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| Name | Class |
|---|---|
| Merck Serono Norway | INDUSTRY |
| Smerud Medical Research International AS | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Kuvan® | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Kuvan® | Drug | Kuvan® (sapropterin dihydrochloride) oral solution 20 milligram per kilogram (mg/kg) will be given once daily for 28 +/- 1 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline up to Day 28 +/- 1 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | Merck Serono S.A., an affiliate of Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Paediatric Research, Division of Paediatrics, Oslo University Hospital, Rikshospitalet | Oslo | Norway |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | Scriver CR, Kaufman S. Hyperphenylanaemia: phenylalanine hydroxylase deficiency. In: Beaudet AL, Sly WS, Valle D, editors. Metabolic and molecular bases of inherited disease. New York: McGraw-Hill 2001;1667-709 | ||
| 11757784 | Background | Phenylketonuria (PKU): screening and management. NIH Consens Statement. 2000 Oct 16-18;17(3):1-33. | |
| 2014802 |
| Label | URL |
|---|---|
| Arnold GL. Phenylketonuria, Publication Link | View source |
Not provided
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| ID | Title | Description |
|---|---|---|
| FG000 | Kuvan® | Kuvan® (sapropterin dihydrochloride) oral solution 20 milligram per kilogram (mg/kg) once daily for 28 +/- 1 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Kuvan® | Kuvan® (sapropterin dihydrochloride) oral solution 20 milligram per kilogram (mg/kg) once daily for 28 +/- 1 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Full analysis set (FAS) population included all the participants with a valid Baseline blood Phe level measure and who received at least one dose of Kuvan®. | Posted | Number | 95% Confidence Interval | Percentage of participants | Baseline up to Day 28 +/- 1 |
|
Baseline up to Day 42 +/- 3
An adverse event 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 IMP, regardless of causal relationship and even if no IMP has been administered.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Kuvan® | Kuvan® (sapropterin dihydrochloride) oral solution 20 milligram per kilogram (mg/kg) once daily for 28 +/- 1 days. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Cardiac disorders | MedDRA (Unspecified) | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merck KGaA Communication Center | Merck Serono, a division of Merck KGaA | +49-6151-72-5200 | service@merckgroup.com |
Not provided
| ID | Term |
|---|---|
| D010661 | Phenylketonurias |
| ID | Term |
|---|---|
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C003402 | sapropterin |
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| 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. | 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). | 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. | 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. | Baseline, Day 28 |
| Background |
| Hofman KJ, Steel G, Kazazian HH, Valle D. Phenylketonuria in U.S. blacks: molecular analysis of the phenylalanine hydroxylase gene. Am J Hum Genet. 1991 Apr;48(4):791-8. |
| 1679029 | Background | Konecki DS, Lichter-Konecki U. The phenylketonuria locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations. Hum Genet. 1991 Aug;87(4):377-88. doi: 10.1007/BF00197152. |
| 2654351 | Background | Kaufman S. An evaluation of the possible neurotoxicity of metabolites of phenylalanine. J Pediatr. 1989 May;114(5):895-900. doi: 10.1016/s0022-3476(89)80161-1. No abstract available. |
| 11043154 | Background | Huttenlocher PR. The neuropathology of phenylketonuria: human and animal studies. Eur J Pediatr. 2000 Oct;159 Suppl 2:S102-6. doi: 10.1007/pl00014371. |
| 12114043 | Background | Walter JH, White FJ, Hall SK, MacDonald A, Rylance G, Boneh A, Francis DE, Shortland GJ, Schmidt M, Vail A. How practical are recommendations for dietary control in phenylketonuria? Lancet. 2002 Jul 6;360(9326):55-7. doi: 10.1016/s0140-6736(02)09334-0. |
| 6434835 | Background | Koch R, Azen C, Friedman EG, Williamson ML. Paired comparisons between early treated PKU children and their matched sibling controls on intelligence and school achievement test results at eight years of age. J Inherit Metab Dis. 1984;7(2):86-90. doi: 10.1007/BF01805813. |
| 15669671 | Background | Brumm VL, Azen C, Moats RA, Stern AM, Broomand C, Nelson MD, Koch R. Neuropsychological outcome of subjects participating in the PKU adult collaborative study: a preliminary review. J Inherit Metab Dis. 2004;27(5):549-66. doi: 10.1023/b:boli.0000042985.02049.ff. |
| 10484807 | Background | Kure S, Hou DC, Ohura T, Iwamoto H, Suzuki S, Sugiyama N, Sakamoto O, Fujii K, Matsubara Y, Narisawa K. Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. J Pediatr. 1999 Sep;135(3):375-8. doi: 10.1016/s0022-3476(99)70138-1. |
| 12501224 | Background | Muntau AC, Roschinger W, Habich M, Demmelmair H, Hoffmann B, Sommerhoff CP, Roscher AA. Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria. N Engl J Med. 2002 Dec 26;347(26):2122-32. doi: 10.1056/NEJMoa021654. |
| 16242984 | Background | Trefz FK, Scheible D, Frauendienst-Egger G, Korall H, Blau N. Long-term treatment of patients with mild and classical phenylketonuria by tetrahydrobiopterin. Mol Genet Metab. 2005 Dec;86 Suppl 1:S75-80. doi: 10.1016/j.ymgme.2005.06.026. Epub 2005 Oct 20. |
| 14681498 | Background | Shintaku H, Kure S, Ohura T, Okano Y, Ohwada M, Sugiyama N, Sakura N, Yoshida I, Yoshino M, Matsubara Y, Suzuki K, Aoki K, Kitagawa T. Long-term treatment and diagnosis of tetrahydrobiopterin-responsive hyperphenylalaninemia with a mutant phenylalanine hydroxylase gene. Pediatr Res. 2004 Mar;55(3):425-30. doi: 10.1203/01.PDR.0000111283.91564.7E. Epub 2003 Dec 17. |
| 16051511 | Background | Hennermann JB, Buhrer C, Blau N, Vetter B, Monch E. Long-term treatment with tetrahydrobiopterin increases phenylalanine tolerance in children with severe phenotype of phenylketonuria. Mol Genet Metab. 2005 Dec;86 Suppl 1:S86-90. doi: 10.1016/j.ymgme.2005.05.013. Epub 2005 Jul 26. |
| 16165389 | Background | Belanger-Quintana A, Garcia MJ, Castro M, Desviat LR, Perez B, Mejia B, Ugarte M, Martinez-Pardo M. Spanish BH4-responsive phenylalanine hydroxylase-deficient patients: evolution of seven patients on long-term treatment with tetrahydrobiopterin. Mol Genet Metab. 2005 Dec;86 Suppl 1:S61-6. doi: 10.1016/j.ymgme.2005.07.024. Epub 2005 Sep 13. |
| 16040265 | Background | Lambruschini N, Perez-Duenas B, Vilaseca MA, Mas A, Artuch R, Gassio R, Gomez L, Gutierrez A, Campistol J. Clinical and nutritional evaluation of phenylketonuric patients on tetrahydrobiopterin monotherapy. Mol Genet Metab. 2005 Dec;86 Suppl 1:S54-60. doi: 10.1016/j.ymgme.2005.05.014. Epub 2005 Jul 22. |
| Background | Kuvan® Package Insert. BioMarin. 2007 |
| 18327672 | Background | Blau N. Defining tetrahydrobiopterin (BH4)-responsiveness in PKU. J Inherit Metab Dis. 2008 Feb;31(1):2-3. doi: 10.1007/s10545-007-9979-1. No abstract available. |
| 17517248 | Background | Fiege B, Blau N. Assessment of tetrahydrobiopterin (BH4) responsiveness in phenylketonuria. J Pediatr. 2007 Jun;150(6):627-30. doi: 10.1016/j.jpeds.2007.02.017. |
| 18036498 | Background | Levy H, Burton B, Cederbaum S, Scriver C. Recommendations for evaluation of responsiveness to tetrahydrobiopterin (BH(4)) in phenylketonuria and its use in treatment. Mol Genet Metab. 2007 Dec;92(4):287-91. doi: 10.1016/j.ymgme.2007.09.017. |
| 17935162 | Background | Zurfluh MR, Zschocke J, Lindner M, Feillet F, Chery C, Burlina A, Stevens RC, Thony B, Blau N. Molecular genetics of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency. Hum Mutat. 2008 Jan;29(1):167-75. doi: 10.1002/humu.20637. |
| Background | Fernhoff P, Burton B, Nowacka M, Hennermann J, Kakkis E, Dorenbaum PKU-008: A Long-Term, Open-Label Study of Sapropterin Dihydrochloride (Kuvan®) in PKU Subjects. Poster at the 2009 American College of Medical Genetics Annual Clinical Genetics Meeting. |
| 17693179 | Background | Levy HL, Milanowski A, Chakrapani A, Cleary M, Lee P, Trefz FK, Whitley CB, Feillet F, Feigenbaum AS, Bebchuk JD, Christ-Schmidt H, Dorenbaum A; Sapropterin Research Group. Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study. Lancet. 2007 Aug 11;370(9586):504-10. doi: 10.1016/S0140-6736(07)61234-3. |
| 19261295 | Background | Trefz FK, Burton BK, Longo N, Casanova MM, Gruskin DJ, Dorenbaum A, Kakkis ED, Crombez EA, Grange DK, Harmatz P, Lipson MH, Milanowski A, Randolph LM, Vockley J, Whitley CB, Wolff JA, Bebchuk J, Christ-Schmidt H, Hennermann JB; Sapropterin Study Group. Efficacy of sapropterin dihydrochloride in increasing phenylalanine tolerance in children with phenylketonuria: a phase III, randomized, double-blind, placebo-controlled study. J Pediatr. 2009 May;154(5):700-7. doi: 10.1016/j.jpeds.2008.11.040. Epub 2009 Mar 4. |
| 11768137 | Background | Luciana M, Sullivan J, Nelson CA. Associations between phenylalanine-to-tyrosine ratios and performance on tests of neuropsychological function in adolescents treated early and continuously for phenylketonuria. Child Dev. 2001 Nov-Dec;72(6):1637-52. doi: 10.1111/1467-8624.00370. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Secondary | 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. | Safety population included all the participants with a valid Baseline blood Phe level measure and who received at least one dose of Kuvan®. | Posted | Number | Participants | Baseline up to Day 42 +/- 3 |
|
|
|
| Secondary | 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. | FAS population included all the participants with a valid Baseline blood Phe level measure and who received at least one dose of Kuvan®. | Posted | Number | 95% Confidence Interval | Percentage of participants | Baseline up to Day 28 +/- 1 |
|
|
|
| Secondary | 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). | FAS population included all the participants with a valid Baseline blood Phe level measure and who received at least one dose of Kuvan®. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure. 'n' signifies number of participants who were evaluable for specified categories at different time points. | Posted | Number | Percentage of participants | Baseline up to Day 28 +/- 1 |
|
|
|
| Secondary | 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. | FAS population included all the participants with a valid Baseline blood Phe level measure and who received at least one dose of Kuvan®. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure. 'n' signifies number of participants who were evaluable for specified categories at different time points. | Posted | Number | Percentage of participants | Baseline up to Day 28 +/- 1 |
|
|
|
| Secondary | 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. | FAS population included all the participants with a valid Baseline blood Phe level measure and who received at least one dose of Kuvan®. 'n' signifies number of participants who were evaluable for specified categories at different time points. | Posted | Mean | Standard Deviation | Ratio | Baseline, Day 28 |
|
|
|
| 0 |
| 59 |
| 58 |
| 59 |
| Ear pain | Ear and labyrinth disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Eye pruritus | Eye disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Aphthous stomatitis | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Gastroenteritis | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Gingival pruritus | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Oropharyngeal pain | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Tongue blistering | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Chest pain | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Discomfort | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Listless | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Malaise | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Excoriation | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Injury | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Joint injury | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Subcutaneous haematoma | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Amino acid level decreased | Investigations | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Iron deficiency | Metabolism and nutrition disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Joint lock | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Tendon pain | Musculoskeletal and connective tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Psychomotor hyperactivity | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Irritability | Psychiatric disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Somatoform disorder | Psychiatric disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Acute tonsillitis | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Nasopharyngitis | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
| Migraine | Vascular disorders | MedDRA (Unspecified) | Non-systematic Assessment |
|
Not provided
| D009422 | Nervous System Diseases |
| D000592 | Amino Acid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| Title | Measurements |
|---|---|
|
| AEs leading to withdrawal |
|
| Title | Measurements |
|---|---|
|
| Non-responders |
|
| Title | Measurements |
|---|---|
|
| Mild HPA: < 10 percent (n=7) |
|
| Mild PKU: >= 30 percent (n=26) |
|
| Mild PKU: 20 to 30 percent (n=26) |
|
| Mild PKU: 10 to 20 percent (n=26) |
|
| Mild PKU: < 10 percent (n=26) |
|
| Classical PKU: >= 30 percent (n=22) |
|
| Classical PKU: 20 to 30 percent (n=22) |
|
| Classical PKU: 10 to 20 percent (n=22) |
|
| Classical PKU: < 10 percent (n=22) |
|
| Title | Measurements |
|---|---|
|
| Mild PKU: Early Responders (n=26) |
|
| Mild PKU: Late Responders (n=26) |
|
| Mild PKU: Partial Responders (n=26) |
|
| Classical PKU: Early Responders (n=23) |
|
| Classical PKU: Late Responders (n=23) |
|
| Classical PKU: Partial Responders (n=23) |
|