A Phase 3 Substudy to Evaluate Executive Function in Adults With PKU Who Are Participating in the Phase 3 Study, 165-302 (PRISM303)

May 21, 2020 updated by: BioMarin Pharmaceutical

A Phase 3 Substudy to Evaluate Executive Function in Adults With Phenylketonuria Who Are Participating in the Phase 3 Study, 165-302

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Actual)

9

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky Medical Center
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Subjects with PKU who are currently enrolled in 165-302 Part 2.

Description

Inclusion Criteria:

  • Are currently participating in Part 1 of Study 165-302 and meet the criteria for participation in Part 2 of 165-302
  • Are willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any research-related procedures.
  • Have the ability to complete the CANTAB and subject global assessment.
  • Are willing and able to comply with all study procedures.

Exclusion Criteria:

  • Any condition that, in the view of the investigator, places the subject at high risk of poor compliance or terminating early from the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Rapid Visual Processing (RVP) Mean Response Latency (CANTAB Task)
Time Frame: Baseline to Part 2 Week 8

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)
Time Frame: Baseline to Part 2 Week 8

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)
Time Frame: Baseline to Part 2 Week 8

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)
Baseline to Part 2 Week 8

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in RVP A Prime - Signal Detection Measure of Sensitivity to the Target (CANTAB Task)
Time Frame: Baseline to Part 2 Week 8

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.
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)
Time Frame: Baseline to Part 2 Week 8

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)
Time Frame: Baseline to Part 2 Week 8

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

BioMarin Pharmaceutical

Investigators

  • Study Director: Debra Lounsbury, Principal Scientist/Medical Monitor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 5, 2015

Primary Completion (Actual)

February 1, 2017

Study Completion (Actual)

February 1, 2017

Study Registration Dates

First Submitted

June 3, 2015

First Submitted That Met QC Criteria

June 8, 2015

First Posted (Estimate)

June 11, 2015

Study Record Updates

Last Update Posted (Actual)

June 4, 2020

Last Update Submitted That Met QC Criteria

May 21, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 165-303

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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