An observational study in Phenylketonuria, sponsored by BioMarin Pharmaceutical. Completed at 4 sites in United States. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2020-06-04.
Sponsored by BioMarin Pharmaceutical · Observational
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.
187 studies on the registry are indexed under Phenylketonurias; 38 are open to participants now.
This study's enrollment of 9 is below the median of 40 across 61 observational studies indexed under Phenylketonurias.
Browse Phenylketonurias studies →BioMarin Pharmaceutical is the lead sponsor of 112 studies on the registry; 13 are open to participants now.
Of its 17 completed or terminated interventional studies of FDA-regulated products, 12 (71%) have results posted.
Counted across the registry records on this site, refreshed daily.
Subjects with PKU who are currently enrolled in 165-302 Part 2.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
At designated visits, subject will perform the CANTAB tasks and complete the Subject Global Assessment Questionnaire
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)
Time frame: 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.
Time frame: 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)
Time frame: Baseline to Part 2 Week 8
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.
Time frame: 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)
Time frame: 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)
Time frame: Baseline to Part 2 Week 8
| Milestone | Pooled Active | Pooled Placebo |
|---|---|---|
| Started | 6 | 3 |
| Completed | 6 | 3 |
| Not completed | 0 | 0 |
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)
| Millisec | Pooled Active | Pooled Placebo |
|---|---|---|
| Change From Baseline in Rapid Visual Processing (RVP) Mean Response Latency (CANTAB Task) | -24.23 ± 60.161 | 18.03 ± 25.532 |
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.
| Number of times | Pooled Active | Pooled Placebo |
|---|---|---|
| Change From Baseline in Spatial Working Memory (SWM) Between Errors 4-8 Boxes (CANTAB Task) | -4.2 ± 3.06 | 3.0 ± 8.54 |
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)
| Millisec | Pooled Active | Pooled Placebo |
|---|---|---|
| Change From Baseline in Stop Signal Task (SST) Stop Signal Reaction T (CANTAB Task) | 8.42 ± 34.498 | 58.93 ± 12.529 |
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.
| Proportion | Pooled Active | Pooled Placebo |
|---|---|---|
| Change From Baseline in RVP A Prime - Signal Detection Measure of Sensitivity to the Target (CANTAB Task) | 0.0117 ± 0.01461 | -0.0247 ± 0.02899 |
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)
| Number of distinct boxes | Pooled Active | Pooled Placebo |
|---|---|---|
| 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) | -0.2 ± 2.32 | -1.0 ± 2.0 |
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)
| Proportion | Pooled Active | Pooled Placebo |
|---|---|---|
| Change From Baseline in SST Proportion of Successful Stops - Measures the Proportion of Completed Stop Trials That Were Successful Stops (CANTAB Task) | -0.0333 ± 0.04916 | 0.0 ± 0.0 |
Collected over 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.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Pooled Active | — | — | — |
| Pooled Placebo | — | — | — |
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.
| Age, Categorical(Participants) | Pooled Active | Pooled Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 6 | 3 | 9 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(years) | Pooled Active | Pooled Placebo | Total |
|---|---|---|---|
| Mean | 28.0 ± 5.10 | 39.7 ± 9.24 | 31.9 ± 8.46 |
| Sex: Female, Male(Participants) | Pooled Active | Pooled Placebo | Total |
|---|---|---|---|
| Female | 4 | 2 | 6 |
| Male | 2 | 1 | 3 |
| Ethnicity (NIH/OMB)(Participants) | Pooled Active | Pooled Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 6 | 3 | 9 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Pooled Active | Pooled Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 6 | 3 | 9 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(Participants) | Pooled Active | Pooled Placebo | Total |
|---|---|---|---|
| United States | 6 | 3 | 9 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: No
Ran from Aug 2015 to primary completion in Feb 2017, 17 months.
Results were first posted in Jun 2020, 3 years 4 months after primary completion.
Of 23 observational studies under Phenylketonurias, half reached primary completion within 45 months of starting (the median), counting those still running; a quarter within 12 and three quarters within 95. This study's 17 months is below that.
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This study is completed, as verified in May 2020. You cannot join it, but the record below documents what was studied.
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