Phenylketonurias
Conditions
Keywords
Phenylalanine Hydroxylase
Brief summary
The primary objective of this study is to evaluate the efficacy of Phenoptin™ (sapropterin dihydrochloride) in reducing blood phenylalanine (Phe) levels in subjects with phenylketonuria.
Interventions
DRUGsapropterin dihydrochloride, 6R-BH4, tetrahydrobiopterin
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
8 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 8 years of age and older * Received at least 7 out of 8 scheduled doses in Study PKU 001 * Responsive to Phenoptin™ in Study PKU-001, defined as a reduction in blood Phenylalanine level of \>/=30% compared with baseline * Blood Phenylalanine level \>/=450 μmol/L at screening * Willing and able to provide written informed consent or, in the case of subjects under the age of 18, provide written assent (if required) and written informed consent by a parent or legal guardian, after the nature of the study has been explained * Negative urine pregnancy test at screening (females of child-bearing potential) * Male and Female subjects of childbearing potential (if sexually active) must be using acceptable birth control measures, as determined by the investigator, and willing to continue to use acceptable birth control measures while participating in the study * Willing and able to comply with study procedures * Willing to continue current diet unchanged while participating in the study
Exclusion criteria
* Perceived to be unreliable or unavailable for study participation or, if under the age of 18, have parents or legal guardians who are perceived to be unreliable or unavailable * Use of any investigational agent other than Phenoptin™ within 30 days prior to screening, or requirement for any investigational agent or investigational vaccine prior to completion of all scheduled study assessments * Pregnant or breastfeeding, or considering pregnancy * ALT \>5 times the upper limit of normal (i.e., Grade 3 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, or insulin-dependent diabetes, or organ transplantation recipient) * Serious neuropsychiatric illness (e.g., major depression) not currently under medical management * Requirement for concomitant treatment with any drug known to inhibit folate synthesis (e.g., methotrexate) * Concurrent use of levodopa * Clinical diagnosis of primary BH4 deficiency
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Blood Phenylalanine Levels From Baseline to Week 6. | baseline to week 6 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sapropterin Dihydrochloride Patients administered 10 mg /kg orally once daily. | 41 |
| Placebo Placebo | 47 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Noncompliant with dosing | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Sapropterin Dihydrochloride | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 21.5 years STANDARD_DEVIATION 9.5 | 19.5 years STANDARD_DEVIATION 9.8 | 20.4 years STANDARD_DEVIATION 9.7 |
| Age, Customized 12 < Age | 35 Years | 36 Years | 71 Years |
| Age, Customized 8 <= Age <= 12 | 6 Years | 11 Years | 17 Years |
| Race/Ethnicity, Customized Asian/Pacific Islander | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Caucasian | 39 participants | 47 participants | 86 participants |
| Race/Ethnicity, Customized Other | 1 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 14 Participants | 23 Participants | 37 Participants |
| Sex: Female, Male Male | 27 Participants | 24 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / — | 34 / — |
| serious Total, serious adverse events | 0 / 41 | 0 / 47 |
Outcome results
Primary
Change in Blood Phenylalanine Levels From Baseline to Week 6.
Time frame: baseline to week 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sapropterin Dihydrochloride | Change in Blood Phenylalanine Levels From Baseline to Week 6. | Baseline Blood Phe Level | 843 micromole per liter | Standard Deviation 300 |
| Sapropterin Dihydrochloride | Change in Blood Phenylalanine Levels From Baseline to Week 6. | Week 6 Blood Phe Level | 607 micromole per liter | Standard Deviation 377 |
| Sapropterin Dihydrochloride | Change in Blood Phenylalanine Levels From Baseline to Week 6. | Mean Change in Blood Phe from Baseline to Week 6 | -239 micromole per liter | Standard Deviation 38 |
| Placebo | Change in Blood Phenylalanine Levels From Baseline to Week 6. | Baseline Blood Phe Level | 888 micromole per liter | Standard Deviation 323 |
| Placebo | Change in Blood Phenylalanine Levels From Baseline to Week 6. | Week 6 Blood Phe Level | 891 micromole per liter | Standard Deviation 348 |
| Placebo | Change in Blood Phenylalanine Levels From Baseline to Week 6. | Mean Change in Blood Phe from Baseline to Week 6 | 6 micromole per liter | Standard Deviation 36 |
p-value: <0.001ANCOVA