BH4 (Kuvan©) treatment in Phenylketonuria - comparing different practices of dosing regimens

Phase 1

• Conditions: Phenylketonuria (PKU; OMIM 261600); Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2021-003777-63-NL
• Lead Sponsor: niversity Medical Center Groningen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-11-24
• Last Update Posted: 29 November 2021

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

In order to be eligible to participate in this study, a subject must meet all of the following criteria:
1. Diagnosed with phenylketonuria by newborn screening.
2. Diagnosed as a BH4-responder after a 48-h BH4 loading test and a treatment trial
3. Currently uses sapropterin as part of treatment (with a minimum of three months)
4. Age = 4 years
5. Good metabolic control for the previous 6 months, meaning 75% of the Phe levels are within therapeutic target levels with a minimum of four values.

Are the trial subjects under 18? yes
Number of subjects for this age range: 8
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study:
Pregnancy, planning pregnancy or lactation

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To establish an optimal dosing regimen for BH4 by comparing diurnal phenylalanine, tyrosine and the phenylalanine/tyrosine ratio variation of three BH4 dosing regimens in different ages. ;Secondary Objective: none;Primary end point(s): The primary outcome of the study is the comparison of phenylalanine levels between the three treatment regimen. The mean, mean standard deviations (SD) and mean coefficient of variation (CV) of the blood phenylalanine concentrations measured 6 times a day of 2 consecutive days, will be compared for 3 different dosage regimen. ;Timepoint(s) of evaluation of this end point: Each period will take one week. Consequently, the total study will take 3 weeks. <br>Participants will start with the allocated BH4 regime at day 1. Day 6 and 7 are the last days of the regime in which patients will collect 6 blood samples per day.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The mean SD and CV of the blood tyrosine concentrations measured 6 times a day of 2 consecutive days, will be compared for 3 different dosage regimen. <br><br>The mean SD and CV of the phenylalanine/tyrosine ratio's, will be compared for 3 different dosage regimen. <br><br>Time of highest and lowest phenylalanine level during the day<br><br>(If feasible: the kinetics of dried blood spot pterin concentrations). <br>;Timepoint(s) of evaluation of this end point: Each period will take one week. Consequently, the total study will take 3 weeks. <br>Participants will start with the allocated BH4 regime at day 1. Day 6 and 7 are the last days of the regime in which patients will collect 6 blood samples per day.