Kuvan Therapy in Phenylketonuria (PKU): The Effect of Blood Phenylalanine Concentration on Kuvan Response
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Acute 24 Hour Component Participants will receive one dose of Kuvan 20 mg/kg on Day 1 and assessed for Acute 24 hour Kuvan response. |
Drug: Kuvan
20mg/kg by mouth once daily
Other Names:
|
| Experimental: Phase 1 Group 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 |
Drug: Kuvan
20mg/kg by mouth once daily
Other Names:
|
| Experimental: Phase 2 Group 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. |
Other: Diet
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.
|
| Experimental: Phase 3 Group 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. |
Drug: Kuvan
20mg/kg by mouth once daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Biochemistry & Molecular Biology | Miami | Florida | United States | 33136 |
Sponsors and Collaborators
- University of Miami
Investigators
- Principal Investigator: Louis J Elsas, MD, University of Miami
Study Documents (Full-Text)
None provided.More Information
Publications
- 20080675
Study Results
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. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | All Participants |
|---|---|
| Arm/Group Description | 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. |
| Period Title: Acute Component (24 Hours) | |
| STARTED | 21 |
| COMPLETED | 21 |
| NOT COMPLETED | 0 |
| Period Title: Acute Component (24 Hours) | |
| STARTED | 18 |
| COMPLETED | 15 |
| NOT COMPLETED | 3 |
| Period Title: Acute Component (24 Hours) | |
| STARTED | 5 |
| COMPLETED | 5 |
| NOT COMPLETED | 0 |
| Period Title: Acute Component (24 Hours) | |
| STARTED | 4 |
| COMPLETED | 4 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | All Participants |
|---|---|
| Arm/Group Description | All participants that was enrolled in the study |
| Overall Participants | 21 |
| Age (Count of Participants) | |
| <=18 years |
13
61.9%
|
| Between 18 and 65 years |
8
38.1%
|
| >=65 years |
0
0%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
12
57.1%
|
| Male |
9
42.9%
|
Outcome Measures
| Title | Percent Change in Blood Phenylalanine |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Ove.Erall Participants |
|---|---|
| Arm/Group Description | All participants enrolled in the study. |
| Measure Participants | 21 |
| Baseline to Day 1 of the Acute phase |
-13.71
(21.62)
|
| Baseline to Day 28 of Phase 1 |
-8.13
(31.84)
|
| Baseline to Day 28 of Phase 3 |
48.75
(61.87)
|
Adverse Events
| Time Frame | 3 months | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | All Participants | |
| Arm/Group Description | All participants that was enrolled in the study | |
All Cause Mortality |
||
| All Participants | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/21 (0%) | |
Serious Adverse Events |
||
| All Participants | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/21 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| All Participants | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/21 (4.8%) | |
| Psychiatric disorders | ||
| Anxiety | 1/21 (4.8%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Judy Schaechter |
|---|---|
| Organization | University of Miami |
| Phone | 305-243-3993 |
| JSchaech@med.miami.edu |
- 20080675