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This multicenter, open label study is designed to evaluate the safety of Kuvan® and its effect on neurocognitive function, blood Phe concentration, and growth in children with PKU who are 0-6 years old.
Rigorous control of diet is typically advocated in children 4 years and under with PKU because brain sensitivity to high Phe concentrations is expected to be greatest during these years of rapid neurocognitive development.
Prolonged high blood Phe concentrations are neurotoxic and lead to impairment of intelligence and other brain functions (such as attentiveness). Reduction of blood Phe concentrations through dietary control is an important determinant of long-term neurologic outcome in PKU patients, and reduction of blood Phe concentrations in patients with PKU has been shown to decrease the long term risk of neurologic injury.
It is difficult for many patients to maintain reduced blood Phe, and many patients with PKU experience some degree of neurological impairment despite efforts to maintain dietary Phe control.
The strongest determinant of intelligence quotient (IQ) and cognitive function is compliance with blood Phe control. Several clinical studies with Kuvan have already demonstrated efficacy in reducing blood Phe in subjects older than 4 years. This study will examine whether addition of Kuvan to the standard of care at an early age in children with well controlled diets can lower blood Phe levels (ie, reach and maintain a goal of ≤ 240 micromole/L) and preserve neurocognitive functioning. In addition, this study will provide data on Kuvan exposure, rate of uptake, half life, and clearance in young children.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| sapropterin dihydrochloride | Experimental | A dose of 20 mg/kg will be administered dissolved in water or apple juice, based on subject's age and ability, and taken orally once daily with food. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sapropterin dihydrochloride | Drug | A dose of 20 mg/kg will be administered dissolved in water or apple juice, based on subject's age and ability, and taken orally once daily with food. |
| Measure | Description | Time Frame |
|---|---|---|
| Full-Scale Intelligence Quotient (FSIQ) Score | Full Scale Intelligence Quotient (FSIQ) is a score derived through administration of selected subtests from age appropriate Wechsler Intelligence assessments. Weschler Preschool and Primary Scale of Intelligence (WPPSI)-III is used for children >30 months and ≤6 years; and Weschler Intelligence Scale for Children (WISC)-IV is used for children >6 years old. The outcome variable will be the FSIQ score from WPPSI-III and/or WISC-IV tests. FSIQ results can range from 40 being the lowest and 160 being the highest. Higher scores are associated with higher intelligence quotient. | Assessments through 84 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects With Adverse Events (AEs) | Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, and that does not necessarily have a causal relationship with this treatment. Drug Related Adverse all noxious and unintended responses to a medical product related to any dose. This means that a causal relationship between a medicinal product and an AE is at least a reasonable possibility, ie, the relationship cannot be ruled out. A serious adverse event (SAE) is an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Joshua Lilienstein, M.D. | BioMarin Pharmaceutical | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| La Jolla | California | United States | ||||
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This was a multicenter study conducted at 20 sites in the U.S. and Canada.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sapropterin Dihydrochloride | A dose of 20 mg/kg dissolved in water or apple juice, administered once daily orally, with food. Part 1: 95 subjects participated in Part 1. Pharmacokinetic (PK) Sub-Study: 94 subjects participated in the PK substudy, one subject declined participation. 6-month Safety/Efficacy Sub-Study: 65 subjects met the minimum required score of 80, Kuvan responders, all 65 subjects participated in Safety/Efficacy Substudy. Part 2: 65 subjects met the minimum required score of 80 at baseline (Month 2) neurocognitive tests, all 65 subjects participated in Part 2. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part 1 (4 Weeks) |
|
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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 | Nov 30, 2010 | Aug 14, 2020 |
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|
| Up to 7 years |
| Change From Baseline in Growth Measurements - Height Z-Scores | Z-scores of Height determined using World Health Organization(WHO) growth charts for children <24 months and Centers for Disease Control and Prevention(CDC) clinical growth charts for children 24 months and older. A height z-score is a standardized height measure after considering important factors like age and gender, in which higher z-scores are associated with taller children. Z-scores (or standard deviation scores) describe how far a measurement is from the median (mean). A z-score of 0 is the same as a 50th percentile; a positive value is a factor of standard deviation (SD) unit above the 50%; and a negative value is a factor of SD unit below 50%. | Baseline and up to 84 months |
| Change From Baseline in Growth Measurements - Weight Z-Scores | Z-scores of Weight determined using World Health Organization(WHO) growth charts for children <24 months and Centers for Disease Control and Prevention(CDC) clinical growth charts for children 24 months or older. A weight z-score is a standardized weight measure after considering important factors like age and gender, in which higher z-scores are associated with heavier children. Z-scores (or standard deviation scores) describe how far a measurement is from the median (mean). A z-score of 0 is the same as a 50th percentile; a positive value is a factor of SD unit above the 50%; and a negative value is a factor of SD unit below 50%. | Baseline and up to 84 months |
| Change From Baseline in Growth Measurements - Head Circumference Z-Scores | Z-scores of Head Circumference determined using World Health Organization(WHO) growth charts for children <24 months and Centers for Disease Control and Prevention(CDC) clinical growth charts for children 24 months and older. A head circumference z-score is a standardized head circumference measure after considering important factors like age and gender, in which higher z-scores are associated with children with larger heads. Z-scores (or standard deviation scores) describe how far a measurement is from the median (mean). A z-score of 0 is the same as a 50th percentile; a positive value is a factor of SD unit above the 50%; and a negative value is a factor of SD unit below 50%. | Baseline and up to 84 months |
| Change From Baseline in Bayley-III Scores - Neurocognitive Testing Results | The Bayley-III is a tool for assessing all facets of development in infants within an age range of 12 to 30 months, with normative data available for infants as young as 16 days. Composite scores are derived for cognitive, language, and motor development and scaled to a metric, with a range of 40 to 160. Higher scores are a better outcome. | At Month 6, 12, 18 and 24 |
| Baseline Concentration of Tetrahydrobiopterin (BH4)(C0) | Baseline concentration of BH4(C0) with associated inter-individual variability. | At predose and postdose - 0.22, 3.2 and 7 hours |
| Absorption Rate Constant (Ka) of Kuvan | Population pharmacokinetic parameter, Absorption Rate Constant (Ka) | At predose and postdose - 0.22, 3.2 and 7 hours |
| Apparent Volume of Distribution (V/F) of Kuvan | Population pharmacokinetic parameter apparent volume of distribution (V/F) | At predose and postdose - 0.22, 3.2 and 7 hours |
| Apparent Clearance (CL/F) of Kuvan | Population pharmacokinetic parameter apparent clearance (CL/F) | At predose and postdose - 0.22, 3.2 and 7 hours |
| Orange |
| California |
| United States |
| Tampa | Florida | United States |
| Chicago | Illinois | United States |
| Boston | Massachusetts | United States |
| Kansas City | Missouri | United States |
| Cleveland | Ohio | United States |
| Columbus | Ohio | United States |
| Hershey | Pennsylvania | United States |
| Nashville | Tennessee | United States |
| Salt Lake City | Utah | United States |
| Milwaukee | Wisconsin | United States |
| Edmonton | Alberta | Canada |
| Vancouver | British Columbia | Canada |
| Winnipeg | Manitoba | Canada |
| Hamilton | Ontario | Canada |
| Toronto | Ontario | Canada |
| Montreal | Quebec | Canada |
| Sainte-Foy | Quebec | Canada |
| COMPLETED |
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| NOT COMPLETED |
|
| PK Sub-Study 2 (4 Weeks) |
|
|
| Safety/Efficacy Sub-Study 1 (6 Months) |
|
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| Part 2 (7 Years) |
|
|
Safety Population consist of all subjects who received any study drug in the Full Analysis Set(FAS).
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| ID | Title | Description |
|---|---|---|
| BG000 | Sapropterin Dihydrochloride | A dose of 20 mg/kg dissolved in water or apple juice, administered once daily orally, with food. |
| 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 |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||||
| Weight | Mean | Standard Deviation | kg |
| |||||||||||||||||
| Height | Mean | Standard Deviation | cm |
|
| 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 | Full-Scale Intelligence Quotient (FSIQ) Score | Full Scale Intelligence Quotient (FSIQ) is a score derived through administration of selected subtests from age appropriate Wechsler Intelligence assessments. Weschler Preschool and Primary Scale of Intelligence (WPPSI)-III is used for children >30 months and ≤6 years; and Weschler Intelligence Scale for Children (WISC)-IV is used for children >6 years old. The outcome variable will be the FSIQ score from WPPSI-III and/or WISC-IV tests. FSIQ results can range from 40 being the lowest and 160 being the highest. Higher scores are associated with higher intelligence quotient. | Efficacy population is based on all subjects from the enrolled population who have at least 2 WPPSI/ WISC assessments. | Posted | Mean | Standard Deviation | score on a scale | Assessments through 84 months. |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Subjects With Adverse Events (AEs) | Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, and that does not necessarily have a causal relationship with this treatment. Drug Related Adverse all noxious and unintended responses to a medical product related to any dose. This means that a causal relationship between a medicinal product and an AE is at least a reasonable possibility, ie, the relationship cannot be ruled out. A serious adverse event (SAE) is an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. | Enrolled Population consists of all subjects who enter Part 2. This population involves subjects who respond to Kuvan and had a Bayley-III or IQ test score ≥80 within 6 weeks of determination of Kuvan responsiveness in Part 1. Kuvan 20 mg/kg once daily. | Posted | Count of Participants | Participants | Up to 7 years |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Growth Measurements - Height Z-Scores | Z-scores of Height determined using World Health Organization(WHO) growth charts for children <24 months and Centers for Disease Control and Prevention(CDC) clinical growth charts for children 24 months and older. A height z-score is a standardized height measure after considering important factors like age and gender, in which higher z-scores are associated with taller children. Z-scores (or standard deviation scores) describe how far a measurement is from the median (mean). A z-score of 0 is the same as a 50th percentile; a positive value is a factor of standard deviation (SD) unit above the 50%; and a negative value is a factor of SD unit below 50%. | Efficacy Population | Posted | Mean | Standard Deviation | Z-score change from baseline | Baseline and up to 84 months |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Growth Measurements - Weight Z-Scores | Z-scores of Weight determined using World Health Organization(WHO) growth charts for children <24 months and Centers for Disease Control and Prevention(CDC) clinical growth charts for children 24 months or older. A weight z-score is a standardized weight measure after considering important factors like age and gender, in which higher z-scores are associated with heavier children. Z-scores (or standard deviation scores) describe how far a measurement is from the median (mean). A z-score of 0 is the same as a 50th percentile; a positive value is a factor of SD unit above the 50%; and a negative value is a factor of SD unit below 50%. | Efficacy Population | Posted | Mean | Standard Deviation | Z-score change from baseline | Baseline and up to 84 months |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Growth Measurements - Head Circumference Z-Scores | Z-scores of Head Circumference determined using World Health Organization(WHO) growth charts for children <24 months and Centers for Disease Control and Prevention(CDC) clinical growth charts for children 24 months and older. A head circumference z-score is a standardized head circumference measure after considering important factors like age and gender, in which higher z-scores are associated with children with larger heads. Z-scores (or standard deviation scores) describe how far a measurement is from the median (mean). A z-score of 0 is the same as a 50th percentile; a positive value is a factor of SD unit above the 50%; and a negative value is a factor of SD unit below 50%. | Efficacy Population, subjects less than 36 months of age. | Posted | Mean | Standard Deviation | Z-score change from baseline | Baseline and up to 84 months |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Bayley-III Scores - Neurocognitive Testing Results | The Bayley-III is a tool for assessing all facets of development in infants within an age range of 12 to 30 months, with normative data available for infants as young as 16 days. Composite scores are derived for cognitive, language, and motor development and scaled to a metric, with a range of 40 to 160. Higher scores are a better outcome. | Efficacy Population, analysis only comprised of subjects less than 30 months of age. | Posted | Mean | Standard Deviation | score on a scale | At Month 6, 12, 18 and 24 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Baseline Concentration of Tetrahydrobiopterin (BH4)(C0) | Baseline concentration of BH4(C0) with associated inter-individual variability. | Eighty patients were evaluable from PKU-015 PK Sub-Study. | Posted | Least Squares Mean | Standard Error | µg/L | At predose and postdose - 0.22, 3.2 and 7 hours |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Absorption Rate Constant (Ka) of Kuvan | Population pharmacokinetic parameter, Absorption Rate Constant (Ka) | Eighty subjects were evaluable from PKU-015 PK Sub-Study. | Posted | Least Squares Mean | Standard Error | l/hour | At predose and postdose - 0.22, 3.2 and 7 hours |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Apparent Volume of Distribution (V/F) of Kuvan | Population pharmacokinetic parameter apparent volume of distribution (V/F) | Eighty subjects were evaluable from PKU-015 PK Sub-Study. | Posted | Mean | Standard Error | L | At predose and postdose - 0.22, 3.2 and 7 hours |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Apparent Clearance (CL/F) of Kuvan | Population pharmacokinetic parameter apparent clearance (CL/F) | Eighty subjects were evaluable from PKU-015 PK Sub-Study. | Posted | Mean | Standard Error | L/hour | At predose and postdose - 0.22, 3.2 and 7 hours |
|
|
Up to 7 years
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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 | Safety Population | All subjects who enrolled in the study (Full Analysis Set) and received any study drug. | 0 | 95 | 12 | 95 | 90 | 95 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Phenylketonuria | Congenital, familial and genetic disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Colitis ulcerative | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Croup infectious | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Airway complication of anaesthesia | Injury, poisoning and procedural complications | MedDRA (15.1) | Systematic Assessment |
| |
| Concussion | Injury, poisoning and procedural complications | MedDRA (15.1) | Systematic Assessment |
| |
| Injury | Injury, poisoning and procedural complications | MedDRA (15.1) | Systematic Assessment |
| |
| Convulsion | Nervous system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Autism spectrum disorder | Psychiatric disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Diet noncompliance | Social circumstances | MedDRA (15.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Conjunctivitis | Eye disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Myopia | Eye disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Teething | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Seasonal allergy | Immune system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Conjunctivitis infective | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Croup infectious | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Hand-foot-and-mouth disease | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Pharyngitis streptococcal | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Streptococcal infection | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (15.1) | Systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | MedDRA (15.1) | Systematic Assessment |
| |
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA (15.1) | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (15.1) | Systematic Assessment |
| |
| Red blood cell sedimentation rate increased | Investigations | MedDRA (15.1) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Attention deficit/hyperactivity disorder | Psychiatric disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Joshua Lilienstein/Medical Director, Global Medical Affairs | BioMarin Pharmaceutical Inc. | 651.523.0310 | MEDINFO@bmrn.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 26, 2019 | Aug 14, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D010661 | Phenylketonurias |
| ID | Term |
|---|---|
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D000592 | Amino Acid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C003402 | sapropterin |
| C046978 | phenoptin |
Not provided
Not provided
Not provided
| Sponsor Decision |
|
| Withdrawal by Subject |
|
| Unknown or Not Reported |
|
| White |
|
| Other |
|
|
| FSIQ Month 24 |
|
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| FSIQ Month 36 |
|
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| FSIQ Month 48 |
|
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| FSIQ Month 60 |
|
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| FSIQ Month 72 |
|
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| FSIQ Month 84 |
|
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Coefficient estimates from a random coefficient model and associated p-values.
| Participants |
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