scholarly journals P097 Incidence of abnormal dreams and nightmares with lemborexant in adults with insomnia: results from two Phase 3 studies

2021 ◽  
Vol 2 (Supplement_1) ◽  
pp. A52-A52
Author(s):  
T Roth ◽  
J Yardley ◽  
K Pinner ◽  
D Kumar ◽  
J Cheng ◽  
...  
Keyword(s):  
Adverse Events ◽  
Extended Release ◽  
Treatment Initiation ◽  
Phase 3 ◽  
Two Phase ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Insomnia Disorder ◽  
Before And After ◽  
Sedative Hypnotics

Abstract Introduction Abnormal dreams and nightmares have been reported by insomnia patients before and after treatment with sedative-hypnotics. Since dual-orexin-receptor-antagonists such as lemborexant (LEM; approved in multiple countries for adult insomnia) increase REM sleep, during which dream content is more likely to be recalled, we assessed the frequency of nightmares/abnormal dreams in Phase 3 studies. Methods Study 303 (SUNRISE-2) was a 12mo, randomized, double-blind, placebo (PBO)-controlled (first 6mo [Period 1]), phase 3 study that enrolled subjects ≥18y with insomnia disorder and ISI scores ≥15. During Period 1, the safety analysis set (SAS) included: PBO, n=319; LEM 5mg, (LEM5), n=314; LEM 10mg (LEM10), n=314. Study 304 (SUNRISE-1) was a 1mo, randomized, double-blind, PBO- and active-controlled (zolpidem tartrate extended-release 6.25mg [ZOL-ER]) study of LEM5 and LEM10. The SAS included: PBO, n=209; ZOL-ER, n=263; LEM5, n=266; LEM10, n=268. Results In Study 303, Period 1, 28/947 subjects (3.0%) reported nightmares (n=12; PBO-1; LEM5-4; LEM10-7) or abnormal dreams (n=17; PBO-6; LEM5-7; LEM10-4) as treatment-emergent adverse events (TEAEs). In Study 304, 12/1006 subjects (1.2%) reported nightmares (n=4; PBO-1; ZOL-ER-0; LEM5-2; LEM10-1) or abnormal dreams (n=8; PBO-1; ZOL-ER-3; LEM5-0; LEM10-4). 32/40 subjects (80.0%) reporting these events were female (% females in the studies: 303=67.9%; 304=86.4%). In the LEM groups, 11/28 subjects (39.3%) reported the TEAE within 3 days of treatment initiation. There were 2 TEAEs of nightmare/abnormal dreams during the PBO run-in prior to randomization. Conclusion Abnormal dreams/nightmares were not common events in either study. Incidence was slightly higher with LEM10 and proportional to enrollment based on sex.

scholarly journals 9 Phase 3 Randomized, Double-blind, Placebo-Controlled Studies Evaluating Efficacy and Safety of Extended-Release Viloxazine for Pediatric ADHD

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 177-178
Author(s):  
Azmi Nasser ◽  
Janet K. Johnson ◽  
Toyin Adewole ◽  
Tesfaye Liranso ◽  
Ronald Marcus
Keyword(s):  
Adverse Events ◽  
Children And Adolescents ◽  
Extended Release ◽  
Rating Scale ◽  
Stress Index ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo

AbstractStudy ObjectivesAlthough stimulants are commonly used for attention-deficit/hyperactivity disorder (ADHD), 10–30% of patients have an inadequate response, adverse events, or comorbidities preventing use. Thus, there is a need for safe, effective nonstimulant options. Extended-release viloxazine (SPN-812), a nonstimulant, is currently in development for the treatment of ADHD in children and adolescents. SPN-812 is a structurally distinct, bicyclic norepinephrine reuptake inhibitor with selective serotonergic activity. Results of the Phase 2 program demonstrated efficacy (improved mean ADHD Rating Scale-IV total score) and safety of SPN-812 in children (6–12 years), as well as an onset of action within 1–2 weeks.MethodFour ongoing Phase 3 randomized, double-blind, placebo-controlled, outpatient, US studies are investigating the efficacy and safety of once-daily SPN-812 for ADHD in children (ages 6–11; 100–400mg) and adolescents (ages 12–17; 200–600mg). Two studies are enrolling children and two are enrolling adolescents. Eligible subjects are required to have minimum baseline scores of ≥28 for ADHD-RS-5 and ≥4 for Clinical Global Impression-Severity scale (CGI-S). These studies will randomize ∼1200 subjects, with ∼800 subjects receiving SPN-812 over a 1–3-week titration and 5-week maintenance period. The primary endpoint in all studies is mean change from baseline to end of study (EOS) in ADHD-RS-5 total score for SPN-812 vs. placebo. Secondary endpoints include change from baseline to EOS in 30% responder rate (% change: ADHD RS 5); Hyperactivity/Impulsivity and Inattention ADHD-RS-5 subscale scores; Conners 3 Rating Scale (parent and self-report); CGI-S/CGI-I (Improvement); Weiss Functional Impairment Rating Scale (parent report); Parenting Stress Index (children); and Stress Index for Parents of Adolescents (adolescents) after 6–8 weeks of treatment. Safety is assessed via adverse events, clinical laboratory tests, vital signs, electrocardiograms, physical examinations, and the Columbia-Suicide Severity Rating Scale. Phase 3 completers are offered the option of enrolling in an open-label extension study (OLE; up to 3 years) with a starting dose of 100/200mg (children/adolescents). Data will be summarized with descriptive statistics and analyzed using appropriate statistical methods.ResultsAs of August 2018, enrollment in 1 child study is complete, and the other 3 trials are at ∼89%; rollover into the OLE is ∼90%.ConclusionsThere is an unmet need for nonstimulant ADHD treatment for children and adolescents that is effective, long-acting, and well tolerated. SPN-812 is being investigated in four Phase 3 randomized, placebo-controlled studies for the treatment of children and adolescents with ADHD, based on demonstrated efficacy and safety in the Phase 2 program.This study is an encore of a poster presentation at the 2018 Annual Meeting of the American Society of Clinical Psychopharmacology (ASCP).Funding Acknowledgements: Supernus Pharmaceuticals, Inc.

scholarly journals A Phase 3, double-blind, placebo-controlled efficacy and safety study of ADS-5102 (Amantadine) extended-release capsules in people with multiple sclerosis and walking impairment

2021 ◽  
pp. 135245852110353
Author(s):  
Jeffrey A Cohen ◽  
Michelle H Cameron ◽  
Myla D Goldman ◽  
Andrew D Goodman ◽  
Aaron E Miller ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Extended Release ◽  
Walking Speed ◽  
Testing Procedure ◽  
Double Blind Study ◽  
Phase 3 ◽  
Timed Up And Go ◽  
Double Blind ◽  
Meaningful Improvement

Background: ADS-5102, a delayed-release, extended-release (DR/ER) amantadine, improved walking speed in MS in a Phase 2 trial. Objective: The aim of this study was to present primary results of a Phase 3, double-blind, ADS-5102 trial (INROADS) for walking speed. Methods: Adult participants with MS and walking impairment, not currently using amantadine or dalfampridine, underwent 4-week placebo run-in before randomization 1:1:1 to placebo, 137 or 274 mg/day ADS-5102 for 12 weeks. Primary outcome was the proportion of responders (20% increase in Timed 25-Foot Walk (T25FW) speed) for 274 mg ADS-5102 versus placebo at end of double-blind (Study Week 16). Additional measures included Timed Up and Go (TUG), 2-Minute Walk Test (2MWT), and 12-item Multiple Sclerosis Walking Scale (MSWS-12). Results: In total, 558 participants were randomized and received double-blind treatment. Significantly more participants responded with 274 mg ADS-5102 (21.1%) versus placebo (11.3%). Mean T25FW speed also significantly improved (0.19 ft/s) versus placebo (0.07 ft/s). Other measures were not significant using prespecified hierarchical testing procedure. Adverse events led to discontinuation for 3.8% (placebo), 6.4% (137 mg ADS-5102), and 20.5% (274 mg ADS-5102). Conclusion: INROADS met its primary endpoint, showing a significantly greater proportion of participants with meaningful improvement in walking speed for 274 mg ADS-5102 versus placebo. Numeric dose response was seen for some secondary efficacy outcomes and adverse events.

scholarly journals Treatment-emergent adverse events occurring early in the treatment course of cladribine tablets in two phase 3 trials in multiple sclerosis

2021 ◽  
Vol 7 (3) ◽  
pp. 205521732110242
Author(s):  
Jiwon Oh ◽  
Bryan Walker ◽  
Gavin Giovannoni ◽  
Dominic Jack ◽  
Fernando Dangond ◽  
...  
Keyword(s):  
Adverse Events ◽  
Treatment Initiation ◽  
Treatment Discontinuation ◽  
Clear Understanding ◽  
Phase 3 ◽  
Two Phase ◽  
Post Hoc Analysis ◽  
Low Incidence ◽  
Post Hoc ◽  
Common Teaes

Background Treatment-emergent adverse events (TEAEs) that occur close to treatment initiation may negatively affect overall tolerability and adherence. It is important to develop a clear understanding of potential early TEAEs after initiating treatment with cladribine tablets. Objective To identify TEAEs that begin early in the course of treatment in patients enrolled in CLARITY and ORACLE-MS studies. Methods This post hoc analysis of CLARITY and ORACLE-MS safety populations assessed the incidence of TEAEs, serious TEAEs, drug-related TEAEs, and TEAEs leading to discontinuation in patients receiving cladribine tablets or placebo within 2, 6, and 12 weeks after treatment initiation. Results By Week 12, 61.3% of patients treated with cladribine tablets 3.5 mg/kg and 55.2% treated with placebo experienced a TEAE. More patients receiving cladribine tablets versus placebo experienced a drug-related TEAE by Week 12 (34.7% vs. 23.2%). The most common TEAEs reported with cladribine tablets were: headache (7.2%), lymphopenia (6.8%), and nausea (6.0%). Patients receiving cladribine tablets and placebo reported similar proportions of serious TEAEs (2.2% vs. 1.7%) and TEAEs leading to treatment discontinuation (1.6% vs. 1.4%). Conclusion Cladribine tablets were well tolerated during the first 12 weeks as evidenced by a low incidence of TEAEs leading to treatment discontinuation.

scholarly journals Specifically Targeting Interleukin-13 with Tralokinumab Improved Sleep in Two Phase 3, Randomized, Double-Blind, Placebo-Controlled Trials in Patients with Atopic Dermatitis

2021 ◽  
Vol 5 (1) ◽  
pp. s9
Author(s):  
Jonathan Silverberg ◽  
Sebastien Barbarot ◽  
Melinda Gooderham ◽  
Jan Simon ◽  
Eric Simpson ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Controlled Trials ◽  
Phase 3 ◽  
Two Phase ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Interleukin 13

Abstract not available.

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