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The PolarisDMD study is a Phase 3, global study to evaluate the efficacy and safety of edasalonexent in pediatric patients with a genetically confirmed diagnosis of DMD. Male patients from 4-7 years of age (up to 8th birthday) will be enrolled.
Edasalonexent is an orally administered small molecule that inhibits NF-kB, which is the key link between loss of dystrophin and disease pathology and plays a fundamental role in the initiation and progression of skeletal and cardiac muscle disease in DMD.
The study includes a 52-week, randomized, double-blind, placebo-controlled period, followed by a 2-week follow- up. Approximately 125 boys with DMD will be enrolled in this trial, with 2 boys receiving edasalonexent for every 1 boy receiving placebo.
Following completion of the treatment period, patients may elect to continue in a separate open-label extension study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose 1 | Experimental | Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day. |
|
| Placebo | Placebo Comparator | Matching placebo |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Edasalonexent | Drug | 100 mg/kg/day |
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| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in North Star Ambulatory Assessment (NSAA) | To assess change from baseline in North Star Ambulatory Assessment(NSAA) Total Score at Wk52. NSAA is clinician-reported outcome instrument designed to measure ambulatory function in males with Duchenne muscular dystrophy(DMD). Patients asked to perform 17 different functional activities,including 10MWT,rising from sit to stand,standing on one leg,climbing & descending a step,stand from supine, lifting the head, standing on heels, & jumping. Each function activity will be scored as0=(unable to achieve independently),scored as1=(modified method but achieves goal independent of physical assistance from another),or scored as2=(no obvious modification of activity)or "Not Scored". If NSAA test was performed & any of the individual items are scored as "not scored"(i.e, for reasons unrelated to patients physical capabilities), corresponding total score will be set to missing. Sum of 17 scores will be used to form an ordinal total score(range 0-34).Higher scores imply better functional status | Baseline (Day 1) to Week 52 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in 10-meter Walk/Run Test | To assess the changes from baseline to Week 52 on the 10-meter walk/run test (10MWT). For timed function tests (TFTs), the time will be set to 12 seconds and the speed to 0 if the TFT assessment meets the following TFT grading criteria. Grade of 1 or 2 (from a 6-point scale). 1=Unable to walk independently 2=Unable to walk independently but can walk with knee-ankle foot orthoses or support from a person 3=Highly adapted wide based lordotic gait. Cannot increase walking speed 4=Moderately adapted gait. Can pick up speed but cannot run 5=Able to pick up speed, but runs with a double stance phase, i.e. cannot achieve both feet off the ground 6=Runs and gets both feet off the ground (with no double stance phase) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Joanne M Donovan, Chief Medical Officer, MD, PhD | Catabasis Pharmaceuticals | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Arkansas Children's Hospital | Little Rock | Arkansas | 72202 | United States | ||
| Children's Hospital of Los Angeles |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34120912 | Derived | Finkel RS, McDonald CM, Lee Sweeney H, Finanger E, Neil Knierbein E, Wagner KR, Mathews KD, Marks W, Statland J, Nance J, McMillan HJ, McCullagh G, Tian C, Ryan MM, O'Rourke D, Muller-Felber W, Tulinius M, Burnette WB, Nguyen CT, Vijayakumar K, Johannsen J, Phan HC, Eagle M, MacDougall J, Mancini M, Donovan JM; (For the PolarisDMD Study Group). A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric Patients with Duchenne Muscular Dystrophy: Results of the PolarisDMD Trial. J Neuromuscul Dis. 2021;8(5):769-784. doi: 10.3233/JND-210689. |
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A total of 151 patients were screened of which 20 failed screening. 131 patients who participated in the study included 126 randomized patients and 5 participants who were dosed siblings of previously randomized patients.
This was a multi-center study conducted by 37 principal investigators at 37 study centers in 8 countries (United States, Canada, United Kingdom, Germany, Ireland, Israel, Sweden, and Australia.)
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose 1 | Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day. Edasalonexent: 100 mg/kg/day |
| FG001 | Placebo | Matching placebo Placebo: Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 16, 2020 | Jan 14, 2022 |
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| Placebo | Drug | Placebo |
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| Baseline (Day 1) to Week 52 |
| Change From Baseline in Time to Stand From Supine | To assess the change from baseline in the stand from supine speed at Week 52. For timed function tests (TFTs) , the time will be set to 12 seconds and the speed to 0 if the TFT assessment meets the following TFT grading criteria. Grade of 1 or 2 (from a 6-point scale). 1 = Unable to stand from supine, even with use of a chair, 2 = Assisted Gowers - requires furniture for assist in arising from supine to full upright posture (no time to be recorded) 3=Rolls over, stands up with both hands "climbing up" the legs to achieve full upright posture 4=Rolls over, stands up with 1 hand support on leg 5=Rolls to the side and stands up with one or both hands on the floor to start to rise but does not touch legs 6=Stands up without rolling over or using hands on legs or floor | Baseline (Day 1) to Week 52 |
| Change From Baseline in 4-stair Climb | To assess the change from baseline to Week 52 on the 4-Stair Climb. For timed function tests (TFTs) , the time will be set to 12 seconds and the speed to 0 if the TFT assessment meets the following TFT grading criteria. Grade of 1(from a 6-point scale)1=Unable to climb 4 standard stairs(no time recorded) 2=Climbs 4 standard stairs "marking time"(climbs one foot at a time, with both feet on a step before moving to next step), uses both arms on one or both handrails or uses 1 handrail and the other arm pushes on the leg 3=Climbs 4 standard stairs "marking time", using one arm on one handrail or one hand pushing on leg or body 4=Climbs 4 standard stairs "marking time", not needing handrail and not using hands to push on leg 5=Climbs 4 standard stairs alternating feet, needs handrail/s for support or uses arms to push on the leg or body 6=Climbs 4 standard stairs alternating feet, not needing handrail support or using arm to push on the leg | Baseline (Day 1) to Week 52 |
| Safety and Tolerability Measured by Number of Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Adverse events that occurred from the time of the administration of the first dose of investigational product (IP) through the end of the safety follow-up were considered treatment-emergent AEs (TEAEs). Serious adverse event (SAE). | Up to Week 52 |
| Los Angeles |
| California |
| 90027 |
| United States |
| UC Davis | Sacramento | California | 95817 | United States |
| Nemours Children's Hospital | Orlando | Florida | 32827 | United States |
| Rare Disease Research, LLC | Atlanta | Georgia | 30318 | United States |
| Rush University Children's Hospital | Chicago | Illinois | 60612 | United States |
| University of Iowa Children's Hospital | Iowa City | Iowa | 52242 | United States |
| University of Kansas Medical Center | Fairway | Kansas | 66205 | United States |
| Kennedy Krieger Institute | Baltimore | Maryland | 21205 | United States |
| Johns Hopkins School of Medicine | Baltimore | Maryland | 21287 | United States |
| Boston Children's Hospital | Boston | Massachusetts | 02115 | United States |
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| Las Vegas Clinic | Las Vegas | Nevada | 89145 | United States |
| Cincinnati Children's Hospital | Cincinnati | Ohio | 45229 | United States |
| MetroHealth Medical Center | Cleveland | Ohio | 44109 | United States |
| Shriners Hospitals for Children | Portland | Oregon | 97239 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37212 | United States |
| Cook Children's Medical Center | Fort Worth | Texas | 76104 | United States |
| University of Texas Health Science Center at San Antonio | San Antonio | Texas | 78229 | United States |
| University of Utah | Salt Lake City | Utah | 84112 | United States |
| Children's Hospital of the King's Daughters | Norfolk | Virginia | 23510 | United States |
| Children's Hospital of Richmond at VCU | Richmond | Virginia | 23298 | United States |
| The Children's Hospital at Westmead | Westmead | New South Wales | 2145 | Australia |
| Children's Health Queensland Children's Hospital and Health Service | South Brisbane | Queensland | 4101 | Australia |
| Royal Children's Hospital | Parkville | Victoria | 3052 | Australia |
| Alberta Children's Hospital | Calgary | Alberta | T3B 6A8 | Canada |
| London Health Sciences Centre - Children's Hospital | London | Ontario | N6A 4G5 | Canada |
| Children's Hospital of Eastern Ontario | Ottawa | Ontario | K1H 8L1 | Canada |
| CHU Sainte-Justine | Montreal | Quebec | H3T 1C5 | Canada |
| University of Hamburg | Hamburg | 20246 | Germany |
| University of Munich | Munich | 80337 | Germany |
| Children's University Hospital | Dublin | 1 | Ireland |
| Hadassah Medical Center | Jerusalem | 9124001 | Israel |
| Queen Silvia Children's Hospital | Gothenburg | 41685 | Sweden |
| Bristol Children's Hospital | Bristol | BS2 8AE | United Kingdom |
| Evelina Children's Hospital | London | SE1 7EU | United Kingdom |
| Great Ormond Street Hospital (GOSH) | London | WC1N 3JH | United Kingdom |
| Royal Manchester Children's Hospital | Manchester | M13 9WL | United Kingdom |
| COMPLETED |
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| NOT COMPLETED |
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Safety Population: All patients who received at least 1 dose of study drug, with patients analyzed based on the actual study treatment received. This included the set of patients who were assigned the same treatment as their randomized sibling.
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| ID | Title | Description |
|---|---|---|
| BG000 | Dose 1 | Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day. Edasalonexent: 100 mg/kg/day |
| BG001 | Placebo | Matching placebo Placebo: Placebo |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Race is missing for one subject. A patient who reported more than 1 race was categorized as multiracial. | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in North Star Ambulatory Assessment (NSAA) | To assess change from baseline in North Star Ambulatory Assessment(NSAA) Total Score at Wk52. NSAA is clinician-reported outcome instrument designed to measure ambulatory function in males with Duchenne muscular dystrophy(DMD). Patients asked to perform 17 different functional activities,including 10MWT,rising from sit to stand,standing on one leg,climbing & descending a step,stand from supine, lifting the head, standing on heels, & jumping. Each function activity will be scored as0=(unable to achieve independently),scored as1=(modified method but achieves goal independent of physical assistance from another),or scored as2=(no obvious modification of activity)or "Not Scored". If NSAA test was performed & any of the individual items are scored as "not scored"(i.e, for reasons unrelated to patients physical capabilities), corresponding total score will be set to missing. Sum of 17 scores will be used to form an ordinal total score(range 0-34).Higher scores imply better functional status | Full Analysis population: All patients in the Randomized Population who received at least 1 dose of study drug and provided at least 1 valid post Baseline NSAA efficacy assessment. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day 1) to Week 52 |
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| Secondary | Change From Baseline in 10-meter Walk/Run Test | To assess the changes from baseline to Week 52 on the 10-meter walk/run test (10MWT). For timed function tests (TFTs), the time will be set to 12 seconds and the speed to 0 if the TFT assessment meets the following TFT grading criteria. Grade of 1 or 2 (from a 6-point scale). 1=Unable to walk independently 2=Unable to walk independently but can walk with knee-ankle foot orthoses or support from a person 3=Highly adapted wide based lordotic gait. Cannot increase walking speed 4=Moderately adapted gait. Can pick up speed but cannot run 5=Able to pick up speed, but runs with a double stance phase, i.e. cannot achieve both feet off the ground 6=Runs and gets both feet off the ground (with no double stance phase) | Full Analysis population: All patients in the Randomized Population who received at least 1 dose of study drug and provided at least 1 valid post Baseline NSAA efficacy assessment. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day 1) to Week 52 |
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| Secondary | Change From Baseline in Time to Stand From Supine | To assess the change from baseline in the stand from supine speed at Week 52. For timed function tests (TFTs) , the time will be set to 12 seconds and the speed to 0 if the TFT assessment meets the following TFT grading criteria. Grade of 1 or 2 (from a 6-point scale). 1 = Unable to stand from supine, even with use of a chair, 2 = Assisted Gowers - requires furniture for assist in arising from supine to full upright posture (no time to be recorded) 3=Rolls over, stands up with both hands "climbing up" the legs to achieve full upright posture 4=Rolls over, stands up with 1 hand support on leg 5=Rolls to the side and stands up with one or both hands on the floor to start to rise but does not touch legs 6=Stands up without rolling over or using hands on legs or floor | Full Analysis population: All patients in the Randomized Population who received at least 1 dose of study drug and provided at least 1 valid post Baseline NSAA efficacy assessment. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day 1) to Week 52 |
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| Secondary | Change From Baseline in 4-stair Climb | To assess the change from baseline to Week 52 on the 4-Stair Climb. For timed function tests (TFTs) , the time will be set to 12 seconds and the speed to 0 if the TFT assessment meets the following TFT grading criteria. Grade of 1(from a 6-point scale)1=Unable to climb 4 standard stairs(no time recorded) 2=Climbs 4 standard stairs "marking time"(climbs one foot at a time, with both feet on a step before moving to next step), uses both arms on one or both handrails or uses 1 handrail and the other arm pushes on the leg 3=Climbs 4 standard stairs "marking time", using one arm on one handrail or one hand pushing on leg or body 4=Climbs 4 standard stairs "marking time", not needing handrail and not using hands to push on leg 5=Climbs 4 standard stairs alternating feet, needs handrail/s for support or uses arms to push on the leg or body 6=Climbs 4 standard stairs alternating feet, not needing handrail support or using arm to push on the leg | Full Analysis Population: All patients in the Randomized Population who received at least 1 dose of study drug and provided at least 1 valid post Baseline NSAA efficacy assessment). | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day 1) to Week 52 |
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| Secondary | Safety and Tolerability Measured by Number of Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Adverse events that occurred from the time of the administration of the first dose of investigational product (IP) through the end of the safety follow-up were considered treatment-emergent AEs (TEAEs). Serious adverse event (SAE). | Safety population: All patients who received at least 1 dose of study drug, with patients analyzed based on the actual study treatment received. This included the set of patients who were assigned the same treatment as their randomized sibling. | Posted | Number | participants | Up to Week 52 |
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Up to Week 52
Subjects with more than one AE of the same system organ class (SOC) / preferred term (PT) were counted only once for that SOC / PT.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dose 1 | Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day. Edasalonexent: 100 mg/kg/day | 0 | 88 | 1 | 88 | 85 | 88 |
| EG001 | Placebo | Matching placebo Placebo: Placebo | 0 | 43 | 1 | 43 | 41 | 43 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastroenteritis norovirus | Infections and infestations | 21.0 | Systematic Assessment |
| |
| Bronchiolitis | Infections and infestations | 21.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 21.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | 21.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | 21.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | 21.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | 21.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | 21.0 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | 21.0 | Systematic Assessment |
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| Dental caries | Gastrointestinal disorders | 21.0 | Systematic Assessment |
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| Faeces soft | Gastrointestinal disorders | 21.0 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | 21.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | 21.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | 21.0 | Systematic Assessment |
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| Ear infection | Infections and infestations | 21.0 | Systematic Assessment |
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| Influenza | Infections and infestations | 21.0 | Systematic Assessment |
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| Pharyngitis streptococcal | Infections and infestations | 21.0 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | 21.0 | Systematic Assessment |
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| Gastroenteritis viral | Infections and infestations | 21.0 | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | 21.0 | Systematic Assessment |
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| Conjunctivitis | Infections and infestations | 21.0 | Systematic Assessment |
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| Impetigo | Infections and infestations | 21.0 | Systematic Assessment |
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| Tonsillitis | Infections and infestations | 21.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
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| Sinus congestion | Respiratory, thoracic and mediastinal disorders | 21.0 | Systematic Assessment |
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| Pyrexia | General disorders | 21.0 | Systematic Assessment |
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| Fatigue | General disorders | 21.0 | Systematic Assessment |
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| Influenza like illness | General disorders | 21.0 | Systematic Assessment |
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| Non-cardiac chest pain | General disorders | 21.0 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | 21.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | 21.0 | Systematic Assessment |
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| Ligament sprain | Injury, poisoning and procedural complications | 21.0 | Systematic Assessment |
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| Arthropod bite | Injury, poisoning and procedural complications | 21.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | 21.0 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | 21.0 | Systematic Assessment |
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| Headache | Nervous system disorders | 21.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | 21.0 | Systematic Assessment |
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| Attention deficit hyperactivity disorder | Psychiatric disorders | 21.0 | Systematic Assessment |
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| Weight increased | Investigations | 21.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | 21.0 | Systematic Assessment |
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| Chromaturia | Renal and urinary disorders | 21.0 | Systematic Assessment |
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| Pollakiuria | Renal and urinary disorders | 21.0 | Systematic Assessment |
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| Ear pain | Ear and labyrinth disorders | 21.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Andrew Nichols, PhD - Chief Scientific Officer | Astria Therapeutics, Inc | 617-349-1971 | anichols@astriatx.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 5, 2020 | Jan 14, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D020388 | Muscular Dystrophy, Duchenne |
| D009136 | Muscular Dystrophies |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
| ID | Term |
|---|---|
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| C000622102 | edasalonexent |
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