Response to Kuvan� in Subjects With Phenylketonuria (PKU) in a 4 Weeks Testing Period
Information source: Merck KGaA
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Phenylketonuria
Intervention: Kuvan® (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Merck KGaA Official(s) and/or principal investigator(s): Medical Responsible, Study Director, Affiliation: Merck Serono S.A., an affiliate of Merck KGaA, Darmstadt, Germany
Summary
The primary objective of the study is to evaluate the proportion of responders (that is,
greater than or equal to [>=] 30 percent reduction from Baseline in blood phenylalanine
[Phe] level) to treatment with Kuvan® (sapropterin dihydrochloride) 20 milligram per
kilogram per day (mg/kg/day) for 28 days.
Clinical Details
Official title: ENDURE: A Phase IV, Prospective, Open-label, Uncontrolled, Multi-centre Cohort Trial to Assess the Responsiveness of Subjects With Phenylketonuria (PKU) to Treatment With Kuvan® 20 mg/kg/Day for 28 Days
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Percentage of Participants With at Least 30 Percent Reduction From Baseline in Blood Phenylalanine (Phe) Level
Secondary outcome: Number of Participants With Adverse Events (AEs), Treatment Emergent Adverse Events, Treatment Related Adverse Events and AEs Leading to WithdrawalPercentage of Early-, Late-, Partial-Responders and Non-responders to Treatment With Kuvan® Percentage of Participants With Greater Than or Equal to (>=) 30 Percent, 20 to 30 Percent, 10 to 20 Percent and Less Than (<) 10 Percent Reduction in Blood Phe Levels According to Phenylketonuria (PKU) Phenotypes Percentage of Early-, Late- and Partial-Responders According to Phenotype Mean Change From Baseline in Blood Phenylalanine-to-tyrosine Ratio
Eligibility
Minimum age: 4 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Subjects aged 4 years or older at the time the informed consent is obtained
- Subjects diagnosed with PKU (subgroups defined as: classic PKU [blood Phe greater
than {>}1200 micromole per liter {mcmol/L}], mild PKU [blood Phe 600 to1200 mcmol/L]
or mild hyperphenylalaninemia (HPA) [blood Phe 300 to 600 mcmol/L]
- Subjects who have received no previous treatment with sapropterin dihydrochloride
(either Kuvan® or any other formulations of tetrahydrobiopterin [BH4])
- Subjects adherent to their normal diet and willing to adhere to the given diet for
the 4 weeks study period
- Subjects who provide a signed (by parent if below 18 years) written informed consent
- Subjects with documented genotyping for both phenylalanine hydroxylase (PAH)
mutations (PKU genotype)
- Phenylketonuria (PKU) diagnosis should be documented with at least two historical
blood Phe levels above 400 mcmol/L
- Female subjects of childbearing potential (and, if appropriate, male subjects with
female partners of childbearing potential) must be willing to avoid pregnancy by
using an adequate method of contraception (defined as two barrier methods or one
barrier method with spermicide, or intrauterine device or use of the oral female
contraceptive) for 4 weeks prior to, during and 12 weeks after the last dose of trial
medication
- Women of childbearing potential (for the purpose of this trial, women of childbearing
potential are defined as "All female subjects after puberty unless they are
post-menopausal for at least 2 years, are surgically sterile or are sexually
inactive") must have a negative urine pregnancy test at the Baseline visit
Exclusion Criteria:
- Subjects who have documented BH4 deficiency
- Subjects who have any contraindications to receive Kuvan® as outlined in the summary
of product characteristics (SmPC) not willing or able to comply with the study
procedures
- Subjects who are pregnant, planning for pregnancy or breastfeeding
- Subjects who have been exposed to any investigational medicinal drugs or treatments
within 30 days or 5 half-lives, whichever is longer, prior to the Screening visit
- Subjects using concomitant treatment with folate synthesis inhibiting drugs
- Subjects with concurrent use of Levodopa
- Subjects with concurrent use of inhibitors of dihydrofolate reductase (for example,
methotrexate, trimethoprim)
- Subjects with concurrent use of agents that cause vasodilation, including those
administered topically, by affecting nitric oxide (NO) metabolism or action including
classical NO donors (for example, glyceryl trinitrate (GTN), isosorbide dinitrate
(ISDN), sodium nitroprusside (SNP), molsidomin), phosphodiesterase type 5 (PDE-5)
inhibitors and minoxidil
- Subjects who have a concurrent disease potentially interfering safety (for example,
seizure disorder, oral steroid dependent asthma, other conditions requiring systemic
corticosteroids, or insulin-dependent diabetes mellitus)
- Subjects who have inadequate liver function, defined by alanine aminotransferase
(ALT) >= 2 times upper limit of normal (ULN)
- Subjects who have clinically significant renal dysfunction, defined by serum
creatinine > 250 mcmol/L
- Have any medical condition that, in the judgment of the investigator, would
jeopardize the subject's safety following exposure to study drug or would
significantly interfere with the subject's ability to comply with the provisions of
the protocol
Locations and Contacts
Department of Paediatric Research, Division of Paediatrics, Oslo University Hospital, Rikshospitalet, Oslo, Norway
Additional Information
PAH database, Publication Link Arnold GL. Phenylketonuria, Publication Link
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Starting date: May 2010
Last updated: January 26, 2014
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