A Phase 4 interventional study of Kuvan® in Phenylketonuria, sponsored by Merck KGaA, Darmstadt, Germany. Completed at 1 site in Norway. Open to participants aged 4 Years and older. Per ClinicalTrials.gov, last updated 2014-02-27.
Sponsored by Merck KGaA, Darmstadt, Germany · Phase 4, Interventional, and Treatment
The primary objective of the study is to evaluate the proportion of responders (that is, greater than or equal to [>=] 30 percent reduction from Baseline in blood phenylalanine [Phe] level) to treatment with Kuvan® (sapropterin dihydrochloride) 20 milligram per kilogram per day (mg/kg/day) for 28 days.
187 studies on the registry are indexed under Phenylketonurias; 38 are open to participants now.
This study's enrollment of 59 is above the median of 25 across 117 interventional studies indexed under Phenylketonurias.
Browse Phenylketonurias studies →Merck KGaA, Darmstadt, Germany is the lead sponsor of 275 studies on the registry; none are open to participants now.
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Exclusion Criteria:
Drug: Kuvan®
Kuvan® (sapropterin dihydrochloride) oral solution 20 milligram per kilogram (mg/kg) will be given once daily for 28 +/- 1 days.
Also known as: Sapropterin dihydrochloride
Percentage of Participants With at Least 30 Percent Reduction From Baseline in Blood Phenylalanine (Phe) Level
Response to treatment was defined as 30 percent reduction from Baseline in blood phenylalanine (Phe) Level during the 28 +/- 1 days.
Time frame: Baseline up to Day 28 +/- 1
Number of Participants With Adverse Events (AEs), Treatment Emergent Adverse Events, Treatment Related Adverse Events and AEs Leading to Withdrawal
An Adverse Event (AE) is defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to Baseline during a clinical study with an investigational medicinal product (IMP), regardless of causal relationship and even if no IMP has been administered.
Time frame: Baseline up to Day 42 +/- 3
Percentage of Early-, Late-, Partial-Responders and Non-responders to Treatment With Kuvan®
Early responders defined as percentage of participants with at least 30 percent reduction in Phe levels within the first seven days of treatment. Late responders defined as percentage of participants with less than 30 percent reduction in Phe levels within first seven days of treatment, but at least 30 percent reduction in Phe levels within 28 +/- 1 days of treatment. Partial responders defined as percentage of participants with Phe levels reduction between 10 and 30 percent at any blood measurement within the 28 +/- 1 days of treatment. Non-responders defined as percentage of participants with a Phe level reduction of less than 10 percent within 28 +/- 1 days.
Time frame: Baseline up to Day 28 +/- 1
Percentage of Participants With Greater Than or Equal to (>=) 30 Percent, 20 to 30 Percent, 10 to 20 Percent and Less Than (<) 10 Percent Reduction in Blood Phe Levels According to Phenylketonuria (PKU) Phenotypes
The Phenylketonuria (PKU) is categorized as per phenotype into classical PKU: (blood Phe levels greater than \[\>\] 1200 micromole per liter \[mcmol/l\]), mild PKU (blood Phe levels 600 to 1200 mcmol/l), mild Hyperphenylalaninaemia (HPA) (blood Phe levels 300 to 600 mcmol/l).
Time frame: Baseline up to Day 28 +/- 1
Percentage of Early-, Late- and Partial-Responders According to Phenotype
The PKU is categorized as per phenotype into classical PKU: (blood Phe levels \> 1200 mcmol/l), mild PKU (blood Phe levels 600 to 1200 mcmol/l), mild HPA (blood Phe levels 300 to 600 mcmol/l). Early responders defined as percentage of participants with at least 30 percent reduction in Phe levels within the first seven days of treatment. Late responders defined as percentage of participants with less than 30 percent reduction in Phe levels within first seven days of treatment, but at least 30 percent reduction in Phe levels within 28 +/- 1 days of treatment. Partial responders defined as percentage of participants with Phe levels reduction between 10 and 30 percent at any blood measurement within the 28 +/- 1 days of treatment.
Time frame: Baseline up to Day 28 +/- 1
Mean Change From Baseline in Blood Phenylalanine-to-tyrosine Ratio
Phenylalanine-to-tyrosine ratio is the best indicator of dopamine availability in PKU. The change in blood phenylalanine-to-tyrosine ratio at Day 28 was calculated as blood phenylalanine-to-tyrosine ratio at Day 28 minus blood phenylalanine-to-tyrosine ratio at Baseline.
Time frame: Baseline, Day 28
| Milestone | Kuvan® |
|---|---|
| Started | 59 |
| Completed | 58 |
| Not completed | 1 |
| Withdrew: Adverse event | 1 |
Response to treatment was defined as 30 percent reduction from Baseline in blood phenylalanine (Phe) Level during the 28 +/- 1 days.
| Percentage of participants | Kuvan® |
|---|---|
| Percentage of Participants With at Least 30 Percent Reduction From Baseline in Blood Phenylalanine (Phe) Level | 75 (62 to 85) |
An Adverse Event (AE) is defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to Baseline during a clinical study with an investigational medicinal product (IMP), regardless of causal relationship and even if no IMP has been administered.
| Participants | Kuvan® |
|---|---|
| AEs | 58 |
| Treatment Emergent AEs | 57 |
| Treatment Related AEs | 36 |
| AEs leading to withdrawal | 1 |
Early responders defined as percentage of participants with at least 30 percent reduction in Phe levels within the first seven days of treatment. Late responders defined as percentage of participants with less than 30 percent reduction in Phe levels within first seven days of treatment, but at least 30 percent reduction in Phe levels within 28 +/- 1 days of treatment. Partial responders defined as percentage of participants with Phe levels reduction between 10 and 30 percent at any blood measurement within the 28 +/- 1 days of treatment. Non-responders defined as percentage of participants with a Phe level reduction of less than 10 percent within 28 +/- 1 days.
| Percentage of participants | Kuvan® |
|---|---|
| Early Responders | 64.4 (50.9 to 76.4) |
| Late Responders | 10.2 (3.8 to 20.8) |
| Partial Responders | 25.4 (15.0 to 38.4) |
| Non-responders | 0 (0 to 0) |
The Phenylketonuria (PKU) is categorized as per phenotype into classical PKU: (blood Phe levels greater than \[\>\] 1200 micromole per liter \[mcmol/l\]), mild PKU (blood Phe levels 600 to 1200 mcmol/l), mild Hyperphenylalaninaemia (HPA) (blood Phe levels 300 to 600 mcmol/l).
| Percentage of participants | Kuvan® |
|---|---|
| Mild HPA: >= 30 percent (n=7) | 57 |
| Mild HPA: 20 to 30 percent (n=7) | 29 ± 24.9 |
| Mild HPA: 10 to 20 percent (n=7) | 0 ± 25.4 |
| Mild HPA: < 10 percent (n=7) | 14 ± 33.4 |
| Mild PKU: >= 30 percent (n=26) | 69 ± 96.2 |
| Mild PKU: 20 to 30 percent (n=26) | 8 ± 64.9 |
| Mild PKU: 10 to 20 percent (n=26) | 4 ± 60.8 |
| Mild PKU: < 10 percent (n=26) | 19 ± 69.3 |
| Classical PKU: >= 30 percent (n=22) | 45 ± 83.8 |
| Classical PKU: 20 to 30 percent (n=22) | 0 |
| Classical PKU: 10 to 20 percent (n=22) | 23 |
| Classical PKU: < 10 percent (n=22) | 32 |
The PKU is categorized as per phenotype into classical PKU: (blood Phe levels \> 1200 mcmol/l), mild PKU (blood Phe levels 600 to 1200 mcmol/l), mild HPA (blood Phe levels 300 to 600 mcmol/l). Early responders defined as percentage of participants with at least 30 percent reduction in Phe levels within the first seven days of treatment. Late responders defined as percentage of participants with less than 30 percent reduction in Phe levels within first seven days of treatment, but at least 30 percent reduction in Phe levels within 28 +/- 1 days of treatment. Partial responders defined as percentage of participants with Phe levels reduction between 10 and 30 percent at any blood measurement within the 28 +/- 1 days of treatment.
| Percentage of participants | Kuvan® |
|---|---|
| Mild HPA: Early Responders (n=7) | 86 |
| Mild HPA: Late Responders (n=7) | 0 |
| Mild HPA: Partial Responders (n=7) | 14 |
| Mild PKU: Early Responders (n=26) | 85 |
| Mild PKU: Late Responders (n=26) | 4 |
| Mild PKU: Partial Responders (n=26) | 12 |
| Classical PKU: Early Responders (n=23) | 39 |
| Classical PKU: Late Responders (n=23) | 17 |
| Classical PKU: Partial Responders (n=23) | 43 |
Phenylalanine-to-tyrosine ratio is the best indicator of dopamine availability in PKU. The change in blood phenylalanine-to-tyrosine ratio at Day 28 was calculated as blood phenylalanine-to-tyrosine ratio at Day 28 minus blood phenylalanine-to-tyrosine ratio at Baseline.
| Ratio | Kuvan® |
|---|---|
| Baseline (n=59) | 10.978 ± 5.978 |
| Change at Day 28 (n=58) | -2.136 ± 3.948 |
Collected over Baseline up to Day 42 +/- 3. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Kuvan® | — | 0/59 (0%) | 58/59 (98.3%) |
| Event | Kuvan® |
|---|---|
| HeadacheNervous system disorders | 25/59 |
| Amino acid level decreasedInvestigations | 21/59 |
| DiarrhoeaGastrointestinal disorders | 14/59 |
| NauseaGastrointestinal disorders | 14/59 |
| NasopharyngitisRespiratory, thoracic and mediastinal disorders | 11/59 |
| Abdominal pain upperGastrointestinal disorders | 6/59 |
| Upper respiratory tract infectionInfections and infestations | 6/59 |
| FatigueGeneral disorders | 5/59 |
| PyrexiaGeneral disorders | 5/59 |
| Abdominal painGastrointestinal disorders | 4/59 |
| Age, Continuous(years) | Kuvan® |
|---|---|
| Mean | 21.0 ± 12.1 |
| Sex: Female, Male(Participants) | Kuvan® |
|---|---|
| Female | 34 |
| Male | 25 |
The record gives a start of May 2010, a primary completion of May 2012 and a completion of May 2012. It does not say whether these dates are actual or estimated.
Results were first posted in Aug 2013, 1 year 3 months after primary completion.
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This study is completed, as verified in Jan 2014. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Sapropterin
Merck KGaA, Darmstadt, Germany →