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Phase 3 Open-label Study to Evaluate the Response and Safety of Kuvan® in Subjects With Phenylketonuria
This study has been completed.
Sponsor:
Merck KGaA
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01732471
First received: November 19, 2012
Last updated: July 25, 2014
Last verified: July 2014
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
| Phenylketonuria | Drug: Kuvan® | Phase 3 |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
MedlinePlus related topics:
Phenylketonuria
Genetic and Rare Diseases Information Center resources:
Phenylketonuria
Inborn Amino Acid Metabolism Disorder
U.S. FDA Resources
Further study details as provided by Merck KGaA:
Primary Outcome Measures:
- 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.
Secondary Outcome Measures:
- Percent Change From Baseline in Blood Phenylalanine Levels at Day 8 in Overall Population [ Time Frame: Baseline, Day 8 ]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.
- Percent Change From Baseline in Blood Phenylalanine Levels at Day 8 in Sub-population of Responders [ Time Frame: Baseline, Day 8 ]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.
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) in Overall Safety Population [ Time Frame: Baseline up to Week 11 ]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.
| Enrollment: | 90 |
| Study Start Date: | November 2012 |
| Study Completion Date: | October 2013 |
| Primary Completion Date: | October 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Kuvan® |
Drug: Kuvan®
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.
Other Names:
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Eligibility| Ages Eligible for Study: | 4 Years to 18 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01732471
Please refer to this study by its ClinicalTrials.gov identifier: NCT01732471
Locations
| Germany | |
| Please contact Merck KGaA Communication Center | |
| Darmstadt, Germany | |
Sponsors and Collaborators
Merck KGaA
More Information
| Responsible Party: | Merck KGaA |
| ClinicalTrials.gov Identifier: | NCT01732471 History of Changes |
| Other Study ID Numbers: |
EMR 700773_510 |
| Study First Received: | November 19, 2012 |
| Results First Received: | June 24, 2014 |
| Last Updated: | July 25, 2014 |
Keywords provided by Merck KGaA:
|
EMR 700733_510, Genetic disorder, Phenylketonuria, phenylalanine, Kuvan, sapropterin dihydrochloride |
Additional relevant MeSH terms:
|
Phenylketonurias Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Amino Acid Metabolism, Inborn Errors Metabolism, Inborn Errors |
Genetic Diseases, Inborn Metabolic Diseases Verapamil Anti-Arrhythmia Agents Calcium Channel Blockers Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Vasodilator Agents |
ClinicalTrials.gov processed this record on July 21, 2017