A Phase I, Randomized, Double-Blind, Laser-Evoked Potential Study to Evaluate the Analgesic/Antihyperalgesic Effect of ASP9226, a State-Dependent N-Type Voltage-Gated Calcium Channel Inhibitor, in Healthy Male Subjects

Abstract

ObjectiveEvaluate the analgesic/antihyperalgesic effects of ASP9226, a state-dependent N-type voltage-gated calcium channel inhibitor, in healthy male subjects.DesignRandomized, double-blind, double-dummy, placebo- and active comparator–controlled crossover study.SettingHPR Dr. Schaffler GmbH, Munich, Germany.SubjectHealthy male subjects aged 18–55 years.MethodsTwenty-four eligible subjects were randomly assigned to one of four treatment sequences and received single doses of ASP9226 (30 mg or 50 mg), pregabalin (150 mg), or placebo during four treatment periods. Laser-evoked potentials (LEP) and postlaser pain visual analog scales (VAS) on capsaicin-treated skin were assessed during main assessment days (the first day of each study period). Primary and secondary end points were the differences in LEP N2-P2 peak-to-peak (PtP) amplitudes and VAS score, respectively, in all subjects.ResultsOverall, treatment with pregabalin resulted in a significantly lower LEP N2-P2 PtP amplitude vs placebo (–3.30 μV, P < 0.0001). There were no clinically relevant differences in N2-P2 PtP amplitudes between placebo and either ASP9226 dose (–0.31 μV and –0.27 μV). Furthermore, subjects reported significantly lower VAS pain scores with pregabalin vs placebo (–9.90%, P < 0.0001) in contrast to ASP9226 30 mg (–2.1%) and ASP9226 50 mg (1.2%) vs placebo. Subgroup analysis of LEP and VAS pain in participants with positive prestudy capsaicin response (n = 13) were in keeping with results in all subjects.ConclusionsASP9226 was well tolerated; however, there was no improvement in LEP and VAS pain scores with ASP9226 at either dose vs placebo.

Revealing the time course of laser‐evoked potential habituation by high temporal resolution analysis

“…Thus, compared to the conventional analysis, HTR has the quality to provide additional information in an even shorter time. The shortening of the LEP‐recording process is a gain for experimental approaches investigating central pain processing, studies assessing the efficacy of analgesic drugs (Schaffler et al., 2017, 2018; Truini et al., 2010) and clinical practice. The time‐consuming character being one of the hurdles causal to the lacking establishment of LEP usage in clinical practice (Schlereth, 2020), a shorter test protocol providing more information in even shorter time seems very welcome.…”