LAUSR

We are conducting a double-blind, randomized, clinical study in Delayed Sleep-Wake Phase Disorder (DSWPD) participants with extensive clinical phenotyping. We evaluated screening Dim Light Melatonin Onset (DLMO) assessments in participants with a DSWPD diagnosis to determine the proportion of participants with and without a circadian delay. Delayed DLMO is DLMO occurring after or within 30 minutes before desired bedtime, and after 21:30. Each DLMO assessment consisted of eight saliva collections performed at five, four, three, two, and one hour before bedtime, at planned bedtime, and one and three hours after bedtime. Salivary DLMO assessments were distributed to participants at Visit 1 (screening) and Visit 3 (treatment) with a questionnaire to record planned and actual collection times. Participants were instructed to wear blue-light blocking glasses during the assessment period. The Morningness-Eveningness Questionnaire (MEQ) was also completed by participants at V1 to evaluate circadian and sleep rhythm patterns. DLMO was calculated for each phase assessment and defined as the clock time when the melatonin concentration exceeded the mean of three low consecutive values, plus twice the standard deviation of these points. Thirty-four participants with DSWPD completed the screening DLMO assessment, 33 of which had a delayed DLMO (97.06%). Sub-analyses were conducted on participants with DSWPD who had delayed DLMO (n = 33). Within this subset, the average DLMO time was 23:52 (SD = 1:58) and the average MEQ score was 34.27 (SD = 10.39). Of these 33 participants, 14 had a DLMO time after 00:00 (42.42%). These initial data indicate that, on average, participants with DSWPD that completed the screening DLMO assessment had delayed DLMO. Further analyses show that almost half of this subset had a significantly delayed DLMO (00:00 or later). This study is currently ongoing and blinded. Further data will be analyzed as more participants enroll. ‘Phase typing’ will be important in further understanding the underlying pathophysiology and in the treatment selection for patients with DSWPD. This work was supported by Vanda Pharmaceuticals Inc.