PhenylketonuriaPhase 3NCT01732471
Phase 3 Open-label Study to Evaluate the Response and Safety of Kuvan® in Subjects With Phenylketonuria
A Phase 3 study testing Kuvan® in people with Phenylketonuria, run by Merck KGaA, Darmstadt, Germany at 1 site in Germany.
Trial summary
This is an open-label, non-comparative, Phase 3 study to evaluate the degree, frequency of response and safety of Kuvan® (sapropterin dihydrochloride) in subjects aged 4 to 18 years who have phenylketonuria and with elevated blood phenylalanine level of greater than or equal to 450 micromole per liter. Read more about this study
- Who is it for?
- Ages 4 to 18 years
- Conditions the study is for
- Phenylketonuria
- What is being tested?
- Kuvan®
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteGermany
- Study dates
- Nov 2012to Oct 2013
- 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 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Willing and able to provide written informed consent (for children under 18 years old the parent[s]/guardians give informed consent, subjects 14-17 years old give additionally their own written informed consent)
- Age of 4 - 18 years, inclusive
- Confirmed clinical and biochemical hyperphenylalaninemia due to phenylketonuria documented by past medical history with at least 2 blood phenylalanine level greater than or equal to 400 micromole per liter obtained in 2 separate occasions
- Blood phenylalanine level at screening greater than or equal to 450 micromole per liter (mean of two measurements)
- For women of childbearing potential, a negative urine pregnancy test is required at screening and willingness to use a highly effective method of contraception is required while participating in the study
- Subject and/or the parent/guardian willing and able to comply with study procedures
- Subject and/or the parent/guardian willing to continue current diet unchanged during the 8 days response test and to adapt the diet according to phenylalanine therapeutic target range during the 6 week treatment period
Who cannot join
- Subject already assessed for responsiveness to sapropterin dihydrochloride or other tetrahydrobiopterin (BH4)
- Used any investigational agent other than Kuvan® (sapropterin dihydrochloride) within 30 days of screening, or required any investigational agent or vaccine prior to completion of all scheduled study assessments
- Pregnant or breastfeeding, or considering pregnancy
- Concurrent disease or conditions that would interfere with study participation or safety (for example, seizure disorder, asthma or other condition requiring oral or parenteral corticosteroid administration, insulin-dependent diabetes, or organ transplantation recipient)
- Concurrent use of required concomitant treatment with any drug known to inhibit folate synthesis (for example, methotrexate), levodopa, phosphodiesterase type-5 (PDE-5) inhibitors (such as, sildenafil, vardenafil or tadalafil), medications that are known to affect nitric oxide synthesis metabolism or action
- Any conditions, that, in the view of the Principal Investigator renders the subject at high risk for failure to comply with treatment or to complete the study
- Clinical diagnosis of primary BH4 deficiency
- Known hypersensitivity to Kuvan® (sapropterin dihydrochloride) or its excipients or to other approved or non-approved formulation of tetrabiopterin
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase III Non-comparative Open-label Clinical Study to Evaluate the Response to and Safety of Kuvan (Sapropterin Dihydrochloride) After 6 Weeks of Treatment in Patients of 4 to 18 Years of Age With Phenylketonuria Who Have Elevated Blood Phenylalanine Levels
This is an open-label, non-comparative, Phase 3 study to evaluate the degree, frequency of response and safety of Kuvan® (sapropterin dihydrochloride) in subjects aged 4 to 18 years who have phenylketonuria and with elevated blood phenylalanine level of greater than or equal to 450 micromole per liter.
- Conditions
- Phenylketonuria
- Being tested
- Kuvan®
- Keywords
- EMR 700733_510, Genetic disorder, Phenylketonuria, phenylalanine, Kuvan, sapropterin dihydrochloride
- Medical subject headings
- Phenylketonurias, Genetic Diseases, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Kuvan®Drug
Also called Sapropterin dihydrochloride, 6R-BH4 tetrahydrobiopterin
Kuvan® (sapropterin dihydrochloride) will be administered orally at a dose of 20 milligram per kilogram per day (mg/kg/day) once daily for 8 days. If there is 30 percent (%) decrease in blood phenylalanine levels from baseline at the end of Day 8, then treatment will be continued at the same dose for further 6 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Kuvan® | Experimental | Not described Receives: Drug: Kuvan® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Response to Kuvan® (Sapropterin Dihydrochloride) Treatment
Response to Kuvan® (sapropterin dihydrochloride) treatment was defined as a reduction in blood phenylalanine levels of greater than or equal to 30% at Day 8 as compared to baseline.
Measured: Day 8
Secondary outcomes (3)
Percent Change From Baseline in Blood Phenylalanine Levels at Day 8 in Overall Population
Percent change in blood phenylalanine levels after 8-day Kuvan® therapy (response test period) was calculated as (blood phenylalanine level at Day 8 minus blood phenylalanine level at baseline)*100/ blood phenylalanine level at baseline.
Measured: Baseline, Day 8
Percent Change From Baseline in Blood Phenylalanine Levels at Day 8 in Sub-population of Responders
Percent change in blood phenylalanine levels after 8-day Kuvan® therapy (response test period) was calculated as (blood phenylalanine level at Day 8 minus blood phenylalanine level at baseline)*100/ blood phenylalanine level at baseline.
Measured: Baseline, Day 8
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) in Overall Safety Population
An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Measured: Baseline up to Week 11
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2012 (estimated)
- Study startNov 2012
- Primary completionOct 2013
- Study completionOct 2013
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.
- Other trials for PhenylketonuriaStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01732471
- Sponsor's protocol ID
- EMR 700773_510
- Status last verified
- Jul 2014
- First submitted
- 19 Nov 2012
- Last updated
- 28 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Non-comparative Open-label Clinical Study to Evaluate the Response to and Safety of Kuvan (Sapropterin Dihydrochloride) After 6 Weeks of Treatment in Patients of 4 to 18 Years of Age With Phenylketonuria Who Have Elevated Blood Phenylalanine Levels
- ClinicalTrials.gov ID
- NCT01732471
- Acronym / sponsor ID
- EMR 700773_510
- Conditions
- Phenylketonuria
- Keywords
- EMR 700733_510, Genetic disorder, Phenylketonuria, phenylalanine, Kuvan, sapropterin dihydrochloride
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- Nov 2012
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 22 Nov 2012 (estimated)
- Results
- Posted 28 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, non-comparative, Phase 3 study to evaluate the degree, frequency of response and safety of Kuvan® (sapropterin dihydrochloride) in subjects aged 4 to 18 years who have phenylketonuria and with elevated blood phenylalanine level of greater than or equal to 450 micromole per liter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Kuvan® | Experimental | Drug: Kuvan® |
Who may qualify
- Ages
- 4 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Willing and able to provide written informed consent (for children under 18 years old the parent[s]/guardians give informed consent, subjects 14-17 years old give additionally their own written informed consent)
- Age of 4 - 18 years, inclusive
- Confirmed clinical and biochemical hyperphenylalaninemia due to phenylketonuria documented by past medical history with at least 2 blood phenylalanine level greater than or equal to 400 micromole per liter obtained in 2 separate occasions
- Blood phenylalanine level at screening greater than or equal to 450 micromole per liter (mean of two measurements)
- For women of childbearing potential, a negative urine pregnancy test is required at screening and willingness to use a highly effective method of contraception is required while participating in the study
Key exclusion criteria (8 listed)
- Subject already assessed for responsiveness to sapropterin dihydrochloride or other tetrahydrobiopterin (BH4)
- Used any investigational agent other than Kuvan® (sapropterin dihydrochloride) within 30 days of screening, or required any investigational agent or vaccine prior to completion of all scheduled study assessments
- Pregnant or breastfeeding, or considering pregnancy
- Concurrent disease or conditions that would interfere with study participation or safety (for example, seizure disorder, asthma or other condition requiring oral or parenteral corticosteroid administration, insulin-dependent diabetes, or organ transplantation recipient)
- Concurrent use of required concomitant treatment with any drug known to inhibit folate synthesis (for example, methotrexate), levodopa, phosphodiesterase type-5 (PDE-5) inhibitors (such as, sildenafil, vardenafil or tadalafil), medications that are known to affect nitric oxide synthesis metabolism or action
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 |
|---|---|---|
| Kuvan®Also: Sapropterin dihydrochloride, 6R-BH4 tetrahydrobiopterinKuvan® (sapropterin dihydrochloride) will be administered orally at a dose of 20 milligram per kilogram per day (mg/kg/day) once daily for 8 days. If there is 30 percent (%) decrease in blood phenylalanine levels from baseline at the end of Day 8, then treatment will be continued at the same dose for further 6 weeks. | Drug | Kuvan® |
Primary outcome
Percentage of Participants With Response to Kuvan® (Sapropterin Dihydrochloride) Treatment
Time frame: Day 8
Response to Kuvan® (sapropterin dihydrochloride) treatment was defined as a reduction in blood phenylalanine levels of greater than or equal to 30% at Day 8 as compared to baseline.
3 secondary outcomes
Percent Change From Baseline in Blood Phenylalanine Levels at Day 8 in Overall Population
Time frame: Baseline, Day 8
Percent Change From Baseline in Blood Phenylalanine Levels at Day 8 in Sub-population of Responders
Time frame: Baseline, Day 8
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) in Overall Safety Population
Time frame: Baseline up to Week 11
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Kuvan® in people with Phenylketonuria, run by Merck KGaA, Darmstadt, Germany at 1 site in Germany.
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 7 inclusion and 8 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 28 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 1 site in Germany. 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 28 Jul 2014). 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?
Percentage of Participants With Response to Kuvan® (Sapropterin Dihydrochloride) Treatment (time frame: Day 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Jul 2014.