Efficacy and safety of DFN-11 (sumatriptan injection, 3 mg) in adults with episodic migraine: a multicenter, randomized, double-blind, placebo-controlled study.

BackgroundIn a previous randomized, double-blind, proof-of-concept study in rapidly escalating migraine, a 3 mg dose of subcutaneous sumatriptan (DFN-11) was associated with fewer and shorter triptan sensations than a 6 mg dose. The primary objective of the study was to assess the efficacy and safety of acute treatment with DFN-11 compared with placebo in episodic migraine.MethodsThis was a multicenter, randomized, double-blind, placebo-controlled efficacy and safety study of DFN-11 in the acute treatment of adults with episodic migraine (study RESTOR). The primary endpoint was the proportion of subjects taking DFN-11 who were pain free at 2 h postdose in the double-blind period compared with placebo. Secondary endpoints included earlier postdose timepoints, assessments of pain relief and subjects' freedom from their most bothersome symptom (MBS) (among nausea, photophobia, and phonophobia). Safety and tolerability were assessed.ResultsA total of 392 subjects was screened, 268 (68.4%) were randomized, and 234 (87.3% of those randomized) completed the double-blind treatment period. The proportion of subjects who were pain free at 2 h postdose was significantly greater in the DFN-11 group than in the placebo group (51.0% vs 30.8%, P  =  0.0023). Compared with placebo, significantly higher proportions of subjects treated with DFN-11 were also pain free at 30, 60, and 90 min postdose (P  ≤  0.0195). DFN-11 was significantly superior to placebo for pain relief at 60 min, 90 min, and 2 h postdose (P ≤ 0.0179). At 2 h postdose, DFN-11 was also significantly superior to placebo for freedom from photophobia (P  =  0.0056) and phonophobia (P  =  0.0167). Overall, 33.3% (37/111) who received DFN-11 and 13.4% (16/119) who received placebo experienced at least 1 treatment-emergent adverse event (TEAE), the most common of which were injection site swelling (7.2% vs 0.8%) and pain (7.2% vs 5.9%). Chest discomfort was about half as common in the DFN-11 treatment group as it was in the placebo group (0.9% vs 1.7%).ConclusionsThis study met its primary endpoint, pain freedom at 2 h postdose, with DFN-11 significantly better than placebo, and the incidence of TEAEs and triptan sensations with DFN-11 was low. The 3 mg dose of sumatriptan in DFN-11 appears to be an effective alternative to a 6 mg SC dose of sumatriptan, with good safety and tolerability. ( clinicaltrials.gov : NCT02569853; registered 07 October 2015)

Transient Analysis of Analyte Desorption Due to Thermal Cycling with Varying Pulse Duration

This paper introduces heating pulse duration modulation on a chemically sensitive, polymer-coated resonant cantilever platform for analyte discrimination during the desorption phase. As in our previous work, the embedded heaters enable real-time measurements of analyte sorption into the polymer film, without the need for traditional valve systems and reference gases [1-2]. This work particularly looks at the effects of varying pulse lengths on the sensor responses, while holding the heating power constant. A model differential equation is developed for the sensor response based on both the device sensitivity and transient response. This model can then be used together with estimation theory for analyte identification and quantification, even in mixtures

Cantilever-based Resonant Microsensors with Integrated Temperature Modulation for Transient Chemical Analysis

This work introduces a resonant cantilever platform with integrated temperature modulation for real-time chemical sensing. Embedded heaters allow for rapid thermal cycling of individual sensors, thereby enabling real-time transient signal analysis without the need for a microfluidic setup to switch between analyte and reference gases. Compared to traditional mass-sensitive microsensors operating in steady state, the on-chip generation of signal transients provides additional information for analyte discrimination

A Multi-Modal Continuous-Systems Model of a Novel High-Q Disk Resonator in a Viscous Liquid

International audienc

Geometrical Considerations for the Design of Liquid-phase Biochemical Sensors Using a Cantilever\u27s Fundamental In-plane Mode

The influence of the beam geometry on the quality factor and resonance frequency of resonant silicon cantilever beams vibrating in their fundamental in-plane flexural mode in water has been investigated. Compared to cantilevers vibrating in their first out-of-plane flexural mode, utilizing the in-plane mode results in reduced damping and reduced mass loading by the surrounding fluid. Quality factors as high as 86 have been measured in water for cantilevers with a 20 μm thick silicon layer. Based on the experimental data, design guidelines are established for beam dimensions that ensure maximal Q-factors and minimal mass loading by the surrounding fluid, thus improving the limit-of-detection of mass-sensitive biochemical sensors. Elementary theory is also presented to help explain the observed trends. Additional discussion focuses on the tradeoffs that exist in designing liquid-phase biochemical sensors using in-plane cantilevers

Resonant Characteristics of Rectangular Microcantilevers Vibrating Torsionally in Viscous Liquid Media

The resonant characteristics of rectangular microcantilevers vibrating in the torsional mode in viscous liquid media are investigated. The hydrodynamic load (torque per unit length) on the vibrating beam due to the liquid was first determined using a finite element model. An analytical expression of the hydrodynamic function in terms of the Reynolds number and aspect ratio, h/b (with thickness, h, and width, b) was then obtained by fitting the numerical results. This allowed for the resonance frequency and quality factor to be investigated as functions of both beam geometry and medium properties. Moreover, the effects of the aspect ratio on the cross-section\u27s torsional constant, K, which affects the microcantilever\u27s torsional stiffness, and on its polar moment of inertia, Jp, which is associated with the beam\u27s rotational inertia, are also considered when obtaining the resonance frequency and quality factor. Compared with microcantilevers under out-of-plane (transverse) flexural vibration, the results show that microcantilevers that vibrate in their 1st torsional or 1st in-plane (lateral) flexural resonant modes have higher resonance frequency and quality factor. The increase in resonance frequency and quality factor results in higher mass sensitivity and reduced frequency noise, respectively. The improvement in the sensitivity and quality factor are expected to yield much lower limits of detection in liquid-phase chemical sensing applications

Resonant Characteristics of Rectangular Hammerhead Microcantilevers Vibrating Laterally in Viscous Liquid Media

The resonant characteristics of laterally vibrating rectangular hammerhead microcantilevers in viscous liquid media are investigated. The rectangular hammerhead microcantilever is modeled as an Euler-Bernoulli beam (stem) and a rigid body (head). A modified semi-analytical expression for the hydrodynamic function in terms of the Reynolds number, Re, and aspect ratio, h/b, is proposed to rapidly evaluate the sensing characteristics. Using this expression, the resonance frequency, quality factor and normalized surface mass sensitivity are investigated as a function of the dimensions of the microcantilever and liquid properties. Guidelines for design of hammerhead microcantilever geometry are proposed to achieve efficient sensing platforms for liquid-phase operation. The improvement in the sensing area and characteristics are expected to yield higher sensitivity of detection and improved signal-to-noise ratio in liquid-phase chemical sensing applications

An Analytical Model of a Thermally Excited Microcantilever Vibrating Laterally in a Viscous Fluid

To achieve higher quality factors (Q) for microcantilevers used in liquid-phase sensing applications, recent studies have explored the use of the lateral (in-plane) flexural mode. In particular, we have recently shown that this mode may be excited electrothermally using integrated heating resistors near the micro cantilever support, and that the resulting increase in Q helps to make low-ppb limits of detection a possibility in liquids. However, because the use of electrothermally excited, liquid-phase, microcantilever-based sensors in lateral flexure is relatively new, theoretical models are lacking. Therefore, we present here a new analytical model for predicting the vibratory response of these devices. The model is also used to successfully confirm the validity of our previously derived Q formula, which was based on a single-degree-of-freedom (SDOF) model and a harmonic tip force. Comparisons with experimental data show that the present model and, thus, the analytical formula provide excellent Q estimates for sufficiently thin beams vibrating laterally in water and reasonable upper-bound estimates for thicker beams

Analytical Modeling of a Novel High-\u3cem\u3eQ\u3c/em\u3e Disk Resonator for Liquid-Phase Applications

To overcome the detrimental effects of liquid environments on microelectromechanical systems resonator performance, the in-fluid vibration of a novel disk resonator supported by two electrothermally driven legs is investigated through analytical modeling and the effects of the system’s geometric/material parameters on the dynamic response are explored. The all-shear interaction device (ASID) is based on engaging the surrounding fluid primarily through shearing action. The theory comprises a continuous-system, multimodal model, and a single-degree-of-freedom model, the latter yielding simple formulas for the fundamental-mode resonant characteristics that often furnish excellent estimates to the results based on the more general model. Comparisons between theoretical predictions and previously published liquid-phase quality factor (Q) data (silicon devices in heptane) show that the theoretical results capture the observed trends and also give very good quantitative estimates, particularly for the highest Q devices. Moreover, the highest Q value measured in the earlier study (304) corresponded to a specimen whose disk radius-to-thickness ratio was 2.5, a value that compares well with the optimal value of 2.3 predicted by the present model. The insight furnished by the proposed theory is expected to lead to further improvements in ASID design to achieve unprecedented levels of performance for a wide variety of liquid-phase resonator applications