Study of Phenoptin to Increase Phenylalanine Tolerance in Phenylketonuric Children on a Phenylalanine-restricted Diet

Study Overview
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Brief Summary
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The primary objective of this trial is to evaluate the ability of Phenoptin to increase phenylalanine (phe) tolerance in children with phenylketonuria who are following a phe-restricted diet.

Official Title
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A Phase 3, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Phenoptin to Increase Phenylalanine Tolerance in Phenylketonuric Children on a Phenylalanine-restricted Diet

Conditions
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Phenylketonurias

Intervention / Treatment
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* Drug: Sapropterin Dihydrochloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of PKU with hyperphenylalaninemia (HPA) documented by at least one blood Phe measurement >/=360 umol/L (6 mg/dL) Under dietary control with a Phe-restricted diet as evidenced by:· Estimated daily Phe tolerance </=1000 mg/day At least 6 months of blood Phe control (mean level of </=480 μmol/L) prior to enrolling in the study Aged 4 to 12 years inclusive at screening A blood Phe level </=480 μmol/L at screening Female subjects of childbearing potential (as determined by the principal investigator) must have a negative blood or urine pregnancy test at entry (prior to the first dose). Note: All female subjects of childbearing potential and sexually mature male subjects must be advised to use a medically accepted method of contraception throughout the study. Female subjects of childbearing potential must be willing to undergo periodic pregnancy tests during the course of the study Willing and able to comply with all study procedures Willing to provide written assent (if applicable) and written informed consent by a parent or legal guardian after the nature of the study has been explained and prior to any research-related procedures Exclusion Criteria: Any condition that, in the view of the PI, renders the subject at high risk from treatment compliance and/or completing the study Prior history of organ transplantation Perceived to be unreliable or unavailable for study participation or have parents or legal guardians who are perceived to be unreliable or unavailable Use of any investigational agent within 30 days prior to screening, or requirement for any investigational agent or vaccine prior to completion of all scheduled study assessments ALT > 2 times the upper limit of normal (i.e., Grade 1 or higher based on World Health Organization Toxicity Criteria) at screening Concurrent disease or condition that would interfere with study participation or safety (e.g., seizure disorder, oral steroid-dependent asthma or other condition requiring oral or parenteral corticosteroid administration, or insulin-dependent diabetes)

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sapropterin Dihydrochloride<br>Phenoptin, provided in tablets containing 100 mg of sapropterin dihydrochloride each, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4-8 oz (120-240 mL) of water or apple juice for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study. | Drug: Sapropterin Dihydrochloride<br>* Phenoptin, provided in tablets containing 100 mg of sapropterin dihydrochloride each, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4-8 oz (120-240 mL) of water or apple juice for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.<br>|
| Placebo Comparator: Placebo<br>Placebo, provided as tablets similar to Phenoptin tablets, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4 8 oz (120-240 mL) of water or apple juice. for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study. | Drug: Placebo<br>* Placebo, provided as tablets similar to Phenoptin tablets, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4 8 oz (120-240 mL) of water or apple juice. for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of Dietary Supplemented Phenylalanine (Phe)Tolerated in Children With Phenylketonuria |  | at Week 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Phenylalanine Levels From Baseline to Week 3 |  | Baseline to Week 3 |