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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acute 24 Hour Component | Experimental | Participants will receive one dose of Kuvan 20 mg/kg on Day 1 and assessed for Acute 24 hour Kuvan response. |
|
| Phase 1 Group | Experimental | After completion of acute 24 hour component, participants can enroll in Phase 1 and will receive Kuvan 20 mg/kg by mouth once daily for 28 consecutive days |
|
| Phase 2 Group | Experimental | Participants in Phase 1 that was not responsive will continue on to the Phase 2 of the study. Positive response is defined as a decrease of blood phenylalanine of 30% or greater from baseline taken from morning blood serum. The Phase 2 component of the study will be a 2 week period of dietary restriction. |
|
| Phase 3 Group | Experimental | Participants in Phase 2 that achieves a fasting blood phenylalanine of less than 600 umol/l after 2 week dietary restriction will be retreated with Kuvan 20 mg/kg by mouth once daily for a period of 28 consecutive days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Kuvan | Drug | 20mg/kg by mouth once daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline to Day 1 of the Acute Phase, Baseline to Day 28 of Phase 1, Baseline to Day 28 of Phase 3 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Louis J Elsas, MD | University of Miami | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Biochemistry & Molecular Biology | Miami | Florida | 33136 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17846916 | Background | Burton BK, Grange DK, Milanowski A, Vockley G, Feillet F, Crombez EA, Abadie V, Harding CO, Cederbaum S, Dobbelaere D, Smith A, Dorenbaum A. The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicentre, open-label, screening study. J Inherit Metab Dis. 2007 Oct;30(5):700-7. doi: 10.1007/s10545-007-0605-z. Epub 2007 Sep 12. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | All Participants | All participants were enrolled into the four arms of the study. The 24-hour component consisted of participants received one dose of Kuvan 20 mg/kg on Day 1 and assessed for Acute 24 hour Kuvan response. The Phase 1 arm consisted of participants who after completion of the acute 24-hour component, enrolled and received Kuvan 20 mg/kg by mouth once daily for 28 consecutive days. The Phase 2 arm consisted of participants in Phase 1 that were not responsive and continued on to Phase 2 of the study. Positive response is defined as a decrease of blood phenylalanine of 30% or greater from baseline taken from morning blood serum. The Phase 2 component of the study will be a 2 week period of dietary restriction. The Phase 3 arm of the study consisted of participants in Phase 2 that achieved a fasting blood phenylalanine of less than 600 umol/l after 2-week dietary restriction will be retreated with Kuvan 20 mg/kg by mouth once daily for a period of 28 consecutive days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Acute Component (24 Hours) |
| |||||||||||||
| Phase 1 (28 Days) |
| |||||||||||||
| Phase 2 (2 Weeks) |
| |||||||||||||
| Phase 3 (28 Days) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | All participants that was enrolled in the study |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Mean | Standard Deviation | 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 |
|
3 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Participants | All participants that was enrolled in the study | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anxiety | Psychiatric disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Judy Schaechter | University of Miami | 305-243-3993 | JSchaech@med.miami.edu |
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| ID | Term |
|---|---|
| D010661 | Phenylketonurias |
| ID | Term |
|---|---|
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C003402 | sapropterin |
| D004032 | Diet |
| ID | Term |
|---|---|
| D009747 | Nutritional Physiological Phenomena |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
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| Diet | Other | 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. |
|
|
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| 21 |
| 0 |
| 21 |
| 1 |
| 21 |
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| D009422 | Nervous System Diseases |
| D000592 | Amino Acid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |