Back to resultsStudy of Ataluren (PTC124) in Nonambulatory Participants With Nonsense-Mutation-Mediated Duchenne/Becker Muscular Dystrophy (nmDMD/BMD)
Primary Purpose
Duchenne Muscular Dystrophy, Becker Muscular Dystrophy
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ataluren
Chronic Corticosteroid Therapy
Sponsored by
About this trial
This is an interventional treatment trial for Duchenne Muscular Dystrophy focused on measuring Duchenne muscular dystrophy, Becker muscular dystrophy, Nonsense mutation, Premature stop codon, DMD, BMD, Ataluren, PTC124
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of DMD or BMD
- Presence of a nonsense mutation in the dystrophin gene
- Unable to ambulate independently for ≥1 year due to DMD/BMD
- Presence of sufficient shoulder and elbow function to perform study-related functional procedures (for example, 9-hole peg test)
- Adequate hepatic, renal, and adrenal function
- Ability to provide evaluable pretreatment echocardiogram and lung function assessments
- Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions
- Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if <18 years of age)
Exclusion Criteria:
- Initiation of systemic corticosteroid therapy within 6 months prior to start of study treatment or use of systemic aminoglycoside antibiotic within 3 months prior to start of study treatment
- Use of any intermittent systemic corticosteroid therapy regimen (for example, 10 days on followed by 10 days off, weekend dosing, every-other-day dosing); note that participants must have either been receiving a daily dosing regimen of prednisone, prednisolone, or deflazacort at the time of enrollment into the study or must have not been receiving any systemic corticosteroids
- Any change in treatment for congestive heart failure within 3 months prior to start of study treatment
- Ongoing warfarin or phenytoin therapy
- Prior therapy with ataluren
- Known hypersensitivity to any of the ingredients or excipients of ataluren (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 1 month prior to start of study treatment or expectation of major surgical procedure (for example, scoliosis surgery) during the 48-week treatment period of the study
- Ongoing immunosuppressive therapy (other than corticosteroids)
- Ongoing participation in any other clinical trial
- Requirement for daytime ventilator assistance
- Uncontrolled clinical symptoms and signs of congestive heart failure
- Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, electrocardiogram (ECG) 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
Sites / Locations
- University of California-Davis
- Children's Hospital of Boston
- University of Minnesota
- Washington University Medical School
- Nationwide Children's Hospital
- University of Newcastle
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ataluren
Arm Description
Ataluren was provided as a vanilla-flavored powder to be mixed with water, apple juice, or milk. Study drug dosing was based on milligrams of drug per kilogram of body weight. The dose level for ataluren was 20 milligrams/kilograms (mg/kg) in the morning, 20 mg/kg at midday, and 40 mg/kg in the evening. Administration within 30 minutes after a meal was recommended. Study drug was taken for up to 50 days.
Outcomes
Primary Outcome Measures
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
A TEAE is any untoward medical occurrence or undesirable event(s) experienced in a participant that begins or worsens following administration of the study drug or study treatment, whether or not considered related to the treatment by the Investigator. A serious adverse event (SAE) was an adverse event (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), or persistent or significant disability/incapacity not related to nmDBMD. AEs included both SAEs and non-serious AEs. AEs were classified according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (CTCAE) and coded using the Medical Dictionary for Regulatory Activities (MedDRA). A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Secondary Outcome Measures
Time to Complete Upper Limb Function Tasks as Measured by the Jebsen Test
Arm and hand function were assessed using the Jebsen test, a standardized clinical evaluation of tasks important to daily living. The test comprises of unilateral subtests performed with each hand (the dominant [DOM] hand and the non-DOM hand): moving and stacking light (250 grams) and heavy (500 grams) objects; picking up small, commonly encountered objects; stacking checkers; simulated feeding; simulated page turning; and writing. Participant performance of each task was timed. Longer time to complete the test indicates worse hand function.
Upper Limb Function as Measured by the Brooke Upper Extremity Functional Rating Scale
Upper extremity function was assessed using the Brooke Upper Extremity Functional Rating Scale, following standardized procedures. The Brooke Upper Extremity Functional Rating Scale graded arm and shoulder function from 1 to 6, with higher values indicating less function. A rating of "1" was used when the participant was able to abduct his arms in a full circle until they touch above his head, whereas a rating of "6" was used when the participant was unable to raise his hands to his mouth and had no useful function of hands.
Participant Activities of Daily Living as Assessed Using the Egen Klassifikation (EK) Scale
Activities of daily living after loss of ambulation were measured using the EK scale. The EK scale is an ordinal scale ranging from 0 to 30 points where 0 represents the highest level of independent function and 30 the lowest. The scale consists of 10 categories (each scored 0 to 3), involving different functional domains including 1) ability to use wheelchair, 2) ability to transfer from wheelchair, 3) ability to stand, 4) ability to balance in the wheelchair, 5) ability to move arms, 6) ability to use hands and arms when eating, 7) ability to turn in bed, 8) ability to cough, 9) ability to speak, and 10) physical well-being. The administration of the EK scale consisted of an interview of the participant to capture how he performs the tasks of daily life (as described by Categories 1 to 9) and how he perceives his wellbeing (as described by Category 10). The interviewer observed the participant and assigned the final score for the tasks that could be observed in the clinic.
Shoulder, Elbow, and Wrist Passive and Active Range of Motion as Measured by Goniometry
Goniometry was performed to test active and passive range-of motion (RoM) of the left (L) and right (R) shoulder, elbow, and wrist following standardized procedures. The observed angle for passive and active motion for each joint was measured in degrees. Greater degree of motion indicates better response.
Force Exerted During Elbow Flexion and Extension, Shoulder Abduction, Hand Grip, Key Grip, and Finger Pinch as Assessed by Upper Extremity Myometry
Upper extremity myometry was performed using a hand-held dynamometer following standardized procedures. The measured strength (peak force) was reported in Newtons. There are 0.22 pounds (lbs) in 1 Newton and approximately 10 Newton (9.80665 Newton) in 1 kilogram (kg). The threshold/range of the hand-held dynamometer is 0 to 500 Newtons. Bilateral assessments were done, and 3 measurements were recorded from each muscle group on each side, when possible. When the measurements were done in duplicate or triplicate, the best value was used. Greater value indicates better measurement.
Time to Complete Hand Fine Motor Coordination and Dexterity Tasks as Measured by 9-Hole Peg Test (9HPT)
Hand fine motor coordination and dexterity were assessed using the 9HPT using standardized procedures. The 9HPT is a unilateral test in which 9 pegs were placed in a board and then removed with the dominate and non-dominate hand within a 5-minute time limit. The amount of time required to put the pegs in the holes and remove them again with each hand was recorded. Each test was conducted twice per hand. Longer time to complete the test indicates worse hand fine motor coordination and dexterity.
Forced Vital Capacity (FVC) as Measured by Spirometry
Pulmonary function was assessed as FVC in participants by spirometry using a study-specific spirometer. Multiple tests were conducted, if needed.
Systolic and Diastolic Function as Measured by Echocardiography With Tissue Doppler
Cardiac function was assessed by echocardiography, which included standard parameters (for example, ejection fraction, left ventricle diastolic and systolic dimensions), as well as parameters integrating Doppler flow analysis with imaging to evaluate perturbations in wall motion. A standardized data collection process harmonized data from all participating institutions and allowed for centralized review.
Heart Rate as Assessed by Radial Pulse
Heart rate was measured with the radial pulse. Following the Jebsen test, the participant rested for 5 minutes in a sitting position, and the heart rate for the last minute of this rest period was collected as the resting heart rate.
Verbal Memory and Attention as Assessed by the Digit Span Task
A series of digits (0-9) were presented to the participant in an auditory format only. The task had 2 parts: in the Forward Condition, the participant 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.
HRQL as Measured by the PedsQL Inventory Generic Core Scale
Health-related quality of life (HRQL) was measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory Generic Core Scale. The generic core module comprised of 23 questions evaluating physical, emotional, social, and school functioning. Examples of items in each of the generic core module scales included: "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 response scale from 0 (never a problem) to 4 (almost always a problem). The appropriate age-specific version was completed. PedsQL Inventory Generic Core Scale data at Week 6 is presented.
HRQL as Measured by the PedsQL Multidimensional Fatigue Scale
HRQL was measured by the PedsQL Multidimensional Fatigue Scale. The fatigue-specific module comprised of 18 questions evaluating general fatigue, sleep/rest fatigue, and cognitive fatigue. 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 response scale from 0 (never a problem) to 4 (almost always a problem). The appropriate age-specific version was completed. PedsQL Multidimensional Fatigue Scale data at Week 6 is presented.
HRQL as Measured by the INQoL
HRQL was measured by the Individualized Neuromuscular Quality of Life Questionnaire (INQoL). The INQoL consisted of 45 questions within 10 sections. Four of the sections evaluate key muscle disease symptoms (that is, weakness, locking [myotonia], pain, and fatigue), 5 sections evaluate the degree and importance of the impact of muscle disease on particular areas of life, and 1 section asks about the positive and negative effects of treatment. A higher score indicates greater symptom impact or worse HRQL, with a range of 0-7.
Muscle Fragility as Determined by Serum Creatine Kinase (CK) Levels
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. The reference range was based on the age of the participant.
Gastrocnemius Muscle Dystrophin Expression as Determined by Immunofluoresence or by Western Blotting Techniques
The gastrocnemius muscle was to be biopsied from 1 leg to assess for the production of dystrophin at Week 36. The production of dystrophin was to be measured by immunofluorescene staining of the sarcolemmal membrane or by Western blotting techniques with an antibody to the C-terminal portion of the dystrophin protein (excluding revertant fibers).
Study Drug Compliance
Study drug compliance was assessed by the participant daily diary and quantification of used and unused study drug. Compliance was assessed in terms of the amount of drug actually taken relative to the amount that should have been taken during the study.
Pharmacokinetics: Ataluren Plasma Exposure
Blood for ataluren concentrations over a 24-hour period was to be collected on Days 2 and 3 of Week 6. Analysis of the blood samples was to be conducted using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method.
Full Information
NCT ID
NCT01009294
First Posted
November 5, 2009
Last Updated
July 27, 2020
Sponsor
PTC Therapeutics
Collaborators
Genzyme, a Sanofi Company
1. Study Identification
Unique Protocol Identification Number
NCT01009294
Brief Title
Study of Ataluren (PTC124) in Nonambulatory Participants With Nonsense-Mutation-Mediated Duchenne/Becker Muscular Dystrophy (nmDMD/BMD)
Official Title
A Phase 2a Study of Ataluren (PTC124) in Nonambulatory Patients With Nonsense-Mutation-Mediated Duchenne/Becker Muscular Dystrophy
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Terminated
Why Stopped
Terminated early because a similar study with Ataluren exhibited lack of efficacy at the high dose (not due to safety concerns).
Study Start Date
January 13, 2010 (Actual)
Primary Completion Date
March 23, 2010 (Actual)
Study Completion Date
March 23, 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PTC Therapeutics
Collaborators
Genzyme, a Sanofi Company
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Duchenne/Becker muscular dystrophy (DMD/BMD) is a genetic disorder that develops in boys. It is caused by a mutation in the gene for dystrophin, a protein that is important for maintaining normal muscle structure and function. Loss of dystrophin causes muscle fragility that leads to weakness and loss of walking ability during childhood and teenage years. A specific type of mutation, called a nonsense (premature stop codon) mutation is the cause of DMD/BMD in approximately 10-15% of boys with the disease. Ataluren (PTC124) is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 2a trial that enrolled boys with nonsense mutation DMD/BMD who have lost independent mobility due to the disease. This study evaluated the safety and tolerability of ataluren (PTC124) and also evaluated efficacy outcomes in this participant population.
Detailed Description
It was planned that this Phase 2a, open-label, safety and efficacy study to be performed at 5 sites in the US and 1 site in the United Kingdom.
The study was to enroll ~30 boys with nonsense mutation DMD/BMD (nmDBMD) who have been nonambulatory for at least 1 year. Enrollment was to be stratified to ensure evaluation of ~15 participants who were receiving chronic corticosteroid therapy and of ~15 participants who were not receiving chronic corticosteroid therapy. Participants were to take ataluren 3 times per day (at breakfast, lunch, and dinner) for 48 weeks (~1 year). Study assessments were to be performed at clinic visits during screening, every 6 weeks for 2 visits and then every 12 weeks until the end of the study. Additional safety laboratory testing was to be required 4 times during the course of the study; this could have been performed at the investigational site, at an accredited local laboratory or clinic, or in the participant's home using a nursing service. When the blind for a similar study (PTC124-GD-007-DMD; NCT00592553) was revealed, the results indicated lack of efficacy for the high dose. Therefore, even though an independent data monitoring committee (DMC) agreed that both ataluren dose levels were well tolerated by the participants, the DMC recommended discontinuing ongoing studies with participants with nmDBMD receiving high-dose ataluren.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Duchenne Muscular Dystrophy, Becker Muscular Dystrophy
Keywords
Duchenne muscular dystrophy, Becker muscular dystrophy, Nonsense mutation, Premature stop codon, DMD, BMD, Ataluren, PTC124
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ataluren
Arm Type
Experimental
Arm Description
Ataluren was provided as a vanilla-flavored powder to be mixed with water, apple juice, or milk. Study drug dosing was based on milligrams of drug per kilogram of body weight. The dose level for ataluren was 20 milligrams/kilograms (mg/kg) in the morning, 20 mg/kg at midday, and 40 mg/kg in the evening. Administration within 30 minutes after a meal was recommended. Study drug was taken for up to 50 days.
Intervention Type
Drug
Intervention Name(s)
Ataluren
Other Intervention Name(s)
PTC124
Intervention Description
Oral powder
Intervention Type
Drug
Intervention Name(s)
Chronic Corticosteroid Therapy
Intervention Description
Enrollment was stratified to ensure evaluation of approximately half of the participants were receiving chronic corticosteroid therapy and approximately half of participants were not receiving chronic corticosteroid therapy. Therefore, 3 out of 6 participants were receiving chronic corticosteriod therapy. For the participants receiving chronic corticosteriod therapy, a stable corticosteriod regimen was to be maintained during the study.
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Description
A TEAE is any untoward medical occurrence or undesirable event(s) experienced in a participant that begins or worsens following administration of the study drug or study treatment, whether or not considered related to the treatment by the Investigator. A serious adverse event (SAE) was an adverse event (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), or persistent or significant disability/incapacity not related to nmDBMD. AEs included both SAEs and non-serious AEs. AEs were classified according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (CTCAE) and coded using the Medical Dictionary for Regulatory Activities (MedDRA). A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Time Frame
Baseline up to Day 50
Secondary Outcome Measure Information:
Title
Time to Complete Upper Limb Function Tasks as Measured by the Jebsen Test
Description
Arm and hand function were assessed using the Jebsen test, a standardized clinical evaluation of tasks important to daily living. The test comprises of unilateral subtests performed with each hand (the dominant [DOM] hand and the non-DOM hand): moving and stacking light (250 grams) and heavy (500 grams) objects; picking up small, commonly encountered objects; stacking checkers; simulated feeding; simulated page turning; and writing. Participant performance of each task was timed. Longer time to complete the test indicates worse hand function.
Time Frame
Baseline and Week 6
Title
Upper Limb Function as Measured by the Brooke Upper Extremity Functional Rating Scale
Description
Upper extremity function was assessed using the Brooke Upper Extremity Functional Rating Scale, following standardized procedures. The Brooke Upper Extremity Functional Rating Scale graded arm and shoulder function from 1 to 6, with higher values indicating less function. A rating of "1" was used when the participant was able to abduct his arms in a full circle until they touch above his head, whereas a rating of "6" was used when the participant was unable to raise his hands to his mouth and had no useful function of hands.
Time Frame
Baseline and Week 6
Title
Participant Activities of Daily Living as Assessed Using the Egen Klassifikation (EK) Scale
Description
Activities of daily living after loss of ambulation were measured using the EK scale. The EK scale is an ordinal scale ranging from 0 to 30 points where 0 represents the highest level of independent function and 30 the lowest. The scale consists of 10 categories (each scored 0 to 3), involving different functional domains including 1) ability to use wheelchair, 2) ability to transfer from wheelchair, 3) ability to stand, 4) ability to balance in the wheelchair, 5) ability to move arms, 6) ability to use hands and arms when eating, 7) ability to turn in bed, 8) ability to cough, 9) ability to speak, and 10) physical well-being. The administration of the EK scale consisted of an interview of the participant to capture how he performs the tasks of daily life (as described by Categories 1 to 9) and how he perceives his wellbeing (as described by Category 10). The interviewer observed the participant and assigned the final score for the tasks that could be observed in the clinic.
Time Frame
Baseline and Week 6
Title
Shoulder, Elbow, and Wrist Passive and Active Range of Motion as Measured by Goniometry
Description
Goniometry was performed to test active and passive range-of motion (RoM) of the left (L) and right (R) shoulder, elbow, and wrist following standardized procedures. The observed angle for passive and active motion for each joint was measured in degrees. Greater degree of motion indicates better response.
Time Frame
Baseline and Week 6
Title
Force Exerted During Elbow Flexion and Extension, Shoulder Abduction, Hand Grip, Key Grip, and Finger Pinch as Assessed by Upper Extremity Myometry
Description
Upper extremity myometry was performed using a hand-held dynamometer following standardized procedures. The measured strength (peak force) was reported in Newtons. There are 0.22 pounds (lbs) in 1 Newton and approximately 10 Newton (9.80665 Newton) in 1 kilogram (kg). The threshold/range of the hand-held dynamometer is 0 to 500 Newtons. Bilateral assessments were done, and 3 measurements were recorded from each muscle group on each side, when possible. When the measurements were done in duplicate or triplicate, the best value was used. Greater value indicates better measurement.
Time Frame
Baseline and Week 6
Title
Time to Complete Hand Fine Motor Coordination and Dexterity Tasks as Measured by 9-Hole Peg Test (9HPT)
Description
Hand fine motor coordination and dexterity were assessed using the 9HPT using standardized procedures. The 9HPT is a unilateral test in which 9 pegs were placed in a board and then removed with the dominate and non-dominate hand within a 5-minute time limit. The amount of time required to put the pegs in the holes and remove them again with each hand was recorded. Each test was conducted twice per hand. Longer time to complete the test indicates worse hand fine motor coordination and dexterity.
Time Frame
Baseline and Week 6
Title
Forced Vital Capacity (FVC) as Measured by Spirometry
Description
Pulmonary function was assessed as FVC in participants by spirometry using a study-specific spirometer. Multiple tests were conducted, if needed.
Time Frame
Baseline and Week 6
Title
Systolic and Diastolic Function as Measured by Echocardiography With Tissue Doppler
Description
Cardiac function was assessed by echocardiography, which included standard parameters (for example, ejection fraction, left ventricle diastolic and systolic dimensions), as well as parameters integrating Doppler flow analysis with imaging to evaluate perturbations in wall motion. A standardized data collection process harmonized data from all participating institutions and allowed for centralized review.
Time Frame
Week 24 and Week 48
Title
Heart Rate as Assessed by Radial Pulse
Description
Heart rate was measured with the radial pulse. Following the Jebsen test, the participant rested for 5 minutes in a sitting position, and the heart rate for the last minute of this rest period was collected as the resting heart rate.
Time Frame
Baseline and Week 6
Title
Verbal Memory and Attention as Assessed by the Digit Span Task
Description
A series of digits (0-9) were presented to the participant in an auditory format only. The task had 2 parts: in the Forward Condition, the participant 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.
Time Frame
Baseline and Week 6
Title
HRQL as Measured by the PedsQL Inventory Generic Core Scale
Description
Health-related quality of life (HRQL) was measured by the Pediatric Quality of Life Inventory (PedsQL) Inventory Generic Core Scale. The generic core module comprised of 23 questions evaluating physical, emotional, social, and school functioning. Examples of items in each of the generic core module scales included: "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 response scale from 0 (never a problem) to 4 (almost always a problem). The appropriate age-specific version was completed. PedsQL Inventory Generic Core Scale data at Week 6 is presented.
Time Frame
Week 6
Title
HRQL as Measured by the PedsQL Multidimensional Fatigue Scale
Description
HRQL was measured by the PedsQL Multidimensional Fatigue Scale. The fatigue-specific module comprised of 18 questions evaluating general fatigue, sleep/rest fatigue, and cognitive fatigue. 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 response scale from 0 (never a problem) to 4 (almost always a problem). The appropriate age-specific version was completed. PedsQL Multidimensional Fatigue Scale data at Week 6 is presented.
Time Frame
Week 6
Title
HRQL as Measured by the INQoL
Description
HRQL was measured by the Individualized Neuromuscular Quality of Life Questionnaire (INQoL). The INQoL consisted of 45 questions within 10 sections. Four of the sections evaluate key muscle disease symptoms (that is, weakness, locking [myotonia], pain, and fatigue), 5 sections evaluate the degree and importance of the impact of muscle disease on particular areas of life, and 1 section asks about the positive and negative effects of treatment. A higher score indicates greater symptom impact or worse HRQL, with a range of 0-7.
Time Frame
Week 24 and Week 48
Title
Muscle Fragility as Determined by Serum Creatine Kinase (CK) Levels
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. The reference range was based on the age of the participant.
Time Frame
Baseline and Week 6
Title
Gastrocnemius Muscle Dystrophin Expression as Determined by Immunofluoresence or by Western Blotting Techniques
Description
The gastrocnemius muscle was to be biopsied from 1 leg to assess for the production of dystrophin at Week 36. The production of dystrophin was to be measured by immunofluorescene staining of the sarcolemmal membrane or by Western blotting techniques with an antibody to the C-terminal portion of the dystrophin protein (excluding revertant fibers).
Time Frame
Week 36
Title
Study Drug Compliance
Description
Study drug compliance was assessed by the participant daily diary and quantification of used and unused study drug. Compliance was assessed in terms of the amount of drug actually taken relative to the amount that should have been taken during the study.
Time Frame
Baseline to Day 50
Title
Pharmacokinetics: Ataluren Plasma Exposure
Description
Blood for ataluren concentrations over a 24-hour period was to be collected on Days 2 and 3 of Week 6. Analysis of the blood samples was to be conducted using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method.
Time Frame
0, 2, 3, 6, 8, 9, 12, 14, 15, and 24 hours after the morning dose
10. Eligibility
Sex
Male
Gender Based
Yes
Gender Eligibility Description
Male participants only are being studied.
Minimum Age & Unit of Time
7 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of DMD or BMD
Presence of a nonsense mutation in the dystrophin gene
Unable to ambulate independently for ≥1 year due to DMD/BMD
Presence of sufficient shoulder and elbow function to perform study-related functional procedures (for example, 9-hole peg test)
Adequate hepatic, renal, and adrenal function
Ability to provide evaluable pretreatment echocardiogram and lung function assessments
Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions
Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if <18 years of age)
Exclusion Criteria:
Initiation of systemic corticosteroid therapy within 6 months prior to start of study treatment or use of systemic aminoglycoside antibiotic within 3 months prior to start of study treatment
Use of any intermittent systemic corticosteroid therapy regimen (for example, 10 days on followed by 10 days off, weekend dosing, every-other-day dosing); note that participants must have either been receiving a daily dosing regimen of prednisone, prednisolone, or deflazacort at the time of enrollment into the study or must have not been receiving any systemic corticosteroids
Any change in treatment for congestive heart failure within 3 months prior to start of study treatment
Ongoing warfarin or phenytoin therapy
Prior therapy with ataluren
Known hypersensitivity to any of the ingredients or excipients of ataluren (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 1 month prior to start of study treatment or expectation of major surgical procedure (for example, scoliosis surgery) during the 48-week treatment period of the study
Ongoing immunosuppressive therapy (other than corticosteroids)
Ongoing participation in any other clinical trial
Requirement for daytime ventilator assistance
Uncontrolled clinical symptoms and signs of congestive heart failure
Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, electrocardiogram (ECG) 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leone Atkinson, MD, PhD
Organizational Affiliation
PTC Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
University of California-Davis
City
Davis
State/Province
California
ZIP/Postal Code
95616
Country
United States
Facility Name
Children's Hospital of Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Washington University Medical School
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
University of Newcastle
City
Newcastle upon Tyne
ZIP/Postal Code
NE1 3BZ
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.ptcbio.com
Description
Related Info
Learn more about this trial
Study of Ataluren (PTC124) in Nonambulatory Participants With Nonsense-Mutation-Mediated Duchenne/Becker Muscular Dystrophy (nmDMD/BMD)
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