Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2007-006044-22 | EudraCT Number |
Not provided
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| Name | Class |
|---|---|
| Covance | INDUSTRY |
| PharmaNet | INDUSTRY |
| PRA Health Sciences | INDUSTRY |
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The objective of this study is to determine the safety of once weekly dosing of idursulfase 0.5 mg/kg administered by intravenous (IV) infusion for male Hunter syndrome patients ≤ 5 years old.
This study will provide a basis for evaluating the safety of idursulfase administered to Hunter syndrome patients who are ≤ 5 years old. Additionally, this study will provide a basis for evaluating the idursulfase single- and repeated-dose pharmacokinetic profiles as well as the pharmacodynamic effect (as measured by urinary GAG excretion) in this pediatric population. Additional exploratory measures will include abdominal ultrasound measurements of liver and spleen volumes, assessments of growth with comparisons to normal population growth data, assessments of annualized growth velocity, assessments of routine developmental milestones using the Denver II, and assessments of clinical events, including the first occurrence of certain hearing-related events (e.g., hearing loss, otitis media), respiratory-related events (e.g., upper and lower respiratory infections), and specific surgical procedures (e.g., adenoidectomy, placement of PE tubes).
All patients in this open-label study will receive once-weekly infusions of idursulfase at a dose of 0.5 mg/kg.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Idursulfase | Other | Open-label treatment with idursulfase |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Idursulfase | Biological | Solution for intravenous infusion, 0.5 mg/kg weekly |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety Evaluation | An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered as a pharmaceutical product that did not necessarily have a causal relationship with this treatment. A 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. Number of participants with AEs occurred after start of study treatment until 30 days after the last infusion of idursulfase, were reported. | From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline to Week 53 in Normalized Urinary Glycosaminoglycan (GAG) Levels | Analysis of urinary GAG levels was performed at baseline, Week 18, Week 36, and Week 53 as an assessment of the pharmacodynamic effects of Elaprase (idursulfase). | Baseline, Weeks 18, 36 and 53 |
| Single- and Repeat-Dose Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) |
Not provided
Inclusion Criteria:
The patient has a diagnosis of Hunter syndrome based upon biochemical criteria either documented in their medical history or established at Screening:
A deficiency in iduronate-2-sulfatase (I2S) enzyme activity of ≤ 10 % of the lower limit of the normal range as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory)
AND
A normal enzyme activity level of one other sulfatase as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory).
The patient is 5 years of age and under.
The patient is male.
The patient's parent(s), or patient's legal guardian must have voluntarily signed an Institutional Review Board approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient's parent(s), or the patient's legal guardian.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital de Clinicas de Porto Alegre, Servico de Genetica Medica | Porto Alegre | Rio Grande do Sul | 90035-903 | Brazil | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17185020 | Background | Muenzer J, Gucsavas-Calikoglu M, McCandless SE, Schuetz TJ, Kimura A. A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome). Mol Genet Metab. 2007 Mar;90(3):329-37. doi: 10.1016/j.ymgme.2006.09.001. Epub 2006 Dec 20. | |
| 16912578 | Background | Muenzer J, Wraith JE, Beck M, Giugliani R, Harmatz P, Eng CM, Vellodi A, Martin R, Ramaswami U, Gucsavas-Calikoglu M, Vijayaraghavan S, Wendt S, Puga AC, Ulbrich B, Shinawi M, Cleary M, Piper D, Conway AM, Kimura A. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. 2006 Aug;8(8):465-73. doi: 10.1097/01.gim.0000232477.37660.fb. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Idursulfase | Open-label treatment with idursulfase |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety population was defined as all enrolled participants who received at least one study dose (or any portion of a dose) of idursulfase.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Idursulfase | Open-label treatment with idursulfase |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Safety Evaluation | An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered as a pharmaceutical product that did not necessarily have a causal relationship with this treatment. A 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. Number of participants with AEs occurred after start of study treatment until 30 days after the last infusion of idursulfase, were reported. | Safety population was defined as all enrolled participants who received at least one study dose (or any portion of a dose) of idursulfase. | Posted | Number | participants | From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks |
|
From the start of study treatment until 30 days after the last infusion of idursulfase, up to 53 weeks
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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 | Idursulfase | Open-label treatment with idursulfase |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bronchopneumonia | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
Not provided
| ID | Term |
|---|---|
| D016532 | Mucopolysaccharidosis II |
| D013398 | Sudden Infant Death |
| D016464 | Lysosomal Storage Diseases |
| ID | Term |
|---|---|
| D038901 | X-Linked Intellectual Disability |
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
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| ID | Term |
|---|---|
| C517982 | idursulfase |
Not provided
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| Weeks 1 and 27 |
| Single- and Repeat-Dose Pharmacokinetics - Time of Maximum Observed Serum Concentration (Tmax) | Weeks 1 and 27 |
| Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to the Final Time Point With a Concentration of at Least Lower Limit of Quantitation (AUClast) | Weeks 1 and 27 |
| Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf) | Weeks 1 and 27 |
| Single- and Repeat-Dose Pharmacokinetics - Elimination Half-Life (t1/2) | t1/2 refers to the elimination of the drug. It is the time taken for the blood plasma concentration to reach half the concentration in the terminal phase of elimination. It is expressed in minutes and derived from the terminal slope of the concentration versus time curve. | Weeks 1 and 27 |
| Single- and Repeat-Dose Pharmacokinetics - Mean Residence Time From Time 0 to Infinity (MRTinf) | MRTinf is an average duration of the drug in the body from time zero to infinity, and is expressed in minutes. | Weeks 1 and 27 |
| Single- and Repeat-Dose Pharmacokinetics - Clearance (CL) | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. | Weeks 1 and 27 |
| Single- and Repeat-Dose Pharmacokinetics - Volume of Distribution at Steady State (Vss) | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the apparent volume of distribution at steadystate. | Weeks 1 and 27 |
| Instytut Pomnik Centrum Zdrowia Dziecka, Klinika Chorob Metaboliczynch, Endokrynologii i Diabetologii |
| Warsaw |
| 04-730 |
| Poland |
| National Taiwan University Hospital, Dept. of Pediatrics and Medical Genetics | Taipei | 10016 | Taiwan |
| 25902842 | Result | Pano A, Barbier AJ, Bielefeld B, Whiteman DA, Amato DA. Immunogenicity of idursulfase and clinical outcomes in very young patients (16 months to 7.5 years) with mucopolysaccharidosis II (Hunter syndrome). Orphanet J Rare Dis. 2015 Apr 24;10:50. doi: 10.1186/s13023-015-0265-2. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Baseline Normalized Urinary Glycosaminoglycan (GAG) Level | Mean | Standard Deviation | microgram per milligram creatinine |
|
Open-label treatment with idursulfase |
|
|
| Secondary | Mean Change From Baseline to Week 53 in Normalized Urinary Glycosaminoglycan (GAG) Levels | Analysis of urinary GAG levels was performed at baseline, Week 18, Week 36, and Week 53 as an assessment of the pharmacodynamic effects of Elaprase (idursulfase). | Safety population. In the categories listed below, 'N' signifies the number of participants evaluable for the timepoint. | Posted | Mean | Standard Deviation | microgram/milligram creatinine | Baseline, Weeks 18, 36 and 53 |
|
|
|
| Secondary | Single- and Repeat-Dose Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) | Pharmacokinetic (PK) population was defined as all enrolled participants who had at least one serum concentration measurement available. In the categories listed below, "N" signifies the number of participants evaluable for the timepoint. | Posted | Mean | Standard Deviation | nanogram per milliliter | Weeks 1 and 27 |
|
|
|
| Secondary | Single- and Repeat-Dose Pharmacokinetics - Time of Maximum Observed Serum Concentration (Tmax) | PK population. In the categories listed below, "N" signifies the number of participants evaluable for the timepoint. | Posted | Mean | Standard Deviation | minutes | Weeks 1 and 27 |
|
|
|
| Secondary | Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to the Final Time Point With a Concentration of at Least Lower Limit of Quantitation (AUClast) | PK population. In the categories listed below, "N" signifies the number of participants evaluable for the timepoint. | Posted | Mean | Standard Deviation | minute*nanogram per milliliter | Weeks 1 and 27 |
|
|
|
| Secondary | Single- and Repeat-Dose Pharmacokinetics - Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf) | PK population with evaluable participants for this endpoint. In the categories listed below, "N" signifies the number of participants evaluable for the timepoint. | Posted | Mean | Standard Deviation | minute*nanogram per milliliter | Weeks 1 and 27 |
|
|
|
| Secondary | Single- and Repeat-Dose Pharmacokinetics - Elimination Half-Life (t1/2) | t1/2 refers to the elimination of the drug. It is the time taken for the blood plasma concentration to reach half the concentration in the terminal phase of elimination. It is expressed in minutes and derived from the terminal slope of the concentration versus time curve. | PK population with evaluable participants for this endpoint. In the categories listed below, "N" signifies the number of participants evaluable for the timepoint. | Posted | Mean | Standard Deviation | minutes | Weeks 1 and 27 |
|
|
|
| Secondary | Single- and Repeat-Dose Pharmacokinetics - Mean Residence Time From Time 0 to Infinity (MRTinf) | MRTinf is an average duration of the drug in the body from time zero to infinity, and is expressed in minutes. | PK population with evaluable participants for this endpoint. In the categories listed below, "N" signifies the number of participants evaluable for the timepoint. | Posted | Mean | Standard Deviation | minutes | Weeks 1 and 27 |
|
|
|
| Secondary | Single- and Repeat-Dose Pharmacokinetics - Clearance (CL) | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. | PK population with evaluable participants for this endpoint. In the categories listed below, "N" signifies the number of participants evaluable for the timepoint. | Posted | Mean | Standard Deviation | milliliter/minute/kilogram | Weeks 1 and 27 |
|
|
|
| Secondary | Single- and Repeat-Dose Pharmacokinetics - Volume of Distribution at Steady State (Vss) | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Vss is the apparent volume of distribution at steadystate. | PK population with evaluable participants for this endpoint. In the categories listed below, "N" signifies the number of participants evaluable for the timepoint. | Posted | Mean | Standard Deviation | milliliter per kilogram | Weeks 1 and 27 |
|
|
|
| 13 |
| 28 |
| 28 |
| 28 |
| Otitis media | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Gastrointestinal infection | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Viral pharyngitis | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (10.1) | Systematic Assessment |
|
| Catheter site haematoma | General disorders | MedDRA (10.1) | Systematic Assessment |
|
| Irritability | General disorders | MedDRA (10.1) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (10.1) | Systematic Assessment |
|
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Skin hypertrophy | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Microcytic anaemia | Blood and lymphatic system disorders | MedDRA (10.1) | Systematic Assessment |
|
| Food poisoning | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Muscle contracture | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Atonic seizures | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA (10.1) | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Otitis media acute | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Upper respiratory tract infection bacterial | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Bronchopneumonia | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Gastrointestinal infection | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Otitis externa | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Viral pharyngitis | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Herpes virus infection | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Laryngitis | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Abscess limb | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Body tinea | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Candidiasis | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Catheter site infection | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Lice infestation | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Otitis media chronic | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Rash pustular | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Tinea versicolour | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Tonsillitis bacterial | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Varicella | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Viral diarrhoea | Infections and infestations | MedDRA (10.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (10.1) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (10.1) | Systematic Assessment |
|
| Catheter site haematoma | General disorders | MedDRA (10.1) | Systematic Assessment |
|
| Catheter site haemorrhage | General disorders | MedDRA (10.1) | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA (10.1) | Systematic Assessment |
|
| Irritability | General disorders | MedDRA (10.1) | Systematic Assessment |
|
| Malaise | General disorders | MedDRA (10.1) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (10.1) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Allergic cough | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Sleep apnea syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Choking | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Lung infiltration | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Respiratory disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Dermatitis diaper | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Heat rash | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Intertrigo | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Skin hypertrophy | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Skin hypopigmentation | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Urticaria papular | Skin and subcutaneous tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Dental caries | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Anal fissure | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Faeces hard | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Food poisoning | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Gingivitis | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Pruritus ani | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Umbilical hernia | Gastrointestinal disorders | MedDRA (10.1) | Systematic Assessment |
|
| Deafness | Ear and labyrinth disorders | MedDRA (10.1) | Systematic Assessment |
|
| Hypoacusis | Ear and labyrinth disorders | MedDRA (10.1) | Systematic Assessment |
|
| Cerumen impaction | Ear and labyrinth disorders | MedDRA (10.1) | Systematic Assessment |
|
| Conductive deafness | Ear and labyrinth disorders | MedDRA (10.1) | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA (10.1) | Systematic Assessment |
|
| Hearing impaired | Ear and labyrinth disorders | MedDRA (10.1) | Systematic Assessment |
|
| Otorrhoea | Ear and labyrinth disorders | MedDRA (10.1) | Systematic Assessment |
|
| Burns second degree | Injury, poisoning and procedural complications | MedDRA (10.1) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (10.1) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (10.1) | Systematic Assessment |
|
| Head injury | Injury, poisoning and procedural complications | MedDRA (10.1) | Systematic Assessment |
|
| Limb injury | Injury, poisoning and procedural complications | MedDRA (10.1) | Systematic Assessment |
|
| Mouth injury | Injury, poisoning and procedural complications | MedDRA (10.1) | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (10.1) | Systematic Assessment |
|
| Sunburn | Injury, poisoning and procedural complications | MedDRA (10.1) | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA (10.1) | Systematic Assessment |
|
| Sleep disorder | Psychiatric disorders | MedDRA (10.1) | Systematic Assessment |
|
| Bipolar disorder | Psychiatric disorders | MedDRA (10.1) | Systematic Assessment |
|
| Crying | Psychiatric disorders | MedDRA (10.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (10.1) | Systematic Assessment |
|
| Learning disorder | Psychiatric disorders | MedDRA (10.1) | Systematic Assessment |
|
| Left ventricular hypertrophy | Cardiac disorders | MedDRA (10.1) | Systematic Assessment |
|
| Aortic valve incompetence | Cardiac disorders | MedDRA (10.1) | Systematic Assessment |
|
| Cardiomyopathy | Cardiac disorders | MedDRA (10.1) | Systematic Assessment |
|
| Cyanosis | Cardiac disorders | MedDRA (10.1) | Systematic Assessment |
|
| Right ventricular hypertrophy | Cardiac disorders | MedDRA (10.1) | Systematic Assessment |
|
| Sinus bradycardia | Cardiac disorders | MedDRA (10.1) | Systematic Assessment |
|
| Ventricular extrasystoles | Cardiac disorders | MedDRA (10.1) | Systematic Assessment |
|
| Hepatic enzyme abnormal | Investigations | MedDRA (10.1) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (10.1) | Systematic Assessment |
|
| Cardiac murmur | Investigations | MedDRA (10.1) | Systematic Assessment |
|
| Electrocardiogram repolarisation abnormality | Investigations | MedDRA (10.1) | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA (10.1) | Systematic Assessment |
|
| Lymphocyte morphology abnormal | Investigations | MedDRA (10.1) | Systematic Assessment |
|
| Monocyte count decreased | Investigations | MedDRA (10.1) | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
|
| Atonic seizures | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
|
| Epilepsy | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (10.1) | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA (10.1) | Systematic Assessment |
|
| Haemorrhage | Vascular disorders | MedDRA (10.1) | Systematic Assessment |
|
| Hyperaemia | Vascular disorders | MedDRA (10.1) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (10.1) | Systematic Assessment |
|
| Eosinophilia | Blood and lymphatic system disorders | MedDRA (10.1) | Systematic Assessment |
|
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA (10.1) | Systematic Assessment |
|
| Splenomegaly | Blood and lymphatic system disorders | MedDRA (10.1) | Systematic Assessment |
|
| Muscle contracture | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Lordosis | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (10.1) | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (10.1) | Systematic Assessment |
|
| Obesity | Metabolism and nutrition disorders | MedDRA (10.1) | Systematic Assessment |
|
| Hypermetropia | Eye disorders | MedDRA (10.1) | Systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA (10.1) | Systematic Assessment |
|
| Hip dysplasia | Congenital, familial and genetic disorders | MedDRA (10.1) | Systematic Assessment |
|
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (10.1) | Systematic Assessment |
|
| Enuresis | Renal and urinary disorders | MedDRA (10.1) | Systematic Assessment |
|
Shire's agreements with investigators vary. All agreements provide Shire the right to embargo communications regarding trial results prior to public release for a period ≤180 days from the time submitted to Shire for review. Shire does not prohibit publication, but can require the removal of confidential information (excluding trial results) and can request postponement of a single-center publication until after disclosure of the trial's multi-center publication.
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D009083 | Mucopolysaccharidoses |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D017520 | Mucinoses |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D003645 | Death, Sudden |
| D003643 | Death |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D066088 | Infant Death |
| Title | Measurements |
|---|---|
|
| Change at Week 53 (N=27) |
|