Phase 3 Open-label Study to Evaluate the Response and Safety of Kuvan® in Patients With Phenylketonuria

This study has been completed.
Information provided by (Responsible Party):
Merck KGaA Identifier:
First received: November 19, 2012
Last updated: December 12, 2013
Last verified: December 2013

This is an open-label, non-comparative, Phase 3 study to evaluate the degree, frequency of response and safety of Kuvan® in subjects aged 4 to 18 years who have phenylketonuria with elevated blood phenylalanine level of greater than or equal to 450 micromole per liter.

Condition Intervention Phase
Drug: Kuvan®
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Non-comparative Open-label Clinical Study to Evaluate the Response to and Safety of Kuvan® (Sapropterin Dihydrochloride) After 6 Weeks of Treatment in Patients of 4 to 18 Years of Age With Phenylketonuria Who Have Elevated Blood Phenylalanine Levels

Resource links provided by NLM:

Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Response to Kuvan® after 8-day treatment defined as a reduction in blood Phenylalanine levels of greater than or equal to 30 percent as compared to beginning of the test prior to dosing [ Time Frame: Day 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage change from baseline in blood phenylalanine level after 8-day Kuvan® therapy [ Time Frame: Baseline and Day 8 ] [ Designated as safety issue: No ]
  • Number of adverse events [ Time Frame: Baseline up to Week 11 (+/- 1 Week) ] [ Designated as safety issue: Yes ]

Enrollment: 90
Study Start Date: November 2012
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Kuvan® Drug: Kuvan®
Kuvan® oral soluble tablet will be administered once daily in the morning, as 20 milligram per kilogram of the subject's body mass. The therapy duration will depend on the response to treatment - either up to 8 days, (if there will be no response), or up to 7 weeks (if there will be response).
Other Names:
  • Sapropterin dihydrochloride
  • 6R-BH4 tetrahydrobiopterin


Ages Eligible for Study:   4 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Willing and able to provide written informed consent (for children under 18 years old the parent(s)/guardians give informed consent, subjects 14-17 years old give additionally their own written informed consent)
  • Age of 4 - 18 years, inclusive
  • Confirmed clinical and biochemical Hyperphenylalaninemia due to phenylketonuria documented by past medical history with at least 2 blood Phenylalanine level greater than or equal to 400 micromole per liter obtained in 2 separate occasions
  • Blood phenylalanine level at screening greater than or equal to 450 micromole per liter (mean of two measurements)
  • For women of childbearing potential, a negative urine pregnancy test is required at screening and willingness to use a highly effective method of contraception is required while participating in the study
  • Subject and/or the parent/guardian willing and able to comply with study procedures
  • Subject and/or the parent/guardian willing to continue current diet unchanged during the 8 days response test and to adapt the diet according to Phenylalanine therapeutic target range during the 6 week treatment period

Exclusion Criteria:

  • Subject already assessed for responsiveness to sapropterin dihydrochloride or other tetrahydrobiopterin (BH4)
  • Used any investigational agent other than Kuvan® within 30 days of screening, or required any investigational agent or vaccine prior to completion of all scheduled study assessments
  • Pregnant or breastfeeding, or considering pregnancy
  • Concurrent disease or conditions that would interfere with study participation or safety (for example, seizure disorder, asthma or other condition requiring oral or parenteral corticosteroid administration, insulin-dependent diabetes, or organ transplantation recipient)
  • Concurrent use of required concomitant treatment with any drug known to inhibit folate synthesis (e.g. methotrexate), levodopa, phosphodiesterase type-5 (PDE-5) inhibitors (such as, sildenafil, vardenafil or tadalafil), medications that are known to affect nitric oxide synthesis metabolism or action
  • Any conditions, 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
  • Clinical diagnosis of primary BH4 deficiency
  • Known hypersensitivity to Kuvan® or its excipients or to other approved or non-approved formulation of tetrabiopterin
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01732471

Please contact Merck KGaA Communication Center located in
Darmstadt, Germany
Sponsors and Collaborators
Merck KGaA
  More Information

No publications provided

Responsible Party: Merck KGaA Identifier: NCT01732471     History of Changes
Other Study ID Numbers: EMR 700773_510
Study First Received: November 19, 2012
Last Updated: December 12, 2013
Health Authority: Russia: Ethics Council at the Ministry of Health of the Russian Federation
Russia: Ministry of Health of the Russian Federation
Russia: Local Ethics Committees
Ukraine: Local Ethics Committee
Ukraine: Ministry of Health of Ukraine
Ukraine: State Expert Center of Ministry of Ukraine

Keywords provided by Merck KGaA:
EMR 700733_510, Genetic disorder, Phenylketonuria, phenylalanine, Kuvan, sapropterin dihydrochloride

Additional relevant MeSH terms:
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 processed this record on July 20, 2014