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Kuvan Therapy in Phenylketonuria (PKU): The Effect of Blood Phenylalanine Concentration on Kuvan Response

Primary Purpose

Phenylketonuria

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Kuvan
Diet
Sponsored by
University of Miami
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Phenylketonuria focused on measuring PKU, Kuvan, BH4, tetrahydrobiopterin

Eligibility Criteria

4 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of Biochemistry & Molecular Biology

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Acute 24 Hour Component

Phase 1 Group

Phase 2 Group

Phase 3 Group

Arm Description

Participants will receive one dose of Kuvan 20 mg/kg on Day 1 and assessed for Acute 24 hour Kuvan response.

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

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
February 10, 2009
Last Updated
November 19, 2019
Sponsor
University of Miami
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1. Study Identification

Unique Protocol Identification Number
NCT00841100
Brief Title
Kuvan Therapy in Phenylketonuria (PKU): The Effect of Blood Phenylalanine Concentration on Kuvan Response
Official Title
Kuvan Therapy in Phenylketonuria (PKU): The Effect of Blood Phenylalanine Concentration on Kuvan Response
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
December 2008 (Actual)
Primary Completion Date
July 19, 2011 (Actual)
Study Completion Date
July 19, 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Miami

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Phenylketonuria
Keywords
PKU, Kuvan, BH4, tetrahydrobiopterin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Acute 24 Hour Component
Arm Type
Experimental
Arm Description
Participants will receive one dose of Kuvan 20 mg/kg on Day 1 and assessed for Acute 24 hour Kuvan response.
Arm Title
Phase 1 Group
Arm Type
Experimental
Arm Description
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
Arm Title
Phase 2 Group
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 3 Group
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Kuvan
Other Intervention Name(s)
sapropterin dihydrochloride, Tetrahydrobiopterin (BH4)
Intervention Description
20mg/kg by mouth once daily
Intervention Type
Other
Intervention Name(s)
Diet
Intervention Description
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.
Primary Outcome Measure Information:
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Louis J Elsas, MD
Organizational Affiliation
University of Miami
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Biochemistry & Molecular Biology
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
17846916
Citation
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.
Results Reference
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Kuvan Therapy in Phenylketonuria (PKU): The Effect of Blood Phenylalanine Concentration on Kuvan Response

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