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

NCT ID: NCT00841100

Last Updated: 2019-12-03

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-12-31

Study Completion Date

2011-07-19

Brief Summary

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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.

Detailed Description

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Conditions

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Phenylketonuria

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Kuvan

Intervention Type DRUG

20mg/kg by mouth once daily

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

Group Type EXPERIMENTAL

Kuvan

Intervention Type DRUG

20mg/kg by mouth once daily

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.

Group Type EXPERIMENTAL

Diet

Intervention Type 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.

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.

Group Type EXPERIMENTAL

Kuvan

Intervention Type DRUG

20mg/kg by mouth once daily

Interventions

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Kuvan

20mg/kg by mouth once daily

Intervention Type DRUG

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.

Intervention Type OTHER

Other Intervention Names

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sapropterin dihydrochloride, Tetrahydrobiopterin (BH4)

Eligibility Criteria

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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
Minimum Eligible Age

4 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Miami

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Louis J Elsas, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

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Department of Biochemistry & Molecular Biology

Miami, Florida, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 17846916 (View on PubMed)

Other Identifiers

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20080675

Identifier Type: -

Identifier Source: org_study_id

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