scholarly journals 0477 Characteristics of Insomnia Subjects Screened for Transitioning from Zolpidem Tartrate to Lemborexant in a Multicenter Pilot Study

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A183-A183
Author(s):  
M Ahmad ◽  
M Malhotra ◽  
J Amchin ◽  
D Kumar ◽  
C Perdomo ◽  
...  
Keyword(s):  
Pilot Study ◽  
Extended Release ◽  
Maintenance Phase ◽  
Treatment Phase ◽  
Usage Frequency ◽  
Titration Period ◽  
Falling Asleep ◽  
Insomnia Treatment ◽  
Waking Up

Abstract Introduction Patients who take insomnia medication may change medications for reasons including lack of efficacy, adverse events, and dependence concerns. A pilot study (NCT04009577, E2006-A001-312) assessed a dosing approach for transitioning patients from zolpidem tartrate (ZOL; immediate or extended-release) to lemborexant, a dual orexin receptor antagonist. Here we describe characteristics of subjects who entered the study Screening Period and their reasons for wanting to change medications. Methods This multicenter pilot study was conducted in the U.S. and enrolled subjects age ≥18y with insomnia diagnosed per DSM-5 criteria, and who used ZOL (self-reported intermittently [3-4 nights/week] or frequently [≥5 nights/week]) as their only insomnia treatment. Subjects entered a 3-week Screening Period, during which frequency/dose of ZOL taken was recorded; subjects also wore an actigraph continuously. Eligible subjects thereafter entered the Treatment Phase to determine lemborexant dosing (5 or 10mg during a 2-week Titration Period with assignment to 1 of 3 treatment schedules based on ZOL usage frequency during Screening), followed by a 12-week Extension (Maintenance) Phase and a 4-week Follow-up Period. Results Forty-nine subjects entered the Screening period and completed the Chief Complaint Form through November 2019; mean(SD) age was 57.1(13.8)y, 67.3% were female, 69.4% were white, and 28.6% were black. 31 subjects reported using ZOL frequently and 15 reported using ZOL intermittently (3 missing). The most common sleep complaint was waking up too early (n=33), followed by difficulty staying asleep (n=13), and difficulty falling asleep (n=3). Reasons for wanting to switch from ZOL included: ZOL not working (n=19), concerns about taking ZOL (n=14), wanting to try something new/potentially better (n=6), side effects (n=5), and residual daytime sleepiness (n=4). 43/49 subjects completed screening through this period. Conclusion This study offers the opportunity to understand patients’ current use of insomnia medication and their motivation for wanting to change insomnia medications. Support Eisai Inc.

337 A Multicenter Open-label Pilot Study Evaluating Next-Dose Transition From Zolpidem to Lemborexant: Analysis of Female Subgroup

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A134-A135
Author(s):  
Maha Ahmad ◽  
Manoj Malhotra ◽  
Jess Amchin ◽  
Dinesh Kumar ◽  
Carlos Perdomo ◽  
...  
Keyword(s):  
Pilot Study ◽  
Extended Release ◽  
Open Label ◽  
Titration Period ◽  
Post Hoc ◽  
Dose Change ◽  
Extension Period ◽  
Common Teaes ◽  
Female Subjects

Abstract Introduction Dosing paradigms for transitioning patients to lemborexant (LEM) from zolpidem (ZOL: immediate [IR] or extended-release [ER]) were examined in E2006-A001-312 (Study 312; NCT04009577), an open-label pilot study. Given insomnia prevalence in women, post hoc analyses in female subjects were conducted. Methods Study 312 included: 3-week Screening Period (subjects continued ZOL); 2-week Titration Period (TITR); 12-week Extension Period (EXT); 4-week Follow-up. Adults with insomnia taking ZOL-IR or ZOL-ER intermittently (3–4 nights/week) or frequently (≥5 nights/week) were enrolled. Subjects with intermittent, or one week each of intermittent and frequent ZOL use, were assigned to Cohort-1 and started TITR with LEM 5mg (LEM5). Frequent ZOL users (Cohort-2) were randomized 1:1 to LEM5 (Cohort-2A) or LEM 10mg (LEM10; Cohort-2B). Subjects who transitioned to LEM could opt into EXT. Subjects could change LEM dose during TITR (only once) and during EXT. The primary endpoint was the proportion of subjects who transitioned to LEM at end of TITR. Treatment-emergent adverse events (TEAEs) were assessed by dose at time of TEAE. Results Overall, 35 subjects were female and 29/35 (82.9%) transitioned to LEM. In Cohort-1, 7 subjects began TITR; all transitioned to LEM (5 subjects ended TITR on LEM5; 2 ended on LEM10). In Cohort-2A, 14 subjects began TITR with LEM5; 12/14 (85.7%) transitioned (6 subjects each ended TITR on LEM5 or LEM10). In Cohort-2B, 14 subjects began TITR with LEM10; 10/14 (71.4%) transitioned to LEM (3 subjects ended TITR on LEM5 and 7 on LEM10). All 29 transitioned subjects opted into EXT, and 27/29 (93.1%) completed the study. Based on modal dose (most frequent dose taken during TITR and EXT combined) groups, median time to first dose change during EXT was 14.5 and 17.0 days for LEM5 and LEM10, respectively. Overall, most TEAEs were mild/moderate in severity. Across TITR and EXT, more TEAEs occurred with LEM10 than with LEM5; the most common TEAEs were somnolence (n=3) and abnormal dreams (n=3). Conclusion Most female subjects successfully transitioned from intermittent or frequent ZOL-IR/ZOL-ER use to LEM and completed the study. LEM was generally well tolerated. The safety profile was consistent with that observed in Phase 3 studies. Support (if any) Eisai Inc.

scholarly journals 0478 A Multicenter Pilot Study to Evaluate Next-Dose Transition from Zolpidem to Lemborexant for the Treatment of Insomnia

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A183-A183
Author(s):  
R Rosenberg ◽  
J Amchin ◽  
D Kumar ◽  
C Perdomo ◽  
M Moline ◽  
...  
Keyword(s):  
Pilot Study ◽  
Receptor Antagonist ◽  
Treatment Phase ◽  
Phase 3 ◽  
Two Phase ◽  
Dsm 5 ◽  
Phase Maintenance ◽  
Titration Period ◽  
Insomnia Treatment ◽  
Cutoff Date

Abstract Introduction Switching of medications for insomnia occurs often in clinical practice based on a variety of reasons. However, few clinical studies have examined methods for transitioning patients between different insomnia medications. This is especially important to consider when the classes of drugs are different (e.g., GABA-ergic agonism vs orexin receptor antagonism); thus, clinical guidance would be valuable. The safety and efficacy of the dual orexin receptor antagonist lemborexant (LEM) for the treatment of insomnia was confirmed in two Phase 3 studies, SUNRISE-1 (NCT02783729, E2006-G000-304) and SUNRISE-2 (NCT02952820, E2006-G000-303). This pilot study (NCT04009577, E2006-A001-312) was designed to assess pre-specified dosing approaches for directly transitioning from the sedative-hypnotic zolpidem (ZOL), a commonly prescribed sleep aid, to LEM. Methods This multicenter pilot study has enrolled subjects age ≥18 years with an insomnia diagnosis (DSM-5 criteria), who used ZOL (intermittently or frequently) as their only insomnia treatment. Following a 3-week Screening period, eligible subjects enter the Treatment Phase (2-week titration period: assigned to 1 of 3 treatment arms based on ZOL use during Screening), and then the Extension Phase (maintenance period up to 12 weeks). During both the Treatment and Extension Phases, the dose of LEM is flexible between 5 and 10 mg, depending on efficacy and tolerability. The primary endpoint is to evaluate the proportion of subjects taking ZOL who successfully transition to LEM (lemborexant 5 mg [LEM5] or lemborexant 10 mg [LEM10]) after 2 weeks of LEM treatment. Results Enrollment began July 15, 2019. It was initially projected that approximately 110 subjects would be screened to provide about 60 subjects for randomization across 3 treatment arms. Interim data will be presented (planned cutoff date Jan 08, 2020). Conclusion This pilot study will help inform on dosing guidance when transitioning a patient from a GABA-ergic drug to an orexin receptor antagonist. Support Eisai Inc.

335 Evaluation of Dose Transition From Zolpidem to Lemborexant Across 14 Weeks: Results From a Multicenter Open-label Pilot Study

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A134-A134
Author(s):  
Russell Rosenberg ◽  
Jess Amchin ◽  
Dinesh Kumar ◽  
Carlos Perdomo ◽  
Norman Atkins ◽  
...  
Keyword(s):  
Pilot Study ◽  
Extended Release ◽  
Open Label ◽  
Phase 3 ◽  
Titration Period ◽  
Study Results ◽  
Dose Change ◽  
Extension Period ◽  
Common Teaes

Abstract Introduction E2006-A001-312 (Study 312; NCT04009577) was an open-label pilot study that examined pre-specified dosing paradigms for transitioning patients from zolpidem (ZOL: immediate [IR] or extended-release [ER]) to the dual orexin receptor antagonist lemborexant (LEM; 5mg [LEM5] or 10mg [LEM10]). Methods Study 312 included a 3-week Screening Period (subjects continued ZOL), 2-week Titration Period (TITR), 12-week Extension Period (EXT), and 4-week Follow-up Period. Adults with insomnia who were intermittent (3–4 nights/week) or frequent (≥5 nights/week) ZOL-IR or ZOL-ER users participated. Intermittent ZOL users and subjects with one week each of intermittent and frequent ZOL usage were assigned to Cohort-1 and began TITR with LEM5. Frequent ZOL users were assigned to Cohort-2 and randomized 1:1 to LEM5 or LEM10. Subjects who successfully transitioned to LEM had the option to enter EXT. During TITR and EXT, subjects could change LEM dose (only once during TITR). The primary endpoint was the proportion of subjects who transitioned to LEM at the end of TITR. Treatment-emergent adverse events (TEAEs) were assessed based on dose at time of TEAE. Results Fifty-three subjects enrolled (Cohort-1, n=10; Cohort-2, n=43). Of these, 43/53 (81.1%) transitioned to LEM at the end of TITR; all 43 (100.0%) entered EXT wherein 41/43 subjects received treatment. Three of these subjects discontinued treatment during EXT, so that 38/41 (92.7%) subjects entered EXT, received treatment and completed EXT. At the end of EXT, 25/41 (61.0%) subjects were receiving LEM10 and 16/41 (39.0%) were receiving LEM5. Based on modal dose (most frequent dose taken during TITR and EXT combined) groups, median time to first dose change was 14.5 days and 36.0 days for LEM5 and LEM10, respectively. The majority of TEAEs were mild/moderate in severity. Across the study (TITR and EXT), more TEAEs occurred with LEM10 than LEM5; the most common TEAEs were somnolence (n=4) and abnormal dreams (n=4). Conclusion Study results support the view that patients can successfully transition directly from ZOL to LEM. LEM was generally well tolerated; the safety profile was consistent with that observed in Phase 3 clinical development. Support (if any) Eisai Inc.

scholarly journals Pilot study of extended-release lorcaserin for cocaine use disorder among men who have sex with men: A double-blind, placebo-controlled randomized trial

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254724
Author(s):  
Glenn-Milo Santos ◽  
Janet Ikeda ◽  
Phillip Coffin ◽  
John E. Walker ◽  
Tim Matheson ◽  
...  
Keyword(s):  
Pilot Study ◽  
Extended Release ◽  
Self Report ◽  
Computer Assisted ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Cocaine Use ◽  
Sex With Men ◽  
Urine Testing

Objective To determine if men who have sex with men (MSM) with cocaine use disorder (CUD) and actively-using cocaine could be enrolled and retained in a pharmacologic intervention trial of lorcaserin—a novel 5-HT2cR agonist—and determine the degree to which participants would adhere to study procedures. Methods This was a phase II randomized, double-blind, placebo-controlled pilot study with 2:1 random parallel group assignment to daily extended-release oral lorcaserin 20 mg versus placebo (clinicaltrials.gov identifier-NCT03192995). Twenty-two of a planned 45 cisgender MSM with CUD were enrolled and had weekly follow-up visits during a 12-week treatment period, with substance use counseling, urine specimen collection, and completion of audio-computer assisted self-interview (ACASI) behavioral risk assessments. Adherence was measured by medication event monitoring systems (MEMS) caps and self-report. This study was terminated early because of an FDA safety alert for lorcaserin’s long-term use. Results Eighty-six percent completed the trial, with 82% of weekly study follow-up visits completed. Adherence was 55.3% (lorcaserin 51.6% vs. placebo 66.2%) by MEMS cap and 56.9% (56.5% vs. placebo 57.9%) by self-report and did not differ significantly by treatment assignment. Intention-to-treat analyses (ITT) did not show differences in cocaine positivity by urine screen between the lorcaserin and placebo groups by 12 week follow-up (incidence risk ratio [IRR]: 0.96; 95%CI = 0.24–3.82, P = 0.95). However, self-reported cocaine use in timeline follow-back declined more significantly in the lorcaserin group compared to placebo (IRR: 0.66; 95%CI = 0.49–0.88; P = 0.004). Conclusion We found that it is feasible, acceptable, and tolerable to conduct a placebo-controlled pharmacologic trial for MSM with CUD who are actively using cocaine. Lorcaserin was not associated with significant reductions in cocaine use by urine testing, but was associated with significant reductions in self-reported cocaine use. Future research may be needed to continue to explore the potential utility of 5-HT2cR agonists.

scholarly journals Can sleep disturbance be a cue of mood spectrum comorbidity? A preliminary study in panic disorder

CNS Spectrums ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 32-37
Author(s):  
Mario Miniati ◽  
Laura Palagini ◽  
Alessandra Maglio ◽  
Donatella Marazziti ◽  
Liliana Dell’Osso
Keyword(s):  
Panic Disorder ◽  
Sleep Disturbances ◽  
Outcome Measure ◽  
Self Report ◽  
Chi Square ◽  
Falling Asleep ◽  
Axis I ◽  
Preliminary Study ◽  
Waking Up

Objective.To investigate if sleep disturbances may affect treatment outcomes of patients with panic disorder (PD).Methods.Eighty-five PD outpatients with no Axis I comorbidity for mood disorders completed a baseline assessment (T1) and were evaluated after 3 (T2), 6 (T3) and 12 months (T4), with the Panic Disorder Severity Scale (PDSS) total score as outcome measure during a 12-month naturalistic follow-up. Patients were assessed with the Mood Spectrum Self-Report (MOODS-SR, Lifetime Version), and the PDSS.Results.Forty-three patients (50.5%) met criteria for remission (PDSS<5) and 42 (49.5%) for no remission. In a logistic regression model withremissionas the dependent variable, MOODS-SRsleep disturbanceswas the only determinant for a lower likelihood of PD remission. The items accounting for this result were the following:Repeated difficulty falling asleep(chi-square = 4.4; df = 1;p= 0.036), andRepeatedly waking up in the middle of the night(chi-square = 5.2; df = 1;p= 0.022).Conclusion.Lifetime sleep disturbances would represent a cue of mood spectrum (in absence of overt affective comorbidity) that may impair remission in PD.

A Pilot Study of Mobile Telephone Message Interventions with Suicide Attempters in China

Crisis ◽  
2010 ◽  
Vol 31 (2) ◽  
pp. 109-112 ◽  
Author(s):  
Hui Chen ◽  
Brian L. Mishara ◽  
Xiao Xian Liu
Keyword(s):  
Pilot Study ◽  
Effective Means ◽  
Text Message ◽  
Text Messages ◽  
Mobile Telephone ◽  
Future Research ◽  
Quick Method ◽  
Suicide Attempters ◽  
To Receive

Background: In China, where follow-up with hospitalized attempters is generally lacking, there is a great need for inexpensive and effective means of maintaining contact and decreasing recidivism. Aims: Our objective was to test whether mobile telephone message contacts after discharge would be feasible and acceptable to suicide attempters in China. Methods: Fifteen participants were recruited from suicide attempters seen in the Emergency Department in Wuhan, China, to participate in a pilot study to receive mobile telephone messages after discharge. All participants have access to a mobile telephone, and there is no charge for the user to receive text messages. Results: Most participants (12) considered the text message contacts an acceptable and useful form of help and would like to continue to receive them for a longer period of time. Conclusions: This suggests that, as a low-cost and quick method of intervention in areas where more intensive follow-up is not practical or available, telephone messages contacts are accessible, feasible, and acceptable to suicide attempters. We hope that this will inspire future research on regular and long-term message interventions to prevent recidivism in suicide attempters.

Prognostic significance of C1–C2 facet malalignment after surgical decompression in adult Chiari malformation type I: a pilot study based on the Chicago Chiari Outcome Scale

2020 ◽  
pp. 1-7
Author(s):  
Michael Lumintang Loe ◽  
Tito Vivas-Buitrago ◽  
Ricardo A. Domingo ◽  
Johan Heemskerk ◽  
Shashwat Tripathi ◽  
...  
Keyword(s):  
Pilot Study ◽  
Chiari Malformation ◽  
Prognostic Significance ◽  
Foramen Magnum ◽  
Bivariate Analysis ◽  
Type I ◽  
Foramen Magnum Decompression ◽  
Swallowing Function ◽  
Chiari Malformation Type I

OBJECTIVEThe authors assessed the prognostic significance of various clinical and radiographic characteristics, including C1–C2 facet malalignment, in terms of surgical outcomes after foramen magnum decompression of adult Chiari malformation type I.METHODSThe electronic medical records of 273 symptomatic patients with Chiari malformation type I who were treated with foramen magnum decompression, C1 laminectomy, and duraplasty at Mayo Clinic were retrospectively reviewed. Preoperative and postoperative Neurological Scoring System scores were compared using the Friedman test. Bivariate analysis was conducted to identify the preoperative variables that correlated with the patient Chicago Chiari Outcome Scale (CCOS) scores. Multiple linear regression analysis was subsequently performed using the variables with p < 0.05 on the bivariate analysis to check for independent associations with the outcome measures. Statistical software SPSS version 25.0 was used for the data analysis. Significance was defined as p < 0.05 for all analyses.RESULTSFifty-two adult patients with preoperative clinical and radiological data and a minimum follow-up of 12 months were included. Motor deficits, syrinx, and C1–C2 facet malalignment were found to have significant negative associations with the CCOS score at the 1- to 3-month follow-up (p < 0.05), while at the 9- to 12-month follow-up only swallowing function and C1–C2 facet malalignment were significantly associated with the CCOS score (p < 0.05). Multivariate analysis showed that syrinx presence and C1–C2 facet malalignment were independently associated with the CCOS score at the 1- to 3-month follow-up. Swallowing function and C1–C2 facet malalignment were found to be independently associated with the CCOS score at the 9- to 12-month follow-up.CONCLUSIONSThe observed results in this pilot study suggest a significant negative correlation between C1–C2 facet malalignment and clinical outcomes evaluated by the CCOS score at 1–3 months and 9–12 months postoperatively. Prospective studies are needed to further validate the prognostic value of C1–C2 facet malalignment and the potential role of atlantoaxial fixation as part of the treatment.

Short-Term Ultramicronized Palmitoylethanolamide Therapy in Patients with Myasthenia Gravis: a Pilot Study to Possible Future Implications of Treatment

2019 ◽  
Vol 18 (3) ◽  
pp. 232-238 ◽  
Author(s):  
Emanuela Onesti ◽  
Vittorio Frasca ◽  
Marco Ceccanti ◽  
Giorgio Tartaglia ◽  
Maria Cristina Gori ◽  
...  
Keyword(s):  
Pilot Study ◽  
Myasthenia Gravis ◽  
Repetitive Nerve Stimulation ◽  
Beneficial Effects ◽  
Antibody Titers ◽  
The Stability ◽  
Ultramicronized Palmitoylethanolamide ◽  
Open Pilot

Background: The cannabinoid system may be involved in the humoral mechanisms at the neuromuscular junction. Ultramicronized-palmitoylethanolamide (μm-PEA) has recently been shown to reduce the desensitization of Acetylcholine (ACh)-evoked currents in denervated patients modifying the stability of ACh receptor (AChR) function. <p> Objective: To analyze the possible beneficial effects of μm-PEA in patients with myasthenia gravis (MG) on muscular fatigue and neurophysiological changes. <p> Method: The duration of this open pilot study, which included an intra-individual control, was three weeks. Each patient was assigned to a 1-week treatment period with μm-PEA 600 mg twice a day. A neurophysiological examination based on repetitive nerve stimulation (RNS) of the masseteric and the axillary nerves was performed, and the quantitative MG (QMG) score was calculated in 22 MG patients every week in a three-week follow-up period. AChR antibody titer was investigated to analyze a possible immunomodulatory effect of PEA in MG patients. <p> Results: PEA had a significant effect on the QMG score (p=0.03418) and on RNS of the masseteric nerve (p=0.01763), thus indicating that PEA reduces the level of disability and decremental muscle response. Antibody titers did not change significantly after treatment. <p> Conclusion: According to our observations, μm-PEA as an add-on therapy could improve muscular response to fatigue in MG. The possible modulation of AChR currents as a means of eliciting a direct effect from PEA on the conformation of ACh receptors should be investigated. The co-role of cytokines also warrants an analysis. Given the rapidity and reversibility of the response, we suppose that PEA acts directly on AChR, though further studies are needed to confirm this hypothesis.

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