Phase 3 Open-label Study to Evaluate the Response and Safety of Kuvan® in Subjects With Phenylketonuria

Phenylketonuria Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01732471
• Other study ID #: EMR 700773_510
• Status: Completed
• Phase: Phase 3
• First received: November 19, 2012
• Last updated: July 25, 2014
• Start date: November 2012
• Est. completion date: October 2013

Study information

• Verified date: July 2014
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Russia: Ethics Council at the Ministry of Health of the Russian FederationRussia: Ministry of Health of the Russian FederationRussia: Local Ethics CommitteesUkraine: Local Ethics CommitteeUkraine: Ministry of Health of UkraineUkraine: State Expert Center of Ministry of Ukraine
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 4 Years to 18 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Phenylketonuria
• Phenylketonurias

Intervention

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.

Locations

Country	Name	City	State
Germany	Please contact Merck KGaA Communication Center	Darmstadt

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 8	No
Secondary	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.	Baseline, Day 8	No
Secondary	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.	Baseline, Day 8	No
Secondary	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.	Baseline up to Week 11	Yes