Phenylketonuria
Conditions
Keywords
PKU, Kuvan, BH4, tetrahydrobiopterin
Brief summary
The investigators will investigate the effect of blood phenylalanine on Kuvan responsiveness in the same patients with PKU when their blood phenylalanine concentrations are altered by diet. Lowering blood phenylalanine concentrations in Kuvan non-responsive patients with PKU will increase the frequency of Kuvan responsiveness.
Interventions
DRUGKuvan
20mg/kg by mouth once daily
OTHERDiet
Phenylalanine-restricted diet (4-10 mg/kg/day phenylalanine) using the prescribed phenylalanine-free medical formula and low protein foods tested with the patients for taste and acceptance to lower blood phenylalanine levels below 600 umol/l.
Sponsors
University of Miami
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* all patients with a diagnosis of phenylketonuria * patients who are over the age of 4 years, * patients with a fasting blood phenylalanine ≥600µmol/l
Exclusion criteria
* female patients who are pregnant or attempting to become pregnant * children under four years of age * Concurrent disease of condition that would interfere with study participation or safety such as history of neurological compromise or major medical, psychiatric or learning disorder unrelated to PKU * Any condition that, in the view of the Investigators, places subject at high risk of poor treatment compliance or of not completing the study * Use of L-Dopa, methotrexate, or other drugs that may inhibit folate metabolism
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Blood Phenylalanine | Baseline to Day 1 of the Acute Phase, Baseline to Day 28 of Phase 1, Baseline to Day 28 of Phase 3 | Percent change in phenylalanine in (uM) on Kuvan Response evaluated via fasting morning blood serum. A decrease of 30% or greater indicates positive response on Kuvan. |
Countries
United States
Participant flow
Recruitment details
All participants enrolled in the acute phase were eligible to continue onto the Phase 1 component of the trial. Only the participants who were non-responsive on the Phase 1 component of the study continued on to Phase 2. Only Phase 2 participants who achieved a fasting blood phenylalanine of less than 600 umol/l can continue to Phase 3.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants that was enrolled in the study | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Phase 1 (28 Days) | Adverse Event | 1 |
| Phase 1 (28 Days) | Participant non-compliance | 2 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 13 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 21 |
| other Total, other adverse events | 1 / 21 |
| serious Total, serious adverse events | 0 / 21 |
Outcome results
Primary
Percent Change in Blood Phenylalanine
Percent change in phenylalanine in (uM) on Kuvan Response evaluated via fasting morning blood serum. A decrease of 30% or greater indicates positive response on Kuvan.
Time frame: Baseline to Day 1 of the Acute Phase, Baseline to Day 28 of Phase 1, Baseline to Day 28 of Phase 3
Population: 3 participants from the acute phase elected not to continue to the Phase 1 component of the study. Participants who were non-responsive on the Phase 1 component of the study continued on to Phase 2. Participants who achieved a fasting blood phenylalanine of \<600 umol/l can in Phase 2, continued to Phase 3.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ove.Erall Participants | Percent Change in Blood Phenylalanine | Baseline to Day 1 of the Acute phase | -13.71 Percent change in blood phenylalanine | Standard Deviation 21.62 |
| Ove.Erall Participants | Percent Change in Blood Phenylalanine | Baseline to Day 28 of Phase 1 | -8.13 Percent change in blood phenylalanine | Standard Deviation 31.84 |
| Ove.Erall Participants | Percent Change in Blood Phenylalanine | Baseline to Day 28 of Phase 3 | 48.75 Percent change in blood phenylalanine | Standard Deviation 61.87 |