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

University of Miami

Status and phase: Completed; Phase 2

Conditions: Phenylketonuria

Treatments: Other: Diet; Drug: Kuvan

Study type: Interventional

Funder types: Other

Identifiers

NCT00841100

20080675

Details and patient eligibility

About

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.

Enrollment: 21 patients

Sex: All

Ages: 4+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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21 participants in 4 patient groups

Acute 24 Hour Component

Experimental group

Description:

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

Treatment:

Drug: Kuvan

Phase 1 Group

Experimental group

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

Treatment:

Drug: Kuvan

Phase 2 Group

Experimental group

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.

Treatment:

Other: Diet

Phase 3 Group

Experimental group

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.

Treatment:

Drug: Kuvan