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Clinical trials

An oral TRPV1 antagonist attenuates laser radiant-heat-evoked potentials and pain ratings from UVB-inflamed and normal skin

  1. Klaus Schaffler1,*,
  2. Peter Reeh2,
  3. W. Rachel Duan3,
  4. Andrea E. Best3,
  5. Ahmed A. Othman4,6,
  6. Connie R. Faltynek5,
  7. Charles Locke4,
  8. Wolfram Nothaft3

Article first published online: 10 JAN 2013

DOI: 10.1111/j.1365-2125.2012.04377.x

Issue

British Journal of Clinical Pharmacology

British Journal of Clinical Pharmacology

Volume 75, Issue 2, pages 404–414, February 2013

Additional Information

How to Cite

Schaffler, K., Reeh, P., Duan, W. R., Best, A. E., Othman, A. A., Faltynek, C. R., Locke, C. and Nothaft, W. (2013), An oral TRPV1 antagonist attenuates laser radiant-heat-evoked potentials and pain ratings from UVB-inflamed and normal skin. British Journal of Clinical Pharmacology, 75: 404–414. doi: 10.1111/j.1365-2125.2012.04377.x

Author Information

  1. 1

    HPR Dr. Schaffler GmbH, Aschheim-Dornach, Munich, Germany

  2. 2

    Institute of Physiology and Pathophysiology, University of Erlangen-Nuremberg, Erlangen, Germany

  3. 3

    Abbott Pain Care, Abbott Park, IL, USA

  4. 4

    Abbott Clinical Pharmacology & Pharmacometrics, Abbott Park, IL, USA

  5. 5

    Abbott Neuroscience and Pain Discovery, Abbott Park, IL, USA

  6. 6

    Department of Pharmaceutics, Faculty of Pharmacy, Cairo University, Cairo, Egypt

* Correspondence
Dr Klaus Schaffler MD, Managing and Medical Director, HPR Dr. Schaffler GmbH, Heisenbergbogen 1, Europa Forum, D-85609 Aschheim-Dornach/Munich, Germany.
Tel.: +49 (0) 8999 3220
Fax: +49 (0)89 9932 2299
E-mail: hpr.pharmacodynamics@t-online.de

  1. Data previously presented at 13th World Congress on Pain, August 29–September 2, 2010, Montreal, Quebec, Canada

Publication History

  1. Issue published online: 10 JAN 2013
  2. Article first published online: 10 JAN 2013
  3. Accepted manuscript online: 10 JUL 2012 05:44AM EST
  4. Manuscript Accepted: 25 JUN 2012
  5. Manuscript Received: 23 AUG 2011

Funded by

  • Abbott

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Keywords:

  • analgesia;
  • hyperalgesia;
  • laser evoked potentials;
  • phase 1;
  • UV-inflamed skin;
  • visual analogue scale

Aims

Laser (radiant-heat) evoked potentials (LEPs) from vertex-EEG peak-to-peak (PtP) amplitude were used to determine acute antinociceptive/antihyperalgesic efficacy of ABT-102, a novel TRPV1 antagonist efficacious in preclinical pain models, compared with active controls and placebo in normal and UVB-inflamed skin.

Methods

This was a randomized, placebo- and active-controlled, double-blind, intra-individual, crossover trial. Twenty-four healthy subjects received six sequences of single doses of ABT-102 (0.5, 2, 6 mg), etoricoxib 90 mg, tramadol 100 mg and placebo. Painful stimuli were induced by CO2-laser on normal and UVB-inflamed skin. LEPs and visual analogue scale (VAS-pain) ratings were taken at baseline and hourly up to 8 h post-dose from both skin types.

Results

Compared with placebo, significant mean decreases in the primary variable of LEP PtP-amplitude from UVB-inflamed skin were observed with ABT-102 6 mg (P < 0.001), ABT-102 2 mg (P = 0.002), tramadol 100 mg (P < 0.001), and etoricoxib 90 mg (P = 0.001) over the 8 h period; ABT-102 0.5 mg was similar to placebo. ABT-102 6 mg was superior to active controls over the 8 h period (P < 0.05) whereas ABT-102 2 mg was comparable. Improvements in VAS scores compared with placebo were observed with ABT-102 6 mg (P < 0.001) and ABT-102 2 mg (P = 0.002). ABT-102 average plasma concentrations were 1.3, 4.4 and 9.4 ng ml−1 for the 0.5, 2 and 6 mg doses, respectively. There were no clinically significant safety findings.

Conclusions

TRPV-1 antagonism appears promising in the management of clinical pain, but requires further investigation.

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