Trial Outcomes & Findings for Study of Phenoptin in Subjects With Phenylketonuria Who Participated in Protocols PKU-004 or PKU-006 (NCT NCT00332189)
NCT ID: NCT00332189
Last Updated: 2012-11-16
Results Overview
Safety was assessed with regards to the rate and type of AEs, clinically significant changes to vital signs and/or physical examination findings, and clinically significant changes in laboratory test results.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
111 participants
Primary outcome timeframe
Baseline through Final Visit (a Maximum of 30 months) with AEs collected at month 3 and 6 then at 6 month intervals
Results posted on
2012-11-16
Participant Flow
Subjects had to have previously participated in study PKU-004 (NCT00225615) or PKU-006 (NCT00272792)
The last assessment obtained in PKU-004 or PKU-006 could be used to determine eligibility for this study provided assessment was conducted fewer than six weeks prior to PKU-008 Day 1.
Participant milestones
| Measure |
Total Patient Population
Phenoptin will be taken orally once daily as the number of tablets equivalent to that of the last prescribed dose of the previous study (PKU-004 NCT00225615 or PKU-006 NCT00272792). Subjects who participated in PKU-006 NCT00272792 will receive Phenoptin as the number of tablets equivalent to 20 mg/kg/day at enrollment. The Phenoptin dose may be adjusted up or down as needed at the discretion of the investigator in increments of approximately 5 mg/kg/day within a range of 5 mg/kg/day to 20 mg/kg/day to control blood Phe to levels consistent with local clinical site recommendations for blood Phe control.
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|---|---|
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Overall Study
STARTED
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111
|
|
Overall Study
COMPLETED
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90
|
|
Overall Study
NOT COMPLETED
|
21
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Reasons for withdrawal
| Measure |
Total Patient Population
Phenoptin will be taken orally once daily as the number of tablets equivalent to that of the last prescribed dose of the previous study (PKU-004 NCT00225615 or PKU-006 NCT00272792). Subjects who participated in PKU-006 NCT00272792 will receive Phenoptin as the number of tablets equivalent to 20 mg/kg/day at enrollment. The Phenoptin dose may be adjusted up or down as needed at the discretion of the investigator in increments of approximately 5 mg/kg/day within a range of 5 mg/kg/day to 20 mg/kg/day to control blood Phe to levels consistent with local clinical site recommendations for blood Phe control.
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|---|---|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
Uncooperative/Noncompliant
|
3
|
|
Overall Study
Withdrawal by Subject
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9
|
|
Overall Study
Lack of Efficacy
|
4
|
|
Overall Study
Moved out of country
|
2
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Baseline Characteristics
Study of Phenoptin in Subjects With Phenylketonuria Who Participated in Protocols PKU-004 or PKU-006
Baseline characteristics by cohort
| Measure |
Total Patient Population
n=111 Participants
The mean (+/- SD) daily dose of study drug was 16.4 (+/-4.4) mg/kg. The final dose prescribed was 20 mg/kg/day for 73 (65.8%) subjects, 10 mg/kg/day for 33 (29.7%) subjects, and 5 mg/kg/day for 5 (4.5%) subjects.
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|---|---|
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Age Continuous
|
16.4 years
STANDARD_DEVIATION 10.2 • n=93 Participants
|
|
Age, Customized
>=4 to <8
|
20 participants
n=93 Participants
|
|
Age, Customized
>=8 to <12
|
24 participants
n=93 Participants
|
|
Age, Customized
>=12 to <18
|
28 participants
n=93 Participants
|
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Age, Customized
>=18
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39 participants
n=93 Participants
|
|
Sex: Female, Male
Female
|
44 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
67 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
108 participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Asian/Asian Pacific Islander
|
1 participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
1 participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 participants
n=93 Participants
|
|
Region of Enrollment
North America
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54 participants
n=93 Participants
|
|
Region of Enrollment
Europe
|
57 participants
n=93 Participants
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PRIMARY outcome
Timeframe: Baseline through Final Visit (a Maximum of 30 months) with AEs collected at month 3 and 6 then at 6 month intervalsPopulation: Percentage of total population who experienced an AE or SAE presented here. For full list of SAEs, and AEs experienced with a frequency of greater than 5%, see the Reported Adverse Event section.
Safety was assessed with regards to the rate and type of AEs, clinically significant changes to vital signs and/or physical examination findings, and clinically significant changes in laboratory test results.
Outcome measures
| Measure |
Total Patient Population
n=111 Participants
The safety analysis population includes all subjects who received at least one dose of study drug during the study.
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|---|---|
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Tabulation of the Incidence and Frequency of All AEs and SAEs That Occur Throughout the Study.
% of Subjects Reporting Any Adverse Event
|
83.8 percentage of subjects reporting events
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Tabulation of the Incidence and Frequency of All AEs and SAEs That Occur Throughout the Study.
% of Subjects Reporting Related Adverse Events
|
33.3 percentage of subjects reporting events
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Tabulation of the Incidence and Frequency of All AEs and SAEs That Occur Throughout the Study.
% of Subjects Reporting Serious Adverse Events
|
6.3 percentage of subjects reporting events
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Tabulation of the Incidence and Frequency of All AEs and SAEs That Occur Throughout the Study.
% of Subjects Reporting Related Serious AEs
|
0.9 percentage of subjects reporting events
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SECONDARY outcome
Timeframe: Baseline through Final Visit (a Maximum of 30 months) with blood phe samples taken at months 3 and 6 then at 6 month intervalsPopulation: The population includes all subjects who received at least one dose of study drug during the study and had at least one measurement of blood Phe level.
There were no pre-specified efficacy analysis, blood Phe samples were taken at each visit. Blood Phe concentrations remained within levels consistent with local clinical site recommendations for blood Phe control.
Outcome measures
| Measure |
Total Patient Population
n=111 Participants
The safety analysis population includes all subjects who received at least one dose of study drug during the study.
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|---|---|
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Following Blood Phe Levels.
Baseline Blood Phe Level (N=111)
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607.4 micromoles per liter
Standard Deviation 328.44
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|
Following Blood Phe Levels.
Month 3 Blood Phe Level (N=109)
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504.6 micromoles per liter
Standard Deviation 316.33
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|
Following Blood Phe Levels.
Month 3 Change from Baseline (N=109)
|
-105.7 micromoles per liter
Standard Deviation 287.20
|
|
Following Blood Phe Levels.
Month 6 Blood Phe Level (N=104)
|
529.9 micromoles per liter
Standard Deviation 332.45
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|
Following Blood Phe Levels.
Month 6 Change from Baseline (N=104)
|
-68.0 micromoles per liter
Standard Deviation 310.76
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|
Following Blood Phe Levels.
Month 12 Blood Phe Level (N=97)
|
494.4 micromoles per liter
Standard Deviation 330.57
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|
Following Blood Phe Levels.
Month 12 Change from Baseline (N=97)
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-95.7 micromoles per liter
Standard Deviation 304.81
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|
Following Blood Phe Levels.
Month 18 Blood Phe Level (N=58)
|
526.9 micromoles per liter
Standard Deviation 357.43
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|
Following Blood Phe Levels.
Month 18 Change from Baseline (N=58)
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-92.8 micromoles per liter
Standard Deviation 306.02
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|
Following Blood Phe Levels.
Month 24 Blood Phe Level (N=45)
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482.0 micromoles per liter
Standard Deviation 322.55
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Following Blood Phe Levels.
Month 24 Change from Baseline (N=45)
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-122.2 micromoles per liter
Standard Deviation 281.03
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Following Blood Phe Levels.
Month 30 Blood Phe Level (N=1)
|
808.0 micromoles per liter
Standard Deviation NA
There was only one subject that had a 30 month visit.
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|
Following Blood Phe Levels.
Month 30 Change from Baseline (N=1)
|
542.0 micromoles per liter
Standard Deviation NA
There was only one subject that had a 30 month visit.
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Adverse Events
Total Patient Population
Serious events: 7 serious events
Other events: 93 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Total Patient Population
n=111 participants at risk
The mean (+/- SD) daily dose of study drug was 16.4 (+/-4.4) mg/kg. The final dose prescribed was 20 mg/kg/day for 73 (65.8%) subjects, 10 mg/kg/day for 33 (29.7%) subjects, and 5 mg/kg/day for 5 (4.5%) subjects.
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|---|---|
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Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.90%
1/111 • Number of events 1 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Reproductive system and breast disorders
Testicular mass
|
0.90%
1/111 • Number of events 1 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Surgical and medical procedures
Tonsillectomy
|
0.90%
1/111 • Number of events 1 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
0.90%
1/111 • Number of events 1 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.90%
1/111 • Number of events 2 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Injury, poisoning and procedural complications
Hand Fracture
|
0.90%
1/111 • Number of events 2 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Surgical and medical procedures
Surgery
|
0.90%
1/111 • Number of events 1 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Surgical and medical procedures
Lymphadenectomy
|
0.90%
1/111 • Number of events 1 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.90%
1/111 • Number of events 1 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
Other adverse events
| Measure |
Total Patient Population
n=111 participants at risk
The mean (+/- SD) daily dose of study drug was 16.4 (+/-4.4) mg/kg. The final dose prescribed was 20 mg/kg/day for 73 (65.8%) subjects, 10 mg/kg/day for 33 (29.7%) subjects, and 5 mg/kg/day for 5 (4.5%) subjects.
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|---|---|
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Infections and infestations
Bronchitis
|
5.4%
6/111 • Number of events 7 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
18.9%
21/111 • Number of events 28 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Gastrointestinal disorders
Diarrhoea
|
9.0%
10/111 • Number of events 16 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Infections and infestations
Gastroenteritis
|
6.3%
7/111 • Number of events 7 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Infections and infestations
Gastroenteritis viral
|
7.2%
8/111 • Number of events 9 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Nervous system disorders
Headache
|
11.7%
13/111 • Number of events 48 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Infections and infestations
Influenza
|
8.1%
9/111 • Number of events 15 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
8.1%
9/111 • Number of events 13 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Infections and infestations
Nasopharyngitis
|
18.0%
20/111 • Number of events 30 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Infections and infestations
Pharyngitis
|
6.3%
7/111 • Number of events 13 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
9.0%
10/111 • Number of events 15 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
General disorders
Pyrexia
|
16.2%
18/111 • Number of events 25 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
5.4%
6/111 • Number of events 8 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Infections and infestations
Upper respiratory tract infection
|
19.8%
22/111 • Number of events 28 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Infections and infestations
Viral infection
|
7.2%
8/111 • Number of events 12 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
|
|
Gastrointestinal disorders
Vomiting
|
18.0%
20/111 • Number of events 24 • Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.
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Additional Information
Medical Information Services
BioMarin Pharmaceutical, Inc.
Phone: 1-800-983-4587
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The first publication of the results shall be made in a joint publication. If such a multi-center publication is not submitted within 12 months after conclusion of the study, the PI may publish the results from their site individually, subject however, to compliance with the other terms of the agreement.
- Publication restrictions are in place
Restriction type: OTHER