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

Phase 2

Completed

• Conditions: Phenylketonuria
• Interventions: Drug: Kuvan; Other: Diet

• Registration Number: NCT00841100
• Lead Sponsor: University of Miami

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-12
• Study First Submitted: 2009-02-10
• Study First Submitted QC: 2009-02-10
• Study First Posted: 2009-02-11
• Primary Completion: 2011-07-19
• Study Completion: 2011-07-19
• Results First Submitted: 2019-09-17
• Results First Submitted QC: 2019-09-17
• Results First Posted: 2019-10-08
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-19
• Last Update Posted: 2019-12-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 3 Group	Kuvan	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.
Acute 24 Hour Component	Kuvan	Participants will receive one dose of Kuvan 20 mg/kg on Day 1 and assessed for Acute 24 hour Kuvan response.
Phase 1 Group	Kuvan	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	Diet	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.

Primary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Department of Biochemistry & Molecular Biology; 🇺🇸 Miami, Florida, United States