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A double-blind, placebo-controlled, multicentre study with an open-label extension to evaluate the efficacy and safety of tetrahydrobiopterin (BH4) in children and adolescents with hyperphenylalaninemia caused by phenylalanine hydroxylase deficiency

Conditions
Hyperphenylalaninemia due to phenylalanine hydroxylase deficiency. Phenotypes: classic phenylketonuria (PKU), mild PKU (MPK) or mild hyperphenylalaninemia (HPA).
MedDRA version: 81Level: LLTClassification code 10034873
Registration Number
EUCTR2006-000648-15-AT
Lead Sponsor
ORPHANETICS Pharma Entwicklungs- GmbH
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
75
Inclusion Criteria

Inclusion criteria for the screening phase
1.Female and male patients, aged 4-18 years
2.Phenylalanine-4-hydroxylase (PAH) deficiency shown by mutation analysis
3.Blood phenylalanine concentration in the 42-240 µmol/L for patients <10yrs otherwise 42-360 µmol/L range under dietary treatment
4.Achievement of phenylalanine equilibrium for at least 1 week before the screening phase
5.Written consent of patient (if only enough understand) and a parent or legal representative of the paediatric or adolescent patient after being given oral and written information on the study
6.Informed consent of the patient if she/he is able to understand the advantages/disadvantages of the participation in the study (this can be expected at a minimum age of 8 years). Written consent of an adolescent patient after oral and written information or oral consent procedure with an impartial witness is acceptable.
7.Assumed availability within the period of study participation
8.Patients/parents willing and able to follow the recommended diet
9.Use of an effective method of contraception in female patients of child bearing potential
Inclusion criteria for the treatment phase
1.BH4-responsiveness determined by a combined phenylalanine-BH4 test (see Section 7.5.2 Combined phenylalanine-BH4-loading test)
2.Achievement of phenylalanine intake equilibrium for at least 1 week
with subsequent determination of baseline phenylalanine tolerance (Phe-Tol0)
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

?BH4-deficiency due to genetic disorders in biosynthesis or recycling of BH4
?History or current evidence of poor diet compliance
?History or current evidence of clinically relevant allergic or idiosyncratic reactions to drugs or food
?History of allergic reactions to BH4 or its excipients
?History or current evidence of any clinically relevant cardiovascular, pulmonary, renal, gastrointestinal, haematological, endocrinological, metabolic, neurological or other diseases as judged by the investigator
?History of malignancy within the past 5 years
?Relevant chronic or relevant current acute infections
?History of orthostatic deregulation, fainting or blackout
?Abuse of alcohol or drugs
?Positive pregnancy test (ß-HCG in serum) and lactating females
?Participation in other drug trials within the last 30 days before start for the study
?Patient already receiving BH4 treatment or who has received it within the last 1 month

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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