Response to Kuvan® in Subjects With Phenylketonuria (PKU) in a 4 Weeks Testing Period
NCT ID: NCT01082328
Last Updated: 2014-02-27
Study Results
Results available
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
COMPLETED
Clinical Phase
PHASE4
Total Enrollment
59 participants
Study Classification
INTERVENTIONAL
Study Start Date
2010-05-31
Study Completion Date
2012-05-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Phase 3 Open-label Study to Evaluate the Response and Safety of Kuvan® in Subjects With Phenylketonuria
NCT01732471
Phenylketonuria
COMPLETED
PHASE3
Kuvan® in Phenylketonuria Patients Less Than 4 Years Old
NCT01376908
Phenylketonuria
COMPLETED
PHASE3
Kuvan®'s Effect on the Cognition of Children With Phenylketonuria
NCT01965912
Phenylketonuria
COMPLETED
PHASE4
Effect of Kuvan on Neurocognitive Function, Blood Phenylalanine Level, Safety, and Pharmacokinetics in Children With PKU
NCT00838435
Phenylketonuria
COMPLETED
PHASE3
Phenylketonuria, Oxidative Stress, and BH4
NCT01395394
Phenylketonuria
TERMINATED
PHASE2
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Phenylketonuria
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Allocation Method
NON_RANDOMIZED
Intervention Model
SINGLE_GROUP
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Kuvan®
Group Type
EXPERIMENTAL
Kuvan®
Intervention Type
DRUG
Kuvan® (sapropterin dihydrochloride) oral solution 20 milligram per kilogram (mg/kg) will be given once daily for 28 +/- 1 days.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Kuvan®
Kuvan® (sapropterin dihydrochloride) oral solution 20 milligram per kilogram (mg/kg) will be given once daily for 28 +/- 1 days.
Intervention Type
DRUG
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Sapropterin dihydrochloride
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
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
* 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
* 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
Minimum Eligible Age
4 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Merck Serono Norway
INDUSTRY
Sponsor Role
collaborator
Smerud Medical Research International AS
OTHER
Sponsor Role
collaborator
Merck KGaA, Darmstadt, Germany
INDUSTRY
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Responsibility Role
SPONSOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Medical Responsible
Role: STUDY_DIRECTOR
Merck Serono S.A., an affiliate of Merck KGaA, Darmstadt, Germany
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Department of Paediatric Research, Division of Paediatrics, Oslo University Hospital, Rikshospitalet
Oslo, , Norway
Site Status
Countries
Review the countries where the study has at least one active or historical site.
Norway
References
Explore related publications, articles, or registry entries linked to this study.
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
Reference Type
BACKGROUND
Phenylketonuria (PKU): screening and management. NIH Consens Statement. 2000 Oct 16-18;17(3):1-33.
Reference Type
BACKGROUND
Hofman KJ, Steel G, Kazazian HH, Valle D. Phenylketonuria in U.S. blacks: molecular analysis of the phenylalanine hydroxylase gene. Am J Hum Genet. 1991 Apr;48(4):791-8.
Reference Type
BACKGROUND
Konecki DS, Lichter-Konecki U. The phenylketonuria locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations. Hum Genet. 1991 Aug;87(4):377-88. doi: 10.1007/BF00197152.
Reference Type
BACKGROUND
Kaufman S. An evaluation of the possible neurotoxicity of metabolites of phenylalanine. J Pediatr. 1989 May;114(5):895-900. doi: 10.1016/s0022-3476(89)80161-1. No abstract available.
Reference Type
BACKGROUND
Huttenlocher PR. The neuropathology of phenylketonuria: human and animal studies. Eur J Pediatr. 2000 Oct;159 Suppl 2:S102-6. doi: 10.1007/pl00014371.
Reference Type
BACKGROUND
Walter JH, White FJ, Hall SK, MacDonald A, Rylance G, Boneh A, Francis DE, Shortland GJ, Schmidt M, Vail A. How practical are recommendations for dietary control in phenylketonuria? Lancet. 2002 Jul 6;360(9326):55-7. doi: 10.1016/s0140-6736(02)09334-0.
Reference Type
BACKGROUND
Koch R, Azen C, Friedman EG, Williamson ML. Paired comparisons between early treated PKU children and their matched sibling controls on intelligence and school achievement test results at eight years of age. J Inherit Metab Dis. 1984;7(2):86-90. doi: 10.1007/BF01805813.
Reference Type
BACKGROUND
Brumm VL, Azen C, Moats RA, Stern AM, Broomand C, Nelson MD, Koch R. Neuropsychological outcome of subjects participating in the PKU adult collaborative study: a preliminary review. J Inherit Metab Dis. 2004;27(5):549-66. doi: 10.1023/b:boli.0000042985.02049.ff.
Reference Type
BACKGROUND
Kure S, Hou DC, Ohura T, Iwamoto H, Suzuki S, Sugiyama N, Sakamoto O, Fujii K, Matsubara Y, Narisawa K. Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. J Pediatr. 1999 Sep;135(3):375-8. doi: 10.1016/s0022-3476(99)70138-1.
Reference Type
BACKGROUND
Muntau AC, Roschinger W, Habich M, Demmelmair H, Hoffmann B, Sommerhoff CP, Roscher AA. Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria. N Engl J Med. 2002 Dec 26;347(26):2122-32. doi: 10.1056/NEJMoa021654.
Reference Type
BACKGROUND
Trefz FK, Scheible D, Frauendienst-Egger G, Korall H, Blau N. Long-term treatment of patients with mild and classical phenylketonuria by tetrahydrobiopterin. Mol Genet Metab. 2005 Dec;86 Suppl 1:S75-80. doi: 10.1016/j.ymgme.2005.06.026. Epub 2005 Oct 20.
Reference Type
BACKGROUND
Shintaku H, Kure S, Ohura T, Okano Y, Ohwada M, Sugiyama N, Sakura N, Yoshida I, Yoshino M, Matsubara Y, Suzuki K, Aoki K, Kitagawa T. Long-term treatment and diagnosis of tetrahydrobiopterin-responsive hyperphenylalaninemia with a mutant phenylalanine hydroxylase gene. Pediatr Res. 2004 Mar;55(3):425-30. doi: 10.1203/01.PDR.0000111283.91564.7E. Epub 2003 Dec 17.
Reference Type
BACKGROUND
Hennermann JB, Buhrer C, Blau N, Vetter B, Monch E. Long-term treatment with tetrahydrobiopterin increases phenylalanine tolerance in children with severe phenotype of phenylketonuria. Mol Genet Metab. 2005 Dec;86 Suppl 1:S86-90. doi: 10.1016/j.ymgme.2005.05.013. Epub 2005 Jul 26.
Reference Type
BACKGROUND
Belanger-Quintana A, Garcia MJ, Castro M, Desviat LR, Perez B, Mejia B, Ugarte M, Martinez-Pardo M. Spanish BH4-responsive phenylalanine hydroxylase-deficient patients: evolution of seven patients on long-term treatment with tetrahydrobiopterin. Mol Genet Metab. 2005 Dec;86 Suppl 1:S61-6. doi: 10.1016/j.ymgme.2005.07.024. Epub 2005 Sep 13.
Reference Type
BACKGROUND
Lambruschini N, Perez-Duenas B, Vilaseca MA, Mas A, Artuch R, Gassio R, Gomez L, Gutierrez A, Campistol J. Clinical and nutritional evaluation of phenylketonuric patients on tetrahydrobiopterin monotherapy. Mol Genet Metab. 2005 Dec;86 Suppl 1:S54-60. doi: 10.1016/j.ymgme.2005.05.014. Epub 2005 Jul 22.
Reference Type
BACKGROUND
Kuvan® Package Insert. BioMarin. 2007
Reference Type
BACKGROUND
Blau N. Defining tetrahydrobiopterin (BH4)-responsiveness in PKU. J Inherit Metab Dis. 2008 Feb;31(1):2-3. doi: 10.1007/s10545-007-9979-1. No abstract available.
Reference Type
BACKGROUND
Fiege B, Blau N. Assessment of tetrahydrobiopterin (BH4) responsiveness in phenylketonuria. J Pediatr. 2007 Jun;150(6):627-30. doi: 10.1016/j.jpeds.2007.02.017.
Reference Type
BACKGROUND
Levy H, Burton B, Cederbaum S, Scriver C. Recommendations for evaluation of responsiveness to tetrahydrobiopterin (BH(4)) in phenylketonuria and its use in treatment. Mol Genet Metab. 2007 Dec;92(4):287-91. doi: 10.1016/j.ymgme.2007.09.017.
Reference Type
BACKGROUND
Zurfluh MR, Zschocke J, Lindner M, Feillet F, Chery C, Burlina A, Stevens RC, Thony B, Blau N. Molecular genetics of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. Hum Mutat. 2008 Jan;29(1):167-75. doi: 10.1002/humu.20637.
Reference Type
BACKGROUND
Fernhoff P, Burton B, Nowacka M, Hennermann J, Kakkis E, Dorenbaum PKU-008: A Long-Term, Open-Label Study of Sapropterin Dihydrochloride (Kuvan®) in PKU Subjects. Poster at the 2009 American College of Medical Genetics Annual Clinical Genetics Meeting.
Reference Type
BACKGROUND
Levy HL, Milanowski A, Chakrapani A, Cleary M, Lee P, Trefz FK, Whitley CB, Feillet F, Feigenbaum AS, Bebchuk JD, Christ-Schmidt H, Dorenbaum A; Sapropterin Research Group. Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study. Lancet. 2007 Aug 11;370(9586):504-10. doi: 10.1016/S0140-6736(07)61234-3.
Reference Type
BACKGROUND
Trefz FK, Burton BK, Longo N, Casanova MM, Gruskin DJ, Dorenbaum A, Kakkis ED, Crombez EA, Grange DK, Harmatz P, Lipson MH, Milanowski A, Randolph LM, Vockley J, Whitley CB, Wolff JA, Bebchuk J, Christ-Schmidt H, Hennermann JB; Sapropterin Study Group. Efficacy of sapropterin dihydrochloride in increasing phenylalanine tolerance in children with phenylketonuria: a phase III, randomized, double-blind, placebo-controlled study. J Pediatr. 2009 May;154(5):700-7. doi: 10.1016/j.jpeds.2008.11.040. Epub 2009 Mar 4.
Reference Type
BACKGROUND
Luciana M, Sullivan J, Nelson CA. Associations between phenylalanine-to-tyrosine ratios and performance on tests of neuropsychological function in adolescents treated early and continuously for phenylketonuria. Child Dev. 2001 Nov-Dec;72(6):1637-52. doi: 10.1111/1467-8624.00370.
Reference Type
BACKGROUND
Related Links
Access external resources that provide additional context or updates about the study.
http://emedicine.medscape.com/article/947781-overview
Arnold GL. Phenylketonuria, Publication Link
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
EMR 700773-503
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.
Nutritional and Neurotransmitter Changes in PKU Subjects on BH4
NCT00688844
COMPLETED
Kuvan Therapy in Phenylketonuria (PKU): The Effect of Blood Phenylalanine Concentration on Kuvan Response
NCT00841100
COMPLETED
PHASE2
Effects of Synergy on Nutrient Intake and Acceptability in Phenylketonuria (PKU)
NCT03777826
COMPLETED
NA
Sapropterin in Individuals With Phenylketonuria
NCT00730080
COMPLETED
Evaluation of Behavior, Executive Function, Neurotransmitter Function and Genomic Expression Kuvan Nonresponders
NCT01274026
COMPLETED
PKUDOS: Phenylketonuria (PKU) Demographic, Outcomes, and Safety Registry
NCT00778206
COMPLETED
A Dose-finding Study to Evaluate mRNA-3210 in Participants With Phenylketonuria
NCT06147856
WITHDRAWN
PHASE1/PHASE2
The Effects of Kuvan on Functional Brain Connectivity in Individuals With Phenylketonuria (PKU)
NCT00964236
COMPLETED
The Effectiveness of Kuvan in Amish PKU Patients
NCT02677870
COMPLETED
PHASE4
Safety and Tolerability of RTX-134 in Adults With Phenylketonuria
NCT04110496
TERMINATED
PHASE1
Trial of Kuvan in Lesch-Nyhan Disease
NCT00935753
WITHDRAWN
PHASE2/PHASE3
A Study of Sepiapterin in Participants With Phenylketonuria (PKU)
NCT06302348
RECRUITING
PHASE3
Study of Phenoptin in Subjects With Phenylketonuria Who Participated in Protocols PKU-004 or PKU-006
NCT00332189
COMPLETED
PHASE3
Evaluation of PKU Explore
NCT03168399
COMPLETED
NA
Sapropterin on Cognitive Abilities in Young Adults With Phenylketonuria
NCT01977820
TERMINATED
PHASE2
A Phase 3, Multicenter, Open-Label Extension Study of Phenoptin in Subjects With PKU Who Have Elevated Phenylalanine Levels
NCT00225615
COMPLETED
PHASE3
Study to Evaluate the Effects of Kuvan on Individuals With Phenylketonuria (PKU) With Maladaptive Behaviors
NCT00728676
COMPLETED
Pharmacodynamics, Safety, Tolerability and Pharmacokinetics of CDX-6114 in Patients With Phenylketonuria (PKU)
NCT04085666
COMPLETED
PHASE1
Market Research - Acceptability Trial for a New PKU Amino Acid Based Protein Substitute
NCT04309331
COMPLETED
NA
A Phase 1/Phase 2 Open-label Study to Evaluate the Safety, Tolerability, and Efficacy of a Single Intravenous Administration of SAR444836 in Adult Participants With Phenylketonuria
NCT05972629
ACTIVE_NOT_RECRUITING
PHASE1/PHASE2
Evaluation of BH4 Responsiveness in Our PKU Patients
NCT07255599
ACTIVE_NOT_RECRUITING
PHASE1
Fluorodeoxyglucose Positron Emission Tomography (FDG PET) Findings in Patients With Phenylketonuria Before and After KUVAN Therapy
NCT00986973
COMPLETED
NA
Natural History Clinical Study in Adult PKU
NCT04768348
TERMINATED
Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of CDX 6114 in PKU Patients
NCT04256655
WITHDRAWN
PHASE1