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Safety and Therapeutic Effects of Sapropterin Dihydrochloride on Neuropsychiatric Symptoms in Phenylketonuria (PKU) Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT01114737
First received: April 27, 2010
Last updated: December 24, 2015
Last verified: December 2015
Results First Received: August 19, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Phenylketonuria
Interventions: Drug: Sapropterin dihydrochloride
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Placebo Placebo: Placebo (tablet without active ingredient) is dosed once/day for the first 13 weeks of the study(double-blinded randomized treatment period); then treated with sapropterin dihydrochloride 20 mg/kg/day for an additional 13 weeks (open label treatment period).
6R-BH4 20 mg/kg/Day Sapropterin dihydrochloride: A dose of 20 mg/kg/day will be administered. Route of administration is oral (intact). Patient will be treated for 26 weeks, the first 13 weeks were double-blinded randomized treatment period, the second 13 weeks open label treatment period

Participant Flow for 2 periods

Period 1:   Randomized Treatment Period
    Placebo   6R-BH4 20 mg/kg/Day
STARTED   108   98 
COMPLETED   105   97 
NOT COMPLETED   3   1 
Withdrawal by Subject                1                0 
Lost to Follow-up                1                1 
Pregnancy                1                0 

Period 2:   Open-Label Treatment Period
    Placebo   6R-BH4 20 mg/kg/Day
STARTED   105 [1]   97 [2] 
COMPLETED   100   95 
NOT COMPLETED   5   2 
Withdrawal by Subject                1                1 
Lost to Follow-up                3                1 
Difficult Personal Events                1                0 
[1] One subject did not receive a single dose of the study drug
[2] Two subjects did not receive a single dose of the study drug



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo Placebo: Placebo (tablet without active ingredient) is dosed once/day for the first 13 weeks of the study(double-blinded randomized treatment period); then treated with sapropterin dihydrochloride 20 mg/kg/day for an additional 13 weeks (open label treatment period).
6R-BH4 20 mg/kg/Day Sapropterin dihydrochloride: A dose of 20 mg/kg/day will be administered. Route of administration is oral (intact). Patient will be treated for 26 weeks, the first 13 weeks were double-blinded randomized treatment period, the second 13 weeks open label treatment period
Total Total of all reporting groups

Baseline Measures
   Placebo   6R-BH4 20 mg/kg/Day   Total 
Overall Participants Analyzed 
[Units: Participants]
 108   98   206 
Age 
[Units: Years]
Mean (Standard Deviation)
 22.5  (10.42)   23.6  (12.69)   23.1  (11.54) 
Age, Customized 
[Units: Participants]
     
<18 years   43   43   86 
>=18 years   65   55   120 
Gender 
[Units: Participants]
     
Female   54   41   95 
Male   54   57   111 
Ethnicity (NIH/OMB) 
[Units: Participants]
     
Hispanic or Latino   3   5   8 
Not Hispanic or Latino   105   93   198 
Unknown or Not Reported   0   0   0 
Race/Ethnicity, Customized 
[Units: Participants]
     
American Indian or Alaska Native   1   0   1 
Asian   1   1   2 
Native Hawaiian or Other Pacific Islander   0   0   0 
Black or African American   2   0   2 
White   102   96   198 
Other   2   1   3 
Region of Enrollment 
[Units: Participants]
     
Canada   38   31   69 
United States   70   67   137 


  Outcome Measures
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1.  Primary:   Change in Attention-Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS) / Adult ADHD Self-Report Scale (ASRS) Total Score From Baseline to Week 13   [ Time Frame: Baseline to Week 13 ]

2.  Primary:   Number of Participants With a Score of 1 or 2 in Global Function Evaluation (CGI-I) From Baseline to Week 13.   [ Time Frame: 13 weeks ]

3.  Secondary:   Change in Hamilton Anxiety Rating Scale (HAM-A) Score From Baseline to Week 13   [ Time Frame: Baseline to Week 13 ]

4.  Secondary:   Change in Hamilton Depression Rating Scale (HAM-D) Score From Baseline to Week 13   [ Time Frame: Baseline to Week 13 ]

5.  Secondary:   Change in Clinical Global Impression-Severity (CGI-S) From Baseline to Week 13   [ Time Frame: Baseline to Week 13 ]

6.  Secondary:   Change in Behavior Rating Inventory of Executive Function (BRIEF) Adult-Global Executive Composite (GEC) T Score From Baseline to Week 13   [ Time Frame: Baseline to Week 13 ]

7.  Secondary:   Change in Behavior Rating Inventory of Executive Function (BRIEF) Parent-Global Executive Composite (GEC) T Score From Baseline to Week 13   [ Time Frame: Baseline to Week 13 ]

8.  Secondary:   Change in Attention-Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS) / Adult ADHD Self-Report Scale (ASRS) Total Score From Week 13 to Week 26   [ Time Frame: Week 13 to Week 26 ]

9.  Secondary:   Change in Hamilton Anxiety Rating Scale (HAM-A) Score From Week 13 to Week 26   [ Time Frame: Week 13 to Week 26 ]

10.  Secondary:   Change in Hamilton Depression Rating Scale (HAM-D) Score From Week 13 to Week 26   [ Time Frame: Week 13 to Week 26 ]

11.  Secondary:   Change in Clinical Global Impression-Severity (CGI-S) From Week 13 to Week 26   [ Time Frame: Week 13 to Week 26 ]

12.  Secondary:   Change in Behavior Rating Inventory of Executive Function (BRIEF) Adult-Global Executive Composite (GEC) T Score From Week 13 to Week 26   [ Time Frame: Week 13 to Week 26 ]

13.  Secondary:   Change in Behavior Rating Inventory of Executive Function (BRIEF) Parent-Global Executive Composite (GEC) T Score From Week 13 to Week 26   [ Time Frame: Week 13 to Week 26 ]

14.  Secondary:   Change in Attention-Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS) / Adult ADHD Self-Report Scale (ASRS) Total Score From Baseline to Week 26   [ Time Frame: Baseline to Week 26 ]

15.  Secondary:   Change in Hamilton Anxiety Rating Scale (HAM-A) Score From Baseline to Week 26   [ Time Frame: Baseline to Week 26 ]

16.  Secondary:   Change in Hamilton Rating Scale For Depression (HAM-D) Score From Baseline to Week 26   [ Time Frame: Baseline to Week 26 ]

17.  Secondary:   Change in Clinical Global Impression-Severity (CGI-S) From Baseline to Week 26   [ Time Frame: Baseline to Week 26 ]

18.  Secondary:   Change in Behavior Rating Inventory of Executive Function (BRIEF) Adult-Global Executive Composite (GEC) T Score From Baseline to Week 26   [ Time Frame: Baseline to Week 26 ]

19.  Secondary:   Change in Behavior Rating Inventory of Executive Function (BRIEF) Parent-Global Executive Composite (GEC) T Score From Baseline to Week 26   [ Time Frame: Baseline to Week 26 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
As specified in the SAP, no multiplicity adjustment was made in the analyses; therefore, the family-wise error rate was not controlled in this study


  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Medical Information Services
Organization: BioMarin Pharmaceutical Inc.
phone: 1-800-983-4587
e-mail: medinfo@bmrn.com



Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT01114737     History of Changes
Other Study ID Numbers: PKU-016
PKU Ascend ( Other Identifier: BioMarin Pharmaceutical )
Study First Received: April 27, 2010
Results First Received: August 19, 2015
Last Updated: December 24, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada