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Background The FACE-Q patient-reported outcome assesses patient experiences/outcomes with aesthetic facial procedure. A recent trial of abobotulinumtoxinA (ASI, liquid formulation) was the first to our knowledge to assess satisfaction with FACE-Q after glabellar line (GL) injection. Objectives The authors sought to evaluate patient satisfaction with ASI for GL treatment employing 3 FACE-Q scales: facial appearance, psychological well-being, and aging appearance. Methods This was a Phase 3, randomized, double-blind, placebo-controlled trial (NCT02353871) of ASI 50 units in adults with moderate-to-severe GL with 6-month follow-up. Results Significantly greater least squares mean changes from baseline were associated with ASI treatment (N = 125) vs placebo (N = 59) for satisfaction with facial appearance at all visits until day 148 (5 months; P < 0.0001-0.0037), psychological well-being at all visits (P < 0.0001-0.0279), and aging appearance at all visits except day 148 (P < 0.0001-0.0409). Significant differences (ASI vs placebo) were observed at all visits for individual items: “how rested your face looks” (P < 0.0001-0.0415), “I feel okay about myself” (P = 0.0011-0.0399), and “I feel attractive” (P < 0.0001-0.0102). Maximal least squares mean (standard error) changes in aging appearance score were −1.4 (0.3; ASI) and −0.3 (0.4; placebo). Investigators’ live assessment of GL at maximum frown significantly correlated with improvements in FACE-Q facial appearance and psychological scales (all patients: r = −0.41 and r = −0.36 [both P < 0.0001], respectively). Conclusions Significant improvements in patient satisfaction with aging, facial appearance, and, importantly, psychological well-being were demonstrated with ASI employing FACE-Q scales up to 5 to 6 months post-injection. Results support a long duration of efficacy with ASI and use of FACE-Q in future trials and clinical practice. Level of Evidence: 1

Background Safety and efficacy of botulinum toxin A for glabellar line (GL) treatment are well established. Currently approved formulations require reconstitution before injection. Objectives The authors sought to assess 6-month efficacy, safety, and patient satisfaction of new ready-to-use abobotulinumtoxinA solution for injection (ASI) in patients with moderate-to-severe GL at maximum frown. Methods The authors conducted a phase 3, double-blind, randomized, placebo-controlled trial (NCT02353871). Patients (N = 185) were randomized (2:1) to receive ASI 50 U or placebo. GL severity was evaluated at days 8, 15, 29, 57, 85, 113, 148, and 183 employing a 4-point scale for investigator’s live assessment (ILA) and subject's self-assessment (SSA). Primary endpoint was ILA of GL at maximum frown at day 29, and secondary endpoints were ILA and SSA of GL at maximum frown (all time points), patient satisfaction with GL appearance, time to onset, and duration of action. Results Responder rates were significantly higher for ASI vs placebo (88.3% vs 1.4%; P < 0.0001) at day 29 by ILA and all time points by ILA (P < 0.0001-0.0441) and SSA (P < 0.0001-0.0036). Sixty percent of patients reported onset of treatment response on or before day 3 (P < 0.0001 vs placebo), and in 5% of patients, efficacy by ILA lasted 6 months (day 183; P = 0.0441 vs placebo). Patient satisfaction rates were significantly higher for ASI vs placebo at all visits (P < 0.0001). Safety was comparable with the known abobotulinumtoxinA profile. Conclusions ASI was significantly efficacious for improving moderate or severe GL vs placebo by investigator and patient assessment. ASI was associated with high patient satisfaction, a long duration of action, and comparable safety profile to abobotulinumtoxinA. Level of Evidence: 1

Oral sulphate solution(OSS: sodium sulphate, potassium sulphate and magnesium sulphate) is a low-volume osmotic agent for cleansing the intestines.Aim:in a multicentre, prospective, randomized, 3rd phase study with two parallel groups, the effectiveness, safety and tolerability of OSS was evaluated in comparison with Macrogol 4000 with electrolytes (a reference preparation for bowel cleansing in Russia) in adult patients who were scheduled for routine diagnostic colonoscopy.Methods.This study was conducted in three Russian research centres during the March–December, 2015 period. Men and women over the age of 18 scheduled to undergo routine diagnostic colonoscopy were randomly assigned either to the OSS group or to the Macrogol group with a fractional use mode before the colonoscopy. The colonoscopy researchers were not aware of which preparation had been taken by the patients. Anonymized video records were centrally analysed by three experts. The primary end point was the proportion of patients with a successful bowel preparation for colonoscopy ≥6 points, as determined by theBoston Bowel Preparation Scale of quality assessment(BBPS scale).Results.296 patients were randomized in the study (147 patients were treated with OSS, 149 patients received Macrogol); 294 participants were included in theIntention to Treat population(ITT-population), and 274 participants were included in thepopulation of patients who completed the study according to the protocol(Per-Protocol; PP-population) (139 patients received OSS, 135 patients received Macrogol). The proportion of patients with a successful bowel preparation (BBPS ≥6 scores) was high in both groups (OSS [PP-population]: 97.2 % (95 % confidence interval [CI] 89.5–99.3), Macrogol [PP-population]: 97.7 % (95 % CI: 90.7–99.4)). The corrected difference between the groups was -0.5 % (95 % CI: -4.2–3.3), thereby demonstrating “no less effective” of OSS as compared to Macrogol. Compliance with the drug use regime was higher in the OSS group than in the Macrogol group (95.7 % versus 82.3 %, respectively, p-value = 0.0011, ITT-population).The most common symptom reported in patients was nausea (27.9 % in the OSS group and 12.9 % in the Macrogol group). The proportion of patients who developed nausea was significantly higher in the OSS group than in the Macrogol group (25.2 % compared with 10.2 % when taking the first dose of the preparation (p = 0.0008) and 19.7 % compared with 6.8 % when taking the second dose of the preparation (p = 0.0016)). Differences in other symptoms (bloating, abdominal pain or abdominal discomfort) between the groups were not significant, with the severity of symptoms being generally mild. The safety profile of the investigated preparations in patients withinflammatory bowel disease(IBD) in remission did not differ from that in the general patient population.The differences in terms of secondary endpoints were not identified, including BBPS assessment for different sections of the colon, the level of polyp detection, the duration and completeness of colonoscopy, and the investigator’s satisfaction with the procedure. The analysis by subgroups also did not reveal any significant differences.Conclusion.In this study, the “not less effectiveness” of the sulphate solution was demonstrated as compared to Macrogol in a fractional use mode. Both preparations were well tolerated. Despite the higher incidence of nausea in the OSS group, the patients showed significantly higher compliance with the OSS mode as compared to that of Macrogol.This study is registered with the ClinicalTrials.gov Registry of Clinical Trials, No. NCT02321462.

Category: Bunion Introduction/Purpose: Hallux valgus (HV) is a progressive foot deformity affecting nearly 25% of adults, characterized by pain and functional disability, and morphological changes in foot appearance due to progressive lateral deviation of the hallux. HV is initially managed with orthotic interventions, which are often ineffective. Corrective surgery can be efficacious, but is associated with significant pain, long recovery times and, potentially, recurrence. AbobotulinumtoxinA (aboBoNT-A, Dysport®) injections may correct the underlying muscle imbalance (resulting from hypertonia of specific forefoot muscles governing the hallux) thought to cause deformity, thereby reducing pain and disability associated with HV. Therefore, the aim of this phase II, placebo-controlled, parallel-group, multicenter study (NCT03569098) was to evaluate the effect of aboBoNT-A on pain and disability associated with HV in adults. Methods: Patients were randomized (1:1:1) to receive aboBoNT-A 300U, 500U, or placebo in a ≥12-week double-blind (DB) phase, followed by a 24-week open-label (OL) phase (OL Cycle 1, 300U [all patients]; OL Cycle 2, 300U or 500U). Total doses were divided equally into four specific foot muscles involved in hallux function. Eligible patients were aged 18–75 years with an HV angle 15–30° and numeric pain rating scale (NPRS) score of ≥4 (0, no pain; 10, worst possible pain). NPRS score was self-reported for 7 days before baseline and before each post-baseline visit. The primary endpoint was change from baseline in NPRS score (7- day average) before DB Week 8. Two post-hoc endpoints were defined as the percentage of days patients’ NPRS scores were: 1) lower than their lowest NPRS score before baseline; and 2) ≥2 points lower than mean baseline NPRS score. Adverse events (AEs) were monitored throughout the study. Results: No statistically significant differences were observed for aboBoNT-A 300U (n=63) or 500U (n=60) versus placebo (n=63) in NPRS scores at DB Week 8 (least squares mean [standard error]: -1.7 [0.3], -2.4 [0.3], versus -2.0 [0.3], respectively). Scores showed a trend towards pain reduction at Week 12 for aboBoNT-A 500U (-2.4 [0.3]) versus placebo (-1.7 [0.3]; p=0.06). Scores reduced further in OL Cycle 1. Post-hoc analyses showed that patients treated with aboBoNT-A 500U spent significantly more days with reduced pain before DB Week 8 compared with those treated with placebo: analysis 1) 63% versus 38% of days, respectively (pConclusion: Although the primary endpoint was not met at Week 8, a trend towards significant pain reduction versus placebo was reported for patients with HV at Week 12 following aboBoNT-A 500U injection. Pain was further reduced with repeat injection. Post-hoc analyses indicate that HV patients spent a greater proportion of time with reduced pain following aboBoNT-A 500U injection compared with placebo. This may be a more clinically relevant assessment of benefit than NPRS score averaged over 7 days. Safety results were in line with the known profile of aboBoNT-A.

Background The effects of botulinum toxin are transient, and repeat injections are required in children with lower-limb spasticity. However, the efficacy of botulinum toxin in patients who have received previous injections has remained largely unexplored. Methods We present subgroup analyses of a phase III study conducted in ambulatory children (aged two to 17) with spastic equinus foot. Patients were randomized to single doses of abobotulinumtoxinA 10 U/kg/leg, 15 U/kg/leg, or placebo injected into the gastrocnemius-soleus complex (one or both legs). The first analysis was prespecified to review the effect of abobotulinumtoxinA in children previously treated with botulinum toxin versus those children new to the treatment; a second post hoc analysis evaluated the effect of abobotulinumtoxinA in children who changed botulinum toxin formulation. Results Of the 241 randomized patients, 113 had previously received botulinum toxin, including 86 who had been treated with another formulation. In both analyses, muscle tone (Modified Ashworth Scale) and the Physicians Global Assessment, at week 4, improved with abobotulinumtoxinA treatment versus placebo, regardless of baseline botulinum toxin status. Placebo responses in patients new to treatment were consistently higher than in the previously treated group. Conclusions These results demonstrate similar abobotulinumtoxinA efficacy and safety profiles in children with spasticity who are new to botulinum toxin treatment and those children who were previously treated. The efficacy and safety of abobotulinumtoxinA treatment in these previously treated patients were comparable with the overall trial population, indicating that doses of 10 and 15 U/kg/leg are suitable starting doses for children with spasticity regardless of the previous botulinum toxin preparation used.

Naturally occurring botulinum toxin (BoNT) serotypes have different pharmacological features of therapeutic and aesthetic interest. This phase 1, double-blind, placebo-controlled study (EudraCT: 2016–002609-20) assessed safety, tolerability and pharmacodynamics (PD) of the first recombinant BoNT serotype E (rBoNT-E) versus abobotulinumtoxinA (Dysport®), administered to extensor digitorum brevis (EDB) of healthy males. Subjects were randomised 3:1 (n = 28) to single ascending rBoNT-E (0.04–3.6 ng) doses or placebo. A further 24 subjects received abobotulinumtoxinA (20, 40, or 70 U) or placebo. PD were assessed using compound muscle action potential (CMAP) amplitude. Demographics were similar between groups. All rBoNT-E doses were well tolerated (no severe treatment-emergent adverse events [TEAEs], serious adverse events, or treatment-related toxicities). Most TEAEs were mild/moderate and treatment-unrelated. rBoNT-E had a faster onset of action (days 1–2 post-injection), greater peak effect (>90% CMAP inhibition), and shorter duration of effect at highest tested doses versus abobotulinumtoxinA (onset of action ≤7 days post-injection; 70% maximal CMAP inhibition). rBoNT-E duration of effect was 2–7 weeks versus >26 weeks for abobotulinumtoxinA. Dose-dependent effects were observed for magnitude and duration of EDB CMAP inhibition, plateauing at 0.9 and 3.6 ng. rBoNT-E demonstrated a good safety profile and a PD profile that may address unmet therapeutic and aesthetic patient needs.

Background Preclinical research indicates that BN82451B has potential to interfere with excitotoxicity, and possesses antioxidant, anti-inflammatory, and mitochondrial protection properties. In-vivo studies in tgHD mice suggested neuroprotective and antidyskinetic effects. Aims The safety and tolerability of BN82451B was tested in Huntington’s Disease (HD) alongside exploratory efficacy with a focus on motor symptoms. Methods This 4-week, randomized, placebo-controlled, double-blind, in-patient, proof-of-concept study explored escalating doses (40 – 80 mg BID) of BN82451B in symptomatic HD subjects. Primary objective was safety and tolerability, secondary objectives were motor symptoms assessed by Q-Motor and the UHDRS-TMS. Results A total of 30 subjects were planned to be included, but the study was terminated after inclusion of 17 subjects (14 BN82451B/3 placebo). Recruitment in this study was complicated by an obligatory in-patient setting at a phase-1 research-unit for four weeks. There were no severe safety issues, but 6 of the 14 treated subjects (43%) developed cutaneous adverse events (rash) which led to discontinuation of treatment in 3 cases and resolved after discontinuation of treatment in all 6 cases. Another 2 subjects were withdrawn due to nausea and vomiting. BN82451B treatment did not differentiate from placebo in the exploratory outcome variables. While placebo subjects showed a mean improvement in the UHDRS-TMS, Q-Motor measures indicated no change in the placebo group. However, mean Q-Motor changes of BN82451B treated patients suggested a none-significant deterioration of motor performance while on drug, which reverted after drug discontinuation. Conclusions BN82451B induced skin rash in 43% of exposed patients and increased nausea/vomiting. Exploratory analysis did suggest a potential for deterioration of motor symptoms in HD subjects under treatment. Q-Motor measures showed much less variance and no placebo response in repeated assessments compared to the UHDRS-TMS. It was decided to discontinue the study.

Background AbobotulinumtoxinA has beneficial effects on spasticity and active movements in hemiparetic adults with upper limb spasticity (ULS). However, evidence-based information on optimal dosing for clinical use is limited. Objective To describe joint-specific dose effects of abobotulinumtoxinA in adults with ULS. Design Secondary analysis of a phase 3 study (NCT01313299). Setting Multicenter, international, double-blind, placebo-controlled clinical trial. Participants A total of 243 adults with ULS >6 months after stroke or traumatic brain injury, aged 52.8 (13.5) years and 64.3% male, randomized 1:1:1 to receive a single-injection cycle of placebo or abobotulinumtoxinA 500 U or 1000 U (total dose). Methods The overall effects of injected doses were assessed in the primary analysis, which showed improvement of angles of catch in finger, wrist, and elbow flexors and of active range of motion against these muscle groups. This secondary analysis was performed at each of the possible doses received by finger, wrist, and elbow flexors to establish possible dose effects. Main Outcome Measures Angle of arrest (X V1 ) and angle of catch (X V3 ) were assessed with the Tardieu Scale, and active range of motion (X A ). Results At each muscle group level (finger, wrist, and elbow flexors) improvements in all outcome measures assessed (X V1 , X V3 , X A ) were observed. In each muscle group, increases in abobotulinumtoxinA dose were associated with greater improvements in X V3 and X A , suggesting a dose-dependent effect. Conclusions Previous clinical trials have established the clinical efficacy of abobotulinumtoxinA by total dose only. The wide range of abobotulinumtoxinA doses per muscle groups used in this study allowed observation of dose-dependent improvements in spasticity and active movement. This information provides a basis for future abobotulinumtoxinA dosing recommendations for health care professionals based on treatment objectives and quantitative assessment of spasticity and active range of motion at individual joints. Level of Evidence I