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

NCT00841100 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 20080675
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Phenylketonuria

Keywords

PKU; Kuvan; BH4; tetrahydrobiopterin

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to Day 1 of the Acute Phase, Baseline to Day 28 of Phase 1, Baseline to Day 28 of Phase 3

Study Arms (4)

Acute 24 Hour Component

EXPERIMENTAL

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

Drug: Kuvan

Phase 1 Group

EXPERIMENTAL

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

Phase 2 Group

EXPERIMENTAL

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

Phase 3 Group

EXPERIMENTAL

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

Interventions

Kuvan DRUG

20mg/kg by mouth once daily

Also known as: sapropterin dihydrochloride, Tetrahydrobiopterin (BH4)

Acute 24 Hour Component; Phase 1 Group; Phase 3 Group

Diet 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 2 Group

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• all patients with a diagnosis of phenylketonuria
• patients who are over the age of 4 years,
• patients with a fasting blood phenylalanine ≥600µmol/l

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Miami: lead

Study Sites (1)

Department of Biochemistry & Molecular Biology

Miami, Florida, 33136, United States

Location

Related Publications (1)

• 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.

  PMID: 17846916 BACKGROUND

MeSH Terms

Conditions

Phenylketonurias

Interventions

sapropterin; Diet

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Results Point of Contact

• Title: Judy Schaechter
• Organization: University of Miami

JSchaech@med.miami.edu

305-243-3993

Study Officials

• Louis J Elsas, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2009
• First Posted: February 11, 2009
• Study Start: December 1, 2008
• Primary Completion: July 19, 2011
• Study Completion: July 19, 2011
• Last Updated: December 3, 2019
• Results First Posted: October 8, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)