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

This study has been completed.
Sponsor:
Information provided by:
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT00355264
First received: July 19, 2006
Last updated: June 7, 2010
Last verified: June 2010

July 19, 2006
June 7, 2010
August 2006
June 2009   (final data collection date for primary outcome measure)
  • control of blood phenylalanine levels, as measured by the proportion of subjects [ Time Frame: every other week ] [ Designated as safety issue: No ]
  • whose blood Phe level at Week 10 is < 360 mmol/L; [ Time Frame: week 10 ] [ Designated as safety issue: No ]
  • the mean blood Phe level at Week 10 among all subjects. [ Time Frame: week 10 ] [ Designated as safety issue: No ]
  • control of blood phenylalanine levels, as measured by the proportion of subjects
  • whose blood Phe level at Week 10 is < 360 mmol/L;
  • the mean blood Phe level at Week 10 among all subjects.
Complete list of historical versions of study NCT00355264 on ClinicalTrials.gov Archive Site
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Safety and Efficacy Study of Phenoptin in Subjects With Hyperphenylalaninemia Due to BH4 Deficiency
Phase 2, Multicenter, Open Label Study of Phenoptin in Subjects With Hyperphenylalaninemia Due to Primary BH4 Deficiency

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.

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.
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Tetrahydrobiopterin Deficiencies
  • Hyperphenylalaninemia, Non-Phenylketonuric
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
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
June 2009
June 2009   (final data collection date for primary outcome measure)

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
Both
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No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00355264
PKU-007
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Alex Dorenbaum, Medical Director, BioMarin Pharmaceutical Inc.
BioMarin Pharmaceutical
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BioMarin Pharmaceutical
June 2010

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