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Safety and Efficacy Study of Phenoptin in Subjects With Hyperphenylalaninemia Due to BH4 Deficiency

This study has been completed.
Information provided by (Responsible Party):
BioMarin Pharmaceutical Identifier:
First received: July 19, 2006
Last updated: August 11, 2014
Last verified: August 2014
The purpose of this study is to evaluate the ability of Phenoptin to control blood phenylalanine levels in subjects who have hyperphenylalaninemia due to a primary BH4 deficiency and to evaluate the safety of Phenoptin in this population.

Condition Intervention Phase
Tetrahydrobiopterin Deficiencies
Hyperphenylalaninemia, Non-Phenylketonuric
Drug: Phenoptin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2, Multicenter, Open Label Study of Phenoptin in Subjects With Hyperphenylalaninemia Due to Primary BH4 Deficiency

Resource links provided by NLM:

Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:
  • control of blood phenylalanine levels, as measured by the proportion of subjects [ Time Frame: every other week ]
  • whose blood Phe level at Week 10 is < 360 mmol/L; [ Time Frame: week 10 ]
  • the mean blood Phe level at Week 10 among all subjects. [ Time Frame: week 10 ]

Enrollment: 12
Study Start Date: August 2006
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm on Active Drug
5mg/kg/day orally, dose may be adjusted to between 5-20 mg/kg/day by investigator at week 6 to control blood Phe levels
Drug: Phenoptin
5mg/kg/day orally, dose may be adjusted to between 5-20 mg/kg/day by investigator at week 6 to control blood Phe levels

Detailed Description:

Within 4 weeks of completing screening assessments to determine eligibility, subjects will be enrolled in the study. The study will be conducted in two parts.

Part 1: After screening, all subjects will be followed for two weeks without modification of their baseline medical or dietary care.

Part 2: Beginning at Week 2, subjects who were receiving non-registered formulations of BH4 at enrollment will suspend this treatment and within one day will start Phenoptin at approximately the same dose of the non-registered BH4 formulation. Subjects not receiving BH4 at enrollment will begin treatment with Phenoptin at approximately 5 mg/kg/day, given orally, prior to meals.

At the discretion of the Investigator, the Phenoptin dose may be adjusted up or down at the Week 6 visit to control blood Phe levels (<360 mmol/L), or to optimize the clinical effect. The maximum dose allowed will be approximately 20 mg/kg/day. All subjects will receive Phenoptin for a total of 8 weeks. Subjects will be instructed to continue their usual diet without modification. Study visits will occur every other week.

Tyrosine, biopterin and neopterin will be analyzed at the following visits: Week 0 (enrollment), Week 2 (prior to dosing with Phenoptin), Week 8 (after 6 weeks of treatment with Phenoptin) and Week 10 (after 8 weeks of treatment with Phenoptin).During each visit, blood Phe level will be measured (2.5-5 hours after a meal), and safety evaluations will be performed. Safety will be assessed by monitoring adverse events and vital signs, performing physical examinations, assessing signs and symptoms of primary BH4 deficiency (i.e., neurological symptoms such as seizures, changes in muscle tone, weakness, etc.) and clinical laboratory tests (chemistry, hematology and urinalysis).

Extension: Upon completion of 8 weeks of treatment (i.e., at the Week 10 visit), subjects will be offered the option to continue treatment with Phenoptin in an extension of this study. Participation in the study extension will continue until one of the following occurs:

  1. the subject withdraws consent and discontinues from the study,
  2. the subject is discontinued from the study at the discretion of the investigator,
  3. the study drug is available through the appropriate marketing approval, or
  4. the study is terminated. During the extension period, study drug will be dispensed to subjects monthly, and study visits will be required every 3 months. The Phenoptin dose may be adjusted at any visit during the study extension at the discretion of the Investigator. The maximum dose allowed will be approximately 20 mg/kg/day.

Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Documented history of blood Phe level > 180 mmol/L on at least one occasion
  • Established diagnosis of HPA due to primary BH4 deficiency with a documented defect in biopterin metabolism with blood or urine tests
  • Willing and able to provide written informed consent or, in the case of subjects under the age of 18 years, provide written assent (if required) and written informed consent by a parent or legal guardian
  • Negative urine pregnancy test at screening for females of child-bearing potential
  • Male and female subjects of childbearing potential (if sexually active and non-sterile) must be using acceptable birth control measures and be willing to continue to use acceptable birth control measures while participating in the study
  • Willing and able to comply with all study procedures
  • Able to take medication orally

Exclusion Criteria:

  • Perceived to be unreliable or unavailable for study participation or, if under the age of 18 years, have parents or legal guardians who are perceived to be unreliable or unavailable
  • Use of any investigational agent (other than BH4) within 30 days prior to screening, or requirement for any investigational agent or vaccine prior to completion of all scheduled study assessments
  • Positive urine pregnancy test at screening (non-sterile females of child bearing potential only), already known to be pregnant or breastfeeding or planning a pregnancy in self or partner during the study
  • 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, insulin-dependent diabetes, or organ transplantation)
  • Serious neuropsychiatric illness (e.g., major depression) not currently under medical control
  • Requirement for concomitant treatment with any drug known to inhibit folate synthesis (e.g., methotrexate)
  • Clinical diagnosis of phenylketonuria (PKU) due to phenylalanine hydroxylase deficiency
  • Any condition that, in the view of the PI, renders the subject at high risk from treatment compliance and/or completing the study
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Please refer to this study by its identifier: NCT00355264

United States, California
Los Angeles, California, United States, 90095
United States, Illinois
Chicago, Illinois, United States, 60614
United States, Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
New York, New York, United States, 10029
United States, North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Oregon
Portland, Oregon, United States, 97239
United States, Utah
Salt Lake City, Utah, United States, 84132
United States, Washington
Seattle, Washington, United States, 98195
United States, Wisconsin
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
BioMarin Pharmaceutical
  More Information

Additional Information:
Responsible Party: BioMarin Pharmaceutical Identifier: NCT00355264     History of Changes
Other Study ID Numbers: PKU-007
Study First Received: July 19, 2006
Last Updated: August 11, 2014

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
Anti-Arrhythmia Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents processed this record on April 27, 2017