Trial Outcomes & Findings for Phase 3 Open-label Study to Evaluate the Response and Safety of Kuvan® in Subjects With Phenylketonuria (NCT NCT01732471)
NCT ID: NCT01732471
Last Updated: 2014-07-28
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
90 participants
Primary outcome timeframe
Day 8
Results posted on
2014-07-28
Participant Flow
Participant milestones
| Measure |
Kuvan®
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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|---|---|
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Overall Study
STARTED
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90
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Overall Study
COMPLETED
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89
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Overall Study
NOT COMPLETED
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1
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Reasons for withdrawal
| Measure |
Kuvan®
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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Overall Study
Withdrawal by Subject
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1
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Baseline Characteristics
Phase 3 Open-label Study to Evaluate the Response and Safety of Kuvan® in Subjects With Phenylketonuria
Baseline characteristics by cohort
| Measure |
Kuvan®
n=90 Participants
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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Age, Continuous
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9.59 years
STANDARD_DEVIATION 4.09 • n=5 Participants
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Sex: Female, Male
Female
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41 Participants
n=5 Participants
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Sex: Female, Male
Male
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49 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Day 8Population: Overall (ITT) population included all participants who had efficacy assessment result from at least 1 visit except for the inclusion visit.
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.
Outcome measures
| Measure |
Kuvan®
n=90 Participants
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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Percentage of Participants With Response to Kuvan® (Sapropterin Dihydrochloride) Treatment
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33.3 percentage of participants
Interval 23.7 to 44.1
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SECONDARY outcome
Timeframe: Baseline, Day 8Population: Overall (ITT) population included all participants who had efficacy assessment result from at least 1 visit except for the inclusion visit.
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.
Outcome measures
| Measure |
Kuvan®
n=90 Participants
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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Percent Change From Baseline in Blood Phenylalanine Levels at Day 8 in Overall Population
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-14.14 percent change
Standard Deviation 28.35
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SECONDARY outcome
Timeframe: Baseline, Day 8Population: 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.
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.
Outcome measures
| Measure |
Kuvan®
n=30 Participants
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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|---|---|
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Percent Change From Baseline in Blood Phenylalanine Levels at Day 8 in Sub-population of Responders
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-44.25 percent change
Standard Deviation 15.13
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SECONDARY outcome
Timeframe: Baseline up to Week 11Population: Overall safety population included all participants who received at least 1 dose of investigational medicinal product.
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.
Outcome measures
| Measure |
Kuvan®
n=90 Participants
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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Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) in Overall Safety Population
SAEs
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1 participants
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Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) in Overall Safety Population
AEs
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24 participants
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Adverse Events
Kuvan®
Serious events: 1 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Kuvan®
n=90 participants at risk
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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Injury, poisoning and procedural complications
Upper limb fracture
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1.1%
1/90 • Baseline up to Week 11
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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Other adverse events
| Measure |
Kuvan®
n=90 participants at risk
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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Blood and lymphatic system disorders
Anaemia
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1.1%
1/90 • Baseline up to Week 11
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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Respiratory, thoracic and mediastinal disorders
Bronchitis
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1.1%
1/90 • Baseline up to Week 11
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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Gastrointestinal disorders
Diarrhoea
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1.1%
1/90 • Baseline up to Week 11
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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Reproductive system and breast disorders
Dysmenorrhoea
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1.1%
1/90 • Baseline up to Week 11
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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Gastrointestinal disorders
Faeces pale
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1.1%
1/90 • Baseline up to Week 11
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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Gastrointestinal disorders
Gastroduodenitis
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1.1%
1/90 • Baseline up to Week 11
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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Reproductive system and breast disorders
Genital labial adhesions
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1.1%
1/90 • Baseline up to Week 11
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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Renal and urinary disorders
Haematuria
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1.1%
1/90 • Baseline up to Week 11
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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Injury, poisoning and procedural complications
Heat stroke
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1.1%
1/90 • Baseline up to Week 11
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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Metabolism and nutrition disorders
Iodine deficiency
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1.1%
1/90 • Baseline up to Week 11
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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Renal and urinary disorders
Leukocyturia
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1.1%
1/90 • Baseline up to Week 11
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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Eye disorders
Myopia
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1.1%
1/90 • Baseline up to Week 11
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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Infections and infestations
Oral herpes
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1.1%
1/90 • Baseline up to Week 11
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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Renal and urinary disorders
Phenylketonuria
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2.2%
2/90 • Baseline up to Week 11
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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Respiratory, thoracic and mediastinal disorders
Respiratory tract infection
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2.2%
2/90 • Baseline up to Week 11
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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Respiratory, thoracic and mediastinal disorders
Respiratory tract infection viral
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10.0%
9/90 • Baseline up to Week 11
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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Vascular disorders
Retinal vascular disorder
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2.2%
2/90 • Baseline up to Week 11
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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Skin and subcutaneous tissue disorders
Skin odour abnormal
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1.1%
1/90 • Baseline up to Week 11
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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Vascular disorders
Syncope
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1.1%
1/90 • Baseline up to Week 11
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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Additional Information
Merck KGaA Communication Center
Merck Serono, a division of Merck KGaA
Phone: +49-6151-72-5200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER