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The effect of tolvaptan on autosomal dominant polycystic kidney disease patients: a subgroup analysis of the Japanese patient subset from TEMPO 3:4 trial

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Abstract

Background

Japan is the first country in the world to approve tolvaptan for the treatment of autosomal dominant polycystic kidney disease (ADPKD), which was based on the results of Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4 trial. To evaluate the safety and efficacy of tolvaptan, we performed a subgroup analysis in the participating Japanese ADPKD patient population.

Methods

The primary outcome was the annual rate of percentage change in the total kidney volume (TKV). The secondary endpoint was the rate of kidney function change.

Results

The tolvaptan and placebo groups included 118 and 59 patients, respectively. The annual rate of percentage changes in TKV were 1.3 % [95 % confidence interval (CI) 0.4–2.1] in the tolvaptan group, and 5.0 % (95 % CI 3.9–6.2) in the placebo group (P < 0.001). The annual estimated glomerular filtration rate change was −3.83 mL/min/1.73 m2 in the tolvaptan group and −5.05 mL in the placebo group for a treatment effect of +1.22 mL/min/1.73 m2 (95 % CI 0.41–2.02: P = 0.003). Hepatic function abnormal as a serious adverse event was observed in 3 patients (2.5 %) in the tolvaptan group.

Conclusions

Administration of tolvaptan in the Japanese sub-population reduced the annual rate of TKV growth and slowed the rate of kidney function decline over 36 months compared to patients on placebo, thus providing a novel and effective therapy for the treatment of ADPKD. (TEMPO 3:4 ClinicalTrials.gov number, NCT00428948).

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Acknowledgments

Data analyzed in the present subgroup analysis were all provided by Otsuka Pharmaceutical Development and Commercialization (Maryland, USA) to Department of Medical Affairs (Otsuka Pharmaceutical Co., Ltd. Tokyo, Japan). The authors’ sincere thanks are due to Taku Seriu and Kyoji Imaoka for approval of this project and generous support, are due to Osamu Sato, Tadashi Okada, Mitsuhiro Kondo, Saki Misono, Emi Tomotake and Yoshitaka Yamamura for implementation of the TEMPO 3:4 trial in Japan, and are due to Jaime Blais, Koji Nakajima, Yoshiyuki Shibasaki, Hidetsugu Tsubouchi, Kazumasa Kishi, Hiromi Oka, Sayaka Tachikawa, and Hiroyuki Kobayashi for interpretation of the data, and review and revision of the present manuscript. These study management and editorial assistance were all provided by Department of Clinical Development (Otsuka) and Department of Medical Affairs.

Conflict of interest

SH has received honoraria for presentations and research funding from and has consulted and been an advisory board member for Otsuka Pharmaceutical. EH has received research funding from Otsuka Pharmaceutical and is a member of the Steering Committee for several Otsuka studies involving the TEMPO 3:4 trial. TM and JO are employees of Otsuka. VET is an investigator and Chair of the Steering Committee for several Otsuka studies involving the TEMPO 3:4 trial. All the other authors declared no competing interests.

Author information

Authors and Affiliations

  1. Department of Urology, Teikyo University School of Medicine, Tokyo, Japan

    Satoru Muto

  2. Department of Urology, Juntendo University Graduate School of Medicine, Hongo 3-1-3, Bunkyo-ku, Tokyo, 113-8431, Japan

    Haruna Kawano & Shigeo Horie

  3. Department of ADPKD Research, Kyorin University School of Medicine, Tokyo, Japan

    Eiji Higashihara

  4. Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Ichiei Narita

  5. Nephrology Center and Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan

    Yoshifumi Ubara

  6. Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan

    Takayuki Matsuzaki

  7. Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, MD, USA

    John Ouyang

  8. Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

    Vicente E. Torres

Authors
  1. Satoru Muto
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  2. Haruna Kawano
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  3. Eiji Higashihara
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  4. Ichiei Narita
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  5. Yoshifumi Ubara
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  6. Takayuki Matsuzaki
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  7. John Ouyang
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  8. Vicente E. Torres
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  9. Shigeo Horie
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Corresponding author

Correspondence to Shigeo Horie.

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Muto, S., Kawano, H., Higashihara, E. et al. The effect of tolvaptan on autosomal dominant polycystic kidney disease patients: a subgroup analysis of the Japanese patient subset from TEMPO 3:4 trial. Clin Exp Nephrol 19, 867–877 (2015). https://doi.org/10.1007/s10157-015-1086-2

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  • DOI: https://doi.org/10.1007/s10157-015-1086-2

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