Tolerability and Efficacy of Customized IncobotulinumtoxinA Injections for Essential Tremor: A Randomized, Double-Blind, Placebo-Controlled Study

In this first, double-blind, randomized, placebo-controlled exploratory trial, we evaluate the efficacy and safety of incobotulinumtoxinA and feasibility of using kinematic tremor assessment to aid in the planning of muscle selection in a multicenter setting. Reproducibility of the planning technology to other clinical sites was explored. In this trial (NCT02207946), patients with upper-limb essential tremor (ET) were randomized 2:1 to a single treatment cycle of incobotulinumtoxinA or placebo. A tremor kinematic analytics investigational device was used to define a customized muscle set for injection, related to the pattern of the wrist, forearm, elbow, and shoulder tremor for each patient, and the incobotulinumtoxinA dose per muscle (total ≤ 200 U). Fahn–Tolosa–Marin (FTM) Part B motor performance score, Global Impression of Change Scale (GICS), and kinematic analysis-based efficacy evaluations were assessed. Thirty patients were randomized (incobotulinumtoxinA, n = 19; placebo, n = 11). FTM motor performance scores showed greater improvement with incobotulinumtoxinA versus placebo at Week 4 (p= 0.003) and Week 8 (p= 0.031). The physician-rated GICS score indicated improvement with incobotulinumtoxinA versus placebo at Week 4 (p < 0.05). IncobotulinumtoxinA also decreased accelerometric hand-tremor amplitude versus placebo from baseline to Week 4 (p= 0.004) and Week 8 (p < 0.001), with persistent tremor reduction up to 24 weeks post-injection. IncobotulinumtoxinA produced a slight and transient reduction of maximal grip strength versus placebo; two patients reported localized finger muscle weakness. Customized incobotulinumtoxinA injections decreased tremor severity and improved hand motor function in patients with upper-limb ET after a single injection cycle, with a favorable tolerability profile. The study showed that tremor kinematic analytics technology could be successfully scaled for use in other clinical sites.

Download Full-text

485 Efficacy and Safety of Once- and Twice-Nightly Dosing of Lower-Sodium Oxybate in Adults With Idiopathic Hypersomnia

SLEEP ◽

10.1093/sleep/zsab072.484 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A191-A192

Author(s):

Isabelle Arnulf ◽

Anne Marie Morse ◽

Patricia Chandler ◽

Rupa Parvataneni ◽

Dan Chen ◽

...

Keyword(s):

Sodium Oxybate ◽

Mean Difference ◽

Controlled Study ◽

Efficacy And Safety ◽

Open Label ◽

Double Blind ◽

Patient Global Impression ◽

Idiopathic Hypersomnia ◽

Secondary Endpoints ◽

Global Impression Of Change

Abstract Introduction Idiopathic hypersomnia (IH) is a rare central hypersomnolence disorder. In a randomized, controlled study of lower-sodium oxybate (LXB; Xywav™) in adults with IH (NCT03533114), significant differences for LXB compared with placebo were observed in Epworth Sleepiness Scale (ESS; primary efficacy endpoint), self-reported Patient Global Impression of Change (PGIc), and IH Severity Scale (IHSS; key secondary endpoints). In this clinical study, investigators were permitted to initiate LXB dosing on a once-nightly or twice-nightly regimen. Methods Eligible participants aged 18–75 years began LXB treatment, administered once or twice nightly during an open-label treatment/titration and optimization period (OLTTOP; 10–14 weeks); dose amount/regimen could be adjusted during this period. Participants next entered a 2-week, open-label, stable-dose period (SDP), then were randomized to placebo or to continue LXB treatment during a 2-week, double-blind, randomized withdrawal period (DBRWP). P values are nominal for this exploratory analysis. Results Of 154 enrolled participants, 40 (26%) initiated LXB treatment on a once-nightly regimen. In the efficacy population (n=115), 27 participants were on a once-nightly regimen during SDP (48.1% of whom initiated treatment once nightly during OLTTOP) and 88 participants were on a twice-nightly regimen during SDP (86.4% of whom initiated treatment twice nightly during OLTTOP). During SDP, median (min, max) LXB total dose was 4.5 (2.5, 6) g/night (once-nightly group) and 7.5 (4.5, 9) g/night (twice-nightly group). ESS scores worsened in participants randomized to placebo vs those continuing LXB in the once-nightly group (n=11 and n=15, respectively; LS mean difference [95% CI]: −4.93 [−7.41, −2.46]; P=0.0004) and twice-nightly group (n=47 and n=41, respectively; LS mean difference [95% CI]: −7.44 [−9.15, −5.72]; P<0.0001). Worsening was also observed in PGIc (once-nightly: 81.8% [placebo] vs 26.7% [LXB]; P=0.0077; twice-nightly: 89.4% [placebo] vs 19.5% [LXB]; P<0.0001) and IHSS score (estimated median difference [95% CI], once-nightly: −9.00 [−16.0, −3.0]; P=0.0028; twice-nightly: −12.00 [−15.0, −8.0]; P<0.0001). Common adverse events included nausea (21.4%), headache (16.2%), anxiety (14.9%), dizziness (11.7%), insomnia (11.7%), and vomiting (10.4%). Conclusion The efficacy and safety of LXB in IH were demonstrated for both once-nightly and twice-nightly regimens. The majority of participants initiated and remained on a twice-nightly regimen. Support (if any) Jazz Pharmaceuticals

Download Full-text

Safety and Immunogenicity of the Ad26.RSV.preF Investigational Vaccine Coadministered With an Influenza Vaccine in Older Adults

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa409 ◽

2020 ◽

Cited By ~ 2

Author(s):

Jerald Sadoff ◽

Els De Paepe ◽

Wouter Haazen ◽

Edmund Omoruyi ◽

Arangassery R Bastian ◽

...

Keyword(s):

Older Adults ◽

Influenza Vaccine ◽

Geometric Mean ◽

Controlled Study ◽

Tolerability Profile ◽

Double Blind ◽

Inhibition Antibody ◽

Binding Antibody ◽

Syncytial Virus ◽

Significant Disease

Abstract Background Respiratory syncytial virus (RSV) and influenza cause significant disease burden in older adults. Overlapping RSV and influenza seasonality presents the opportunity to coadminister vaccines for both infections. This study assessed coadministration of the investigational vaccine, Ad26.RSV.preF, an adenovirus serotype 26 (Ad26) vector encoding RSV F protein stabilized in its prefusion conformation (pre-F), with a seasonal influenza vaccine in older adults. Methods In this phase 2a, double-blind, placebo-controlled study, 180 adults aged ≥60 years received Ad26.RSV.preF plus Fluarix on day 1 and placebo on day 29, or placebo plus Fluarix on day 1 and Ad26.RSV.preF on day 29 (control). Results The coadministration regimen had an acceptable tolerability profile. Reactogenicity was generally higher after Ad26.RSV.preF versus Fluarix, but symptoms were generally transient and mild or moderate. At 28 days after the first vaccination, the upper confidence intervals of the hemagglutination inhibition antibody geometric mean ratio (control/coadministration) for all influenza strains were <2, demonstrating noninferiority. Robust neutralizing and binding antibody responses to RSV A2 were observed in both groups. Conclusions Coadministration of Fluarix with Ad26.RSV.preF vaccine had an acceptable safety profile and showed no evidence of interference in immune response. The results are compatible with simultaneous seasonal vaccination with both vaccines. Clinical Trials Registration NCT03339713.

Download Full-text

Double-blind controlled study of primidone in essential tremor: preliminary results.

BMJ ◽

10.1136/bmj.285.6342.608 ◽

1982 ◽

Vol 285 (6342) ◽

pp. 608-608 ◽

Cited By ~ 25

Author(s):

L J Findley ◽

S Calzetti

Keyword(s):

Essential Tremor ◽

Controlled Study ◽

Double Blind ◽

Preliminary Results

Download Full-text

O204 Simultaneous bi-hemispheric repetitive transcranial magnetic stimulation for upper limb motor recovery in chronic stroke: A double blind placebo controlled study

Clinical Neurophysiology ◽

10.1016/j.clinph.2017.07.212 ◽

2017 ◽

Vol 128 (9) ◽

pp. e243-e244

Author(s):

Raffaella Chieffo ◽

Giuseppe Scopelliti ◽

Mario Fichera ◽

Giovanni Di Maggio ◽

Roberto Santangelo ◽

...

Keyword(s):

Transcranial Magnetic Stimulation ◽

Upper Limb ◽

Magnetic Stimulation ◽

Repetitive Transcranial Magnetic Stimulation ◽

Chronic Stroke ◽

Motor Recovery ◽

Controlled Study ◽

Double Blind ◽

Double Blind Placebo

Download Full-text

33. A Double Blind Randomised Placebo Controlled Study of Botulinum Toxin in Upper Limb Spasticity After Stroke or Head Injury Dr. S. J. Smith (Edinburgh, Scotland), E. Ellis, S. White, A. P. Moore (Liverpool, Merseyside, UK

Neurorehabilitation and Neural Repair ◽

10.1177/154596839901300125 ◽

1999 ◽

Vol 13 (1) ◽

pp. 29-29

Keyword(s):

Botulinum Toxin ◽

Head Injury ◽

Upper Limb ◽

Controlled Study ◽

Double Blind ◽

Limb Spasticity

Download Full-text

Modulation of premotor cortex response to sequence motor learning during escitalopram-intake

10.1101/2020.05.19.20105346 ◽

2020 ◽

Author(s):

Eoin N Molloy ◽

Karsten Mueller ◽

Nathalie Beinhoelzl ◽

Maria Bloechl ◽

Fabian Piecha ◽

...

Keyword(s):

Motor Learning ◽

Motor Performance ◽

Selective Serotonin Reuptake Inhibitors ◽

Cortical Plasticity ◽

Premotor Cortex ◽

Learning Performance ◽

Adaptive Plasticity ◽

Controlled Study ◽

Double Blind ◽

Negative Findings

The contribution of selective serotonin reuptake inhibitors (SSRIs) to motor learning by inducing motor cortical plasticity remains controversial given diverse findings from positive preclinical data to negative findings in recent clinical trials. To empirically address this translational disparity, we use functional magnetic resonance imaging (fMRI) in a double-blind, randomized controlled study to assess whether 20 mg escitalopram improves sequence-specific motor performance and modulates cortical motor response in 64 healthy female participants. We found decreased left premotor cortex responses during sequence-specific learning performance comparing single dose and steady escitalopram state. Escitalopram plasma-levels negatively correlated with the premotor cortex response. We did not find evidence in support of improved motor performance after a week of escitalopram-intake. These findings do not support the conclusion that one-week escitalopram intake increases motor performance but could reflect early adaptive plasticity with improved neural processing underlying similar task performance when steady peripheral escitalopram levels are reached.

Download Full-text

Eptinezumab for the prevention of chronic migraine: efficacy and safety through 24 weeks of treatment in the phase 3 PROMISE-2 (Prevention of migraine via intravenous ALD403 safety and efficacy–2) study

The Journal of Headache and Pain ◽

10.1186/s10194-020-01186-3 ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Stephen Silberstein ◽

Merle Diamond ◽

Nada A. Hindiyeh ◽

David M. Biondi ◽

Roger Cady ◽

...

Keyword(s):

Chronic Migraine ◽

Patient Reported Outcomes ◽

Controlled Study ◽

Efficacy And Safety ◽

Phase 3 ◽

Double Blind ◽

Patient Global Impression ◽

Calcitonin Gene ◽

Patient Reported ◽

Global Impression Of Change

Abstract Background PROMISE-2 was a phase 3, randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of repeat intravenous (IV) doses of the calcitonin gene-related peptide–targeted monoclonal antibody eptinezumab (ALD403) for migraine prevention in adults with chronic migraine. This report describes the results of PROMISE-2 through 24 weeks of treatment. Methods Patients received up to two 30-min IV administrations of eptinezumab 100 mg, 300 mg, or placebo separated by 12 weeks. Patients recorded migraine and headache endpoints in a daily eDiary. Additional assessments, including patient-reported outcomes, were performed at regularly scheduled clinic visits throughout the 32-week study period (screening, day 0, and weeks 2, 4, 8, 12, 16, 20, 24, and 32). Results A total of 1072 adults received treatment: eptinezumab 100 mg, n = 356; eptinezumab 300 mg, n = 350; placebo, n = 366. The reduction in mean monthly migraine days observed during the first dosing interval (100 mg, − 7.7 days; 300 mg, − 8.2 days; placebo, − 5.6 days) was further decreased after an additional dose (100 mg, − 8.2 days; 300 mg, − 8.8 days; placebo, − 6.2 days), with both doses of eptinezumab demonstrating consistently greater reductions from baseline compared to placebo. The ≥50% and ≥ 75% migraine responder rates (MRRs) increased after a second dose, with more eptinezumab-treated patients experiencing migraine response than placebo patients (≥50% MRRs weeks 13–24: 100 mg, 61.0%; 300 mg, 64.0%; placebo, 44.0%; and ≥ 75% MRRs weeks 13–24: 100 mg, 39.3%; 300 mg, 43.1%; placebo, 23.8%). The percentages of patients who improved on patient-reported outcomes, including the Headache Impact Test and Patient Global Impression of Change, increased following the second dose administration at week 12, and were greater with eptinezumab than with placebo at all time points. No new safety concerns were identified with the second dose regarding the incidence, nature, and severity of treatment-emergent adverse events. Conclusion Eptinezumab 100 mg or 300 mg administered IV at day 0 and repeated at week 12 provided sustained migraine preventive benefit over a full 24 weeks and demonstrated an acceptable safety profile in patients with chronic migraine. Trial registration ClinicalTrials.gov (Identifier: NCT02974153). Registered November 23, 2016.

Download Full-text