PhenylketonuriasPhase 3NCT00104247

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

A Phase 3 study testing sapropterin dihydrochloride, 6R-BH4, tetrahydrobiopterin in people with Phenylketonurias, run by BioMarin Pharmaceutical at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

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. Read more about this study

Who is it for?: Ages 8 years and older
Conditions the study is for: Phenylketonurias
What is being tested?: sapropterin dihydrochloride, 6R-BH4, tetrahydrobiopterin
How many people: 89 participants
Where: 13 sitesUnited States
Study dates: Mar 2005to Feb 2006
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 8 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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)

Show all 9Show fewer

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

Who cannot join

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

Show all 9Show fewer

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

Trial locations and contacts

13 sites in 1 country.

City, postcode or hospital

13 sites in 1 country

United States13 sites

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

Other trials in United States

About this study

Official title: 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.

Conditions: Phenylketonurias
Being tested: sapropterin dihydrochloride, 6R-BH4, tetrahydrobiopterin
Keywords: Phenylalanine Hydroxylase
Medical subject headings: Phenylketonurias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

sapropterin dihydrochloride, 6R-BH4, tetrahydrobiopterinDrug

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Blood Phenylalanine Levels From Baseline to Week 6.
Measured: baseline to week 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2005Feb 2006

First posted25 Feb 2005 (estimated)
Study startMar 2005
Study completionFeb 2006

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for PhenylketonuriasStudies of the same condition, open and under way.
More trials run by BioMarin PharmaceuticalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Enrolment: 89 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00104247
Sponsor's protocol ID: PKU-003
Status last verified: Jul 2014
First submitted: 24 Feb 2005
Last updated: 23 Jul 2014
Results posted: Yes, on ClinicalTrials.gov

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.
PubMed 17693179

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1
A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-181 in Subjects With Phenylketonuria
Phenylketonuria
RecruitingPhase 2
A Study of MZE782 in Adults With PKU
Phenylketonuria (PKU)
RecruitingPhase 3
A Study of Sepiapterin in Participants With Phenylketonuria (PKU)
Phenylketonuria
Recruiting
Impact of Phenylalanine Elevations on Brain and Cognition in Adult PKU Carriers
Carrier of Phenylketonuria, Healthy
RecruitingPhase 3
A Study of JNT-517 in Participants With Phenylketonuria (PKU)
Phenylketonuria

All Phenylketonurias trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT00104247
Acronym / sponsor ID: PKU-003
Conditions: Phenylketonurias
Keywords: Phenylalanine Hydroxylase
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 89 participants (actual)
Lead sponsor: BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
Study start: Mar 2005
Study completion: Feb 2006 (actual)
First posted: 25 Feb 2005 (estimated)
Results: Posted 16 Apr 2009

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind

Who may qualify

Ages: 8 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (9 listed)

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

Key exclusion criteria (9 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
sapropterin dihydrochloride, 6R-BH4, tetrahydrobiopterin	Drug	–

Primary outcome

Change in Blood Phenylalanine Levels From Baseline to Week 6.
Time frame: baseline to week 6

Results and safety

Results posted to the registry on 16 Apr 2009, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sapropterin Dihydrochloride	42	41
Placebo	47	46

Primary outcome: Change in Blood Phenylalanine Levels From Baseline to Week 6.

Time frame: baseline to week 6. Mean (Standard Deviation). Unit: micromole per liter

Measure	Sapropterin Dihydrochloride n = 41	Placebo n = 46
Baseline Blood Phe Level	843 (300)	888 (323)
Week 6 Blood Phe Level	607 (377)	891 (348)
Mean Change in Blood Phe from Baseline to Week 6	-239 (38)	6 (36)

Sapropterin Dihydrochloride vs Placebo: p <0.001, ANCOVA

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sapropterin Dihydrochloride	0 of 41 (0%)	21 of ?	Not reported
Placebo	0 of 47 (0%)	34 of ?	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 17693179Levy 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.
BioMarin Pharmaceutical Inc. home pageLink provided by the sponsor.
NDA Review PackageLink provided by the sponsor.
Product LabelLink provided by the sponsor.

Related trials for Phenylketonurias

RecruitingPhase 1
A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-181 in Subjects With Phenylketonuria
Phenylketonuria
RecruitingPhase 2
A Study of MZE782 in Adults With PKU
Phenylketonuria (PKU)
RecruitingPhase 3
A Study of Sepiapterin in Participants With Phenylketonuria (PKU)
Phenylketonuria
Recruiting
Impact of Phenylalanine Elevations on Brain and Cognition in Adult PKU Carriers
Carrier of Phenylketonuria, Healthy
RecruitingPhase 3
A Study of JNT-517 in Participants With Phenylketonuria (PKU)
Phenylketonuria

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

13 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing sapropterin dihydrochloride, 6R-BH4, tetrahydrobiopterin in people with Phenylketonurias, run by BioMarin Pharmaceutical at 13 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Apr 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Blood Phenylalanine Levels From Baseline to Week 6. (time frame: baseline to week 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00104247, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2014.