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Effect of ramosetron in female patients with irritable bowel syndrome with diarrhea: a phase III long-term study

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Abstract

Background

The long-term safety of administration of ramosetron in female patients with irritable bowel syndrome with diarrhea (IBS-D) is unknown. The aim of this study was to assess the long-term safety, tolerability, and outcomes with the use of ramosetron in female patients with IBS-D.

Methods

This was a phase III, open-label, uncontrolled, long-term safety trial of the treatment of female Japanese patients with IBS-D, diagnosed according to the Rome III criteria. A total of 151 patients were given 2.5 μg of ramosetron for 4 weeks, and responders continued the same dose for another 48 weeks. Non-responders at 4 weeks were given 5 μg of ramosetron for 48 weeks. At the end of week 52, 106 patients receiving 2.5 μg and 17 patients receiving 5 μg had completed the study. Safety and efficacy including symptoms and quality of life (QOL) were evaluated.

Results

Concerning safety, no serious adverse event related to ramosetron, specifically ischemic colitis, was observed in patients with either dose of ramosetron. However, constipation occurred in 19.7 % of patients given 2.5 μg and 10.5 % of patients given 5 μg of ramosetron. Ramosetron-treated patients showed high rates of global improvement. Stool consistency, abdominal pain and discomfort, and IBS-QOL were also improved at the last evaluation point.

Conclusions

The results provide evidence of the long-term safety and efficacy of treatment with 2.5 and 5 μg of ramosetron in female patients with IBS-D. Clinicians should be aware that one-fifth of women with IBS-D receiving ramosetron may suffer from constipation during treatment (ClinicalTrials.gov ID: NCT01736423).

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Abbreviations

BSFS:

Bristol Stool Form Scale

95 % CI:

95 % confidence interval

FDA:

Food and Drug Administration

HR-QOL:

Health-related quality of life

5-HT:

5-Hydroxytryptamine

5-HT3 :

5-Hydroxytryptamine 3 receptor

IBS:

Irritable bowel syndrome

IBS-C:

Irritable bowel syndrome with constipation

IBS-D:

Irritable bowel syndrome with diarrhea

IBS-M:

Mixed irritable bowel syndrome

IBS-U:

Unsubtyped irritable bowel syndrome

IBS-QOL:

Irritable bowel syndrome-quality of life

MCID:

Minimum clinically important difference

NNT:

Number needed to treat

RR:

Relative risk

SD:

Standard deviation

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Acknowledgments

The authors would like to thank the following investigators for participating in the study: Haruhiro Ankoh, Tetsu Aoki, Takehiro Arai, Masae Banno, Shin Fukui, Tomoaki Hatakeyama, Hitoshi Hongo, Atsushi Isono, Tohoru Isono, Yoshifumi Jinnouchi, Shigeyasu Kamata, Hitoshi Kaneko, Toru Kanematsu, Daijo Kasahara, Hiroyuki Kimura, Toshio Komazaki, Tatsumi Koshiyama, Osamu Kunihiro, Hidenori Kurakata, Yoshio Matsuda, Kiichi Matsuyama, Ikuo Mitani, Shinichi Miyazaki, Koji Mori, Kouetsu Morita, Sanai Noguchi, Hiroshi Nozawa, Hirozumi Obata, Toshiaki Ochiai, Toshihide Ohmori, Tetsuo Ohshima, Teruki Oki, Tetsuya Sanji, Koichi Sato, Koji Sawada, Shigeru Shirota, Tomohiro Tada, Masahiro Takada, Hiroyuki Takahashi, Hirohisa Tanimura, Toshiaki Terada, Satoki Tokito, Osamu Ueda, Yoshiya Umemoto, Nobutoshi Watanabe, Asako Yamada, Norimichi Yamada, and Tadashi Yokoyama. The authors would also like to thank the following investigators for assisting with the study: Akito Nishida, Mayumi Yamano, Hisatake Hayase, and Michie Yagi. Statistical analysis of the entire data set pertaining to efficacy (specifically, the primary and secondary efficacy endpoints) and safety (specifically, serious adverse events as defined in the Japanese guidelines) was performed in accordance with the standard procedures of Astellas Pharma Inc.

Author information

Authors and Affiliations

  1. Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan

    Shin Fukudo

  2. Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan

    Yoshikazu Kinoshita

  3. Department of General Medicine, Asahikawa Medical University, Asahikawa, Japan

    Toshikatsu Okumura

  4. Development Planning and Administration, Astellas Pharma Inc., Tokyo, Japan

    Motoko Ida

  5. Japan/Asia Clinical Development 2, Astellas Pharma Inc., Tokyo, Japan

    Kenta Hayashi & Hiraku Akiho

  6. Data Science, Astellas Pharma Inc., Tokyo, Japan

    Yoshihiro Nakashima

  7. Department of Gastroenterology, Kawasaki Medical School, Kurashiki, Japan

    Ken Haruma

Authors
  1. Shin Fukudo
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  2. Yoshikazu Kinoshita
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  3. Toshikatsu Okumura
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  4. Motoko Ida
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  5. Kenta Hayashi
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  8. Ken Haruma
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Corresponding author

Correspondence to Shin Fukudo.

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Conflict of interest

Shin Fukudo, Yoshikazu Kinoshita, Toshikatsu Okumura, and Ken Haruma are medical consultants under contract with Astellas Pharma Inc.; Motoko Ida, Kenta Hayashi, Hikaru Akiho, and Yoshihiro Nakashima are employees of Astellas Pharma Inc.

Funding

This research was funded by Astellas Pharma Inc., Tokyo, Japan.

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Fukudo, S., Kinoshita, Y., Okumura, T. et al. Effect of ramosetron in female patients with irritable bowel syndrome with diarrhea: a phase III long-term study. J Gastroenterol 51, 874–882 (2016). https://doi.org/10.1007/s00535-016-1165-5

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  • DOI: https://doi.org/10.1007/s00535-016-1165-5

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