Defining a Clinically Meaningful Within-Person Change Threshold for the Psychomotor Vigilance Test in Narcolepsy Type 1
5 affiliations
- 1Takeda Development Center Americas, Inc., 500 Kendall Street, Cambridge, MA 02142 USA
- 2Department of Psychiatry, Yale School of Medicine, New Haven, CT USA
- 3Clinical Outcomes Solutions, Tucson, AZ USA
- 4Cogstate Ltd., Melbourne, Australia
- 5Clinical Outcomes Solutions, Folkstone, Kent, UK
Abstract
Objectives: To establish meaningful within-patient change (MWPC) thresholds for the Psychomotor Vigilance Test (PVT) and evaluate whether treatment with the orexin-2 receptor agonist oveporexton (TAK-861) achieved clinically meaningful improvements in attention in people with narcolepsy type 1 (NT1).
Methods: Attention was assessed as number of lapses (reaction times > 500 ms) on the PVT using data from 2 randomized placebo-controlled phase III trials, The First Light (N = 166) and The Radiant Light (N = 105). Anchor-based methods, supported by distribution-based methods, were used to derive MWPC estimates. Mean changes in square root−transformed PVT lapses (to account for data skewness) were calculated across anchor change categories, with weighted MWPC estimates derived across anchors. Estimates were confirmed with post-hoc receiver operating characteristic (ROC) curve analysis. The proportions of participants meeting MWPC criteria were compared between oveporexton and placebo arms, with odds ratios and 95% confidence intervals.
Results: Across both trials, participants reporting minimal, much, or very much improvement demonstrated progressively fewer PVT lapses. Anchor- and distribution-based analyses supported a reduction of ≥ − 2 PVT lapses, confirmed by ROC curves, as indicating a meaningful improvement in attention. Applying this threshold to unblinded samples, clinically meaningful improvement in attention at day 84 was reported in 66.9% of oveporexton-treated participants versus 25.7% of placebo-treated participants in The First Light and 57.6% versus 17.6% in The Radiant Light (both P ≤ 0.0001).
Conclusions: Improvements in attention with oveporexton in people with NT1 were found to be clinically meaningful, with improvement of ≥ − 2 PVT lapses significantly more likely to occur with oveporexton versus placebo.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s43441-026-01025-8.
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BibTeX
@article{harel2026defining,
title = {{Defining a Clinically Meaningful Within-Person Change Threshold for the Psychomotor Vigilance Test in Narcolepsy Type 1}},
author = {Brian T. Harel and Robert H. Pietrzak and Shruti Dave and Paul Maruff and Heather Romero and Marisa Brimmer and Helen Doll},
journal = {Therapeutic Innovation \& Regulatory Science},
year = {2026},
month = aug,
doi = {10.1007/s43441-026-01025-8},
url = {https://doi.org/10.1007/s43441-026-01025-8},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Defining a Clinically Meaningful Within-Person Change Threshold for the Psychomotor Vigilance Test in Narcolepsy Type 1
AU - Brian T. Harel
AU - Robert H. Pietrzak
AU - Shruti Dave
AU - Paul Maruff
AU - Heather Romero
AU - Marisa Brimmer
AU - Helen Doll
PY - 2026
DA - 2026/08/10
JO - Therapeutic Innovation & Regulatory Science
DO - 10.1007/s43441-026-01025-8
UR - https://doi.org/10.1007/s43441-026-01025-8
AB - Objectives: To establish meaningful within-patient change (MWPC) thresholds for the Psychomotor Vigilance Test (PVT) and evaluate whether treatment with the orexin-2 receptor agonist oveporexton (TAK-861) achieved clinically meaningful improvements in attention in people with narcolepsy type 1 (NT1). Methods: Attention was assessed as number of lapses (reaction times > 500 ms) on the PVT using data from 2 randomized placebo-controlled phase III trials, The First Light (N = 166) and The Radiant Light (N = 105). Anchor-based methods, supported by distribution-based methods, were used to derive MWPC estimates. Mean changes in square root−transformed PVT lapses (to account for data skewness) were calculated across anchor change categories, with weighted MWPC estimates derived across anchors. Estimates were confirmed with post-hoc receiver operating characteristic (ROC) curve analysis. The proportions of participants meeting MWPC criteria were compared between oveporexton and placebo arms, with odds ratios and 95% confidence intervals. Results: Across both trials, participants reporting minimal, much, or very much improvement demonstrated progressively fewer PVT lapses. Anchor- and distribution-based analyses supported a reduction of ≥ − 2 PVT lapses, confirmed by ROC curves, as indicating a meaningful improvement in attention. Applying this threshold to unblinded samples, clinically meaningful improvement in attention at day 84 was reported in 66.9% of oveporexton-treated participants versus 25.7% of placebo-treated participants in The First Light and 57.6% versus 17.6% in The Radiant Light (both P ≤ 0.0001). Conclusions: Improvements in attention with oveporexton in people with NT1 were found to be clinically meaningful, with improvement of ≥ − 2 PVT lapses significantly more likely to occur with oveporexton versus placebo. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s43441-026-01025-8.
SN - 2168-4790
SN - 2168-4804
ER -