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Jin, Zheng, Kim, and Yim: Repeated Administration of Newly Synthesized Aceclofenac Sustained Release Form Causes Agranulocytosis: Case Report of an Unforeseen Adverse Event during the Phase 1 Trial
Original Article

Translational and Clinical Pharmacology 2014;22(1):11-12.

Published online: 30 June 2014

DOI: https://doi.org/10.12793/tcp.2014.22.1.11

Repeated Administration of Newly Synthesized Aceclofenac Sustained Release Form Causes Agranulocytosis: Case Report of an Unforeseen Adverse Event during the Phase 1 Trial

Hui Jin, Renhua Zheng, BoHyung Kim, Sung-Vin Yim∗

Department of Clinical Pharmacology, College of Medicine, Kyung Hee University Hospital, Seoul 130–701, Korea

∗Correspondence: S. V. Yim; Tel: +82-2-958-9567, Fax: +82-2-958-9559, E-mail: ysvin@khu.ac.kr, ysvin@yahoo.co.kr

Received 31 May 2014       Accepted 31 May 2014

Copyright © 2014 Korean Society for Clinical Pharmacology and Therapeutics

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Aceclofenac is a non-steroidal anti-inflammatory drug (NSAIDs) for inflammatory diseases. In this report, we report a serious adverse event (AE) occurred during the phase I clinical trial for a new sustained-release (SR) formulation of aceclofenac. There was a serious adverse event (AE), agranulocytosis, induced by aceclofenac SR form. An open-labeled, repeated-doses, randomized, crossover study was conducted at Kyung Hee University Hospital and 26 Korean healthy male volunteers were enrolled. All subjects received both aceclofenac SR 200 mg once daily and aceclofenac IR 100 mg twice daily for 4 days with 11 days washout period. After 11 days washout period, one subject showed a serious decrease in the segment neutrophil (267/mm3) on a laboratory test prior to the reference drug administration in period 2. We first report a case of agranulocytosis, during a phase I clinical trial.

Keywords: Aceclofenac, Non-steroidal anti-inflam-Matory drug (NSAIDs), Serious adverse event (AE), Agranulocytosis

References

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Table 1.
Subject R17's counts of WBC and segment neutrophil during the clinical trial
Period Screening period Period 1 Period 2 Follow up period
date day −12 day 1 day 5 day 16 day 20 day 23 day 26
WBC (mm3) 6430 6690 5340 3820 2780 4280 6250
Seg. Neutrophil (%) 48.2 45.9 51.7 7 20.2 25.2 46.2
Seg. Neutrophil count (mm3) 3099 3070 2760 267 561 1078 2887
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