{
  "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).\n\nMethods: 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.\n\nResults: 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).\n\nConclusions: 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.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s43441-026-01025-8.",
  "abstract_shown": true,
  "affiliations": [
    "Takeda Development Center Americas, Inc., 500 Kendall Street, Cambridge, MA 02142 USA",
    "Department of Psychiatry, Yale School of Medicine, New Haven, CT USA",
    "Clinical Outcomes Solutions, Tucson, AZ USA",
    "Cogstate Ltd., Melbourne, Australia",
    "Clinical Outcomes Solutions, Folkstone, Kent, UK"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Brian T. Harel"
    },
    {
      "affs": [
        1
      ],
      "name": "Robert H. Pietrzak"
    },
    {
      "affs": [
        2
      ],
      "name": "Shruti Dave"
    },
    {
      "affs": [
        3
      ],
      "name": "Paul Maruff"
    },
    {
      "affs": [
        0
      ],
      "name": "Heather Romero"
    },
    {
      "affs": [
        2
      ],
      "name": "Marisa Brimmer"
    },
    {
      "affs": [
        4
      ],
      "name": "Helen Doll"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8acv2jvys69zh.bib",
  "cited_by": 0,
  "doi": "10.1007/s43441-026-01025-8",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13722789/",
  "id": "8acv2jvys69zh",
  "issns": [
    "2168-4790",
    "2168-4804"
  ],
  "landing_url": "https://doi.org/10.1007/s43441-026-01025-8",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2805|Sleep and Wakefulness Research"
    ]
  ],
  "openalex": "W7202084730",
  "pdf_url": "https://link.springer.com/content/pdf/10.1007/s43441-026-01025-8.pdf",
  "pmcid": "PMC13722789",
  "pmid": "42573945",
  "published": "2026-08-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8acv2jvys69zh.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:21:33Z",
      "native_id": "PMC13722789",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s43441-026-01025-8"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2805|Sleep and Wakefulness Research",
      "subfield": "neuroscience"
    }
  ],
  "title": "Defining a Clinically Meaningful Within-Person Change Threshold for the Psychomotor Vigilance Test in Narcolepsy Type 1",
  "title_text": "Defining a Clinically Meaningful Within-Person Change Threshold for the Psychomotor Vigilance Test in Narcolepsy Type 1",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T12:21:33Z",
  "url": "https://research.draconitic.com/paper/8acv2jvys69zh",
  "venue": "Therapeutic Innovation & Regulatory Science",
  "versions": []
}