A Phase 1 randomized, open-label clinical trial to evaluate the effect of a far-infrared emitting patch on local skin perfusion, microcirculation and oxygenation.

Far-infrared radiation (FIR) has been investigated for reduction of pain and improvement of dermal blood flow. The FIRTECH patch is a medical device designed to re-emit FIR radiated by the body. This phase 1 study was conducted to evaluate the local effects of the FIRTECH patch on local skin perfusion, microcirculation and oxygenation. This prospective, randomized, open-label, parallel designed study admitted 20 healthy participants to a medical research facility for treatment for 31 h on three anatomical locations. During treatment, imaging assessments consisting of laser speckle contrast imaging, near-infrared spectroscopy, side-stream dark-field microscopy, multispectral imaging and thermography were conducted regularly on patch-treated skin and contralateral non-treated skin. The primary endpoint was baseline perfusion increase during treatment on the upper back. Secondary endpoints included change in baseline perfusion, oxygen consumption and temperature of treated versus untreated areas. The primary endpoint was not statistically significantly different between treated and non-treated areas. The secondary endpoints baseline perfusion on the forearm (least square means [LSMs] difference 2.63 PU, 95% CI: 0.97, 4.28), oxygen consumption (LSMs difference: 0.42 arbitrary units [AUs], 95% CI: 0.04, 0.81) and skin temperature (LSMs difference 0.35°C, 95% CI: 0.16, 0.6) were statistically significantly higher in treated areas. Adverse events observed during the study were mild and transient. The vascular response to the FIRTECH patch was short-lived suggesting a non-thermal vasodilatory effect of the patch. The FIRTECH patch was well tolerated, with mild and transient adverse events observed during the study. These results support the therapeutic potential of FIR in future investigations.

A randomized, placebo-controlled, double-blind phase III trial investigating the efficacy and safety of incobotulinumtoxinA in the treatment of glabellar frown lines using a stringent composite endpoint.

BACKGROUND: A prospective, randomized, double-blind, multicenter, Phase III trial of incobotulinumtoxinA using new Food and Drug Administration endpoints. OBJECTIVE: To investigate the efficacy and safety of a single dose of incobotulinumtoxinA for the treatment of glabellar frown lines. MATERIALS AND METHODS: Two hundred seventy-one subjects with moderate to severe glabellar frown lines at maximum frown-as assessed by an investigator according to the facial wrinkle scale (FWS)-were randomized 2:1 to receive one treatment of 20 U of incobotulinumtoxinA or placebo, respectively, and assessed over 120 days. The primary efficacy variable was a composite endpoint consisting of patients who were 2-point or more responders at maximum frown on Day 30 according to the investigator's rating on the FWS, and 2-point or more responders at maximum frown on Day 30 according to the patient's assessment on a 4-point scale. Safety analyses were performed throughout the study. RESULTS: IncobotulinumtoxinA was statistically significantly more efficacious than placebo using a new rigorous composite endpoint (p < .0001). CONCLUSION: A single dose of 20 U of incobotulinumtoxinA is superior to placebo in the treatment of glabellar frown lines at Day 30 and is well-tolerated.

Multicenter, randomized, phase III study of a single dose of incobotulinumtoxinA, free from complexing proteins, in the treatment of glabellar frown lines.

BACKGROUND: Botulinum toxin type A is a proven, effective aesthetic treatment for glabellar frown lines. IncobotulinumtoxinA (NT 201, Xeomin/Xeomeen/Bocouture, Merz Pharmaceuticals GmbH, Frankfurt, Germany) is a 150-kDa botulinum toxin type A free of complexing proteins. OBJECTIVE: To assess the efficacy and safety of incobotulinumtoxinA in a randomized, double-blind, placebo-controlled, Phase III study in patients with moderate to severe glabellar frown lines. MATERIALS AND METHODS: Two hundred seventy-six patients were randomized 2:1 to receive a single injection of 20 U of incobotulinumtoxinA or placebo, respectively. Efficacy was assessed at day 30 using a Food and Drug Administration-mandated composite endpoint; a responder was defined as a patient with a 2-point or greater improvement in glabellar frown lines on a 4-point scale as assessed by investigator and patient. Safety was assessed periodically through Day 120. RESULTS: Treatment with a single dose of incobotulinumtoxinA was significantly superior to placebo in the treatment of glabellar frown lines at Day 30 using the composite endpoint (p < .001), with investigators and patients assessing glabellar frown lines as significantly more improved after incobotulinumtoxinA injection than with placebo (p < .001). IncobotulinumtoxinA was well tolerated. CONCLUSION: A single dose of 20 U of incobotulinumtoxinA demonstrated efficacy and safety in the treatment of glabellar frown lines using new Food and Drug Administration efficacy variables.

Long-term results for incobotulinumtoxinA in the treatment of glabellar frown lines.

BACKGROUND: IncobotulinumtoxinA has been approved for treatment of glabellar frown lines (GFL) in the United States, all major European markets, South Korea, and Argentina and in Russia and Mexico for the treatment of mimic wrinkles and hyperkinetic facial lines, respectively. OBJECTIVES: Prospective, 2-year, open-label, multicenter, repeat-dose, Phase III trial investigating the safety and efficacy of incobotulinumtoxinA for the treatment of GFL. METHODS: Subjects with moderate or severe GFL on the Facial Wrinkle Scale (FWS), enrolled from previous trials, were treated with 20 U of incobotulinumtoxinA per cycle (up to eight treatment cycles, treatment interval at least 85 days). Efficacy was measured according to the investigator-assessed percentage of responders on the FWS (subjects with a score of 0 or 1) at rest and maximum frown on Day 30 of each cycle, subject assessments, and onset and duration of treatment effect. RESULTS: In 796 subjects, 77% to 88% were responders at rest, and 79% to 90% were responders at maximum frown. Onset was rapid; subjects reported effects in the first few days after treatment. No new tolerability or safety concerns were reported. CONCLUSIONS: IncobotulinumtoxinA injections were well tolerated and resulted in efficacy in the treatment of GFL for up to 2 years.

Reducing the probability of false positive research findings by pre-publication validation - experience with a large multiple sclerosis database.

BACKGROUND: Published false positive research findings are a major problem in the process of scientific discovery. There is a high rate of lack of replication of results in clinical research in general, multiple sclerosis research being no exception. Our aim was to develop and implement a policy that reduces the probability of publishing false positive research findings. We have assessed the utility to work with a pre-publication validation policy after several years of research in the context of a large multiple sclerosis database. METHODS: The large database of the Sylvia Lawry Centre for Multiple Sclerosis Research was split in two parts: one for hypothesis generation and a validation part for confirmation of selected results. We present case studies from 5 finalized projects that have used the validation policy and results from a simulation study. RESULTS: In one project, the "relapse and disability" project as described in section II (example 3), findings could not be confirmed in the validation part of the database. The simulation study showed that the percentage of false positive findings can exceed 20% depending on variable selection. CONCLUSION: We conclude that the validation policy has prevented the publication of at least one research finding that could not be validated in an independent data set (and probably would have been a "true" false-positive finding) over the past three years, and has led to improved data analysis, statistical programming, and selection of hypotheses. The advantages outweigh the lost statistical power inherent in the process.