Study to Evaluate the Safety and Efficacy of Phenoptin™ in Subjects With Phenylketonuria Who Have Elevated Phenylalanine Levels

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Phenoptin™ in Subjects With Phenylketonuria Who Have Elevated Phenylalanine Levels

The primary objective of this study is to evaluate the efficacy of Phenoptin™ (sapropterin dihydrochloride) in reducing blood phenylalanine (Phe) levels in subjects with phenylketonuria.

Study Overview

• Status: Completed
• Conditions: Phenylketonurias
• Intervention / Treatment: Drug: sapropterin dihydrochloride, 6R-BH4, tetrahydrobiopterin

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 3

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

Description

Inclusion Criteria:

• 8 years of age and older
• Received at least 7 out of 8 scheduled doses in Study PKU 001
• Responsive to Phenoptin™ in Study PKU-001, defined as a reduction in blood Phenylalanine level of >/=30% compared with baseline
• Blood Phenylalanine level >/=450 μmol/L at screening
• 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 (females of child-bearing potential)
• Male and Female subjects of childbearing potential (if sexually active) 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 other than Phenoptin™ within 30 days prior to screening, or requirement for any investigational agent or investigational 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 recipient)
• Serious neuropsychiatric illness (e.g., major depression) not currently under medical management
• 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: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Blood Phenylalanine Levels From Baseline to Week 6.	baseline to week 6

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical

Publications and helpful links

General Publications

• Levy HL, Milanowski A, Chakrapani A, Cleary M, Lee P, Trefz FK, Whitley CB, Feillet F, Feigenbaum AS, Bebchuk JD, Christ-Schmidt H, Dorenbaum A; Sapropterin Research Group. Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study. Lancet. 2007 Aug 11;370(9586):504-10. doi: 10.1016/S0140-6736(07)61234-3.

Helpful Links

• BioMarin Pharmaceutical Inc. home page
• NDA Review Package
• Product Label

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Study Completion (Actual): February 1, 2006

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): July 23, 2014
• Last Update Submitted That Met QC Criteria: July 15, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Phenylalanine Hydroxylase
• 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-003