Clinical Trial Results:
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
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Summary
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EudraCT number |
2015-001650-15 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
04 Oct 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
23 May 2016
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First version publication date |
05 Aug 2015
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
EMR 700773_510
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01732471 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Merck KGaA
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Sponsor organisation address |
Frankfurter Strasse 250, Darmstadt, Germany, 64293
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Public contact |
Communication Centre Merck KGaA, Merck KGaA, +49 6151725200, service@merckgroup.com
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Scientific contact |
Communication Centre Merck KGaA, Merck KGaA, +49 6151725200, service@merckgroup.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
04 Oct 2013
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
04 Oct 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
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.
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Protection of trial subjects |
Subject protection was ensured by following high medical and ethical standards in accordance with the principles laid down in the Declaration of Helsinki, and that are consistent with Good Clinical Practice and applicable regulations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Nov 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Ukraine: 10
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Country: Number of subjects enrolled |
Russian Federation: 80
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Worldwide total number of subjects |
90
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
50
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Adolescents (12-17 years) |
40
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||
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Pre-assignment
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Screening details |
One hundred eight subjects were screened. The trial included 90 subjects with Phenylketonuria. Thirty subjects responded to treatment and continued participation in the trial. | ||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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Kuvan® | ||||||||||
Arm 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. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Sapropterin Dihydrocholoride
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Investigational medicinal product code |
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Other name |
Kuvan
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Pharmaceutical forms |
Soluble tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Sapropterin dihydrochloride was administered orally at a dose of 20 mg/kg/day once daily for 8 days.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
- | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Kuvan®
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Reporting 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. | ||
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End point title |
Percentage of subjects with response to Kuvan® (sapropterin dihydrochloride) treatment [1] | ||||||||
End point 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. Overall (ITT) population included all participants who had efficacy assessment result from at least 1 visit except for the inclusion visit. Overall (ITT) population included all subjects who had efficacy assessment result from at least 1 visit except for the inclusion visit
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End point type |
Primary
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End point timeframe |
Day 8
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be represented in the endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percent change from Baseline in blood phenylalanine levels at Day 8 in overall population | ||||||||
End point 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. Overall (ITT) population included all subjects who had efficacy assessment result from at least 1 visit except for the inclusion visit.
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End point type |
Secondary
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End point timeframe |
Baseline, Day 8
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| No statistical analyses for this end point | |||||||||
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End point title |
Percent change from Baseline in blood phenylalanine levels at Day 8 in sub-population of responders | ||||||||
End point 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. Sub-population of responders included subjects with reduction in blood phenylalanine levels of greater than or equal to 30% at Day 8 as compared to baseline.
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End point type |
Secondary
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End point timeframe |
Baseline, Day 8
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of subjects with adverse events (AEs) and serious adverse events (SAEs) in overall safety population | ||||||||||||
End point 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. Overall safety population included all subjects who received at least 1 dose of investigational medicinal product.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 11
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to Week 11
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Adverse event reporting additional 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.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
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Reporting groups
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Reporting group title |
Kuvan®
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Reporting 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
