Safety Paediatric efficAcy phaRmacokinetic with Kuvan®

Phase 1

• Conditions: Phenylketonuria; MedDRA version: 18.1Level: LLTClassification code 10034873Term: Phenylketonuria (PKU)System Organ Class: 100000004850; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2009-015768-33-BE
• Lead Sponsor: BioMarin International Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-01-19
• Last Update Posted: 13 March 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1.Male or female PKU infants and young children <4 years of age at the scheduled Day 1 visit of the 26-week Study Period (taking into consideration the maximum of 42 days in the Screening Period).
2.At least two previous blood Phe levels = 400 µmol/L obtained on 2 separate occasions.
3. Previously responded, as assessed by the Investigator, to a BH4 test, if all 3 of the following
criteria are satisfied:
a)The BH4 dose was 20 mg/kg/day.
b)The duration of the test was at least for 24 hours.
c)A 30% decrease in blood Phe levels.
NOTE: If a patient has not undergone a BH4 test prior to Screening, such a test must be performed, (Please refer to the note , section 7.1.1 bullet point #7).
4.Defined level of dietary Phe tolerance consistent with the diagnosis of PKU;
5.Good adherence to dietary treatment, including prescribed dietary Phe restriction and prescribed amounts of Phe-free protein supplements and low-Phe foods.
6. Maintenance of blood Phe levels within the therapeutic target range of 120-360 µmol/L
(defined as =120 to < 360 µmol/L) over a 4-month period prior to Screening, as assessed by
the Investigator. At least, the last 4 values of phenylalanine (either from venous blood or dry
blood spot) should be assessed, out of which 75% should be within the above therapeutic
range.
7.Parent(s) and/or guardian(s) willing to comply with all study procedures, maintain strict adherence to the diet, and willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any study procedures.

Are the trial subjects under 18? yes
Number of subjects for this age range: 50
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1.Use of Kuvan®, Biopten®, or any unregistered preparation of tetrahydrobiopterin within the previous 30 days, unless for the purposes of a BH4 responsiveness test.
2.Previous exposure to Kuvan®, Biopten®, or any unregistered preparation of tetrahydrobiopterin for >30 days.
3.Known hypersensitivity to Kuvan® or its excipients.
4.Known hypersensitivity to other approved or non-approved formulations of tetrahydrobiopterin.
5.Previous diagnosis of BH4 deficiency.
6.Current use of methotrexate, trimethoprim, or other dihydrofolate reductase inhibitors.
7.Current use of medications that are known to affect nitric oxide synthesis, metabolism or action.
8.Current use of levodopa.
9.Current use of experimental or unregistered drugs that may affect the study outcomes.
10.Inability to comply with study procedures.
11.Inability to tolerate oral intake.
12.History of organ transplantation.
13.Concurrent disease or condition that would interfere with study participation or increase the risk for adverse events, including seizure disorders, corticosteroid administration, active malignancy, diabetes mellitus, severe congenital heart disease, renal or hepatic failure.
14.Other significant disease that in the Investigator’s opinion would exclude the subject from the trial.
15.Any condition that, in the view of the Principal Investigator renders the subject at high risk for failure to comply with treatment or to complete the study.

Study & Design

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