Defining a Clinically Meaningful Within-Person Change Threshold for the Psychomotor Vigilance Test in Narcolepsy Type...

Area of Science:

• Neuroscience
• Clinical Pharmacology
• Sleep Medicine

Background:

• Narcolepsy type 1 (NT1) is a chronic neurological disorder characterized by excessive daytime sleepiness and impaired attention.
• The Psychomotor Vigilance Test (PVT) is a key measure for assessing attention, with lapses (reaction times > 500 ms) being a primary indicator of impairment.
• Establishing meaningful within-patient change (MWPC) thresholds is crucial for evaluating treatment efficacy in NT1.

Purpose of the Study:

• To define MWPC thresholds for the PVT in individuals with NT1.
• To assess if the orexin-2 receptor agonist oveporexton (TAK-861) provides clinically meaningful improvements in attention for NT1 patients.

Main Methods:

• Utilized data from two Phase III randomized placebo-controlled trials (The First Light and The Radiant Light) involving 271 participants with NT1.
• Employed anchor-based and distribution-based methods to derive MWPC estimates for PVT lapses.
• Analyzed mean changes in square root-transformed PVT lapses and confirmed thresholds using receiver operating characteristic (ROC) curve analysis.

Main Results:

• Anchor-based analyses, supported by distribution-based methods and ROC curves, identified a reduction of ≥ -2 PVT lapses as a meaningful attention improvement.
• In The First Light trial, 66.9% of oveporexton-treated participants achieved meaningful attention improvement versus 25.7% on placebo (P ≤ 0.0001).
• In The Radiant Light trial, 57.6% of oveporexton-treated participants achieved meaningful attention improvement versus 17.6% on placebo (P ≤ 0.0001).

Conclusions:

• Treatment with oveporexton resulted in clinically meaningful improvements in attention for individuals with narcolepsy type 1.
• A reduction of ≥ -2 PVT lapses was significantly more likely in the oveporexton group compared to placebo, confirming treatment efficacy.