Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
A Phase 3 substudy to evaluate executive function in adults with phenylketonuria who are participating in the phase 3 Study, 165-302. Approximately 100 subjects, aged ≥ 18 to ≤ 70 years old, with PKU will be enrolled.
Study 165-303, is a Phase 3 substudy enrolling approximately 100 subjects, aged ≥ 18 to ≤ 70 years old, with PKU who are participating in the Phase 3 study, 165-302.
Per the 165-303 protocol, the investigator does not assign a specific intervention to the study participants. In accordance with the protocol for Study 165-303, subjects were asked to perform selected set of three tasks from the CANTAB tool (Rapid Visual Processing [RVP], Spatial Working Memory [SWM], and Stop Signal Task [SST]) to assess executive function and each subject's self perception of their current state was measured using a subject global assessment questionnaire that contains seven questions about current state perception of attention, energy level, tiredness, confusion, sadness, anger and tension.
The time points for administering the above tools are as follows, which coincide with time points in part 2 and part 4 of Study 165-302: screening (entry into Part 2 165-302 Day 1 of Week 1), baseline visit (Part 2 Week 8), and 3 additional study visits at different time points in the Part 4 of 165-302 study.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Administration of CANTAB and Subject Global Assessment | Other | At designated visits, subject will perform the CANTAB tasks and complete the Subject Global Assessment Questionnaire |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Rapid Visual Processing (RVP) Mean Response Latency (CANTAB Task) | The RVP task measures sustained attention. In this task, a series of random digits continuously appears in the middle of the screen. Subjects are asked to recognize a specific sequence of digits and are asked to press a button on the screen whenever this specific sequence of digits appears within this series of continuous digits. RVP mean latency is the mean response latency during assessment sequence blocks where the subject responded correctly (Latency units are milliseconds). Lower scores represent better performance. Observed range for Pooled Active: -103.1 to 65.5 (change from baseline) Observed range for Pooled Placebo: -10.4 to 39.0 (change from baseline) | Baseline to Part 2 Week 8 |
| Change From Baseline in Spatial Working Memory (SWM) Between Errors 4-8 Boxes (CANTAB Task) | The SWM task measures visuospatial working memory. During this task, a number of boxes appears on a screen. The objective of the task is to find a token under a box and to place this token in a designated area. There is only one token under one box during each round and the location of the token rotates in each round to a different box, other than a box within which the token was found in previous rounds. The subject is therefore asked to remember which boxes previously contained tokens so as to better the chances and speed of finding tokens under boxes which did not previously contain tokens. SWM between errors measures the total number of times the subject revisits a box in which a token has previously been found in the same problem (calculated for assessed problems only). Observed range for Pooled Active: -8 to 1 (change from baseline) Observed range for Pooled Placebo: -5 to 12 (change from baseline) Lower scores represent better performance. | Baseline to Part 2 Week 8 |
| Change From Baseline in Stop Signal Task (SST) Stop Signal Reaction T (CANTAB Task) | The SST task measures inhibitory control and cognitive flexibility. The SST is a 2-part task. During part 1, an arrow appears on the screen and subjects are asked to press an arrow button on the screen corresponding with the direction of the arrow displayed. During part 2 of the task, subjects follow the same instructions as in part 1; however, they are asked to withhold their response (do not press an arrow button) if they hear an auditory signal (beep) when the arrow is displayed. SST stop signal delay is the length of time between the go stimulus and the stop stimulus at which the subject is able to successfully inhibit their response on 50% of trials. Lower time represents better performance. Observed range for Pooled Active: -31.6 to 48.7 (change from baseline) Observed range for Pooled Placebo: 47.8 to 72.5 (change from baseline) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in RVP A Prime - Signal Detection Measure of Sensitivity to the Target (CANTAB Task) | The RVP task measures sustained attention. In this task, a series of random digits continuously appears in the middle of the screen. Subjects are asked to recognize a specific sequence of digits and are asked to press a button on the screen whenever this specific sequence of digits appears within this series of continuous digits. RVP A prime represents the signal detection measure of sensitivity to the target, regardless of response tendency. In essence, measure of how good the subject is at detecting target sequences. Observed range for Pooled Active: -0.004 to 0.030 (change from baseline) Observed range for Pooled Placebo: -0.057 to -0.001 (change from baseline) A higher score on the test represents a better performance. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Subjects with PKU who are currently enrolled in 165-302 Part 2.
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Debra Lounsbury | Principal Scientist/Medical Monitor | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Kentucky Medical Center | Lexington | Kentucky | 40536 | United States | ||
| University of Nebraska Medical Center |
Not provided
| Label | URL |
|---|---|
| BioMarin Pharmaceutical Website | View source |
| BioMarin sponsored PKU educational/community website | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Pooled Results: This is a sub-study of 165-302, with a randomized, placebo-control discontinuation design in Part 2. 9 subjects were enrolled in 165-303: 3 in 20mg/day and 3 in 40mg/day Active arm, 2 in 20mg/day and 1 in 40mg/day Placebo arm. Data interpretability was extremely limited, hence planned analysis was using the pooled treatment groups.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Pooled Active | Subjects randomized to receive active drug in study 165-302 part 2 |
| FG001 | Pooled Placebo | Subjects randomized to receive placebo in study 165-302 part 2 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 29, 2016 | Jun 22, 2018 |
Not provided
Not provided
Not provided
Not provided
| Baseline to Part 2 Week 8 |
| Baseline to Part 2 Week 8 |
| Change From the Baseline in SWM Strategy 6-8 Boxes - Number of Distinct Boxes Used by the Subject to Begin a New Search for a Token(CANTAB Task) | The SWM task measures visuospatial working memory. During this task, a number of boxes appears on a screen. The objective of the task is to find a token under a box and to place this token in a designated area. There is only one token under one box during each round and the location of the token rotates in each round to a different box, other than a box within which the token was found in previous rounds. The subject is therefore asked to remember which boxes previously contained tokens so as to better the chances and speed of finding tokens under boxes which did not previously contain tokens. For assessed problems with six boxes or more, SWM strategy is the number of distinct boxes used by the subject to begin a new search for a token (within the same problem). A high score represents poor use of this strategy and a low score equates to effective use. Observed range for Pooled Active: -3 to 3 (change from baseline) Observed range for Pooled Placebo: -3 to 1(change from baseline) | Baseline to Part 2 Week 8 |
| Change From Baseline in SST Proportion of Successful Stops - Measures the Proportion of Completed Stop Trials That Were Successful Stops (CANTAB Task) | The SST task measures inhibitory control and cognitive flexibility. The SST is a 2-part task. During part 1, an arrow appears on the screen and subjects are asked to press an arrow button on the screen corresponding with the direction of the arrow displayed. During part 2 of the task, subjects follow the same instructions as in part 1; however, they are asked to withhold their response (do not press an arrow button) if they hear an auditory signal (beep) when the arrow is displayed. SST stop signal delay is the length of time between the go stimulus and the stop stimulus at which the subject is able to successfully inhibit their response on 50% of trials. SST proportion of successful stops measures the proportion of completed stop trials that were successful stops. A higher score on the test represents a better performance. Observed range for Pooled Active: -0.1 to 0.05 (change from baseline) Observed range for Pooled Placebo: 0.0 to 0.0 (change from baseline) | Baseline to Part 2 Week 8 |
| Omaha |
| Nebraska |
| 68198 |
| United States |
| University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | 73104 | United States |
| Oregon Health and Science University | Portland | Oregon | 97239 | United States |
| COMPLETED |
|
| NOT COMPLETED |
|
Pooled Results: This is a sub-study of 165-302, with a randomized, placebo-control discontinuation design in Part 2. 9 subjects were enrolled in 165-303: 3 in 20mg/day and 3 in 40mg/day Active arm, 2 in 20mg/day and 1 in 40mg/day Placebo arm. Data interpretability was extremely limited, hence planned analysis was using the pooled treatment groups.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Pooled Active | Subjects randomized to receive active drug in study 165-302 part 2 |
| BG001 | Pooled Placebo | Subjects randomized to receive placebo in study 165-302 part 2 |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
|
| 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 | Change From Baseline in Rapid Visual Processing (RVP) Mean Response Latency (CANTAB Task) | The RVP task measures sustained attention. In this task, a series of random digits continuously appears in the middle of the screen. Subjects are asked to recognize a specific sequence of digits and are asked to press a button on the screen whenever this specific sequence of digits appears within this series of continuous digits. RVP mean latency is the mean response latency during assessment sequence blocks where the subject responded correctly (Latency units are milliseconds). Lower scores represent better performance. Observed range for Pooled Active: -103.1 to 65.5 (change from baseline) Observed range for Pooled Placebo: -10.4 to 39.0 (change from baseline) | Pooled Results: This is a sub-study of 165-302, with a randomized, placebo-control discontinuation design in Part 2. 9 subjects were enrolled in 165-303: 3 in 20mg/day and 3 in 40mg/day Active arm, 2 in 20mg/day and 1 in 40mg/day Placebo arm. Data interpretability was extremely limited, hence planned analysis was using the pooled treatment groups. | Posted | Mean | Standard Deviation | Millisec | Baseline to Part 2 Week 8 |
|
|
| ||||||||||||||||||||||||||||
| Primary | Change From Baseline in Spatial Working Memory (SWM) Between Errors 4-8 Boxes (CANTAB Task) | The SWM task measures visuospatial working memory. During this task, a number of boxes appears on a screen. The objective of the task is to find a token under a box and to place this token in a designated area. There is only one token under one box during each round and the location of the token rotates in each round to a different box, other than a box within which the token was found in previous rounds. The subject is therefore asked to remember which boxes previously contained tokens so as to better the chances and speed of finding tokens under boxes which did not previously contain tokens. SWM between errors measures the total number of times the subject revisits a box in which a token has previously been found in the same problem (calculated for assessed problems only). Observed range for Pooled Active: -8 to 1 (change from baseline) Observed range for Pooled Placebo: -5 to 12 (change from baseline) Lower scores represent better performance. | Pooled Results: This is a sub-study of 165-302, with a randomized, placebo-control discontinuation design in Part 2. 9 subjects were enrolled in 165-303: 3 in 20mg/day and 3 in 40mg/day Active arm, 2 in 20mg/day and 1 in 40mg/day Placebo arm. Data interpretability was extremely limited, hence planned analysis was using the pooled treatment groups. | Posted | Mean | Standard Deviation | Number of times | Baseline to Part 2 Week 8 |
| ||||||||||||||||||||||||||||||
| Primary | Change From Baseline in Stop Signal Task (SST) Stop Signal Reaction T (CANTAB Task) | The SST task measures inhibitory control and cognitive flexibility. The SST is a 2-part task. During part 1, an arrow appears on the screen and subjects are asked to press an arrow button on the screen corresponding with the direction of the arrow displayed. During part 2 of the task, subjects follow the same instructions as in part 1; however, they are asked to withhold their response (do not press an arrow button) if they hear an auditory signal (beep) when the arrow is displayed. SST stop signal delay is the length of time between the go stimulus and the stop stimulus at which the subject is able to successfully inhibit their response on 50% of trials. Lower time represents better performance. Observed range for Pooled Active: -31.6 to 48.7 (change from baseline) Observed range for Pooled Placebo: 47.8 to 72.5 (change from baseline) | Pooled Results: This is a sub-study of 165-302, with a randomized, placebo-control discontinuation design in Part 2. 9 subjects were enrolled in 165-303: 3 in 20mg/day and 3 in 40mg/day Active arm, 2 in 20mg/day and 1 in 40mg/day Placebo arm. Data interpretability was extremely limited, hence planned analysis was using the pooled treatment groups. | Posted | Mean | Standard Deviation | Millisec | Baseline to Part 2 Week 8 |
| ||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in RVP A Prime - Signal Detection Measure of Sensitivity to the Target (CANTAB Task) | The RVP task measures sustained attention. In this task, a series of random digits continuously appears in the middle of the screen. Subjects are asked to recognize a specific sequence of digits and are asked to press a button on the screen whenever this specific sequence of digits appears within this series of continuous digits. RVP A prime represents the signal detection measure of sensitivity to the target, regardless of response tendency. In essence, measure of how good the subject is at detecting target sequences. Observed range for Pooled Active: -0.004 to 0.030 (change from baseline) Observed range for Pooled Placebo: -0.057 to -0.001 (change from baseline) A higher score on the test represents a better performance. | Pooled Results: This is a sub-study of 165-302, with a randomized, placebo-control discontinuation design in Part 2. 9 subjects were enrolled in 165-303: 3 in 20mg/day and 3 in 40mg/day Active arm, 2 in 20mg/day and 1 in 40mg/day Placebo arm. Data interpretability was extremely limited, hence planned analysis was using the pooled treatment groups. | Posted | Mean | Standard Deviation | Proportion | Baseline to Part 2 Week 8 |
| ||||||||||||||||||||||||||||||
| Secondary | Change From the Baseline in SWM Strategy 6-8 Boxes - Number of Distinct Boxes Used by the Subject to Begin a New Search for a Token(CANTAB Task) | The SWM task measures visuospatial working memory. During this task, a number of boxes appears on a screen. The objective of the task is to find a token under a box and to place this token in a designated area. There is only one token under one box during each round and the location of the token rotates in each round to a different box, other than a box within which the token was found in previous rounds. The subject is therefore asked to remember which boxes previously contained tokens so as to better the chances and speed of finding tokens under boxes which did not previously contain tokens. For assessed problems with six boxes or more, SWM strategy is the number of distinct boxes used by the subject to begin a new search for a token (within the same problem). A high score represents poor use of this strategy and a low score equates to effective use. Observed range for Pooled Active: -3 to 3 (change from baseline) Observed range for Pooled Placebo: -3 to 1(change from baseline) | Pooled Results: This is a sub-study of 165-302, with a randomized, placebo-control discontinuation design in Part 2. 9 subjects were enrolled in 165-303: 3 in 20mg/day and 3 in 40mg/day Active arm, 2 in 20mg/day and 1 in 40mg/day Placebo arm. Data interpretability was extremely limited, hence planned analysis was using the pooled treatment groups. | Posted | Mean | Standard Deviation | Number of distinct boxes | Baseline to Part 2 Week 8 |
| ||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in SST Proportion of Successful Stops - Measures the Proportion of Completed Stop Trials That Were Successful Stops (CANTAB Task) | The SST task measures inhibitory control and cognitive flexibility. The SST is a 2-part task. During part 1, an arrow appears on the screen and subjects are asked to press an arrow button on the screen corresponding with the direction of the arrow displayed. During part 2 of the task, subjects follow the same instructions as in part 1; however, they are asked to withhold their response (do not press an arrow button) if they hear an auditory signal (beep) when the arrow is displayed. SST stop signal delay is the length of time between the go stimulus and the stop stimulus at which the subject is able to successfully inhibit their response on 50% of trials. SST proportion of successful stops measures the proportion of completed stop trials that were successful stops. A higher score on the test represents a better performance. Observed range for Pooled Active: -0.1 to 0.05 (change from baseline) Observed range for Pooled Placebo: 0.0 to 0.0 (change from baseline) | Pooled Results: This is a sub-study of 165-302, with a randomized, placebo-control discontinuation design in Part 2. 9 subjects were enrolled in 165-303: 3 in 20mg/day and 3 in 40mg/day Active arm, 2 in 20mg/day and 1 in 40mg/day Placebo arm. Data interpretability was extremely limited, hence planned analysis was using the pooled treatment groups. | Posted | Mean | Standard Deviation | Proportion | Baseline to Part 2 Week 8 |
|
AE's were not monitored during this study (Adverse events were monitored through the parent 165-302 study (NCT01889862)), so this section is not applicable.
Adverse Events were not collected as part of this observational sub study, but were reported to the parent 165-302 study
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 | Pooled Active | Subjects randomized to receive active drug in study 165-302 part 2. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG001 | Pooled Placebo | Subjects randomized to receive placebo in study 165-302 part 2 | 0 | 0 | 0 | 0 | 0 | 0 |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Karen Gu/Director, BioStatistics | BioMarin Pharmaceutical Inc. | 650-829-4017 | kgu@bmrn.com |
| SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Apr 24, 2015 | Jun 22, 2018 | Prot_001.pdf |
| ID | Term |
|---|---|
| D010661 | Phenylketonurias |
| ID | Term |
|---|---|
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| 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 |
Not provided
Not provided
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Pooled Placebo |
Subjects randomized to receive placebo in study 165-302 part 2 |
|
|
Subjects randomized to receive placebo in study 165-302 part 2
|
|
|
|
| OG001 | Pooled Placebo | Subjects randomized to receive placebo in study 165-302 part 2 |
|
|
| OG001 | Pooled Placebo | Subjects randomized to receive placebo in study 165-302 part 2 |
|
|