Study to Evaluate the Response to and Safety of an 8-Day Course of Phenoptin™ Treatment in Subjects With Phenylketonuria

A Phase 2, Multicenter, Open-Label Study to Evaluate the Response to and Safety of an 8-Day Course of Phenoptin™ Treatment in Subjects With Phenylketonuria Who Have Elevated Phenylalanine Levels

The primary objective is to evaluate the degree and frequency of response to Phenoptin™ (sapropterin dihydrochloride), as demonstrated by a reduction in blood phenylalanine (Phe) level among subjects with phenylketonuria (PKU) who have elevated Phe levels. A secondary objective of this study is to evaluate the safety of Phenoptin™ treatment in this subject population, and identify individuals in this subject population who respond to Phenoptin™ treatment with a reduction in blood Phe level.

Study Overview

• Status: Completed
• Conditions: Phenylketonurias
• Intervention / Treatment: Drug: sapropterin dihydrochloride

• Study Type: Interventional
• Enrollment: 700
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States
    • Oakland, California, United States
  • Connecticut
    • New Haven, Connecticut, United States
  • Illinois
    • Chicago, Illinois, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • Minnesota
    • Minneapolis, Minnesota, United States
  • Missouri
    • St. Louis, Missouri, United States
  • New York
    • New York, New York, United States
  • Oregon
    • Portland, Oregon, United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States
  • Texas
    • Dallas, Texas, United States
  • Utah
    • Salt Lake City, Utah, United States
  • Wisconsin
    • Madison, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age >/= 8 years
• Blood Phe level >/= 450 umol/L at screening
• Clinical diagnosis of PKU with hyperphenylalaninemia documented by past medical history of at least one blood Phe measurement >/= 360 umol/L (6 mg/dL)
• Willing and able to provide written informed consent or, in the case of subjects under the age of 18, provide written assent (if required) and written informed consent by a parent or legal guardian, after the nature of the study has been explained
• Negative urine pregnancy test at screening (non-sterile females of child-bearing potential only)
• Male and Female subjects of childbearing potential childbearing potential (if sexually active and non-sterile) must be using acceptable birth control measures, as determined by the investigator, and willing to continue to use acceptable birth control measures while participating in the study
• Willing and able to comply with study procedures
• Willing to continue current diet unchanged while participating in the study

Exclusion Criteria:

• Perceived to be unreliable or unavailable for study participation or, if under the age of 18, 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
• Pregnant or breastfeeding, or considering pregnancy
• ALT > 5 times the upper limit of normal (i.e., Grade 3 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, 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)
• Concurrent use of levodopa
• Clinical diagnosis of primary BH4 deficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Evaluate the degree and frequency of response to Phenoptin™, as demonstrated by a reduction in blood Phe level among subjects with PKU who have elevated Phe levels

Secondary Outcome Measures

Outcome Measure
Evaluate the safety of Phenoptin™ treatment in this subject population, and identify individuals in this subject population who respond to Phenoptin™ treatment with a reduction in blood Phe level

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Study Completion (Actual): November 1, 2005

Study Registration Dates

• First Submitted: February 24, 2005
• First Submitted That Met QC Criteria: February 24, 2005
• First Posted (Estimate): February 25, 2005

Study Record Updates

• Last Update Posted (Estimate): April 9, 2007
• Last Update Submitted That Met QC Criteria: April 5, 2007
• Last Verified: April 1, 2007

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Phenylketonurias; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Verapamil
• Other Study ID Numbers: PKU-001