Trial · NCT01114737

Safety and Therapeutic Effects of Sapropterin Dihydrochloride on Neuropsychiatric Symptoms in Phenylketonuria (PKU) Patients

NCT01114737, Phase 3, Completed, BioMarin Pharmaceutical; results first posted 2016-02-01

3 sourcestrials-2026-11-12-0.5.0

Cite this record

ConductScience Library. Safety and Therapeutic Effects of Sapropterin Dihydrochloride on Neuropsychiatric Symptoms in Phenylketonuria (PKU) Patients. Trials, record NCT01114737. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01114737

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Trial

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

Title: Safety and Therapeutic Effects of Sapropterin Dihydrochloride on Neuropsychiatric Symptoms in Phenylketonuria (PKU) Patients
NCT number: NCT01114737
Status: Completed
Phases: Phase 3
Enrollment: 206 participants, actual
Lead sponsor: BioMarin Pharmaceutical
Conditions: Phenylketonuria
Interventions: Sapropterin dihydrochloride, Placebo
First posted: 2010-05-03
Last updated: 2016-02-01
Results first posted: 2016-02-01
Limitations and caveats: As specified in the SAP, no multiplicity adjustment was made in the analyses; therefore, the family-wise error rate was not controlled in this study

Source ClinicalTrials.gov

Registered outcomes19

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

List	Outcome	Time frame	Description
Primary	Change in Attention-Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS) / Adult ADHD Self-Report Scale (ASRS) Total Score From Baseline to Week 13	Baseline to Week 13	Effects of 6R-BH4 on symptoms of ADHD in PKU subjects who had symptoms of ADHD at screening in the subjects that had a blood Phe level reduction after treatment with 6R-BH4. The total ADHD-RS score and the corrected total ARS score range from 0 to 54, with higher scores corresponding to worse severity of ADHD symptoms.
Primary	Number of Participants With a Score of 1 or 2 in Global Function Evaluation (CGI-I) From Baseline to Week 13.	13 weeks	Effects of 6R-BH4 on global function in PKU subjects in subjects that had a blood Phe level reduction after treatment with 6R-BH4 at screening. The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.
Secondary	Change in Hamilton Anxiety Rating Scale (HAM-A) Score From Baseline to Week 13	Baseline to Week 13	Effects of 6R-BH4 on symptoms of anxiety in PKU subjects who had a blood Phe level reduction after treatment with 6R-BH4. HAM-A Score is a total score ranging from 0 to 56 with higher scores corresponding to worse severity of anxiety symptoms. The HAM-A has 14 items, each measuring specific anxiety symptom clusters. Each item is given a 5-point-score as: 0, absent; 1, mild; 2, moderate; 3, severe; or 4, incapacitating.
Secondary	Change in Hamilton Depression Rating Scale (HAM-D) Score From Baseline to Week 13	Baseline to Week 13	Effects of 6R-BH4 on symptoms of depression in PKU subjects who had a blood Phe level reduction after treatment with 6R-BH4. HAM-D Score is a total score ranging from 0 to 48 with higher scores corresponding to worse severity of depression. The HAM-D is a 17-item depression rating scale. Nine of the items are scored on a 5-point scale as: 0, absence of depressive symptom being measured; 1, doubt concerning the presence of the symptom; 2, mild symptoms; 3, moderate symptoms; or 4, severe symptoms. The remaining 8 items are scored on a 3-point scale as: 0, absence; 1, doubt on the presence of the symptom; or 2, clear presence of symptoms.
Secondary	Change in Clinical Global Impression-Severity (CGI-S) From Baseline to Week 13	Baseline to Week 13	Effects of 6R-BH4 on global function in PKU subjects who had a blood Phe level reduction after treatment with 6R-BH4. CGI-S is a 7-point scale that requires the clinician to rate the severity of the subject's mental illness at the time of assessment, relative to clinician's past experience with subjects who have the same diagnosis. Considering total clinical experience, a subject is assessed on the severity of mental illness at the time of rating as: 1, normal, not at all ill; 2, borderline ill; 3, mildly ill; 4, moderately ill; 6, severely ill; or 7, among the most extremely ill.
Secondary	Change in Behavior Rating Inventory of Executive Function (BRIEF) Adult-Global Executive Composite (GEC) T Score From Baseline to Week 13	Baseline to Week 13	Effects of 6R-BH4 on executive function in PKU subjects who had a blood Phe level reduction after treatment with 6R-BH4. The scoring for the GEC T Score is complex and is achieved using proprietary software designed to generate scores based on raw data collected. Higher scores suggest a higher level of dysfunction.
Secondary	Change in Behavior Rating Inventory of Executive Function (BRIEF) Parent-Global Executive Composite (GEC) T Score From Baseline to Week 13	Baseline to Week 13	Effects of 6R-BH4 on executive function in PKU subjects who had a blood Phe level reduction after treatment with 6R-BH4. The scoring for the GEC T Score is complex and is achieved using proprietary software designed to generate scores based on raw data collected. Higher scores suggest a higher level of dysfunction.
Secondary	Change in Attention-Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS) / Adult ADHD Self-Report Scale (ASRS) Total Score From Week 13 to Week 26	Week 13 to Week 26	Durability of the therapeutic effect of 6R-BH4 on ADHD through 26 weeks in subjects who had a blood Phe level reduction after treatment with 6R-BH4. The total ADHD-RS score and the corrected total ARS score range from 0 to 54, with higher scores corresponding to worse severity of ADHD symptoms.
Secondary	Change in Hamilton Anxiety Rating Scale (HAM-A) Score From Week 13 to Week 26	Week 13 to Week 26	Durability of the therapeutic effect of 6R-BH4 on anxiety through 26 weeks in subjects who had a blood Phe level reduction after treatment with 6R-BH4. HAM-A Score is a total score ranging from 0 to 56 with higher scores corresponding to worse severity of anxiety symptoms. The HAM-A has 14 items, each measuring specific anxiety symptom clusters. Each item is given a 5-point-score as: 0, absent; 1, mild; 2, moderate; 3, severe; or 4, incapacitating.
Secondary	Change in Hamilton Depression Rating Scale (HAM-D) Score From Week 13 to Week 26	Week 13 to Week 26	Durability of the therapeutic effect of 6R-BH4 on depression through 26 weeks in subjects who had a blood Phe level reduction after treatment with 6R-BH4. HAM-D Score is a total score ranging from 0 to 48 with higher scores corresponding to worse severity of depression. The HAM-D is a 17-item depression rating scale. Nine of the items are scored on a 5-point scale as: 0, absence of depressive symptom being measured; 1, doubt concerning the presence of the symptom; 2, mild symptoms; 3, moderate symptoms; or 4, severe symptoms. The remaining 8 items are scored on a 3-point scale as: 0, absence; 1, doubt on the presence of the symptom; or 2, clear presence of symptoms.

1 to 10 of 19Source ClinicalTrials.gov

See all 19 registered outcomes

Outcomes19

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

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Change in Attention-Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS) / Adult ADHD Self-Report Scale (ASRS) Total Score From Baseline to Week 13	Baseline to Week 13		units on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change in Hamilton Anxiety Rating Scale (HAM-A) Score From Baseline to Week 13	Baseline to Week 13		units on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change in Hamilton Depression Rating Scale (HAM-D) Score From Baseline to Week 13	Baseline to Week 13		units on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change in Clinical Global Impression-Severity (CGI-S) From Baseline to Week 13	Baseline to Week 13	Phe Responders	units on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change in Behavior Rating Inventory of Executive Function (BRIEF) Adult-Global Executive Composite (GEC) T Score From Baseline to Week 13	Baseline to Week 13	Phe Responders who are \>=18 Years of Age	T score	LEAST_SQUARES_MEAN
SECONDARY	Change in Behavior Rating Inventory of Executive Function (BRIEF) Parent-Global Executive Composite (GEC) T Score From Baseline to Week 13	Baseline to Week 13	Phe Responders who are \<18 Years of Age	T score	LEAST_SQUARES_MEAN
SECONDARY	Change in Attention-Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS) / Adult ADHD Self-Report Scale (ASRS) Total Score From Week 13 to Week 26	Week 13 to Week 26	Phe Responders with ADHD Symptoms	units on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change in Hamilton Anxiety Rating Scale (HAM-A) Score From Week 13 to Week 26	Week 13 to Week 26	Phe Responders	units on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change in Hamilton Depression Rating Scale (HAM-D) Score From Week 13 to Week 26	Week 13 to Week 26	Phe Responders	units on a scale	LEAST_SQUARES_MEAN
SECONDARY	Change in Clinical Global Impression-Severity (CGI-S) From Week 13 to Week 26	Week 13 to Week 26	Phe Responders	units on a scale	LEAST_SQUARES_MEAN

1 to 10 of 19Source ClinicalTrials.gov

See all 19 outcomes

Results by group38

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

Outcome	Group	Value	Spread	Units
Change in Attention-Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS) / Adult ADHD Self-Report Scale (ASRS) Total Score From Baseline to Week 13	Responders in Placebo Arm With ADHD Symptoms	-4.9	95% Confidence Interval -8.9 to -0.9	units on a scale
Change in Attention-Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS) / Adult ADHD Self-Report Scale (ASRS) Total Score From Baseline to Week 13	Responders in 6R-BH4 20 mg/kg/Day Arm With ADHD Symptoms	-9.1	95% Confidence Interval -13.5 to -4.7	units on a scale
Change in Hamilton Anxiety Rating Scale (HAM-A) Score From Baseline to Week 13	Responders in Placebo Arm	-3.6	95% Confidence Interval -5.4 to -1.9	units on a scale
Change in Hamilton Anxiety Rating Scale (HAM-A) Score From Baseline to Week 13	Responders in 6R-BH4 20 mg/kg/Day Arm	-3.2	95% Confidence Interval -5.1 to -1.4	units on a scale
Change in Hamilton Depression Rating Scale (HAM-D) Score From Baseline to Week 13	Responders in Placebo Arm	-2.5	95% Confidence Interval -3.9 to -1.1	units on a scale
Change in Hamilton Depression Rating Scale (HAM-D) Score From Baseline to Week 13	Responders in 6R-BH4 20 mg/kg/Day Arm	-2.1	95% Confidence Interval -3.6 to -0.6	units on a scale
Change in Clinical Global Impression-Severity (CGI-S) From Baseline to Week 13	Responders in Placebo Arm	-0.5	95% Confidence Interval -0.8 to -0.2	units on a scale
Change in Clinical Global Impression-Severity (CGI-S) From Baseline to Week 13	Responders in 6R-BH4 20 mg/kg/Day Arm	-0.6	95% Confidence Interval -0.9 to -0.3	units on a scale
Change in Behavior Rating Inventory of Executive Function (BRIEF) Adult-Global Executive Composite (GEC) T Score From Baseline to Week 13	Responders in Placebo Arm	-8.1	95% Confidence Interval -12.6 to -3.6	T score
Change in Behavior Rating Inventory of Executive Function (BRIEF) Adult-Global Executive Composite (GEC) T Score From Baseline to Week 13	Responders in 6R-BH4 20 mg/kg/Day Arm	-9.1	95% Confidence Interval -14.6 to -3.5	T score

1 to 10 of 38Source ClinicalTrials.gov

See all 38 results by group

Participant flow12

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

Period	Milestone	Group	Participants
Randomized Treatment Period	STARTED	Placebo	108
Randomized Treatment Period	STARTED	6R-BH4 20 mg/kg/Day	98
Randomized Treatment Period	COMPLETED	Placebo	105
Randomized Treatment Period	COMPLETED	6R-BH4 20 mg/kg/Day	97
Randomized Treatment Period	NOT COMPLETED	Placebo	3
Randomized Treatment Period	NOT COMPLETED	6R-BH4 20 mg/kg/Day	1
Open-Label Treatment Period	STARTED	Placebo	105
Open-Label Treatment Period	STARTED	6R-BH4 20 mg/kg/Day	97
Open-Label Treatment Period	COMPLETED	Placebo	100
Open-Label Treatment Period	COMPLETED	6R-BH4 20 mg/kg/Day	95

1 to 10 of 12Source ClinicalTrials.gov

See all 12 participant flow

Adverse events144

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	Events
other	Abdominal pain upper	Gastrointestinal disorders	Randomized Treatment Period - Placebo	5	108	5
other	Abdominal pain upper	Gastrointestinal disorders	Randomized Treatment Period - 6R-BH4	4	98	5
other	Abdominal pain upper	Gastrointestinal disorders	Randomized Treatment Period - Overall	9	206	10
other	Abdominal pain upper	Gastrointestinal disorders	Open-Label Treatment Period - Placebo-6R-BH4	2	104	2
other	Abdominal pain upper	Gastrointestinal disorders	Open-Label Treatment Period - 6R-BH4	7	95	7
other	Abdominal pain upper	Gastrointestinal disorders	Open-Label Treatment Period - Overall	9	199	9
other	Abdominal pain upper	Gastrointestinal disorders	6R-BH4 Treatment Period - 6R-BH4	9	98	12
other	Abdominal pain upper	Gastrointestinal disorders	6R-BH4 Treatment Period - Combined	11	202	14
other	Diarrhoea	Gastrointestinal disorders	Randomized Treatment Period - Placebo	4	108	5
other	Diarrhoea	Gastrointestinal disorders	Randomized Treatment Period - 6R-BH4	10	98	12

1 to 10 of 144Source ClinicalTrials.gov

See all 144 adverse events

Adverse event totals24

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Randomized Treatment Period - Placebo
Total, all-cause mortality	Randomized Treatment Period - 6R-BH4
Total, all-cause mortality	Randomized Treatment Period - Overall
Total, all-cause mortality	Open-Label Treatment Period - Placebo-6R-BH4
Total, all-cause mortality	Open-Label Treatment Period - 6R-BH4
Total, all-cause mortality	Open-Label Treatment Period - Overall
Total, all-cause mortality	6R-BH4 Treatment Period - 6R-BH4
Total, all-cause mortality	6R-BH4 Treatment Period - Combined
Total, other adverse events	Randomized Treatment Period - Placebo	80	108
Total, other adverse events	Randomized Treatment Period - 6R-BH4	79	98

1 to 10 of 24Source ClinicalTrials.gov

See all 24 adverse event totals

Papers1

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as
37263523	DERIVED

Source PubMed

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.

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Read this trial from software.

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

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