Trial Outcomes & Findings for Safety and Efficacy Study of Phenoptin in Subjects With Hyperphenylalaninemia Due to BH4 Deficiency (NCT NCT00355264)
NCT ID: NCT00355264
Last Updated: 2020-09-25
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
12 participants
Primary outcome timeframe
At Baseline, Week 4 through Extension Week 130
Results posted on
2020-09-25
Participant Flow
This study was a multicenter study, conducted at 8 sites in the United States of America and one site in Germany
A sample size planned of 10 to 15 subjects considered adequate based on clinical considerations. Actual enrolled and treated are 12 subjects.
Participant milestones
| Measure |
Phenoptin
In Part 1, subjects continued their usual treatment regimen.
In Part 2, subjects on non-registered formulations of Tetrahydrobiopterin (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 of the dose was administered orally twice daily, to achieve a full dose per day.
In Part 3 (concurrent with Extension), subjects had the option of receiving 10 mg/kg/day Phenoptin administered orally twice daily 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.
All 12 subjects participated in Part 1, Part 2 and Extension Phase. Subjects that completed Part 2 were offered the option of participating in Part 3. Among 12 subjects, 2 participated in Part 3 that took place concurrent with the Extension study.
|
|---|---|
|
Part 1 (2 Weeks)
STARTED
|
12
|
|
Part 1 (2 Weeks)
COMPLETED
|
12
|
|
Part 1 (2 Weeks)
NOT COMPLETED
|
0
|
|
Part 2 (8 Weeks)
STARTED
|
12
|
|
Part 2 (8 Weeks)
COMPLETED
|
12
|
|
Part 2 (8 Weeks)
NOT COMPLETED
|
0
|
|
Part 3 (7 Weeks of Extension)
STARTED
|
2
|
|
Part 3 (7 Weeks of Extension)
COMPLETED
|
2
|
|
Part 3 (7 Weeks of Extension)
NOT COMPLETED
|
0
|
|
Extension (Variable Duration)
STARTED
|
12
|
|
Extension (Variable Duration)
COMPLETED
|
10
|
|
Extension (Variable Duration)
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Phenoptin
In Part 1, subjects continued their usual treatment regimen.
In Part 2, subjects on non-registered formulations of Tetrahydrobiopterin (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 of the dose was administered orally twice daily, to achieve a full dose per day.
In Part 3 (concurrent with Extension), subjects had the option of receiving 10 mg/kg/day Phenoptin administered orally twice daily 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.
All 12 subjects participated in Part 1, Part 2 and Extension Phase. Subjects that completed Part 2 were offered the option of participating in Part 3. Among 12 subjects, 2 participated in Part 3 that took place concurrent with the Extension study.
|
|---|---|
|
Extension (Variable Duration)
Adverse Event
|
1
|
|
Extension (Variable Duration)
Withdrew Consent
|
1
|
Baseline Characteristics
Safety and Efficacy Study of Phenoptin in Subjects With Hyperphenylalaninemia Due to BH4 Deficiency
Baseline characteristics by cohort
| Measure |
Phenoptin
n=12 Participants
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.
|
|---|---|
|
Age, Continuous
|
13.5 years
STANDARD_DEVIATION 9.6 • n=93 Participants
|
|
Age, Customized
<18 years of age
|
10 Participants
n=93 Participants
|
|
Age, Customized
>=18 and <65 years of age
|
2 Participants
n=93 Participants
|
|
Age, Customized
>=65 years of age
|
0 Participants
n=93 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Race · Caucasian
|
10 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Race · Other
|
2 Participants
n=93 Participants
|
|
Region of Enrollment
North America
|
10 participants
n=93 Participants
|
|
Region of Enrollment
Europe
|
2 participants
n=93 Participants
|
|
Height
|
142.1 cm
STANDARD_DEVIATION 27.6 • n=93 Participants
|
|
Weight
|
45.2 kg
STANDARD_DEVIATION 27.1 • n=93 Participants
|
|
Type of Enzyme Defects
Synthesis
|
9 participants
n=93 Participants
|
|
Type of Enzyme Defects
Recycling
|
3 participants
n=93 Participants
|
|
Blood Phe at Screening Visit
|
164.5 µmol/L
STANDARD_DEVIATION 186.8 • n=93 Participants
|
PRIMARY outcome
Timeframe: At Baseline, Week 4 through Extension Week 130Population: Efficacy analysis population are the subjects received at least 1 dose of Phenoptin and has at least 1 post-treatment measurement of blood Phe.
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.
Outcome measures
| Measure |
All Subjects
n=12 Participants
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, half a dose administered orally twice daily 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.
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.
|
Subgroup: Subjects With Synthesis Enzymatic Defect
n=9 Participants
Subjects primary BH4 deficiency due to defects in the genes encoding the enzymes involved in BH4 biosynthesis, guanosine triphosphate (GTP) cyclohydrolase I (GCH1), 6-pyruvoyl-tetrahydropterin synthase (PTPS), and sepiapterin reductase (SR).
|
Subgroup: Subjects With Recycling Enzyme Defect
n=3 Participants
Subjects with BH4 deficiency due to defects in the genes encoding the enzymes involved in BH4 recycling, pterin-4a-carbinolamine dehydratase (PCD) and dihydropteridine reductase (DHPR).
|
|---|---|---|---|
|
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints
Extension : Week 118
|
124.3 μmol/L
Standard Deviation 119.4
|
73.1 μmol/L
Standard Deviation 22.8
|
277.7 μmol/L
Standard Deviation 171.1
|
|
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints
Extension: Week 130
|
124.9 μmol/L
Standard Deviation 118.2
|
74.6 μmol/L
Standard Deviation 14.9
|
276.0 μmol/L
Standard Deviation 173.9
|
|
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints
Baseline
|
132.9 μmol/L
Standard Deviation 134.7
|
72.2 μmol/L
Standard Deviation 13.4
|
315.0 μmol/L
Standard Deviation 180.9
|
|
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints
Part 2: Week 4
|
104.1 μmol/L
Standard Deviation 66.7
|
78.2 μmol/L
Standard Deviation 28.4
|
181.7 μmol/L
Standard Deviation 96.1
|
|
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints
Part 2: Week 6
|
120.8 μmol/L
Standard Deviation 119.0
|
70.2 μmol/L
Standard Deviation 17.2
|
272.7 μmol/L
Standard Deviation 175.1
|
|
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints
Part 2: Week 8
|
112.3 μmol/L
Standard Deviation 106.8
|
66.6 μmol/L
Standard Deviation 13.6
|
249.3 μmol/L
Standard Deviation 156.2
|
|
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints
Part 2: Week 10
|
143.2 μmol/L
Standard Deviation 147.3
|
75.0 μmol/L
Standard Deviation 11.5
|
347.7 μmol/L
Standard Deviation 187.7
|
|
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints
Extension: Week 22
|
94.3 μmol/L
Standard Deviation 76.5
|
63.8 μmol/L
Standard Deviation 8.5
|
185.7 μmol/L
Standard Deviation 123.1
|
|
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints
Extension: Week 34
|
105.0 μmol/L
Standard Deviation 95.3
|
71.9 μmol/L
Standard Deviation 16.6
|
204.3 μmol/L
Standard Deviation 170.8
|
|
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints
Extension: Week 46
|
144.8 μmol/L
Standard Deviation 164.2
|
78.8 μmol/L
Standard Deviation 20.4
|
343.0 μmol/L
Standard Deviation 261.0
|
|
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints
Extension: Week 58
|
151.4 μmol/L
Standard Deviation 173.1
|
72.4 μmol/L
Standard Deviation 17.7
|
388.3 μmol/L
Standard Deviation 226.6
|
|
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints
Extension: Week 70
|
106.7 μmol/L
Standard Deviation 93.8
|
72.0 μmol/L
Standard Deviation 12.6
|
210.7 μmol/L
Standard Deviation 161.6
|
|
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints
Extension: Week 82
|
153.0 μmol/L
Standard Deviation 223.2
|
61.3 μmol/L
Standard Deviation 12.1
|
428.0 μmol/L
Standard Deviation 349.4
|
|
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints
Extension: Week 94
|
186.2 μmol/L
Standard Deviation 305.8
|
63.8 μmol/L
Standard Deviation 10.6
|
553.3 μmol/L
Standard Deviation 494.2
|
|
Blood Phenylalanine(Phe) Levels Measured at Specified Timepoints
Extension: Week 106
|
157.2 μmol/L
Standard Deviation 159.8
|
69.8 μmol/L
Standard Deviation 21.7
|
419.3 μmol/L
Standard Deviation 33.0
|
PRIMARY outcome
Timeframe: At Baseline, Week 4 through Extension Week 130Population: Efficacy analysis population are the subjects received at least 1 dose of Phenoptin and has at least 1 post-treatment measurement of blood Phe.
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.
Outcome measures
| Measure |
All Subjects
n=12 Participants
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, half a dose administered orally twice daily 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.
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.
|
Subgroup: Subjects With Synthesis Enzymatic Defect
Subjects primary BH4 deficiency due to defects in the genes encoding the enzymes involved in BH4 biosynthesis, guanosine triphosphate (GTP) cyclohydrolase I (GCH1), 6-pyruvoyl-tetrahydropterin synthase (PTPS), and sepiapterin reductase (SR).
|
Subgroup: Subjects With Recycling Enzyme Defect
Subjects with BH4 deficiency due to defects in the genes encoding the enzymes involved in BH4 recycling, pterin-4a-carbinolamine dehydratase (PCD) and dihydropteridine reductase (DHPR).
|
|---|---|---|---|
|
Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L
Baseline
|
83.3 percentage of participants
Interval 51.6 to 97.9
|
—
|
—
|
|
Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L
Part 2: Week 4
|
100 percentage of participants
Interval 73.5 to 100.0
|
—
|
—
|
|
Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L
Part 2: Week 6
|
91.7 percentage of participants
Interval 61.5 to 99.8
|
—
|
—
|
|
Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L
Part 2: Week 8
|
91.7 percentage of participants
Interval 61.5 to 99.8
|
—
|
—
|
|
Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L
Part 2: Week 10
|
91.7 percentage of participants
Interval 61.5 to 99.8
|
—
|
—
|
|
Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L
Extension: Week 22
|
100 percentage of participants
Interval 73.5 to 100.0
|
—
|
—
|
|
Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L
Extension: Week 34
|
91.7 percentage of participants
Interval 61.5 to 99.8
|
—
|
—
|
|
Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L
Extension: Week 46
|
83.3 percentage of participants
Interval 51.6 to 97.9
|
—
|
—
|
|
Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L
Extension: Week 58
|
83.3 percentage of participants
Interval 51.6 to 97.9
|
—
|
—
|
|
Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L
Extension: Week 70
|
91.7 percentage of participants
Interval 61.5 to 99.8
|
—
|
—
|
|
Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L
Extension: Week 82
|
83.3 percentage of participants
Interval 51.6 to 97.9
|
—
|
—
|
|
Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L
Extension: Week 94
|
83.3 percentage of participants
Interval 51.6 to 97.9
|
—
|
—
|
|
Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L
Extension: Week 106
|
75 percentage of participants
Interval 42.8 to 94.5
|
—
|
—
|
|
Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L
Extension: Week 118
|
83.3 percentage of participants
Interval 51.6 to 97.9
|
—
|
—
|
|
Percentage of Subjects With Blood Phenylalanine (Last Observation Carried Forward) < 360 μmol/L
Extension: Week 130
|
83.3 percentage of participants
Interval 51.6 to 97.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 35 MonthsIntensity 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.
Outcome measures
| Measure |
All Subjects
n=12 Participants
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, half a dose administered orally twice daily 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.
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.
|
Subgroup: Subjects With Synthesis Enzymatic Defect
Subjects primary BH4 deficiency due to defects in the genes encoding the enzymes involved in BH4 biosynthesis, guanosine triphosphate (GTP) cyclohydrolase I (GCH1), 6-pyruvoyl-tetrahydropterin synthase (PTPS), and sepiapterin reductase (SR).
|
Subgroup: Subjects With Recycling Enzyme Defect
Subjects with BH4 deficiency due to defects in the genes encoding the enzymes involved in BH4 recycling, pterin-4a-carbinolamine dehydratase (PCD) and dihydropteridine reductase (DHPR).
|
|---|---|---|---|
|
Subjects Experiencing Adverse Events(AEs)
Any Serious Adverse Events
|
2 participants
|
—
|
—
|
|
Subjects Experiencing Adverse Events(AEs)
Any Adverse Events
|
12 participants
|
—
|
—
|
|
Subjects Experiencing Adverse Events(AEs)
Study Drug-Related Adverse Events
|
6 participants
|
—
|
—
|
|
Subjects Experiencing Adverse Events(AEs)
Withdrawal from study due to AE
|
1 participants
|
—
|
—
|
|
Subjects Experiencing Adverse Events(AEs)
Withdrawal from Study due to SAE
|
0 participants
|
—
|
—
|
|
Subjects Experiencing Adverse Events(AEs)
TEAE by severity: Mild
|
4 participants
|
—
|
—
|
|
Subjects Experiencing Adverse Events(AEs)
TEAE by severity: Moderate
|
6 participants
|
—
|
—
|
|
Subjects Experiencing Adverse Events(AEs)
TEAE by severity: Severe
|
2 participants
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 35 monthsPopulation: 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.
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.
Outcome measures
| Measure |
All Subjects
n=12 Participants
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, half a dose administered orally twice daily 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.
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.
|
Subgroup: Subjects With Synthesis Enzymatic Defect
Subjects primary BH4 deficiency due to defects in the genes encoding the enzymes involved in BH4 biosynthesis, guanosine triphosphate (GTP) cyclohydrolase I (GCH1), 6-pyruvoyl-tetrahydropterin synthase (PTPS), and sepiapterin reductase (SR).
|
Subgroup: Subjects With Recycling Enzyme Defect
Subjects with BH4 deficiency due to defects in the genes encoding the enzymes involved in BH4 recycling, pterin-4a-carbinolamine dehydratase (PCD) and dihydropteridine reductase (DHPR).
|
|---|---|---|---|
|
AEs Consistent With Signs and/or Symptoms of BH4 Deficiency
Subjects with Any Signs and/or Symptoms of BH4 Def
|
3 Participants
|
—
|
—
|
|
AEs Consistent With Signs and/or Symptoms of BH4 Deficiency
Dystonia
|
1 Participants
|
—
|
—
|
|
AEs Consistent With Signs and/or Symptoms of BH4 Deficiency
Dyskinesia
|
2 Participants
|
—
|
—
|
|
AEs Consistent With Signs and/or Symptoms of BH4 Deficiency
Vertigo
|
1 Participants
|
—
|
—
|
Adverse Events
Phenoptin
Serious events: 2 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phenoptin
n=12 participants at risk
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, either resumed with previously taken BH4 (tetrahydrobiopterin) formulations.
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.
|
|---|---|
|
Infections and infestations
Upper Respiratory Tract Infection
|
8.3%
1/12 • Number of events 1 • Up to 35 months (from enrollment to Study Completion.)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Distress
|
8.3%
1/12 • Number of events 1 • Up to 35 months (from enrollment to Study Completion.)
|
|
Surgical and medical procedures
Medical Device Change
|
8.3%
1/12 • Number of events 1 • Up to 35 months (from enrollment to Study Completion.)
|
|
Nervous system disorders
Dyskinesia
|
8.3%
1/12 • Number of events 1 • Up to 35 months (from enrollment to Study Completion.)
|
|
Renal and urinary disorders
Nephrolithiasis
|
8.3%
1/12 • Number of events 1 • Up to 35 months (from enrollment to Study Completion.)
|
Other adverse events
| Measure |
Phenoptin
n=12 participants at risk
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, either resumed with previously taken BH4 (tetrahydrobiopterin) formulations.
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.
|
|---|---|
|
Infections and infestations
Gastroenteritis bacterial
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Infections and infestations
Gastroenteritis viral
|
16.7%
2/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Infections and infestations
Nasopharyngitis
|
41.7%
5/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Infections and infestations
Otitis media
|
16.7%
2/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Infections and infestations
Candidiasis
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Infections and infestations
Cellulitis
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Infections and infestations
Ear infection
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Infections and infestations
Gastroenteritis
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Blood and lymphatic system disorders
Neutropenia
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Ear and labyrinth disorders
Vertigo
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
16.7%
2/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Gastrointestinal disorders
Constipation
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Gastrointestinal disorders
Diarrhoea
|
58.3%
7/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Gastrointestinal disorders
Dyspepsia
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Gastrointestinal disorders
Nausea
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
4/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
General disorders
Fatigue
|
16.7%
2/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
General disorders
Irritability
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
General disorders
Pyrexia
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Immune system disorders
Seasonal allergy
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Infections and infestations
Bronchitis
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Infections and infestations
Pharyngitis streptococcal
|
16.7%
2/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Infections and infestations
Respiratory tract infection
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Infections and infestations
Sinusitis
|
16.7%
2/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Infections and infestations
Skin candida
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Infections and infestations
Tonsillitis
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Infections and infestations
Urinary tract infection
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Infections and infestations
Viral skin infection
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Infections and infestations
Viral upper respiratory tract infection
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Injury, poisoning and procedural complications
Contusion
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Injury, poisoning and procedural complications
Excoriation
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Injury, poisoning and procedural complications
Eye injury
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Injury, poisoning and procedural complications
Face injury
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Injury, poisoning and procedural complications
Fall
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Investigations
Alanine aminotransferase increased
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Investigations
Aspartate aminotransferase increased
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Investigations
Blood bilirubin increased
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Investigations
Blood calcium increased
|
16.7%
2/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Investigations
Blood creatinine increased
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Investigations
Gamma-glutamyltransferase increased
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Investigations
Lymphocyte count increased
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Investigations
Metabolic function test abnormal
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Investigations
Neutrophil count decreased
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Investigations
Protein urine present
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Investigations
Urine ketone body present
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Investigations
Urine leukocyte esterase positive
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Nervous system disorders
Dizziness
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Nervous system disorders
Dysaesthesia
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Nervous system disorders
Dystonia
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Nervous system disorders
Nervous system disorder
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Nervous system disorders
Neurological symptom
|
16.7%
2/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Nervous system disorders
Paraesthesia
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Psychiatric disorders
Abnormal behaviour
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Psychiatric disorders
Self injurious behaviour
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
2/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
16.7%
2/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal drip
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
16.7%
2/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Respiratory, thoracic and mediastinal disorders
Tonsillar hypertrophy
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Skin and subcutaneous tissue disorders
Ingrowing nail
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Skin and subcutaneous tissue disorders
Rash generalised
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Skin and subcutaneous tissue disorders
Skin inflammation
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Infections and infestations
Upper respiratory tract infection
|
16.7%
2/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Nervous system disorders
Dyskinesia
|
16.7%
2/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Renal and urinary disorders
Nephrolithiasis
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
|
Surgical and medical procedures
Medical device change
|
8.3%
1/12 • Up to 35 months (from enrollment to Study Completion.)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place