Clinical trial NCT01732471: Phase 3 Open-label Study to Evaluate the Response and Safety of Kuvan® in Subjects With Phenylketonuria
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Phenylketonuria
Keywords: EMR 700733_510, Genetic disorder, Phenylketonuria, phenylalanine, Kuvan, sapropterin dihydrochloride
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2012-11-22
Enrollment: 90
Sex: ALL
Minimum age (years): 4
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Response to Kuvan® (Sapropterin Dihydrochloride) Treatment
timeFrame: Day 8
Secondary outcomes:
measure: Percent Change From Baseline in Blood Phenylalanine Levels at Day 8 in Overall Population
timeFrame: Baseline, Day 8
measure: Percent Change From Baseline in Blood Phenylalanine Levels at Day 8 in Sub-population of Responders
timeFrame: Baseline, Day 8
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) in Overall Safety Population
timeFrame: Baseline up to Week 11
Other outcomes:
Locations:
city: Darmstadt
country: Germany
facility: Please contact Merck KGaA Communication Center
Study officials:
References: