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Invited Speech at NIH Pain Workshop Washington DC Nov 15th 2018 (Video Cast)

Dr. med. Schaffler was a invited Speaker at NIH Workshop on the topic
Discovery and Validation of Biomarkers to Develop Non-Addictive Therapeutics for Pain

Session:
Emerging Tools and Approaches in Biomarker Discovery and Development

Title:
Predictive validity of human Laser-EPs in extended phase-I IND analgesic research

Look Video Cast of NIH Pain Workshop in Washington DC:
Link: https://videocast.nih.gov/summary.asp?Live=28514&bhcp=1

Start looking from 1:25h for presentation Day 2 Nov 15th 2018
(about 20min, Dr.K.Schaffler HPR – Discussion later)

A Phase I, randomized, double-blind, laser evoked potential study to evaluate the analgesic/anti-hyperalgesic effect of ASP9226, a state-dependent N-type voltage-gated calcium channel inhibitor, in healthy male subjects

K. Schaffler, A. Fakhoury, W. He, P. Passier, K. Tracy, J. Paul

in print, Pain Medicine, DOI: 10.1093/pm/pnx338

Excerpt:

Abstract

Objective

Evaluate the analgesic/antihyperalgesic effects of ASP9226, a state-dependent N-type voltage-gated calcium channel inhibitor, in healthy male subjects.

Design

Randomized, double-blind, double-dummy, placebo- and active comparator–controlled crossover study.

Setting

HPR Dr. Schaffler GmbH, Munich, Germany.

Subject

Healthy male subjects aged 18–55 years.

Methods

Twenty-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.

Results

Overall, 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.

Conclusions

ASP9226 was well tolerated; however, there was no improvement in LEP and VAS pain scores with ASP9226 at either dose vs placebo.

Investigation of the predictive validity of laser- EPs in normal, UVB-inflamed and capsaicin-irritated skin with four analgesic compounds in healthy volunteers

BCJP_Pred.Validity_LEP_03.2017_T1

Klaus Schaffler, Laurent B. Nicolas, Andreas Borta, Tobias Brand, Peter Reitmeir, Robert Roebling and Joachim Scholpp in Br J Clin Pharmacol (Jan 2017) DOI:10.1111/bcp.13247

Abstract:

AIMS
The aim of the present study was to assess the predictivity of laser-(radiant-heat)-evoked potentials (LEPs) from the vertex electroencephalogram, using an algesimetric procedure, testing the anti-nociceptive/anti-hyperalgesic effects of single oral doses of four marketed analgesics (of different compound classes) vs. placebo, in healthy volunteers with three skin types.
METHODS
This was a randomized, placebo-controlled, single-blind, five-way-crossover trial. Twenty-five healthy male/female Caucasians were included (receiving celecoxib 200 mg, pregabalin 150 mg, duloxetine 60 mg, lacosamide 100 mg or placebo) in a Williams design, with CO2 laser-induced painful stimuli to normal, ultraviolet (UV) B-inflamed and capsaicin-irritated skin. LEPs and visual analogue scale ratings were taken at baseline and hourly for 6 h postdose from all three skin types.
RESULTS
In normal skin, the averaged postdose LEP peak-to-peak-(PtP)-amplitudes were reduced by pregabalin (2.68 μV; 95% confidence interval (CI) 4.16, 1.19) and duloxetine (1.73 μV; 95% CI 3.21, 0.26) but not by lacosamide and celecoxib vs. placebo.
On UVB-irradiated skin, reflecting inflammatory pain, celecoxib induced a pronounced reduction in LEP PtP amplitudes vs. placebo (6.2 μV; 95% CI 7.88, 4.51), with a smaller reduction by duloxetine (4.54 μV; 95% CI 6.21, 2.87) and pregabalin (3.72 μV; 95% CI 5.40, 2.04), whereas lacosamide was inactive.
LEP PtP amplitudes on capsaicin-irritated skin, reflecting peripheral/spinal sensitization, as in neuropathic pain, were reduced by pregabalin (3.78 μV; 95% CI 5.31, 2.25) and duloxetine (2.32 μV; 95% CI 3.82, 0.82) but not by celecoxib or lacosamide vs. placebo, which was in agreement with known clinical profiles. Overall, PtP amplitude reductions were in agreement with subjective ratings.
CONCLUSIONS
LEP algesimetry is sensitive to analgesics with different modes of action and may enable the effects of novel analgesics to be assessed during early clinical development.