Abstract Details

Title Impact of the Oral Orexin Receptor 2 Agonist TAK-994 on Sustained Attention in Patients with Narcolepsy Type 1: Exploratory Results from a Phase 2 Study

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P11 - Poster Session 11 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-012

Objective To evaluate the effect of TAK-994 on sustained attention and vigilance in patients with narcolepsy type 1 (NT1).

Background NT1 is a rare, chronic, neurologic disorder characterized by sleep-wake instability. The oral orexin receptor 2 (OX2R)-selective agonist TAK-994 was developed for the potential treatment of narcolepsy; clinical development was discontinued owing to associated hepatotoxicity.

Design/Methods A multi-part, phase 2, randomized, double-blind, placebo-controlled study evaluated the safety (Part A) and efficacy (Part B) of twice-daily oral TAK-994 in patients with narcolepsy type 1 (NCT04096560). Exploratory endpoints included Psychomotor Vigilance Task (PVT; Part A), and Sustained Attention to Response Test (SART; Part B).

Results

In Part A, 22 patients were randomized (placebo, n=7; 120mg TAK-994, n=7; 180mg TAK-994, n=8) and 21 completed. In Part B, 73 patients were randomized (placebo, n=17; 30mg TAK-994, n=17; 90mg TAK-994, n=20; 180mg TAK-994, n=19); 43 completed owing to study termination. Change from baseline to week 4 in PVT lapses were greater with TAK-994 (Cohen’s d: 0.78 [120mg], 2.22 [180mg]) than placebo (-0.23); corresponding baseline adjusted changes in LSMEANS were significant: p=0.009 (120mg TAK-994), p<0.001 (180mg TAK-994). In Part B, Cohen’s d for change from baseline to week 8 for SART scores were greater with TAK-994 (0.84 [30mg], 1.22 [90mg], 1.11 [180mg]) than placebo (-0.48); corresponding baseline adjusted changes in LSMEANS were significant with TAK-994 for the two highest doses: p=0.089 (30mg), p=0.022 (90mg), p=0.026 (180mg). Treatment-emergent adverse events were reported by 2 (28.6%), 6 (85.7%) and 7 (87.5%) patients with placebo, 120mg and 180mg TAK-994 in part A.

Conclusions

Significant improvements on the PVT and SART were achieved with TAK-994 versus placebo, suggesting potential use for OX2R agonists to address attention deficits in patients with narcolepsy.

Authors/Disclosures
Brian Harel, PhD PRESENTER	Brian Harel, PhD has received personal compensation for serving as an employee of Takeda. An immediate family member of Brian Harel, PhD has received personal compensation for serving as an employee of Astra Zeneca. Brian Harel, PhD has or had stock in Takeda, Merck, Day One Biopharmaceuticals. An immediate family member of Brian Harel, PhD has or had stock in Eli Lilly, Pfizer, Astra Zeneca.Brian Harel, PhD has or had stock in Cogstate.
Yves Dauvilliers, MD, PhD (Hopital Gui De Chaulliac)	Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for idorsia. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for JAZZ. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avadel. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alkermes. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Centessa. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bioprojet. Yves Dauvilliers, MD, PhD has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Harmony Bioscience.
Giuseppe Plazzi, MD (University di Bologna)	The institution of Dr. Plazzi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TAKEDA. The institution of Dr. Plazzi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BIOPROJET. The institution of Dr. Plazzi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for JAZZ. The institution of Dr. Plazzi has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for OREXIA. The institution of Dr. Plazzi has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for OREXIA/CENTESSA.
Elena Koundourakis (Takeda)	Elena Koundourakis has nothing to disclose.
Yeting Du (Takeda)	Yeting Du has received personal compensation for serving as an employee of Takeda Pharmaceuticals.
Christian Von Hehn	No disclosure on file
Dmitri Volfson (Takeda)	Dmitri Volfson has received personal compensation for serving as an employee of Takeda.
Robert Latzman (Takeda)	Robert Latzman has received personal compensation for serving as an employee of Takeda Pharmaceuticals. Robert Latzman has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Society for Personality Assessment. Robert Latzman has stock in Takeda Pharmaceutical Co Ltd.

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