PhenylketonuriaPhase 3NCT00332189

Study of Phenoptin in Subjects With Phenylketonuria Who Participated in Protocols PKU-004 or PKU-006

A Phase 3 study testing sapropterin dihydrochloride in people with Phenylketonuria, run by BioMarin Pharmaceutical at 14 sites in United States.

Completed

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

Official record

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Trial summary

The objective of this study is to evaluate the safety of long-term treatment with Phenoptin in subjects with phenylketonuria (PKU) who participated in Phase 3 clinical studies with Phenoptin. Read more about this study

Who is it for?: Ages 4 years and older
Conditions the study is for: Phenylketonuria
What is being tested?: sapropterin dihydrochloride
Type of treatment: Pill or oral medicine
How many people: 111 participants
Where: 14 sitesUnited States
Study dates: Jul 2006to Aug 2009
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 4 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Participation in study PKU-004 or PKU-006
Willing and able to provide written, signed 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, after the nature of the study has been explained, and prior to any research-related procedures
Negative urine pregnancy test at screening (females of child-bearing potential)
Willing and able to comply with all study procedures

Who cannot join

Non-responsive to prior treatment with Phenoptin based on participation in PKU-004 or PKU-006
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
Terminated early from PKU-004 or PKU-006, except for subjects in PKU-004 that rolled into PKU-008 at Week 22, subjects in PKU-006 that rolled into PKU-008 at Week 10, or subjects in PKU-006 that terminated due to elevated Phe levels following dietary Phe increases
Use of any investigational product other than Phenoptin within 30 days prior to screening, or anticipated requirement for any investigational agent 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
Female subjects of childbearing potential must be using an effective method of birth control, as determined by the PI, and willing to continue to use acceptable birth control measures

Show all 14Show fewer

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)
Any condition that, in the view of the PI, renders the subject at high risk from treatment compliance and/or completing 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 (see Appendix 2)
Serious neuropsychiatric illness (e.g., major depression) not currently under medical control
Prior history of organ transplantation
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

14 sites in 1 country.

City, postcode or hospital

14 sites in 1 country

United States14 sites

Study site
Atlanta, Georgia
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
Portland, Oregon
Study site
Sacramento, California
Study site
Salt Lake City, Utah
Study site
San Jose, California
Study site
Seattle, Washington
Study site
St Louis, Missouri

Other trials in United States

About this study

Official title: A Phase 3b, Multicenter, Open-Label Extension Study of Phenoptin in Subjects With Phenylketonuria Who Participated in Protocols PKU-004 or PKU-006

The objective of this study is to evaluate the safety of long-term treatment with Phenoptin in subjects with phenylketonuria (PKU) who participated in Phase 3 clinical studies with Phenoptin.

Conditions: Phenylketonuria
Being tested: sapropterin dihydrochloride
Keywords: PKU
Medical subject headings: Phenylketonurias

What participants receive

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

sapropterin dihydrochlorideDrug
Also called Kuvan
5-20mg/kg/day orally, dose may be adjusted up or down as needed at the discretion of the investigator in increments of 5mg/kg/day.

What is being measured

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

Tabulation of the Incidence and Frequency of All AEs and SAEs That Occur Throughout the Study.
Safety was assessed with regards to the rate and type of AEs, clinically significant changes to vital signs and/or physical examination findings, and clinically significant changes in laboratory test results.
Measured: Baseline through Final Visit (a Maximum of 30 months) with AEs collected at month 3 and 6 then at 6 month intervals

Secondary outcomes (1)

Following Blood Phe Levels.
There were no pre-specified efficacy analysis, blood Phe samples were taken at each visit. Blood Phe concentrations remained within levels consistent with local clinical site recommendations for blood Phe control.
Measured: Baseline through Final Visit (a Maximum of 30 months) with blood phe samples taken at months 3 and 6 then at 6 month intervals

Timeline

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

Jul 2006Aug 2009

First posted1 Jun 2006 (estimated)
Study startJul 2006
Primary completionAug 2009
Study completionAug 2009

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 PhenylketonuriaStudies 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: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 111 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00332189
Sponsor's protocol ID: PKU-008
Status last verified: Oct 2012
First submitted: 30 May 2006
Last updated: 16 Nov 2012
Results posted: Yes, on ClinicalTrials.gov

Publications

Burton BK, Nowacka M, Hennermann JB, Lipson M, Grange DK, Chakrapani A, Trefz F, Dorenbaum A, Imperiale M, Kim SS, Fernhoff PM. Safety of extended treatment with sapropterin dihydrochloride in patients with phenylketonuria: results of a phase 3b study. Mol Genet Metab. 2011 Aug;103(4):315-22. doi: 10.1016/j.ymgme.2011.03.020. Epub 2011 Mar 31.
PubMed 21646032

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

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

Study at a glance

From the registry record, last updated by the sponsor on 16 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3b, Multicenter, Open-Label Extension Study of Phenoptin in Subjects With Phenylketonuria Who Participated in Protocols PKU-004 or PKU-006
ClinicalTrials.gov ID: NCT00332189
Acronym / sponsor ID: PKU-008
Conditions: Phenylketonuria
Keywords: PKU
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 111 participants (actual)
Lead sponsor: BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
Study start: Jul 2006
Primary completion: Aug 2009 (actual)
Study completion: Aug 2009 (actual)
First posted: 1 Jun 2006 (estimated)
Results: Posted 16 Nov 2012

Clinical summary

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

The objective of this study is to evaluate the safety of long-term treatment with Phenoptin in subjects with phenylketonuria (PKU) who participated in Phase 3 clinical studies with Phenoptin.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)

Who may qualify

Ages: 4 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (4 listed)

Participation in study PKU-004 or PKU-006
Willing and able to provide written, signed 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, after the nature of the study has been explained, and prior to any research-related procedures
Negative urine pregnancy test at screening (females of child-bearing potential)
Willing and able to comply with all study procedures

Key exclusion criteria (14 listed)

Non-responsive to prior treatment with Phenoptin based on participation in PKU-004 or PKU-006
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
Terminated early from PKU-004 or PKU-006, except for subjects in PKU-004 that rolled into PKU-008 at Week 22, subjects in PKU-006 that rolled into PKU-008 at Week 10, or subjects in PKU-006 that terminated due to elevated Phe levels following dietary Phe increases
Use of any investigational product other than Phenoptin within 30 days prior to screening, or anticipated requirement for any investigational agent 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

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 dihydrochlorideAlso: Kuvan5-20mg/kg/day orally, dose may be adjusted up or down as needed at the discretion of the investigator in increments of 5mg/kg/day.	Drug	–

Primary outcome

Tabulation of the Incidence and Frequency of All AEs and SAEs That Occur Throughout the Study.
Time frame: Baseline through Final Visit (a Maximum of 30 months) with AEs collected at month 3 and 6 then at 6 month intervals
Safety was assessed with regards to the rate and type of AEs, clinically significant changes to vital signs and/or physical examination findings, and clinically significant changes in laboratory test results.

1 secondary outcome

Following Blood Phe Levels.
Time frame: Baseline through Final Visit (a Maximum of 30 months) with blood phe samples taken at months 3 and 6 then at 6 month intervals

Results and safety

Results posted to the registry on 16 Nov 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Total Patient Population	111	90

Primary outcome: Tabulation of the Incidence and Frequency of All AEs and SAEs That Occur Throughout the Study.

Time frame: Baseline through Final Visit (a Maximum of 30 months) with AEs collected at month 3 and 6 then at 6 month intervals. Number. Unit: percentage of subjects reporting events

Measure	Total Patient Population n = 111
% of Subjects Reporting Any Adverse Event	83.8
% of Subjects Reporting Related Adverse Events	33.3
% of Subjects Reporting Serious Adverse Events	6.3
% of Subjects Reporting Related Serious AEs	0.9

Population analysed: Percentage of total population who experienced an AE or SAE presented here. For full list of SAEs, and AEs experienced with a frequency of greater than 5%, see the Reported Adverse Event section.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Maximum exposure to study drug was 953 days (2.6 years), with a median duration of 595.0, and a mean (+/- SD) duration of exposure of 658.7 (+/-221.3) days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Total Patient Population	7 of 111 (6.3%)	93 of 111 (83.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 21646032Burton BK, Nowacka M, Hennermann JB, Lipson M, Grange DK, Chakrapani A, Trefz F, Dorenbaum A, Imperiale M, Kim SS, Fernhoff PM. Safety of extended treatment with sapropterin dihydrochloride in patients with phenylketonuria: results of a phase 3b study. Mol Genet Metab. 2011 Aug;103(4):315-22. doi: 10.1016/j.ymgme.2011.03.020. Epub 2011 Mar 31.

Related trials for Phenylketonuria

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
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RecruitingPhase 3
A Study of Sepiapterin in Participants With Phenylketonuria (PKU)
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Recruiting
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RecruitingPhase 3
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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.

14 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 in people with Phenylketonuria, run by BioMarin Pharmaceutical at 14 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 4 inclusion and 14 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 16 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 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 Nov 2012). 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?

Tabulation of the Incidence and Frequency of All AEs and SAEs That Occur Throughout the Study. (time frame: Baseline through Final Visit (a Maximum of 30 months) with AEs collected at month 3 and 6 then at 6 month intervals). 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 NCT00332189, 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 16 Nov 2012.