseline in Mean Total Step Count/Day/Visit During the Active Periods at Week 48, 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. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoint. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Baseline |
5302.31
(1907.058)
|
4870.13
(2165.522)
|
5602.31
(2023.543)
|
| Change at Week 48 |
-615.14
(1468.452)
|
-676.46
(1717.535)
|
-908.34
(1999.969)
|
| Title | Change From Baseline in Mean Total Step Count/Hour During the Active Period at Week 48, 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. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoint. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Baseline |
423.67
(168.754)
|
383.62
(161.911)
|
446.37
(160.666)
|
| Change at Week 48 |
-44.51
(125.154)
|
-42.23
(126.429)
|
-59.62
(153.054)
|
| Title | Change From Baseline in Maximum Continuous 10-minute, 20-minute, 30-minute, and 60-minute Total Step Count at Week 48, 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. Mean obtained during Screening (Week -6 to -1) and following Week 1 visit were used as baseline data for analysis. 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable for this outcome measure for specified categories. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Baseline: 10-minute total step count |
35.77
(10.222)
|
32.24
(11.374)
|
36.76
(8.935)
|
| Change at Week 48: 10-minute total step count |
-2.77
(8.569)
|
-2.79
(6.355)
|
-3.97
(9.720)
|
| Baseline: 20-minute total step count |
29.13
(9.272)
|
25.68
(10.038)
|
29.74
(8.205)
|
| Change at Week 48: 20-minute total step count |
-2.49
(7.407)
|
-2.40
(5.806)
|
-3.55
(8.677)
|
| Baseline: 30-minute total step count |
25.00
(8.053)
|
22.08
(9.206)
|
25.70
(7.350)
|
| Change at Week 48: 30-minute total step count |
-2.08
(6.519)
|
-2.31
(5.505)
|
-3.03
(7.604)
|
| Baseline: 60-minute total step count |
18.58
(6.210)
|
16.52
(7.199)
|
19.50
(5.887)
|
| Change at Week 48: 60-minute total step count |
-1.50
(5.177)
|
-1.85
(4.616)
|
-2.33
(6.241)
|
| Title | Change From Baseline in Percentage of Time During the Active Period Spent at Low Activity (Less Than or Equal to [≤] 15 Steps/Minute), Medium Activity (16-30 Steps/Minute), and High Activity (Greater Than [>]30 Steps/Minute) at Week 48 |
|---|---|
| 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. Proportion of time during active periods spent at low activity(≤15 steps/minute), medium activity(16-30 steps/minute), and high activity(>30 steps/minute) were computed for each participant. Mean obtained during Screening and following Week 1 visit were used as baseline data for analysis. 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable for this outcome measure for specified categories. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Baseline: Time spent at low activity |
32.91
(7.842)
|
32.38
(8.213)
|
32.86
(6.239)
|
| Change at Week 48: Time spent at low activity |
-2.06
(7.903)
|
-1.12
(8.220)
|
-1.11
(5.586)
|
| Baseline: Time spent at medium activity |
11.11
(4.013)
|
10.00
(3.656)
|
11.84
(4.304)
|
| Change at Week 48: Time spent at medium activity |
-1.35
(3.348)
|
-0.69
(3.828)
|
-1.92
(4.178)
|
| Baseline: Time spent at high activity |
6.59
(4.077)
|
5.78
(3.785)
|
7.17
(3.700)
|
| Change at Week 48: Time spent at high activity |
-0.66
(2.790)
|
-0.96
(2.828)
|
-1.03
(3.783)
|
| 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 48 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable for this outcome measure for specified categories. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Baseline: Physical functioning score |
63.63
(20.029)
|
59.27
(22.782)
|
61.87
(19.411)
|
| Change at Week 48: Physical functioning score |
-0.94
(19.125)
|
2.37
(25.105)
|
-1.00
(24.022)
|
| Baseline: Emotional functioning score |
73.92
(20.418)
|
73.70
(20.223)
|
70.13
(19.332)
|
| Change at Week 48: Emotional functioning score |
2.36
(16.742)
|
-1.83
(23.725)
|
4.30
(22.315)
|
| Baseline: Social functioning score |
67.50
(21.749)
|
65.09
(18.421)
|
63.36
(20.476)
|
| Change at Week 48: Social functioning score |
5.37
(20.463)
|
3.89
(21.841)
|
7.75
(18.870)
|
| Baseline: School functioning score |
67.72
(19.276)
|
64.55
(20.396)
|
64.65
(17.841)
|
| Change at Week 48: School functioning score |
3.61
(13.008)
|
6.11
(23.765)
|
4.06
(23.244)
|
| Title | Change From Baseline in Parent/Caregiver- Reported HRQL as Measured by the PedsQL Physical, Emotional, Social, and School Functioning Domain Scores at Week 48 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable for this outcome measure for specified categories. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Baseline: Physical functioning score |
56.15
(19.955)
|
54.96
(20.592)
|
51.47
(19.274)
|
| Change at Week 48: Physical functioning score |
0.03
(17.088)
|
-3.10
(16.550)
|
0.23
(23.712)
|
| Baseline: Emotional functioning score |
70.08
(16.836)
|
69.11
(18.711)
|
65.96
(17.964)
|
| Change at Week 48: Emotional functioning score |
4.07
(15.382)
|
3.39
(18.068)
|
1.21
(17.794)
|
| Baseline: Social functioning score |
61.58
(15.825)
|
62.77
(16.540)
|
55.79
(18.269)
|
| Change at Week 48: Social functioning score |
-0.40
(18.470)
|
-1.09
(14.268)
|
3.71
(14.130)
|
| Baseline: School functioning score |
66.17
(18.258)
|
66.16
(16.320)
|
61.93
(13.587)
|
| Change at Week 48: School functioning score |
2.73
(18.490)
|
-2.32
(15.462)
|
3.48
(13.913)
|
| Title | Change From Baseline in Participant-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 |
|---|---|
| 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 48. |
| Time Frame | Baseline, Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoint. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Baseline |
69.47
(16.525)
|
71.62
(16.474)
|
69.70
(15.263)
|
| Change at Week 48 |
6.95
(13.460)
|
0.45
(23.068)
|
3.92
(16.512)
|
| Title | Change From Baseline in Parent/Caregiver-Reported HRQL as Measured by the Total Fatigue Scale Score at Week 48 |
|---|---|
| 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 48. |
| Time Frame | Baseline, Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoint. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Baseline |
73.39
(13.671)
|
70.71
(12.720)
|
68.27
(13.170)
|
| Change at Week 48 |
1.97
(13.873)
|
1.27
(12.095)
|
2.51
(12.039)
|
| Title | Parent/Caregiver-Reported Treatment Satisfaction Questionnaire for Medication (TSQM) Score |
|---|---|
| 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 | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable for this outcome measure for specified categories. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Effectiveness score |
55.97
(27.796)
|
54.60
(22.307)
|
51.26
(23.536)
|
| Side-effects score |
96.36
(11.199)
|
97.77
(7.578)
|
96.89
(8.874)
|
| Convenience score |
55.85
(17.008)
|
58.23
(19.040)
|
60.91
(16.665)
|
| Global satisfaction score |
61.04
(25.967)
|
61.19
(23.691)
|
57.56
(21.851)
|
| Title | Change From Baseline in Participant/Caregiver-Reported Number of Daily Accidental Falls at Week 48 |
|---|---|
| Description | Number of falls was determined by daily diary records maintained by participants and/or parent/caregivers. |
| Time Frame | Baseline, Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoint. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Baseline |
0.40
(0.597)
|
0.27
(0.480)
|
0.54
(0.943)
|
| Change at Week 48 |
-0.10
(0.466)
|
-0.06
(0.501)
|
0.20
(1.282)
|
| Title | Change From Baseline in Number of Digits Recalled Forwards and Backwards on Digit Span Task at Week 48 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable for this outcome measure for specified categories. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Baseline: Forward condition |
3.59
(2.554)
|
2.89
(2.180)
|
2.84
(1.675)
|
| Change at Week 48: Forward condition |
0.39
(1.677)
|
0.50
(1.767)
|
0.40
(1.550)
|
| Baseline: Backward condition |
1.73
(1.846)
|
1.70
(1.868)
|
1.59
(1.460)
|
| Change at Week 48: Backward condition |
0.56
(1.500)
|
0.33
(1.441)
|
0.59
(1.203)
|
| Title | Change From Baseline in Heart Rate Before, During, and After Each 6MWT at Week 48, 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable for this outcome measure for specified categories. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Baseline: Resting heart rate |
105.47
(12.908)
|
109.70
(9.908)
|
104.07
(11.588)
|
| Change at Week 48: Resting heart rate |
-0.63
(13.008)
|
-0.36
(10.223)
|
-0.26
(15.614)
|
| Baseline: Active heart rate |
142.67
(18.070)
|
141.77
(15.574)
|
136.67
(20.713)
|
| Change at Week 48: Active heart rate |
-5.00
(21.976)
|
2.39
(19.095)
|
1.65
(21.295)
|
| Baseline: Recovery heart rate |
109.90
(12.633)
|
113.48
(10.340)
|
107.86
(12.066)
|
| Change at Week 48: Recovery heart rate |
-0.23
(13.475)
|
-1.33
(13.270)
|
0.54
(15.181)
|
| Title | Change From Baseline in Serum Concentration of Creatine Kinase (CK) at Week 48 |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and received any study treatment; and had a valid baseline, and at least one valid post-baseline 6MWD value. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoint. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Baseline |
10853.65
(6251.136)
|
12084.70
(7772.631)
|
10569.60
(6488.477)
|
| Change at Week 48 |
-1680.09
(4264.769)
|
-2146.32
(7151.944)
|
-1235.13
(4323.943)
|
| Title | Percent Change From Pre-Treatment Visit (1 Week Prior to Baseline Visit) in Biceps Muscle Dystrophin Expression at Post-Treatment Visit (Week 36), as Determined by Immunofluorescence |
|---|---|
| Description | Immunofluorescence evidence of a change in dystrophin expression on biceps muscle biopsy was defined as an increase in the staining of the sarcolemmal membrane with an antibody to the C-terminal portion of the dystrophin protein (excluding revertant fibers) between the pre-treatment (1 week prior to Baseline visit) and post-treatment (Week 36) biopsies. The biceps muscle was biopsied from one arm for confirmation of the absence or reduced levels of dystrophin prior to treatment initiation and from the other arm to assess for production of dystrophin post-treatment. |
| Time Frame | Pre-Treatment (1 week prior to baseline), post-treatment (Week 36) |
Outcome Measure Data
| Analysis Population Description |
|---|
| As-treated population included all randomized participants who actually received any study treatment. Here, 'Number analyzed' signifies participants evaluable for this outcome measure at specified timepoint. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Pre-treatment |
336.096
(138.9753)
|
359.797
(142.7361)
|
357.271
(139.6650)
|
| Percent change post-treatment |
-1.278
(27.7432)
|
-2.128
(28.8287)
|
-0.898
(19.2112)
|
| Title | Percentage 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. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. Treatment-emergent adverse event (TEAE) was defined as an adverse event that occurred or worsened in the period extending from first dose of study drug to 6 weeks after the last dose of study drug. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. |
| Time Frame | Baseline up to Week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| As-treated population included all randomized participants who actually received any study treatment. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Number [percentage of participants] |
95.0
158.3%
|
96.5
169.3%
|
98.2
172.3%
|
| 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 to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| As-treated population included all randomized participants who actually received any study treatment. |
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo |
|---|---|---|---|
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. |
| Measure Participants | 60 | 57 | 57 |
| Median (Full Range) [percentage of drug] |
97.87
|
97.03
|
97.74
|
Adverse Events
| Time Frame | Baseline up to 6 weeks after the last dose of study drug (Week 54) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | As-treated population included all randomized participants who actually received any study treatment. | |||||
| Arm/Group Title | High-Dose Ataluren | Low-Dose Ataluren | Placebo | |||
| Arm/Group Description | 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 48 weeks. | Participants received ataluren suspension orally TID, 10 mg/kg at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 48 weeks. | Participants received placebo matched to ataluren orally TID at morning, midday, and evening for 48 weeks. | |||
All Cause Mortality |
||||||
| High-Dose Ataluren | Low-Dose Ataluren | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| High-Dose Ataluren | Low-Dose Ataluren | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/60 (3.3%) | 2/57 (3.5%) | 3/57 (5.3%) | |||
| Cardiac disorders | ||||||
| Supraventricular tachycardia | 1/60 (1.7%) | 0/57 (0%) | 0/57 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 0/60 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
| Infections and infestations | ||||||
| Appendicitis | 0/60 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
| Influenza | 0/60 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
| Varicella | 0/60 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
| Injury, poisoning and procedural complications | ||||||
| Femur fracture | 0/60 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
| Lower limb fracture | 1/60 (1.7%) | 0/57 (0%) | 0/57 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Dehydration | 0/60 (0%) | 1/57 (1.8%) | 0/57 (0%) | |||
| Nervous system disorders | ||||||
| Grand mal convulsion | 0/60 (0%) | 0/57 (0%) | 1/57 (1.8%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| High-Dose Ataluren | Low-Dose Ataluren | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 58/60 (96.7%) | 56/57 (98.2%) | 57/57 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Lymphadenopathy | 0/60 (0%) | 0 | 2/57 (3.5%) | 2 | 2/57 (3.5%) | 2 |
| Microcytic anaemia | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Cardiac disorders | ||||||
| Arrhythmia | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Dilatation ventricular | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 |
| Left ventricular hypertrophy | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Palpitations | 2/60 (3.3%) | 2 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 |
| Sinus bradycardia | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Supraventricular extrasystoles | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Supraventricular tachycardia | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||||
| Kidney malformation | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Macroglossia | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Ear and labyrinth disorders | ||||||
| Ear congestion | 0/60 (0%) | 0 | 2/57 (3.5%) | 2 | 0/57 (0%) | 0 |
| Ear pain | 1/60 (1.7%) | 1 | 2/57 (3.5%) | 3 | 3/57 (5.3%) | 3 |
| Motion sickness | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Tinnitus | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 2/57 (3.5%) | 2 |
| Tympanic membrane hyperaemia | 2/60 (3.3%) | 2 | 2/57 (3.5%) | 5 | 1/57 (1.8%) | 1 |
| Tympanic membrane perforation | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Endocrine disorders | ||||||
| Goitre | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Eye disorders | ||||||
| Abnormal sensation in eye | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Cataract | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Conjunctivitis | 3/60 (5%) | 3 | 2/57 (3.5%) | 2 | 1/57 (1.8%) | 1 |
| Conjunctivitis allergic | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Eye pain | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Eye pruritus | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Eye swelling | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 |
| Eyelid cyst | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Hypermetropia | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Ocular hyperaemia | 1/60 (1.7%) | 1 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Vision blurred | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Visual impairment | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 2/60 (3.3%) | 2 | 0/57 (0%) | 0 | 4/57 (7%) | 4 |
| Abdominal pain | 12/60 (20%) | 23 | 8/57 (14%) | 8 | 4/57 (7%) | 10 |
| Abdominal pain lower | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Abdominal pain upper | 13/60 (21.7%) | 32 | 9/57 (15.8%) | 18 | 9/57 (15.8%) | 13 |
| Abdominal tenderness | 2/60 (3.3%) | 2 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Aerophagia | 1/60 (1.7%) | 1 | 1/57 (1.8%) | 1 | 2/57 (3.5%) | 2 |
| Anal pruritus | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Aphthous stomatitis | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Chapped lips | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Constipation | 4/60 (6.7%) | 6 | 2/57 (3.5%) | 3 | 2/57 (3.5%) | 2 |
| Diarrhoea | 18/60 (30%) | 39 | 11/57 (19.3%) | 15 | 15/57 (26.3%) | 20 |
| Dyspepsia | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Dysphagia | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Enteritis | 2/60 (3.3%) | 2 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Faecal incontinence | 1/60 (1.7%) | 1 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Flatulence | 10/60 (16.7%) | 10 | 5/57 (8.8%) | 5 | 4/57 (7%) | 4 |
| Frequent bowel movements | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Gastritis | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Gastrooesophageal reflux disease | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Gingival bleeding | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Gingivitis | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Haematemesis | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Ileus | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Lip dry | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Mouth ulceration | 1/60 (1.7%) | 1 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Nausea | 10/60 (16.7%) | 16 | 8/57 (14%) | 16 | 7/57 (12.3%) | 9 |
| Oral pain | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Reflux oesophagitis | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Regurgitation | 1/60 (1.7%) | 1 | 2/57 (3.5%) | 4 | 0/57 (0%) | 0 |
| Stomach discomfort | 5/60 (8.3%) | 7 | 4/57 (7%) | 4 | 0/57 (0%) | 0 |
| Tooth disorder | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Tooth impacted | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Tooth loss | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Toothache | 1/60 (1.7%) | 1 | 2/57 (3.5%) | 2 | 1/57 (1.8%) | 1 |
| Vomiting | 28/60 (46.7%) | 72 | 33/57 (57.9%) | 88 | 22/57 (38.6%) | 48 |
| General disorders | ||||||
| Adhesion | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Asthenia | 4/60 (6.7%) | 5 | 3/57 (5.3%) | 4 | 2/57 (3.5%) | 2 |
| Disease progression | 5/60 (8.3%) | 5 | 4/57 (7%) | 4 | 6/57 (10.5%) | 6 |
| Energy increased | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Fatigue | 6/60 (10%) | 6 | 2/57 (3.5%) | 2 | 2/57 (3.5%) | 3 |
| Feeling abnormal | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Feeling hot | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Gait disturbance | 4/60 (6.7%) | 4 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Ill-defined disorder | 1/60 (1.7%) | 4 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Malaise | 0/60 (0%) | 0 | 2/57 (3.5%) | 2 | 1/57 (1.8%) | 1 |
| Pain | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Pyrexia | 8/60 (13.3%) | 10 | 14/57 (24.6%) | 21 | 12/57 (21.1%) | 14 |
| Thirst | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Immune system disorders | ||||||
| Drug hypersensitivity | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Hypersensitivity | 1/60 (1.7%) | 2 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Seasonal allergy | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 4/57 (7%) | 4 |
| Infections and infestations | ||||||
| Bronchitis | 0/60 (0%) | 0 | 2/57 (3.5%) | 2 | 5/57 (8.8%) | 5 |
| Catheter site infection | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Croup infectious | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Cystitis | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Ear infection | 4/60 (6.7%) | 5 | 3/57 (5.3%) | 4 | 4/57 (7%) | 4 |
| Eczema infected | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Enterobiasis | 1/60 (1.7%) | 1 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Eyelid infection | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Fungal infection | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Gastroenteritis | 6/60 (10%) | 7 | 10/57 (17.5%) | 10 | 4/57 (7%) | 7 |
| Gastroenteritis viral | 3/60 (5%) | 3 | 4/57 (7%) | 4 | 3/57 (5.3%) | 4 |
| Genital candidiasis | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Herpes zoster | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 2/57 (3.5%) | 2 |
| Hordeolum | 2/60 (3.3%) | 4 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Influenza | 7/60 (11.7%) | 9 | 6/57 (10.5%) | 8 | 8/57 (14%) | 9 |
| Infusion site infection | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Lice infestation | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Localised infection | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Lower respiratory tract infection | 1/60 (1.7%) | 1 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 |
| Measles | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Molluscum contagiosum | 1/60 (1.7%) | 1 | 2/57 (3.5%) | 3 | 0/57 (0%) | 0 |
| Nasopharyngitis | 10/60 (16.7%) | 15 | 13/57 (22.8%) | 22 | 13/57 (22.8%) | 17 |
| Oral candidiasis | 1/60 (1.7%) | 2 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Oral herpes | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Otitis externa | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 |
| Otitis media | 2/60 (3.3%) | 2 | 0/57 (0%) | 0 | 4/57 (7%) | 4 |
| Paronychia | 0/60 (0%) | 0 | 4/57 (7%) | 4 | 1/57 (1.8%) | 1 |
| Pharyngitis | 0/60 (0%) | 0 | 2/57 (3.5%) | 2 | 0/57 (0%) | 0 |
| Pharyngitis streptococcal | 2/60 (3.3%) | 3 | 1/57 (1.8%) | 3 | 3/57 (5.3%) | 3 |
| Pharyngotonsillitis | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Pneumonia | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 |
| Post procedural infection | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Postoperative wound infection | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Respiratory tract infection | 1/60 (1.7%) | 3 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Rhinitis | 3/60 (5%) | 4 | 7/57 (12.3%) | 11 | 2/57 (3.5%) | 2 |
| Roseola | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Scarlet fever | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Sinusitis | 2/60 (3.3%) | 2 | 1/57 (1.8%) | 1 | 4/57 (7%) | 7 |
| Skin infection | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Tinea capitis | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Tinea infection | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Tinea pedis | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 4 |
| Tonsillitis | 0/60 (0%) | 0 | 2/57 (3.5%) | 2 | 0/57 (0%) | 0 |
| Upper respiratory tract infection | 12/60 (20%) | 18 | 9/57 (15.8%) | 16 | 12/57 (21.1%) | 17 |
| Urinary tract infection | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Varicella | 0/60 (0%) | 0 | 2/57 (3.5%) | 2 | 1/57 (1.8%) | 1 |
| Viral infection | 3/60 (5%) | 4 | 3/57 (5.3%) | 3 | 1/57 (1.8%) | 1 |
| Viral pharyngitis | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Viral upper respiratory tract infection | 2/60 (3.3%) | 2 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Accident | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Accidental overdose | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Arthropod bite | 1/60 (1.7%) | 1 | 1/57 (1.8%) | 2 | 3/57 (5.3%) | 3 |
| Arthropod sting | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Back injury | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Chillblains | 0/60 (0%) | 0 | 1/57 (1.8%) | 2 | 0/57 (0%) | 0 |
| Contusion | 8/60 (13.3%) | 9 | 8/57 (14%) | 10 | 4/57 (7%) | 4 |
| Excoriation | 3/60 (5%) | 3 | 0/57 (0%) | 0 | 4/57 (7%) | 6 |
| Eye injury | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Face injury | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Fall | 7/60 (11.7%) | 14 | 11/57 (19.3%) | 15 | 7/57 (12.3%) | 7 |
| Femur fracture | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 2 |
| Foot fracture | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Hand fracture | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Head injury | 2/60 (3.3%) | 3 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Humerus fracture | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Iliotibial band syndrome | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Incision site erythema | 1/60 (1.7%) | 1 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Joint injury | 0/60 (0%) | 0 | 5/57 (8.8%) | 5 | 1/57 (1.8%) | 1 |
| Joint sprain | 4/60 (6.7%) | 4 | 4/57 (7%) | 4 | 1/57 (1.8%) | 1 |
| Laceration | 1/60 (1.7%) | 2 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Limb injury | 0/60 (0%) | 0 | 5/57 (8.8%) | 6 | 1/57 (1.8%) | 1 |
| Lower limb fracture | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Lumbar vertebral fracture | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Muscle strain | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Post procedural discomfort | 3/60 (5%) | 3 | 6/57 (10.5%) | 8 | 0/57 (0%) | 0 |
| Post procedural haematoma | 4/60 (6.7%) | 4 | 3/57 (5.3%) | 3 | 2/57 (3.5%) | 2 |
| Post procedural swelling | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Procedural pain | 11/60 (18.3%) | 17 | 10/57 (17.5%) | 13 | 10/57 (17.5%) | 14 |
| Scratch | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Skin laceration | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 3/57 (5.3%) | 3 |
| Spinal compression fracture | 0/60 (0%) | 0 | 1/57 (1.8%) | 2 | 0/57 (0%) | 0 |
| Sunburn | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Suture rupture | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Thermal burn | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Tibia fracture | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 2/57 (3.5%) | 2 |
| Tooth fracture | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Tooth injury | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Traumatic haematoma | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Wound | 2/60 (3.3%) | 2 | 0/57 (0%) | 0 | 2/57 (3.5%) | 2 |
| Wound dehiscence | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 |
| Wrist fracture | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Investigations | ||||||
| Blood aldosterone increased | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Blood alkaline phosphatase increased | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Blood bicarbonate abnormal | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Blood bicarbonate decreased | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Blood calcium increased | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Blood magnesium increased | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Blood pressure increased | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Immunoglobulins decreased | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Renin increased | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Thyroxine free increased | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Thyroxine increased | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Urine colour abnormal | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 3 |
| Weight decreased | 5/60 (8.3%) | 5 | 6/57 (10.5%) | 6 | 1/57 (1.8%) | 1 |
| Weight increased | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 5/60 (8.3%) | 6 | 5/57 (8.8%) | 6 | 2/57 (3.5%) | 2 |
| Dehydration | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Hyperuricaemia | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Iron deficiency | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 7/60 (11.7%) | 9 | 2/57 (3.5%) | 2 | 2/57 (3.5%) | 2 |
| Back pain | 6/60 (10%) | 15 | 9/57 (15.8%) | 9 | 5/57 (8.8%) | 10 |
| Coccydynia | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Groin pain | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 2/57 (3.5%) | 3 |
| Joint contracture | 3/60 (5%) | 3 | 3/57 (5.3%) | 3 | 0/57 (0%) | 0 |
| Joint swelling | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Lordosis | 2/60 (3.3%) | 2 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Muscle contracture | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Muscle spasms | 1/60 (1.7%) | 1 | 3/57 (5.3%) | 4 | 5/57 (8.8%) | 8 |
| Muscle tightness | 1/60 (1.7%) | 1 | 2/57 (3.5%) | 2 | 1/57 (1.8%) | 1 |
| Muscular weakness | 5/60 (8.3%) | 5 | 3/57 (5.3%) | 3 | 2/57 (3.5%) | 2 |
| Musculoskeletal chest pain | 1/60 (1.7%) | 1 | 2/57 (3.5%) | 4 | 1/57 (1.8%) | 1 |
| Musculoskeletal pain | 2/60 (3.3%) | 2 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 |
| Myalgia | 2/60 (3.3%) | 2 | 3/57 (5.3%) | 3 | 2/57 (3.5%) | 2 |
| Neck pain | 1/60 (1.7%) | 1 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Osteoporosis | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Pain in extremity | 8/60 (13.3%) | 16 | 8/57 (14%) | 12 | 6/57 (10.5%) | 7 |
| Scoliosis | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Tendinous contracture | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Tendon disorder | 1/60 (1.7%) | 1 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 |
| Trendelenburg's symptom | 1/60 (1.7%) | 2 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Melanocytic naevus | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Skin papilloma | 1/60 (1.7%) | 1 | 2/57 (3.5%) | 3 | 1/57 (1.8%) | 1 |
| Nervous system disorders | ||||||
| Areflexia | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Convulsion | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Dizziness | 3/60 (5%) | 3 | 3/57 (5.3%) | 4 | 4/57 (7%) | 5 |
| Headache | 16/60 (26.7%) | 85 | 23/57 (40.4%) | 69 | 14/57 (24.6%) | 25 |
| Hypertonia | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Hypotonia | 2/60 (3.3%) | 2 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Lethargy | 1/60 (1.7%) | 1 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Migraine | 1/60 (1.7%) | 2 | 2/57 (3.5%) | 4 | 0/57 (0%) | 0 |
| Psychomotor hyperactivity | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Sinus headache | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Syncope | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Unresponsive to stimuli | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Psychiatric disorders | ||||||
| Abnormal behaviour | 1/60 (1.7%) | 1 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Aggression | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Agitation | 1/60 (1.7%) | 3 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Anger | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Anxiety | 0/60 (0%) | 0 | 2/57 (3.5%) | 2 | 1/57 (1.8%) | 2 |
| Attention deficit/hyperactivity disorder | 3/60 (5%) | 3 | 2/57 (3.5%) | 2 | 0/57 (0%) | 0 |
| Depression | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Emotional disorder | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Encopresis | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Initial insomnia | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Insomnia | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 2/57 (3.5%) | 3 |
| Mood swings | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Obsessive-compulsive disorder | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Oppositional defiant disorder | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Sleep disorder | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Somnambulism | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Stress | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Tic | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 2 |
| Renal and urinary disorders | ||||||
| Dysuria | 1/60 (1.7%) | 1 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 |
| Enuresis | 3/60 (5%) | 4 | 4/57 (7%) | 4 | 0/57 (0%) | 0 |
| Incontinence | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Myoglobinuria | 1/60 (1.7%) | 1 | 1/57 (1.8%) | 3 | 0/57 (0%) | 0 |
| Pollakiuria | 2/60 (3.3%) | 2 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 |
| Pyelocaliectasis | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 |
| Renal cyst | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 |
| Residual urine | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Strangury | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Ureteric dilatation | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Urinary incontinence | 2/60 (3.3%) | 2 | 2/57 (3.5%) | 2 | 2/57 (3.5%) | 2 |
| Urine abnormality | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Balanitis | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Genital erythema | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Pruritus genital | 1/60 (1.7%) | 1 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Testicular pain | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Bronchial hyperreactivity | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Cough | 15/60 (25%) | 27 | 9/57 (15.8%) | 14 | 13/57 (22.8%) | 19 |
| Dyspnoea | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Epistaxis | 3/60 (5%) | 7 | 3/57 (5.3%) | 6 | 1/57 (1.8%) | 1 |
| Nasal congestion | 6/60 (10%) | 8 | 5/57 (8.8%) | 8 | 5/57 (8.8%) | 9 |
| Nasal discomfort | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Oropharyngeal pain | 4/60 (6.7%) | 7 | 6/57 (10.5%) | 7 | 4/57 (7%) | 7 |
| Productive cough | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 |
| Pulmonary congestion | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Rhinitis allergic | 0/60 (0%) | 0 | 1/57 (1.8%) | 3 | 0/57 (0%) | 0 |
| Rhinorrhoea | 1/60 (1.7%) | 1 | 4/57 (7%) | 7 | 6/57 (10.5%) | 8 |
| Sinus congestion | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 2 |
| Sneezing | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Throat irritation | 1/60 (1.7%) | 1 | 1/57 (1.8%) | 2 | 0/57 (0%) | 0 |
| Upper respiratory tract congestion | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 2/57 (3.5%) | 2 |
| Wheezing | 2/60 (3.3%) | 4 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||
| Acne | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Decubitus ulcer | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Dermatitis allergic | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Dermatitis contact | 1/60 (1.7%) | 1 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Dry skin | 0/60 (0%) | 0 | 2/57 (3.5%) | 2 | 3/57 (5.3%) | 3 |
| Ecchymosis | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Eczema | 2/60 (3.3%) | 3 | 1/57 (1.8%) | 1 | 2/57 (3.5%) | 2 |
| Erythema | 1/60 (1.7%) | 1 | 3/57 (5.3%) | 4 | 0/57 (0%) | 0 |
| Exfoliative rash | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Heat rash | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Hyperhidrosis | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Hyperkeratosis | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Ingrowing nail | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 |
| Keratosis pilaris | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Nail disorder | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Night sweats | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Pruritus | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 2/57 (3.5%) | 2 |
| Rash | 8/60 (13.3%) | 8 | 6/57 (10.5%) | 7 | 5/57 (8.8%) | 6 |
| Rash erythematous | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Rash follicular | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Rash generalised | 0/60 (0%) | 0 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Rash maculo-papular | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 |
| Rash papular | 2/60 (3.3%) | 2 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Scar | 5/60 (8.3%) | 9 | 4/57 (7%) | 8 | 4/57 (7%) | 7 |
| Skin discolouration | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Skin irritation | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Skin lesion | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 |
| Urticaria | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 1/57 (1.8%) | 1 |
| Surgical and medical procedures | ||||||
| Endodontic procedure | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Tooth extraction | 0/60 (0%) | 0 | 1/57 (1.8%) | 1 | 0/57 (0%) | 0 |
| Vascular disorders | ||||||
| Flushing | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 1/57 (1.8%) | 1 |
| Hypertension | 0/60 (0%) | 0 | 4/57 (7%) | 6 | 1/57 (1.8%) | 1 |
| Hypotension | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
| Pallor | 1/60 (1.7%) | 1 | 0/57 (0%) | 0 | 0/57 (0%) | 0 |
Limitations/Caveats
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 |
- PTC124-GD-007-DMD
- 2007-005478-29