Trial · NCT00838435

Effect of Kuvan on Neurocognitive Function, Blood Phenylalanine Level, Safety, and Pharmacokinetics in Children With PKU

NCT00838435, Phase 3, Completed, BioMarin Pharmaceutical; results first posted 2020-12-22

3 sourcestrials-2026-11-12-0.5.0

Cite this record

ConductScience Library. Effect of Kuvan on Neurocognitive Function, Blood Phenylalanine Level, Safety, and Pharmacokinetics in Children With PKU. Trials, record NCT00838435. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT00838435

On this page

Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: Effect of Kuvan on Neurocognitive Function, Blood Phenylalanine Level, Safety, and Pharmacokinetics in Children With PKU
NCT number: NCT00838435
Status: Completed
Phases: Phase 3
Enrollment: 95 participants, actual
Lead sponsor: BioMarin Pharmaceutical
Conditions: Phenylketonuria
Interventions: sapropterin dihydrochloride
First posted: 2009-02-06
Last updated: 2020-12-22
Results first posted: 2020-12-22

Source ClinicalTrials.gov

Registered outcomes10

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Full-Scale Intelligence Quotient (FSIQ) Score	Assessments through 84 months.	Full Scale Intelligence Quotient (FSIQ) is a score derived through administration of selected subtests from age appropriate Wechsler Intelligence assessments. Weschler Preschool and Primary Scale of Intelligence (WPPSI)-III is used for children \>30 months and ≤6 years; and Weschler Intelligence Scale for Children (WISC)-IV is used for children \>6 years old. The outcome variable will be the FSIQ score from WPPSI-III and/or WISC-IV tests. FSIQ results can range from 40 being the lowest and 160 being the highest. Higher scores are associated with higher intelligence quotient.
Secondary	Number of Subjects With Adverse Events (AEs)	Up to 7 years	Adverse Event is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, and that does not necessarily have a causal relationship with this treatment. Drug Related Adverse all noxious and unintended responses to a medical product related to any dose. This means that a causal relationship between a medicinal product and an AE is at least a reasonable possibility, ie, the relationship cannot be ruled out. A serious adverse event (SAE) is 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.
Secondary	Change From Baseline in Growth Measurements - Height Z-Scores	Baseline and up to 84 months	Z-scores of Height determined using World Health Organization(WHO) growth charts for children \<24 months and Centers for Disease Control and Prevention(CDC) clinical growth charts for children 24 months and older. A height z-score is a standardized height measure after considering important factors like age and gender, in which higher z-scores are associated with taller children. Z-scores (or standard deviation scores) describe how far a measurement is from the median (mean). A z-score of 0 is the same as a 50th percentile; a positive value is a factor of standard deviation (SD) unit above the 50%; and a negative value is a factor of SD unit below 50%.
Secondary	Change From Baseline in Growth Measurements - Weight Z-Scores	Baseline and up to 84 months	Z-scores of Weight determined using World Health Organization(WHO) growth charts for children \<24 months and Centers for Disease Control and Prevention(CDC) clinical growth charts for children 24 months or older. A weight z-score is a standardized weight measure after considering important factors like age and gender, in which higher z-scores are associated with heavier children. Z-scores (or standard deviation scores) describe how far a measurement is from the median (mean). A z-score of 0 is the same as a 50th percentile; a positive value is a factor of SD unit above the 50%; and a negative value is a factor of SD unit below 50%.
Secondary	Change From Baseline in Growth Measurements - Head Circumference Z-Scores	Baseline and up to 84 months	Z-scores of Head Circumference determined using World Health Organization(WHO) growth charts for children \<24 months and Centers for Disease Control and Prevention(CDC) clinical growth charts for children 24 months and older. A head circumference z-score is a standardized head circumference measure after considering important factors like age and gender, in which higher z-scores are associated with children with larger heads. Z-scores (or standard deviation scores) describe how far a measurement is from the median (mean). A z-score of 0 is the same as a 50th percentile; a positive value is a factor of SD unit above the 50%; and a negative value is a factor of SD unit below 50%.
Secondary	Change From Baseline in Bayley-III Scores - Neurocognitive Testing Results	At Month 6, 12, 18 and 24	The Bayley-III is a tool for assessing all facets of development in infants within an age range of 12 to 30 months, with normative data available for infants as young as 16 days. Composite scores are derived for cognitive, language, and motor development and scaled to a metric, with a range of 40 to 160. Higher scores are a better outcome.
Secondary	Baseline Concentration of Tetrahydrobiopterin (BH4)(C0)	At predose and postdose - 0.22, 3.2 and 7 hours	Baseline concentration of BH4(C0) with associated inter-individual variability.
Secondary	Absorption Rate Constant (Ka) of Kuvan	At predose and postdose - 0.22, 3.2 and 7 hours	Population pharmacokinetic parameter, Absorption Rate Constant (Ka)
Secondary	Apparent Volume of Distribution (V/F) of Kuvan	At predose and postdose - 0.22, 3.2 and 7 hours	Population pharmacokinetic parameter apparent volume of distribution (V/F)
Secondary	Apparent Clearance (CL/F) of Kuvan	At predose and postdose - 0.22, 3.2 and 7 hours	Population pharmacokinetic parameter apparent clearance (CL/F)

Source ClinicalTrials.gov

Outcomes10

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Full-Scale Intelligence Quotient (FSIQ) Score	Assessments through 84 months.	Efficacy population is based on all subjects from the enrolled population who have at least 2 WPPSI/ WISC assessments.	score on a scale	MEAN
SECONDARY	Number of Subjects With Adverse Events (AEs)	Up to 7 years	Enrolled Population consists of all subjects who enter Part 2. This population involves subjects who respond to Kuvan and had a Bayley-III or IQ test score ≥80 within 6 weeks of determination of Kuvan responsiveness in Part 1. Kuvan 20 mg/kg once daily.	Participants	COUNT_OF_PARTICIPANTS
SECONDARY	Change From Baseline in Growth Measurements - Height Z-Scores	Baseline and up to 84 months	Efficacy Population	Z-score change from baseline	MEAN
SECONDARY	Change From Baseline in Growth Measurements - Weight Z-Scores	Baseline and up to 84 months	Efficacy Population	Z-score change from baseline	MEAN
SECONDARY	Change From Baseline in Growth Measurements - Head Circumference Z-Scores	Baseline and up to 84 months	Efficacy Population, subjects less than 36 months of age.	Z-score change from baseline	MEAN
SECONDARY	Change From Baseline in Bayley-III Scores - Neurocognitive Testing Results	At Month 6, 12, 18 and 24	Efficacy Population, analysis only comprised of subjects less than 30 months of age.	score on a scale	MEAN
SECONDARY	Baseline Concentration of Tetrahydrobiopterin (BH4)(C0)	At predose and postdose - 0.22, 3.2 and 7 hours	Eighty patients were evaluable from PKU-015 PK Sub-Study.	µg/L	LEAST_SQUARES_MEAN
SECONDARY	Absorption Rate Constant (Ka) of Kuvan	At predose and postdose - 0.22, 3.2 and 7 hours	Eighty subjects were evaluable from PKU-015 PK Sub-Study.	l/hour	LEAST_SQUARES_MEAN
SECONDARY	Apparent Volume of Distribution (V/F) of Kuvan	At predose and postdose - 0.22, 3.2 and 7 hours	Eighty subjects were evaluable from PKU-015 PK Sub-Study.	L	MEAN
SECONDARY	Apparent Clearance (CL/F) of Kuvan	At predose and postdose - 0.22, 3.2 and 7 hours	Eighty subjects were evaluable from PKU-015 PK Sub-Study.	L/hour	MEAN

Source ClinicalTrials.gov

Results by group76

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Category	Value	Spread	Units
Full-Scale Intelligence Quotient (FSIQ) Score	Kuvan 20 mg/kg Once Daily	FSIQ Baseline	101.06	Standard Deviation 14.039	score on a scale
Full-Scale Intelligence Quotient (FSIQ) Score	Kuvan 20 mg/kg Once Daily	FSIQ Month 12	103.64	Standard Deviation 13.202	score on a scale
Full-Scale Intelligence Quotient (FSIQ) Score	Kuvan 20 mg/kg Once Daily	FSIQ Month 24	104.69	Standard Deviation 11.697	score on a scale
Full-Scale Intelligence Quotient (FSIQ) Score	Kuvan 20 mg/kg Once Daily	FSIQ Month 36	103.78	Standard Deviation 12.759	score on a scale
Full-Scale Intelligence Quotient (FSIQ) Score	Kuvan 20 mg/kg Once Daily	FSIQ Month 48	104.25	Standard Deviation 13.242	score on a scale
Full-Scale Intelligence Quotient (FSIQ) Score	Kuvan 20 mg/kg Once Daily	FSIQ Month 60	100.76	Standard Deviation 14.280	score on a scale
Full-Scale Intelligence Quotient (FSIQ) Score	Kuvan 20 mg/kg Once Daily	FSIQ Month 72	104.57	Standard Deviation 11.012	score on a scale
Full-Scale Intelligence Quotient (FSIQ) Score	Kuvan 20 mg/kg Once Daily	FSIQ Month 84	104.22	Standard Deviation 12.236	score on a scale
Number of Subjects With Adverse Events (AEs)	Part 2	Any Adverse Events (AEs)	65		Participants
Number of Subjects With Adverse Events (AEs)	Part 2	Drug-Related Adverse Events	35		Participants

1 to 10 of 76Source ClinicalTrials.gov

See all 76 results by group

Participant flow12

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Part 1 (4 Weeks)	STARTED	Sapropterin Dihydrochloride	95
Part 1 (4 Weeks)	COMPLETED	Sapropterin Dihydrochloride	95
Part 1 (4 Weeks)	NOT COMPLETED	Sapropterin Dihydrochloride	0
PK Sub-Study 2 (4 Weeks)	STARTED	Sapropterin Dihydrochloride	94
PK Sub-Study 2 (4 Weeks)	COMPLETED	Sapropterin Dihydrochloride	93
PK Sub-Study 2 (4 Weeks)	NOT COMPLETED	Sapropterin Dihydrochloride	1
Safety/Efficacy Sub-Study 1 (6 Months)	STARTED	Sapropterin Dihydrochloride	65
Safety/Efficacy Sub-Study 1 (6 Months)	COMPLETED	Sapropterin Dihydrochloride	63
Safety/Efficacy Sub-Study 1 (6 Months)	NOT COMPLETED	Sapropterin Dihydrochloride	2
Part 2 (7 Years)	STARTED	Sapropterin Dihydrochloride	65

1 to 10 of 12Source ClinicalTrials.gov

See all 12 participant flow

Adverse events69

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk
other	Lymphadenopathy	Blood and lymphatic system disorders	Safety Population	13	95
other	Ear pain	Ear and labyrinth disorders	Safety Population	7	95
other	Conjunctivitis	Eye disorders	Safety Population	9	95
other	Myopia	Eye disorders	Safety Population	5	95
other	Abdominal discomfort	Gastrointestinal disorders	Safety Population	8	95
other	Abdominal pain	Gastrointestinal disorders	Safety Population	14	95
other	Abdominal pain upper	Gastrointestinal disorders	Safety Population	17	95
other	Constipation	Gastrointestinal disorders	Safety Population	11	95
other	Diarrhoea	Gastrointestinal disorders	Safety Population	39	95
other	Nausea	Gastrointestinal disorders	Safety Population	5	95

1 to 10 of 69Source ClinicalTrials.gov

See all 69 adverse events

Adverse event totals3

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Safety Population	0	95
Total, other adverse events	Safety Population	90	95
Total, serious adverse events	Safety Population	12	95

Source ClinicalTrials.gov

Papers0

The papers the trial lists on ClinicalTrials.gov.

None in this release.

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons0

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

None in this release.

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

For software

Read this trial from software.

The record and each of its lists are JSON, twenty rows a page. No key.

GET https://conductscience.org/api/trials/v1/NCT00838435

GET https://conductscience.org/api/trials/v1/NCT00838435/results?page=2

API reference For AI assistants