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Efficacy and safety of sublingual fentanyl orally disintegrating tablet at doses determined by titration for the treatment of breakthrough pain in Japanese cancer patients: a multicenter, randomized, placebo-controlled, double-blind phase III trial

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International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

Breakthrough cancer pain typically has a rapid onset and relatively short duration. Due to this temporal profile, it may not be adequately relieved by oral opioid analgesics. The sublingual fentanyl orally disintegrating tablet is a formulation by which fentanyl can be rapidly absorbed across the oral mucosa producing rapid-onset analgesia, and which may be effective for breakthrough pain treatment.

Methods

A multicenter, randomized, placebo-controlled, double-blind comparative study was conducted to evaluate the efficacy and safety of the sublingual fentanyl tablet at optimized doses for breakthrough pain treatment in cancer patients treated with strong opioid analgesics at fixed intervals. The optimal dose was determined by open-label dose titration. The efficacy and safety of a 12-week extended treatment were also evaluated.

Results

Eleven of 42 subjects who received the sublingual fentanyl tablet experienced adverse drug reactions. Common reactions were somnolence, constipation, nausea, and vomiting. No serious adverse reactions occurred. Sublingual fentanyl tablets at optimal doses and placebo were administered to 37 subjects in a double-blinded manner. A significant analgesic effect of the sublingual fentanyl tablet was present compared to placebo at 30 min after administration. The sublingual fentanyl tablet was also effective and safe during extended treatment, in which changes in basal opioid doses as well as sublingual fentanyl tablet doses were made as needed.

Conclusion

Sublingual fentanyl tablets at doses determined by titration were effective and safe for breakthrough pain treatment in cancer patients treated with strong opioid analgesics at fixed intervals. Extended treatment up to 12 weeks was also effective and safe.

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Notes

  1. Abstral® is a registered trade name of Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan.

  2. National Hospital Organization Hokkaido Cancer Center (Y Iwanami), Dokkyo Medical University Hospital (S Yamaguchi), Omigawa General Hospital (O Teramoto), Showa University Hospital (H Higuchi), Shizuoka Cancer Center (I Osaka), Shizuoka Saiseikai General Hospital (A Suga), National Hospital Organization Nagoya Medical Center (K Kondo), Saito Yukoukai Hospital (I Gomyo), Toyonaka Municipal Hospital (N Meguro), National Hospital Organization Kinki-Chuo Chest Medical Center (A Tokoro), Wakayama Rosai Hospital (Y Kobayashi), Hyogo College of Medicine Hospital (K Murakawa), Foundation for Biomedical Research and Innovation, Institute of Biomedical Research and Innovation Hospital (N Katakami), Shakaihoken Kobe Central Hospital (M Okada), Shimane University Hospital (Y Saito), Nagasaki University Hospital (M Hojo), Kumamoto University Hospital (H Kohrogi), Garatia Hospital (S Kanemura), National Center for Geriatrics and Gerontology (K Nakashima), Ibaraki Prefectural Central Hospital (S Mitsuhashi), Gifu Municipal Hospital (T Ishiguro), Matsue City Hospital (T Iwashita).

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Acknowledgments

The sponsor of this clinical trial was Kyowa Hakko Kirin, Co., Ltd.

Conflict of interest

During the past 3 years, Naohito Shimoyama has had a contract as a medical expert with Kyowa Hakko Kirin Co., Ltd., Nippon Kayaku Co., Ltd. and Mitsubishi Tanabe Pharma Corporation. Naohito Shimoyama also has had a contract with Teikoku Seiyaku Co., Ltd. as a coordinating investigator and a member of independent data monitoring committee. Nobuyuki Yukitoshi and Eri Ohta are employees of Kyowa Hakko Kirin Co., Ltd. The other authors have no conflicts of interest to report.

Author information

Author notes

  1. Ikuo Gomyo

    Present address: Department of Palliative Medicine, Japanese Red Cross Kitami Hospital, 1 Kita-6-jo Higashi-2-chome, Kitami, Hokkaido, 090-8666, Japan

  2. Masakuni Okada

    Present address: Okada Internal Medicine Clinic, 1-7-3 Soyamacho, Kita-ku, Kobe, 651-1145, Japan

Authors and Affiliations

  1. Department of Palliative Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan

    Naohito Shimoyama

  2. Department of Palliative Medicine, Saito Yukoukai Hospital, 7-2-18 Saitoasagi, Ibaraki, Osaka, 567-0085, Japan

    Ikuo Gomyo

  3. Division of Integrated Oncology, Foundation for Biomedical Research and Innovation, Institute of Biomedical Research and Innovation Hospital, 2-2 Minatojima Minamimachi, Chuo-ku, Kobe, 650-0047, Japan

    Nobuyuki Katakami

  4. Department of Internal Medicine, Shakaihoken Kobe Central Hospital, 2-1-1 Soyamacho, Kita-ku, Kobe, 651-1145, Japan

    Masakuni Okada

  5. Development Division, Clinical Development Department 2, Kyowa Hakko Kirin Co., Ltd., 1-6-1 Ohtemachi, Chiyoda-ku, Tokyo, 100-8185, Japan

    Nobuyuki Yukitoshi

  6. Development Division, Clinical Data Evaluation Department, Kyowa Hakko Kirin Co., Ltd., 1-6-1 Ohtemachi, Chiyoda-ku, Tokyo, 100-8185, Japan

    Eri Ohta

  7. Department of Anesthesiology, Teikyo University Chiba Medical Center, 3426-3 Anesaki, Ichihara, Chiba, 299-0111, Japan

    Megumi Shimoyama

Authors
  1. Naohito Shimoyama
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  2. Ikuo Gomyo
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  3. Nobuyuki Katakami
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  4. Masakuni Okada
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  5. Nobuyuki Yukitoshi
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  6. Eri Ohta
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  7. Megumi Shimoyama
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Corresponding author

Correspondence to Naohito Shimoyama.

Additional information

Clinical Trials Government; NCT01326689.

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Shimoyama, N., Gomyo, I., Katakami, N. et al. Efficacy and safety of sublingual fentanyl orally disintegrating tablet at doses determined by titration for the treatment of breakthrough pain in Japanese cancer patients: a multicenter, randomized, placebo-controlled, double-blind phase III trial. Int J Clin Oncol 20, 198–206 (2015). https://doi.org/10.1007/s10147-014-0697-z

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  • DOI: https://doi.org/10.1007/s10147-014-0697-z

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