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

NCT01732471 | Completed Phase 3 Results

• 1 other identifier: EMR 700773_510
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Phenylketonuria

Keywords

EMR 700733_510, Genetic disorder, Phenylketonuria, phenylalanine, Kuvan, sapropterin dihydrochloride

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• Percent Change From Baseline in Blood Phenylalanine Levels at Day 8 in Overall Population

  Baseline, Day 8

• Percent Change From Baseline in Blood Phenylalanine Levels at Day 8 in Sub-population of Responders

  Baseline, Day 8

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) in Overall Safety Population

  Baseline up to Week 11

Study Arms (1)

Kuvan®

EXPERIMENTAL

Drug: Kuvan®

Interventions

Kuvan® DRUG

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.

Also known as: Sapropterin dihydrochloride, 6R-BH4 tetrahydrobiopterin

Kuvan®

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Please contact Merck KGaA Communication Center

Darmstadt, Germany

Location

MeSH Terms

Conditions

Phenylketonurias; Genetic Diseases, Inborn

Interventions

sapropterin

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2012
• First Posted: November 22, 2012
• Study Start: November 1, 2012
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: July 28, 2014
• Results First Posted: July 28, 2014

Record last verified: 2014-07

Locations

DE (1)