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

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ClinicalTrials.gov Identifier: NCT01732471
Recruitment Status : Completed
First Posted : November 22, 2012
Results First Posted : July 28, 2014
Last Update Posted : July 28, 2014
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Phenylketonuria
Intervention Drug: Kuvan®
Enrollment 90
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Kuvan®
Hide Arm/Group Description Kuvan® (sapropterin dihydrochloride) was 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 was continued at the same dose for further 6 weeks.
Period Title: Overall Study
Started 90
Completed 89
Not Completed 1
Reason Not Completed
Withdrawal by Subject             1
Arm/Group Title Kuvan®
Hide Arm/Group Description Kuvan® (sapropterin dihydrochloride) was administered orally at a dose of 20 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 was continued at the same dose for further 6 weeks.
Overall Number of Baseline Participants 90
Hide Baseline Analysis Population Description
Intention to Treat (ITT) population included all participants who had efficacy assessment result from at least 1 visit except for the inclusion visit.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 90 participants
9.59  (4.09)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 90 participants
Female
41
  45.6%
Male
49
  54.4%
1.Primary Outcome
Title Percentage of Participants With Response to Kuvan® (Sapropterin Dihydrochloride) Treatment
Hide Description 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.
Time Frame Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
Overall (ITT) population included all participants who had efficacy assessment result from at least 1 visit except for the inclusion visit.
Arm/Group Title Kuvan®
Hide Arm/Group Description:
Kuvan® (sapropterin dihydrochloride) was administered orally at a dose of 20 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 was continued at the same dose for further 6 weeks.
Overall Number of Participants Analyzed 90
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
33.3
(23.7 to 44.1)
2.Secondary Outcome
Title Percent Change From Baseline in Blood Phenylalanine Levels at Day 8 in Overall Population
Hide Description 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.
Time Frame Baseline, Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
Overall (ITT) population included all participants who had efficacy assessment result from at least 1 visit except for the inclusion visit.
Arm/Group Title Kuvan®
Hide Arm/Group Description:
Kuvan® (sapropterin dihydrochloride) was administered orally at a dose of 20 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 was continued at the same dose for further 6 weeks.
Overall Number of Participants Analyzed 90
Mean (Standard Deviation)
Unit of Measure: percent change
-14.14  (28.35)
3.Secondary Outcome
Title Percent Change From Baseline in Blood Phenylalanine Levels at Day 8 in Sub-population of Responders
Hide Description 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.
Time Frame Baseline, Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
Sub-population of responders included participants with reduction in blood phenylalanine levels of greater than or equal to 30% at Day 8 as compared to baseline.
Arm/Group Title Kuvan®
Hide Arm/Group Description:
Kuvan® (sapropterin dihydrochloride) was administered orally at a dose of 20 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 was continued at the same dose for further 6 weeks.
Overall Number of Participants Analyzed 30
Mean (Standard Deviation)
Unit of Measure: percent change
-44.25  (15.13)
4.Secondary Outcome
Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) in Overall Safety Population
Hide Description 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.
Time Frame Baseline up to Week 11
Hide Outcome Measure Data
Hide Analysis Population Description
Overall safety population included all participants who received at least 1 dose of investigational medicinal product.
Arm/Group Title Kuvan®
Hide Arm/Group Description:
Kuvan® (sapropterin dihydrochloride) was administered orally at a dose of 20 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 was continued at the same dose for further 6 weeks.
Overall Number of Participants Analyzed 90
Measure Type: Number
Unit of Measure: participants
AEs 24
SAEs 1
Time Frame Baseline up to Week 11
Adverse Event Reporting Description An AE is any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE is an AE resulting in any of following outcomes:death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
 
Arm/Group Title Kuvan®
Hide Arm/Group Description Kuvan® (sapropterin dihydrochloride) was administered orally at a dose of 20 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 was continued at the same dose for further 6 weeks.
All-Cause Mortality
Kuvan®
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Kuvan®
Affected / at Risk (%)
Total   1/90 (1.11%) 
Injury, poisoning and procedural complications   
Upper limb fracture * 1  1/90 (1.11%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (16.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Kuvan®
Affected / at Risk (%)
Total   23/90 (25.56%) 
Blood and lymphatic system disorders   
Anaemia * 1  1/90 (1.11%) 
Eye disorders   
Myopia * 1  1/90 (1.11%) 
Gastrointestinal disorders   
Diarrhoea * 1  1/90 (1.11%) 
Faeces pale * 1  1/90 (1.11%) 
Gastroduodenitis * 1  1/90 (1.11%) 
Infections and infestations   
Oral herpes * 1  1/90 (1.11%) 
Injury, poisoning and procedural complications   
Heat stroke * 1  1/90 (1.11%) 
Metabolism and nutrition disorders   
Iodine deficiency * 1  1/90 (1.11%) 
Renal and urinary disorders   
Haematuria * 1  1/90 (1.11%) 
Leukocyturia * 1  1/90 (1.11%) 
Phenylketonuria * 1  2/90 (2.22%) 
Reproductive system and breast disorders   
Dysmenorrhoea * 1  1/90 (1.11%) 
Genital labial adhesions * 1  1/90 (1.11%) 
Respiratory, thoracic and mediastinal disorders   
Bronchitis * 1  1/90 (1.11%) 
Respiratory tract infection * 1  2/90 (2.22%) 
Respiratory tract infection viral * 1  9/90 (10.00%) 
Skin and subcutaneous tissue disorders   
Skin odour abnormal * 1  1/90 (1.11%) 
Vascular disorders   
Retinal vascular disorder * 1  2/90 (2.22%) 
Syncope * 1  1/90 (1.11%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (16.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
All written or oral publications and/or information related to Study and/or results of Study should be submitted at first in writing to Sponsor at least 30 working days for publication and 15 working days for brief review, abstract before planned date of submission. If Sponsor is filing a patent application on Study results, Sponsor can delay its authorization for publication/communication of Study results to Investigator and/or Research Centre until date of international registration of patent.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Merck KGaA Communication Center
Organization: Merck Serono, a division of Merck KGaA
Phone: +49-6151-72-5200
EMail: service@merckgroup.com
Layout table for additonal information
Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT01732471    
Other Study ID Numbers: EMR 700773_510
First Submitted: November 19, 2012
First Posted: November 22, 2012
Results First Submitted: June 24, 2014
Results First Posted: July 28, 2014
Last Update Posted: July 28, 2014