| 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 | 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. | | Posted | | Least Squares Mean | 95% Confidence Interval | units on a scale | | Baseline to Week 13 | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm With ADHD Symptoms | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment with ADHD symptoms at Baseline | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm With ADHD Symptoms | Included all subjects in the 6R-BH4 20 mg/kg/day Arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment with ADHD symptoms at Baseline |
| | | Title | Denominators | Categories |
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| | | Title | Measurements |
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| - OG000-4.9(-8.9 to -0.9)
- OG001-9.1(-13.5 to -4.7)
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| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| | ANCOVA | Adjusted for baseline ADHD-RS/ASRS total score, age group, and ADHD medication. | 0.085 | | Mean Difference (Final Values) | -4.2 | Standard Error of the Mean | 2.3 | 2-Sided | 95 | -8.9 | 0.6 | | | | No | Superiority or Other | | |
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| Secondary | Change in Hamilton Anxiety Rating Scale (HAM-A) Score From 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. | | Posted | | Least Squares Mean | 95% Confidence Interval | units on a scale | | Baseline to Week 13 | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm | Included all subjects in the 6R-BH4 20 mg/kg/day Arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment |
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| Secondary | Change in Hamilton Depression Rating Scale (HAM-D) Score From 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. | | Posted | | Least Squares Mean | 95% Confidence Interval | units on a scale | | Baseline to Week 13 | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm | Included all subjects in the 6R-BH4 20 mg/kg/day Arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment |
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| Secondary | Change in Clinical Global Impression-Severity (CGI-S) From 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. | | Posted | | Least Squares Mean | 95% Confidence Interval | units on a scale | | Baseline to Week 13 | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm | Included all subjects in the 6R-BH4 20 mg/kg/day Arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment |
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| Secondary | Change in Behavior Rating Inventory of Executive Function (BRIEF) Adult-Global Executive Composite (GEC) T Score From 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. | Phe Responders who are >=18 Years of Age | Posted | | Least Squares Mean | 95% Confidence Interval | T score | | Baseline to Week 13 | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm | Included all subjects in the 6R-BH4 20 mg/kg/day Arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment |
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| Secondary | Change in Behavior Rating Inventory of Executive Function (BRIEF) Parent-Global Executive Composite (GEC) T Score From 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. | Phe Responders who are <18 Years of Age | Posted | | Least Squares Mean | 95% Confidence Interval | T score | | Baseline to Week 13 | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment. | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm | Included all subjects in the 6R-BH4 20 mg/kg/day Arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment |
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| 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 | 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. | Phe Responders with ADHD Symptoms | Posted | | Least Squares Mean | 95% Confidence Interval | units on a scale | | Week 13 to Week 26 | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm With ADHD Symptoms | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment with ADHD symptoms at baseline | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm With ADHD Symptoms | Included all subjects in the 6R-BH4 20 mg/kg/day arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment with ADHD symptoms at baseline |
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| Secondary | Change in Hamilton Anxiety Rating Scale (HAM-A) Score From 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. | | Posted | | Least Squares Mean | 95% Confidence Interval | units on a scale | | Week 13 to Week 26 | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment. | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm | Included all subjects in the 6R-BH4 20 mg/kg/day Arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment |
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| Secondary | Change in Hamilton Depression Rating Scale (HAM-D) Score From 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. | | Posted | | Least Squares Mean | 95% Confidence Interval | units on a scale | | Week 13 to Week 26 | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment. | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm | Included all subjects in the 6R-BH4 20 mg/kg/day Arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment |
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| Secondary | Change in Clinical Global Impression-Severity (CGI-S) From Week 13 to Week 26 | Durability of the therapeutic effect of 6R-BH4 on global function through 26 weeks in 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. | | Posted | | Least Squares Mean | 95% Confidence Interval | units on a scale | | Week 13 to Week 26 | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment. | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm | Included all subjects in the 6R-BH4 20 mg/kg/day Arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment |
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| Secondary | Change in Behavior Rating Inventory of Executive Function (BRIEF) Adult-Global Executive Composite (GEC) T Score From Week 13 to Week 26 | Durability of the therapeutic effect of 6R-BH4 on executive function through 26 weeks in 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. | Phe Responders who is >=18 Years of Age | Posted | | Least Squares Mean | 95% Confidence Interval | T score | | Week 13 to Week 26 | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment. | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm | Included all subjects in the 6R-BH4 20 mg/kg/day Arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment |
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| Secondary | Change in Behavior Rating Inventory of Executive Function (BRIEF) Parent-Global Executive Composite (GEC) T Score From Week 13 to Week 26 | Durability of the therapeutic effect of 6R-BH4 on executive function through 26 weeks in 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. | Phe Responders who is <18 Years of Age | Posted | | Least Squares Mean | 95% Confidence Interval | T score | | Week 13 to Week 26 | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment. | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm | Included all subjects in the 6R-BH4 20 mg/kg/day Arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment |
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| Secondary | Change in Attention-Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS) / Adult ADHD Self-Report Scale (ASRS) Total Score From Baseline 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. | | Posted | | Least Squares Mean | 95% Confidence Interval | units on a scale | | Baseline to Week 26 | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm With ADHD Symptoms | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment with ADHD symptoms at baseline | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm With ADHD Symptoms | Included all subjects in the 6R-BH4 20 mg/kg/day arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment with ADHD symptoms at baseline |
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| Secondary | Change in Hamilton Anxiety Rating Scale (HAM-A) Score From Baseline 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. | | Posted | | Least Squares Mean | 95% Confidence Interval | units on a scale | | Baseline to Week 26 | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment. | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm | Included all subjects in the 6R-BH4 20 mg/kg/day Arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment |
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| Secondary | Change in Hamilton Rating Scale For Depression (HAM-D) Score From Baseline 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. | | Posted | | Least Squares Mean | 95% Confidence Interval | units on a scale | | Baseline to Week 26 | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment. | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm | Included all subjects in the 6R-BH4 20 mg/kg/day Arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment |
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| Secondary | Change in Clinical Global Impression-Severity (CGI-S) From Baseline to Week 26 | Durability of the therapeutic effect of 6R-BH4 on global function through 26 weeks in 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. | | Posted | | Mean | 95% Confidence Interval | units on a scale | | Baseline to Week 26 | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment. | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm | Included all subjects in the 6R-BH4 20 mg/kg/day Arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment |
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| Primary | Number of Participants With a Score of 1 or 2 in Global Function Evaluation (CGI-I) From Baseline to Week 13. | 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. | Missing data for 1 subject in the Responders in 6R-BH4 20 mg/kg/day Arm | Posted | | Number | | Number of participants with scale 1 or 2 | | 13 weeks | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm | Included all subjects in the 6R-BH4 20 mg/kg/day Arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment |
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| Secondary | Change in Behavior Rating Inventory of Executive Function (BRIEF) Adult-Global Executive Composite (GEC) T Score From Baseline to Week 26 | Durability of the therapeutic effect of 6R-BH4 on executive function through 26 weeks in 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. | | Posted | | Least Squares Mean | 95% Confidence Interval | T score | | Baseline to Week 26 | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment. | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm | Included all subjects in the 6R-BH4 20 mg/kg/day Arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment |
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| Secondary | Change in Behavior Rating Inventory of Executive Function (BRIEF) Parent-Global Executive Composite (GEC) T Score From Baseline to Week 26 | Durability of the therapeutic effect of 6R-BH4 on executive function through 26 weeks in 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. | | Posted | | Least Squares Mean | 95% Confidence Interval | T score | | Baseline to Week 26 | | | | ID | Title | Description |
|---|
| OG000 | Responders in Placebo Arm | Included all subjects in the Placebo arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment. | | OG001 | Responders in 6R-BH4 20 mg/kg/Day Arm | Included all subjects in the 6R-BH4 20 mg/kg/day Arm who had a blood Phe level reduction ≥ 20% from Baseline within their first 4 weeks of sapropterin treatment |
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