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| Name | Class |
|---|---|
| Cystic Fibrosis Foundation | OTHER |
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The purpose of this study was to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis aged 6 to 11 years who have the G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Ivacaftor is a potent and selective potentiator of wild-type, G551D, F508del, and R117H forms of human CFTR protein. Potentiators are pharmacological agents that increase the chloride ion transport properties of the channel in the presence of cyclic adenosine monophosphate (AMP)-dependent protein kinase A (PKA) activation.
This is a Phase 3, 2-part, randomized, double-blind, placebo-controlled, parallel group multicenter study of orally administered ivacaftor in subjects with cystic fibrosis (CF) 6 to 11 years of age who have the G551D-CFTR mutation and a forced expiratory volume in 1 second (FEV1) between 90% and 105% predicted (using Knudson standards).
Based on in vitro studies and pharmacologic, pharmacokinetic (PK), and safety profiles, ivacaftor was selected for clinical development as a possible treatment for patients with CF. Patients with the G551D mutation were the targeted population for this study because ivacaftor is a potentiator of the gating effect of the CFTR protein, and the most prevalent mutation with a gating defect in CF is the G551D mutation.
This study was conducted in 2 parts. Part A was conducted to analyze the PK properties of ivacaftor and to determine the most appropriate dose to administer to subjects in Part B of this study. Part B explored the safety and efficacy of ivacaftor over long-term treatment in subjects 6 to 11 years of age.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Subjects who received placebo every 12 hours (q12h) for up to 48 weeks. |
|
| 150 mg Ivacaftor q12h | Experimental | Subjects who received 150 mg of ivacaftor q12h for up to 48 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ivacaftor | Drug | 150-mg tablet given orally q12h for up to 48 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24 | Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies. | baseline through 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 48 | Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies. | baseline through 48 weeks |
| Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Through Week 24 and Week 48 (Respiratory Domain Score, Children) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Richard Ahrens, MD | Roy A. & Lucille A. Carver College of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama | Birmingham | Alabama | 35233-1711 | United States | ||
| Emory Cystic Fibrosis Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23590265 | Derived | Davies JC, Wainwright CE, Canny GJ, Chilvers MA, Howenstine MS, Munck A, Mainz JG, Rodriguez S, Li H, Yen K, Ordonez CL, Ahrens R; VX08-770-103 (ENVISION) Study Group. Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. Am J Respir Crit Care Med. 2013 Jun 1;187(11):1219-25. doi: 10.1164/rccm.201301-0153OC. |
| Label | URL |
|---|---|
| Genetics Home Reference | View source |
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Nine subjects were dosed and included in Part A. In Part B, 52 subjects were enrolled and all were randomized to ivacaftor (26 subjects) or placebo (26 subjects). A 2-week run-in period was included to establish the baseline assessments on Day 1 after ensuring that subjects were properly taking their cystic fibrosis (CF) medication regimens.
Part A started on 05 August 2009 (signing of first informed consent). Screening evaluations were completed during Day -28 to Day -2. All subjects completing Part A were offered the opportunity to participate in Part B, which started on 12 March 2010. Screening evaluations were completed during Day -35 to Day -15 before the first dose of study drug.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Oral tablet every 12 hours (q12h) for up to 48 weeks |
| FG001 | 150 mg Ivacaftor q12h | Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Placebo | Drug | Tablet given orally q12h for up to 48 weeks |
|
The CFQ-R is a health-related quality of life measure for subjects with cystic fibrosis. Each domain is scored from 0 (worst) to 100 (best). A difference of at least 4 points in the respiratory domain score of the CFQ-R is considered a minimal clinically important difference (MCID). |
| baseline through 24 weeks and 48 weeks |
| Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48 | The sweat chloride (quantitative pilocarpine iontophoresis) test is a standard diagnostic tool for cystic fibrosis (CF), serving as an indicator of cystic fibrosis transmembrane conductance regulator (CFTR) activity. | baseline through 24 weeks and 48 weeks |
| Absolute Change From Baseline in Weight at Week 24 and Week 48 | As malnutrition is common in patients with cystic fibrosis (CF) because of increased energy expenditures due to lung disease and fat malabsorption, body weight is an important clinical measure of nutritional status. | baseline to 24 weeks and 48 weeks |
| Atlanta |
| Georgia |
| 30322 |
| United States |
| Children's Memorial Hospital | Chicago | Illinois | 60614 | United States |
| The Cystic Fibrosis Center of Chicago | Glenview | Illinois | 60025 | United States |
| Riley Hospital for Children | Indianapolis | Indiana | 46202 | United States |
| University of Iowa Department of Pediatrics | Iowa City | Iowa | 52242 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Children's Hospital Boston | Boston | Massachusetts | 02115 | United States |
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| Children's Hospital of Michigan | Detroit | Michigan | 48201 | United States |
| Helen DeVos Children's Hospital Spectrum Health Hospitals | Grand Rapids | Michigan | 49503 | United States |
| University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| The Children's Mercy Hospital | Kansas City | Missouri | 64108 | United States |
| University of Nebraska Medical Center Pediatric Pulmonary/ CF | Omaha | Nebraska | 68195-5190 | United States |
| East Tennessee Children's Hospital Pediatric Pulmonary and Respiratory Care | Knoxville | Tennessee | 37916 | United States |
| University of Utah Pediatric Pulmonology | Salt Lake City | Utah | 84108 | United States |
| University of Virginia Pediatric Respiratory Medicine | Charlottesville | Virginia | 22908 | United States |
| The Children's Hospital Westmead | Westmead | New South Wales | 2145 | Australia |
| Royal Children's Hospital Brisbane | Herston | Queensland | 4029 | Australia |
| Royal Children's Hospital Melbourne | Parkville | Victoria | 3052 | Australia |
| Princess Margaret Hospital for Children | Subiaco | Western Australia | 6008 | Australia |
| British Columbia Children's Hospital | Vancouver | British Columbia | V6H-3V4 | Canada |
| Hospital for Sick Children CF Center | Toronto | Ontario | M5G 1X8 | Canada |
| Hôpital Robert Debré - Service de gastro-entérologiemucoviscidose et nutrition | Paris | 75935 | France |
| Kinder- und Jugendklinik Universitätsklinikum Erlangen | Erlangen | 91054 | Germany |
| Mukoviszidose-Zentrum am Klinikum der Friedrich-Schiller-Universität Jena, Klinik für Kinder- und Jugendmedizin | Jena | 07740 | Germany |
| Our Lady's Children's Hospital | Dublin | 12 | Ireland |
| The National Children's Hospital | Dublin | 24 | Ireland |
| Dept of Gene Therapy, Imperial College London | London | SW3 6LR | United Kingdom |
| Medline Plus | View source |
| U.S. FDA Resources | View source |
| Completed Treatment Period, Week 24 |
|
| COMPLETED |
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| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Oral tablet every 12 hours (q12h) for up to 48 weeks |
| BG001 | 150 mg Ivacaftor q12h | Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks |
| 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 |
| |||||||||||||||
| Age, Customized | Number | participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Weight | Mean | Standard Deviation | kilograms |
| |||||||||||||||
| Body Mass Index | Mean | Standard Deviation | kilograms per square meter |
| |||||||||||||||
| Sweat Chloride | Mean | Standard Deviation | millimoles per liter |
| |||||||||||||||
| Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) | Percent predicted for age, gender, and height | Number | participants |
| |||||||||||||||
| Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) | Percent predicted for age, gender, and height | Mean | Standard Deviation | percentage |
|
| 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 | Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24 | Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies. | All randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo)and had available assessments during the time frame. | Posted | Least Squares Mean | Standard Error | percent of predicted volume (L) | baseline through 24 weeks |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 48 | Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies. | All randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo) and had available assessments during the time frame. | Posted | Least Squares Mean | Standard Error | percent of predicted volume (L) | baseline through 48 weeks |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Through Week 24 and Week 48 (Respiratory Domain Score, Children) | The CFQ-R is a health-related quality of life measure for subjects with cystic fibrosis. Each domain is scored from 0 (worst) to 100 (best). A difference of at least 4 points in the respiratory domain score of the CFQ-R is considered a minimal clinically important difference (MCID). | All randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo) and had available assessments during the time frame. | Posted | Least Squares Mean | Standard Error | score on a scale | baseline through 24 weeks and 48 weeks |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48 | The sweat chloride (quantitative pilocarpine iontophoresis) test is a standard diagnostic tool for cystic fibrosis (CF), serving as an indicator of cystic fibrosis transmembrane conductance regulator (CFTR) activity. | All randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo) and had available assessments during the time frame. | Posted | Least Squares Mean | Standard Error | millimoles per liter | baseline through 24 weeks and 48 weeks |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Absolute Change From Baseline in Weight at Week 24 and Week 48 | As malnutrition is common in patients with cystic fibrosis (CF) because of increased energy expenditures due to lung disease and fat malabsorption, body weight is an important clinical measure of nutritional status. | All randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo) and had available assessments during the time frame. | Posted | Least Squares Mean | Standard Error | kilograms | baseline to 24 weeks and 48 weeks |
|
|
For enrolled subjects, adverse events (AEs) were collected through the Follow-up visit in each study part. For subjects who completed 48 weeks of treatment and enrolled in the open-label extension study, AEs were only collected through the Week 48 visit.
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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 | Placebo | Oral tablet every 12 hours (q12h) for up to 48 weeks | 6 | 26 | 25 | 26 | ||
| EG001 | 150 mg Ivacaftor q12h | Oral tablet of 150 mg of ivacaftor q12h for up to 48 weeks | 5 | 26 | 26 | 26 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cystic fibrosis lung | Congenital, familial and genetic disorders | MedDRA (12.0) | Systematic Assessment | CF exacerbations were coded as "cystic fibrosis lung." |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Lung consolidation | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA (12.0) | Systematic Assessment |
| |
| Pulmonary function test decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
| |
| Adjustment disorder | Psychiatric disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Affective disorder | Psychiatric disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Conversion disorder | Psychiatric disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Pseudomonas infection | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
| |
| Muscle strain | Injury, poisoning and procedural complications | MedDRA (12.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Rales | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Pharyngeal erythema | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
| |
| Pharyngitis streptococcal | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA (12.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (12.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (12.0) | Systematic Assessment |
| |
| Bacteria sputum identified | Investigations | MedDRA (12.0) | Systematic Assessment |
| |
| Pulmonary function test decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
| |
| Eosinophil count increased | Investigations | MedDRA (12.0) | Systematic Assessment |
| |
| Culture throat positive | Investigations | MedDRA (12.0) | Systematic Assessment |
| |
| Breath sounds abnormal | Investigations | MedDRA (12.0) | Systematic Assessment |
| |
| Forced expiratory volume decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (12.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Excoriation | Injury, poisoning and procedural complications | MedDRA (12.0) | Systematic Assessment |
| |
| Cystic fibrosis lung | Congenital, familial and genetic disorders | MedDRA (12.0) | Systematic Assessment | CF exacerbations were coded as "cystic fibrosis lung." |
|
| Headache | Nervous system disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Seasonal allergy | Immune system disorders | MedDRA (12.0) | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (12.0) | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Monitor | Vertex | 617-444-6777 | medicalinfo@vrtx.com |
| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| D005355 | Fibrosis |
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D030342 | Genetic Diseases, Inborn |
| D007232 | Infant, Newborn, Diseases |
| D010335 | Pathologic Processes |
| ID | Term |
|---|---|
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C545203 | ivacaftor |
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| 9 to 11 Years |
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| > 11 Years |
|
| Male |
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| Other |
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| Not Allowed to Ask Per Local Regulations |
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| Not Hispanic or Latino |
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| Not Allowed to Ask Per Local Regulations |
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| Europe |
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| Australia |
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| ≥ 70% to ≤ 90% |
|
| > 90% |
|
| 18.3 |
| No |
| Superiority or Other |
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