International Journal of Clinical Oncology

, Volume 20, Issue 1, pp 198–206 | Cite as

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

  • Naohito ShimoyamaEmail author
  • Ikuo Gomyo
  • Nobuyuki Katakami
  • Masakuni Okada
  • Nobuyuki Yukitoshi
  • Eri Ohta
  • Megumi Shimoyama
Original Article



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.


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.


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.


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.


Breakthrough pain Cancer pain Sublingual fentanyl tablet Opioid Dose titration 



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.


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Copyright information

© Japan Society of Clinical Oncology 2014

Authors and Affiliations

  • Naohito Shimoyama
    • 1
    Email author
  • Ikuo Gomyo
    • 2
    • 3
  • Nobuyuki Katakami
    • 4
  • Masakuni Okada
    • 5
    • 6
  • Nobuyuki Yukitoshi
    • 7
  • Eri Ohta
    • 8
  • Megumi Shimoyama
    • 9
  1. 1.Department of Palliative MedicineThe Jikei University School of MedicineTokyoJapan
  2. 2.Department of Palliative MedicineSaito Yukoukai HospitalIbarakiJapan
  3. 3.Department of Palliative MedicineJapanese Red Cross Kitami HospitalKitamiJapan
  4. 4.Division of Integrated Oncology, Foundation for Biomedical Research and InnovationInstitute of Biomedical Research and Innovation HospitalKobeJapan
  5. 5.Department of Internal MedicineShakaihoken Kobe Central HospitalKobeJapan
  6. 6.Okada Internal Medicine ClinicKobeJapan
  7. 7.Development Division, Clinical Development Department 2Kyowa Hakko Kirin Co., Ltd.TokyoJapan
  8. 8.Development Division, Clinical Data Evaluation DepartmentKyowa Hakko Kirin Co., Ltd.TokyoJapan
  9. 9.Department of AnesthesiologyTeikyo University Chiba Medical CenterIchiharaJapan

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