Response to Kuvan® in Subjects With Phenylketonuria (PKU) in a 4 Weeks Testing Period (ENDURE)
This study has been completed.
Sponsor:
Merck KGaA
Collaborators:
Merck Serono Norway
Smerud Medical Research International AS
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01082328
First received: March 5, 2010
Last updated: July 20, 2012
Last verified: July 2012
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Purpose
The primary objective of the study is to evaluate the proportion of responders [≥30% reduction from baseline in blood phenylalanine (Phe) level] to 20 mg/kg/day sapropterin dihydrochloride treatment at several time points during 28±1 days.
| Condition | Intervention | Phase |
|---|---|---|
|
Phenylketonuria |
Drug: Kuvan® (Sapropterin dihydrochloride) |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Supportive Care |
| Official Title: | 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 |
Resource links provided by NLM:
Genetics Home Reference related topics:
argininosuccinic aciduria
citrullinemia
N-acetylglutamate synthase deficiency
ornithine translocase deficiency
phenylketonuria
succinic semialdehyde dehydrogenase deficiency
tetrahydrobiopterin deficiency
MedlinePlus related topics:
Phenylketonuria
U.S. FDA Resources
Further study details as provided by Merck KGaA:
Primary Outcome Measures:
- Proportion of subjects with at least 30% reduction from baseline in blood phenylalanine (Phe) level (responder) in any blood sample during the 28±1 days treatment with 20 mg/kg/day sapropterin dihydrochloride (Kuvan®) [ Time Frame: 28±1 days ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Number of subjects with Adverse Events [ Time Frame: 28±1 days ] [ Designated as safety issue: Yes ]
- Proportion of early, late, partial responders and non-responders to treatment with Kuvan [ Time Frame: 28±1 days ] [ Designated as safety issue: No ]
- Evaluation of genetic phenylalanine hydroxylase (PAH) mutations associated with certain traits, i.e. response and adverse events [ Time Frame: 28±1 days ] [ Designated as safety issue: No ]
- Subtypes of subjects associated with the types of response [ Time Frame: 28±1 days ] [ Designated as safety issue: No ]
- Blood phenylalanine-to-tyrosine ratio during a 4 weeks testing period [ Time Frame: 28±1 days ] [ Designated as safety issue: No ]
| Enrollment: | 59 |
| Study Start Date: | May 2010 |
| Primary Completion Date: | April 2012 (Final data collection date for primary outcome measure) |
Intervention Details:
-
Drug: Kuvan® (Sapropterin dihydrochloride)
- Kuvan®
- Sapropterin dihydrochloride
All subjects will receive open-label Kuvan® 20 mg/kg/day for 28±1 days as a tablet dissolved in water.
Other Names:
Eligibility| Ages Eligible for Study: | 4 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Subjects aged 4 years or older at the time the informed consent is obtained
- Subjects diagnosed with phenylketonuria (PKU) (subgroups defined as: classic PKU [blood Phe >1200 µmol/L], mild PKU [blood Phe 600-1200 µmol/L] or mild hyper phenylalaninemia (HPA) [blood Phe 300-600 µmol/L]
- Subjects who have received no previous treatment with sapropterin dihydrochloride (either Kuvan or any other formulations of tetrahydrobiopterin)
- Subjects adherent to 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)
Exclusion Criteria:
- Subjects who have documented tetrahydrobiopterin (BH4) deficiency
- Subjects who have any contraindications to receive Kuvan as outlined in the SmPC not willing or able to comply with the study procedures
- Subjects who are pregnant, planning for pregnancy or breastfeeding subjects
- 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 (e.g. 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 (e.g. 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 (e.g. 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 x upper limit of normal (ULN)
- Subjects who have clinically significant renal dysfunction, defined by serum creatinine > 250 µmol/l
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01082328
Locations
| Norway | |
| Department of Paediatric Research, Division of Paediatrics, Oslo University Hospital, Rikshospitalet | |
| Oslo, Norway | |
Sponsors and Collaborators
Merck KGaA
Merck Serono Norway
Smerud Medical Research International AS
Investigators
| Study Director: | Study Director | Merck Serono S.A., an affiliate of Merck KGaA, Darmstadt, Germany |
More Information
Additional Information:
Publications:
Scriver CR, Kaufman S. Hyperphenylanaemia: phenylalanine hydroxylase deficiency. In: Beaudet AL, Sly WS, Valle D, editors. Metabolic and molecular bases of inherited disease. New York: McGraw-Hill 2001;1667-709
National Institute of Health. Phenylketonuria (PKU): screening and management. National Institute of Health Consensus Statement 2003;17(3):1-33.
| Responsible Party: | Merck KGaA |
| ClinicalTrials.gov Identifier: | NCT01082328 History of Changes |
| Other Study ID Numbers: | EMR 700773-503 |
| Study First Received: | March 5, 2010 |
| Last Updated: | July 20, 2012 |
| Health Authority: | Norway: Norwegian Medicines Agency Denmark: Danish Medicines Agency |
Keywords provided by Merck KGaA:
|
Phenylketonuria (PKU) Hyperphenylalaninemia (HPA) Kuvan |
Sapropterin dihydrochloride Kuvan responder Tetrahydrobiopterin (BH4) |
Additional relevant MeSH terms:
|
Phenylketonurias 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 Metabolic Diseases |
ClinicalTrials.gov processed this record on May 22, 2013