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

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ClinicalTrials.gov Identifier: NCT01732471
Recruitment Status : Completed
First Posted : November 22, 2012
Results First Posted : July 28, 2014
Last Update Posted : July 28, 2014
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Tracking Information
First Submitted Date  ICMJE November 19, 2012
First Posted Date  ICMJE November 22, 2012
Results First Submitted Date  ICMJE June 24, 2014
Results First Posted Date  ICMJE July 28, 2014
Last Update Posted Date July 28, 2014
Study Start Date  ICMJE November 2012
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 25, 2014)
Percentage of Participants With Response to Kuvan® (Sapropterin Dihydrochloride) Treatment [ Time Frame: Day 8 ]
Response to Kuvan® (sapropterin dihydrochloride) treatment was defined as a reduction in blood phenylalanine levels of greater than or equal to 30% at Day 8 as compared to baseline.
Original Primary Outcome Measures  ICMJE
 (submitted: November 19, 2012)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 25, 2014)
  • Percent Change From Baseline in Blood Phenylalanine Levels at Day 8 in Overall Population [ Time Frame: Baseline, Day 8 ]
    Percent change in blood phenylalanine levels after 8-day Kuvan® therapy (response test period) was calculated as (blood phenylalanine level at Day 8 minus blood phenylalanine level at baseline)*100/ blood phenylalanine level at baseline.
  • Percent Change From Baseline in Blood Phenylalanine Levels at Day 8 in Sub-population of Responders [ Time Frame: Baseline, Day 8 ]
    Percent change in blood phenylalanine levels after 8-day Kuvan® therapy (response test period) was calculated as (blood phenylalanine level at Day 8 minus blood phenylalanine level at baseline)*100/ blood phenylalanine level at baseline.
  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) in Overall Safety Population [ Time Frame: Baseline up to Week 11 ]
    An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 19, 2012)
  • Percentage change from baseline in blood phenylalanine level after 8-day Kuvan® therapy [ Time Frame: Baseline and Day 8 ]
  • Number of adverse events [ Time Frame: Baseline up to Week 11 (+/- 1 Week) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 3 Open-label Study to Evaluate the Response and Safety of Kuvan® in Subjects With Phenylketonuria
Official Title  ICMJE 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
Brief Summary This is an open-label, non-comparative, Phase 3 study to evaluate the degree, frequency of response and safety of Kuvan® (sapropterin dihydrochloride) in subjects aged 4 to 18 years who have phenylketonuria and with elevated blood phenylalanine level of greater than or equal to 450 micromole per liter.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Phenylketonuria
Intervention  ICMJE Drug: Kuvan®
Kuvan® (sapropterin dihydrochloride) will be administered orally at a dose of 20 milligram per kilogram per day (mg/kg/day) once daily for 8 days. If there is 30 percent (%) decrease in blood phenylalanine levels from baseline at the end of Day 8, then treatment will be continued at the same dose for further 6 weeks.
Other Names:
  • Sapropterin dihydrochloride
  • 6R-BH4 tetrahydrobiopterin
Study Arms  ICMJE Experimental: Kuvan®
Intervention: Drug: Kuvan®
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 19, 2012)
90
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 2013
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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® (sapropterin dihydrochloride) 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 (for example, 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® (sapropterin dihydrochloride) or its excipients or to other approved or non-approved formulation of tetrabiopterin
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01732471
Other Study ID Numbers  ICMJE EMR 700773_510
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Merck KGaA, Darmstadt, Germany
Study Sponsor  ICMJE Merck KGaA, Darmstadt, Germany
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Merck KGaA, Darmstadt, Germany
Verification Date July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP