Hyperphenylalaninemia, Non-Phenylketonuric, Tetrahydrobiopterin Deficiencies
Conditions
Brief summary
The purpose of this study is to evaluate the ability of Phenoptin to control blood phenylalanine levels in subjects who have hyperphenylalaninemia due to a primary BH4 deficiency and to evaluate the safety of Phenoptin in this population. Some subjects were receiving non-registered formulations of BH4 at enrollment and this treatment was suspended after Part 1 and within one day the subjects started Phenoptin at approximately the same dose.
Detailed description
Within 4 weeks of completing screening assessments to determine eligibility, subjects will be enrolled in the study. The study will be conducted in two parts. Part 1: After screening, all subjects will be followed for two weeks without modification of their baseline medical or dietary care. Part 2: Beginning at Week 2, subjects who were receiving non-registered formulations of BH4 at enrollment will suspend this treatment and within one day will start Phenoptin at approximately the same dose of the non-registered BH4 formulation. Subjects not receiving BH4 at enrollment will begin treatment with Phenoptin at approximately 5 mg/kg/day, given orally, prior to meals. At the discretion of the Investigator, the Phenoptin dose may be adjusted up or down at the Week 6 visit to control blood Phe levels (\<360 µmol/L), or to optimize the clinical effect. The maximum dose allowed will be approximately 20 mg/kg/day. All subjects will receive Phenoptin for a total of 8 weeks. Subjects will be instructed to continue their usual diet without modification. Study visits will occur every other week. Tyrosine, biopterin and neopterin will be analyzed at the following visits: Week 0 (enrollment), Week 2 (prior to dosing with Phenoptin), Week 8 (after 6 weeks of treatment with Phenoptin) and Week 10 (after 8 weeks of treatment with Phenoptin).During each visit, blood Phe level will be measured (2.5-5 hours after a meal), and safety evaluations will be performed. Safety will be assessed by monitoring adverse events and vital signs, performing physical examinations, assessing signs and symptoms of primary BH4 deficiency (i.e., neurological symptoms such as seizures, changes in muscle tone, weakness, etc.) and clinical laboratory tests (chemistry, hematology and urinalysis). Extension: Upon completion of 8 weeks of treatment (i.e., at the Week 10 visit), subjects will be offered the option to continue treatment with Phenoptin in an extension of this study. Participation in the study extension will continue until one of the following occurs: 1. the subject withdraws consent and discontinues from the study, 2. the subject is discontinued from the study at the discretion of the investigator, 3. the study drug is available through the appropriate marketing approval, or 4. the study is terminated. During the extension period, study drug will be dispensed to subjects monthly, and study visits will be required every 3 months. The Phenoptin dose may be adjusted at any visit during the study extension at the discretion of the Investigator. The maximum dose allowed will be approximately 20 mg/kg/day.
Interventions
DRUGPhenoptin
5mg/kg/day orally, dose may be adjusted to between 5-20 mg/kg/day by investigator at week 6 to control blood Phe levels
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Outcomes were to be evaluated for all subjects with primary BH4 disease. Outcomes were also evaluated based on the type of BH4 deficiency either due to defects in the genes encoding the enzymes involved in BH4 biosynthesis, GTPcyclohydrolase I (GCH1), 6-pyruvoyl-tetrahydropterin synthase (PTPS), and sepiapterin reductase (SR); or defects in the genes encoding the enzymes involved in BH4 recycling, pterin-4a-carbinolamine dehydratase (PCD) and dihydropteridine reductase (DHPR)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Documented history of blood Phe level \> 180 µmol/L on at least one occasion * Established diagnosis of hyperphenylalaninemia (HPA) due to primary BH4 deficiency with a documented defect in biopterin metabolism with blood or urine tests * Willing and able to provide written informed consent or, in the case of subjects under the age of 18 years, provide written assent (if required) and written informed consent by a parent or legal guardian * Negative urine pregnancy test at screening for females of child-bearing potential * Male and female subjects of childbearing potential (if sexually active and non-sterile) must be using acceptable birth control measures and be willing to continue to use acceptable birth control measures, as determined by the Investigator, and be willing to continue to use acceptable birth control measures while participating in the study * Willing and able to comply with all study procedures * Able to take medication orally
Exclusion criteria
* Perceived to be unreliable or unavailable for study participation or, if under the age of 18 years, have parents or legal guardians who are perceived to be unreliable or unavailable * Use of any investigational agent (other than BH4) within 30 days prior to screening, or requirement for any investigational agent or vaccine prior to completion of all scheduled study assessments * Positive urine pregnancy test at screening (non-sterile females of child bearing potential only), already known to be pregnant or breastfeeding or planning a pregnancy in self or partner during the study * Female subjects of childbearing potential not using an effective method of birth control, as determined by the PI, or unwilling to continue to use acceptable birth control measures. * Alanine aminotransferase (ALT) \> 2 times the upper limit of normal (i.e., Grade 1 or higher based on World Health Organization Toxicity Criteria) at screening * Concurrent disease or condition that would interfere with study participation or safety (e.g., seizure disorder, oral steroid-dependent asthma or other condition requiring oral or parenteral corticosteroid administration, insulin-dependent diabetes, or organ transplantation) * Serious neuropsychiatric illness (e.g., major depression) not currently under medical control * Requirement for concomitant treatment with any drug known to inhibit folate synthesis (e.g., methotrexate) * Clinical diagnosis of phenylketonuria (PKU) due to phenylalanine hydroxylase deficiency * Any condition that, in the view of the PI, renders the subject at high risk from treatment compliance and/or completing the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | At Baseline, Week 4 through Extension Week 130 | Baseline blood phenylalanine(Phe) value is the latest measurement taken prior to initiation of Phenoptin treatment. The ideal range for blood Phe levels is approximately 120-360 µmol/L. |
| Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L | At Baseline, Week 4 through Extension Week 130 | Baseline blood phenylalanine(Phe) value is the latest measurement taken prior to initiation of Phenoptin treatment. The objective of this outcome was to compare to Phe levels achieved using previous treatment regimens. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subjects Experiencing Adverse Events(AEs) | Up to 35 Months | Intensity was determined by the Investigator. For symptomatic AEs the following definitions were applied. Mild = AE did not limit usual activities. Moderate = AE resulted in some limitation of usual activities. Severe = AE resulted in an inability to carry out usual activities. A treatment-emergent Adverse Events (TEAE) is any Adverse Events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration. Serious AE (SAE) resulted in death, was life-threatening, required in patient hospitalization or prolongation of an existing hospitalization, resulted in persistent or significant disability or incapacity, is a congenital anomaly or birth defect; or was an important medical event. |
Other
| Measure | Time frame | Description |
|---|---|---|
| AEs Consistent With Signs and/or Symptoms of BH4 Deficiency | Up to 35 months | Attention was paid to AEs that may be consistent with signs and/or symptoms associated with primary BH4 deficiency to determine if such signs and symptoms arose or increased in severity or frequency during the study. These included prematurity and low birth weight, inability to control body temperature, low muscle tone, decreased spontaneous movements, poor sucking, movement disorders, difficulty swallowing, hypersalivation, seizures or convulsions, behavioral problems, developmental delay, and mental retardation. |
Countries
Germany, United States
Participant flow
Recruitment details
This study was a multicenter study, conducted at 8 sites in the United States of America and one site in Germany
Pre-assignment details
A sample size planned of 10 to 15 subjects considered adequate based on clinical considerations. Actual enrolled and treated are 12 subjects.
Participants by arm
| Arm | Count |
|---|---|
| Phenoptin In Part 1, subjects continued their usual treatment regimen.
In Part 2, subjects on non-registered formulations of BH4 at enrollment began Phenoptin treatment at approximately the same daily dose; subjects not receiving BH4 at enrollment began treatment at 5mg/kg/day Phenoptin. Half a dose was administered orally twice daily, to achieve a full dose/day.
In Part 3, subjects receives 10 mg/kg/day Phenoptin, administered orally twice for three weeks, followed by 20 mg/kg/day once daily for remaining 4 weeks.
In extension phase, subjects were offered the option to continue treatment with Phenoptin.
The mean Phenoptin dose received during the study was 9.1 mg/kg/day with a minimum of 1.9 mg/kg/day and a maximum of 21 mg/kg/day.
All 12 subjects participated in Part 1, Part 2 and Extension Phase. Subjects completed Part 2 are offered the option of participating in Part 3, Subjects who agreed to participate proceeded to Part 3. Among 12 subjects, 2 participated in Part 3. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Extension (Variable Duration) | Adverse Event | 1 |
| Extension (Variable Duration) | Withdrew Consent | 1 |
Baseline characteristics
| Characteristic | Phenoptin |
|---|---|
| Age, Continuous | 13.5 years STANDARD_DEVIATION 9.6 |
| Age, Customized >=18 and <65 years of age | 2 Participants |
| Age, Customized <18 years of age | 10 Participants |
| Age, Customized >=65 years of age | 0 Participants |
| Blood Phe at Screening Visit | 164.5 µmol/L STANDARD_DEVIATION 186.8 |
| Height | 142.1 cm STANDARD_DEVIATION 27.6 |
| Race/Ethnicity, Customized Race Caucasian | 10 Participants |
| Race/Ethnicity, Customized Race Other | 2 Participants |
| Region of Enrollment Europe | 2 participants |
| Region of Enrollment North America | 10 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 5 Participants |
| Type of Enzyme Defects Recycling | 3 participants |
| Type of Enzyme Defects Synthesis | 9 participants |
| Weight | 45.2 kg STANDARD_DEVIATION 27.1 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 2 / 12 |
Outcome results
Primary
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints
Baseline blood phenylalanine(Phe) value is the latest measurement taken prior to initiation of Phenoptin treatment. The ideal range for blood Phe levels is approximately 120-360 µmol/L.
Time frame: At Baseline, Week 4 through Extension Week 130
Population: Efficacy analysis population are the subjects received at least 1 dose of Phenoptin and has at least 1 post-treatment measurement of blood Phe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Subjects | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Part 2: Week 4 | 104.1 μmol/L | Standard Deviation 66.7 |
| All Subjects | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 82 | 153.0 μmol/L | Standard Deviation 223.2 |
| All Subjects | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 22 | 94.3 μmol/L | Standard Deviation 76.5 |
| All Subjects | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Baseline | 132.9 μmol/L | Standard Deviation 134.7 |
| All Subjects | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 58 | 151.4 μmol/L | Standard Deviation 173.1 |
| All Subjects | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 34 | 105.0 μmol/L | Standard Deviation 95.3 |
| All Subjects | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension : Week 118 | 124.3 μmol/L | Standard Deviation 119.4 |
| All Subjects | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 46 | 144.8 μmol/L | Standard Deviation 164.2 |
| All Subjects | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Part 2: Week 6 | 120.8 μmol/L | Standard Deviation 119 |
| All Subjects | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 70 | 106.7 μmol/L | Standard Deviation 93.8 |
| All Subjects | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 106 | 157.2 μmol/L | Standard Deviation 159.8 |
| All Subjects | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Part 2: Week 8 | 112.3 μmol/L | Standard Deviation 106.8 |
| All Subjects | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 130 | 124.9 μmol/L | Standard Deviation 118.2 |
| All Subjects | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 94 | 186.2 μmol/L | Standard Deviation 305.8 |
| All Subjects | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Part 2: Week 10 | 143.2 μmol/L | Standard Deviation 147.3 |
| Subgroup: Subjects With Synthesis Enzymatic Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 58 | 72.4 μmol/L | Standard Deviation 17.7 |
| Subgroup: Subjects With Synthesis Enzymatic Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Baseline | 72.2 μmol/L | Standard Deviation 13.4 |
| Subgroup: Subjects With Synthesis Enzymatic Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Part 2: Week 4 | 78.2 μmol/L | Standard Deviation 28.4 |
| Subgroup: Subjects With Synthesis Enzymatic Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Part 2: Week 6 | 70.2 μmol/L | Standard Deviation 17.2 |
| Subgroup: Subjects With Synthesis Enzymatic Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Part 2: Week 8 | 66.6 μmol/L | Standard Deviation 13.6 |
| Subgroup: Subjects With Synthesis Enzymatic Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Part 2: Week 10 | 75.0 μmol/L | Standard Deviation 11.5 |
| Subgroup: Subjects With Synthesis Enzymatic Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 22 | 63.8 μmol/L | Standard Deviation 8.5 |
| Subgroup: Subjects With Synthesis Enzymatic Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 34 | 71.9 μmol/L | Standard Deviation 16.6 |
| Subgroup: Subjects With Synthesis Enzymatic Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 46 | 78.8 μmol/L | Standard Deviation 20.4 |
| Subgroup: Subjects With Synthesis Enzymatic Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 70 | 72.0 μmol/L | Standard Deviation 12.6 |
| Subgroup: Subjects With Synthesis Enzymatic Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 82 | 61.3 μmol/L | Standard Deviation 12.1 |
| Subgroup: Subjects With Synthesis Enzymatic Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 94 | 63.8 μmol/L | Standard Deviation 10.6 |
| Subgroup: Subjects With Synthesis Enzymatic Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 106 | 69.8 μmol/L | Standard Deviation 21.7 |
| Subgroup: Subjects With Synthesis Enzymatic Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension : Week 118 | 73.1 μmol/L | Standard Deviation 22.8 |
| Subgroup: Subjects With Synthesis Enzymatic Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 130 | 74.6 μmol/L | Standard Deviation 14.9 |
| Subgroup: Subjects With Recycling Enzyme Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 70 | 210.7 μmol/L | Standard Deviation 161.6 |
| Subgroup: Subjects With Recycling Enzyme Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Part 2: Week 10 | 347.7 μmol/L | Standard Deviation 187.7 |
| Subgroup: Subjects With Recycling Enzyme Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 130 | 276.0 μmol/L | Standard Deviation 173.9 |
| Subgroup: Subjects With Recycling Enzyme Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 82 | 428.0 μmol/L | Standard Deviation 349.4 |
| Subgroup: Subjects With Recycling Enzyme Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Part 2: Week 8 | 249.3 μmol/L | Standard Deviation 156.2 |
| Subgroup: Subjects With Recycling Enzyme Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension : Week 118 | 277.7 μmol/L | Standard Deviation 171.1 |
| Subgroup: Subjects With Recycling Enzyme Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Part 2: Week 6 | 272.7 μmol/L | Standard Deviation 175.1 |
| Subgroup: Subjects With Recycling Enzyme Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Baseline | 315.0 μmol/L | Standard Deviation 180.9 |
| Subgroup: Subjects With Recycling Enzyme Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 34 | 204.3 μmol/L | Standard Deviation 170.8 |
| Subgroup: Subjects With Recycling Enzyme Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 106 | 419.3 μmol/L | Standard Deviation 33 |
| Subgroup: Subjects With Recycling Enzyme Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 46 | 343.0 μmol/L | Standard Deviation 261 |
| Subgroup: Subjects With Recycling Enzyme Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 22 | 185.7 μmol/L | Standard Deviation 123.1 |
| Subgroup: Subjects With Recycling Enzyme Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 94 | 553.3 μmol/L | Standard Deviation 494.2 |
| Subgroup: Subjects With Recycling Enzyme Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Extension: Week 58 | 388.3 μmol/L | Standard Deviation 226.6 |
| Subgroup: Subjects With Recycling Enzyme Defect | Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints | Part 2: Week 4 | 181.7 μmol/L | Standard Deviation 96.1 |
Primary
Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L
Baseline blood phenylalanine(Phe) value is the latest measurement taken prior to initiation of Phenoptin treatment. The objective of this outcome was to compare to Phe levels achieved using previous treatment regimens.
Time frame: At Baseline, Week 4 through Extension Week 130
Population: Efficacy analysis population are the subjects received at least 1 dose of Phenoptin and has at least 1 post-treatment measurement of blood Phe.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Subjects | Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L | Extension: Week 46 | 83.3 percentage of participants |
| All Subjects | Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L | Baseline | 83.3 percentage of participants |
| All Subjects | Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L | Part 2: Week 4 | 100 percentage of participants |
| All Subjects | Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L | Part 2: Week 6 | 91.7 percentage of participants |
| All Subjects | Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L | Part 2: Week 8 | 91.7 percentage of participants |
| All Subjects | Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L | Part 2: Week 10 | 91.7 percentage of participants |
| All Subjects | Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L | Extension: Week 22 | 100 percentage of participants |
| All Subjects | Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L | Extension: Week 34 | 91.7 percentage of participants |
| All Subjects | Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L | Extension: Week 58 | 83.3 percentage of participants |
| All Subjects | Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L | Extension: Week 70 | 91.7 percentage of participants |
| All Subjects | Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L | Extension: Week 82 | 83.3 percentage of participants |
| All Subjects | Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L | Extension: Week 94 | 83.3 percentage of participants |
| All Subjects | Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L | Extension: Week 106 | 75 percentage of participants |
| All Subjects | Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L | Extension: Week 118 | 83.3 percentage of participants |
| All Subjects | Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L | Extension: Week 130 | 83.3 percentage of participants |
Secondary
Subjects Experiencing Adverse Events(AEs)
Intensity was determined by the Investigator. For symptomatic AEs the following definitions were applied. Mild = AE did not limit usual activities. Moderate = AE resulted in some limitation of usual activities. Severe = AE resulted in an inability to carry out usual activities. A treatment-emergent Adverse Events (TEAE) is any Adverse Events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration. Serious AE (SAE) resulted in death, was life-threatening, required in patient hospitalization or prolongation of an existing hospitalization, resulted in persistent or significant disability or incapacity, is a congenital anomaly or birth defect; or was an important medical event.
Time frame: Up to 35 Months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Subjects | Subjects Experiencing Adverse Events(AEs) | Any Adverse Events | 12 participants |
| All Subjects | Subjects Experiencing Adverse Events(AEs) | Study Drug-Related Adverse Events | 6 participants |
| All Subjects | Subjects Experiencing Adverse Events(AEs) | Any Serious Adverse Events | 2 participants |
| All Subjects | Subjects Experiencing Adverse Events(AEs) | Withdrawal from study due to AE | 1 participants |
| All Subjects | Subjects Experiencing Adverse Events(AEs) | Withdrawal from Study due to SAE | 0 participants |
| All Subjects | Subjects Experiencing Adverse Events(AEs) | TEAE by severity: Mild | 4 participants |
| All Subjects | Subjects Experiencing Adverse Events(AEs) | TEAE by severity: Moderate | 6 participants |
| All Subjects | Subjects Experiencing Adverse Events(AEs) | TEAE by severity: Severe | 2 participants |
Other Pre-specified
AEs Consistent With Signs and/or Symptoms of BH4 Deficiency
Attention was paid to AEs that may be consistent with signs and/or symptoms associated with primary BH4 deficiency to determine if such signs and symptoms arose or increased in severity or frequency during the study. These included prematurity and low birth weight, inability to control body temperature, low muscle tone, decreased spontaneous movements, poor sucking, movement disorders, difficulty swallowing, hypersalivation, seizures or convulsions, behavioral problems, developmental delay, and mental retardation.
Time frame: Up to 35 months
Population: AEs that are signs and symptoms of BH4 deficiency were reported for 3 subjects: One SAE of mild dyskinesia (required hospitalization) in one subject; events of severe dystonia and moderate Dyskinesia in one subject; and one event of mild vertigo in one subject. All events resolved and were considered unrelated to Phenoptin except mild vertigo.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Subjects | AEs Consistent With Signs and/or Symptoms of BH4 Deficiency | Subjects with Any Signs and/or Symptoms of BH4 Def | 3 Participants |
| All Subjects | AEs Consistent With Signs and/or Symptoms of BH4 Deficiency | Dystonia | 1 Participants |
| All Subjects | AEs Consistent With Signs and/or Symptoms of BH4 Deficiency | Dyskinesia | 2 Participants |
| All Subjects | AEs Consistent With Signs and/or Symptoms of BH4 Deficiency | Vertigo | 1 Participants |