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Long-term safety profile of tolvaptan in autosomal dominant polycystic kidney disease patients: TEMPO Extension Japan Trial

Authors Muto S, Okada T, Yasuda M, Tsubouchi H, Nakajima K, Horie S

Received 29 May 2017

Accepted for publication 8 August 2017

Published 25 October 2017 Volume 2017:9 Pages 93—104


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Dr Hemalkumar Mehta

Satoru Muto,1 Tadashi Okada,2 Moriyoshi Yasuda,3 Hidetsugu Tsubouchi,4 Koji Nakajima,4 Shigeo Horie1,5

1Department of Advanced Informatics for Genetic Disease, Juntendo University Graduate School of Medicine, Tokyo, 2Department of Clinical Development, 3Pharmacovigilance Department, 4Department of Medical Affairs, Otsuka Pharmaceutical Co, Ltd, 5Department of Urology, Juntendo University Graduate School of Medicine, Tokyo, Japan

Aim: The aim of this trial ( identifier: NCT01280721) was to investigate the long-term safety profile of tolvaptan in Japanese patients with autosomal dominant polycystic kidney disease (ADPKD).
Methods: This open-label multicenter trial was conducted to examine adverse drug reactions (ADRs) related to tolvaptan up to an additional 3 years in 135 Japanese patients who participated in the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and its Outcomes (TEMPO) 3:4 trial at doses of 60–120 mg/d. Blood samples were collected at baseline; at weeks 1, 2, and 3; at month 3; and every 3 months thereafter.
Results: In total, 134/135 (>99%) patients experienced ADRs. The most frequent ADRs were thirst (77.0%), pollakiuria (57.0%), polyuria (37.8%), and hyperuricemia (14.8%). Any unexpected ADRs were not reported in this trial. Most ADRs occurred early during treatment. Fourteen patients (10.4%) experienced hepatic events, and 8 (5.9%) experienced >3-fold increases above the upper limits of normal in serum alanine aminotransferase or aspartate aminotransferase levels between 3 and 9 months following tolvaptan initiation, which recovered after drug interruption. Of the 8 patients, 7 (5.2%) were previously allocated to the placebo arm in the TEMPO 3:4 trial and 4 (3.0%) discontinued due to the hepatic events. One patient (0.7%) was previously allocated to tolvaptan and experienced similar events in the TEMPO 3:4 trial. None of the hepatic ADRs met Hy’s Law laboratory criteria.
Conclusion: ADRs observed in this extension trial were similar to those identified in the TEMPO 3:4 trial and hepatic events were not progressive.

Keywords: autosomal dominant polycystic kidney disease, drug-induced liver injury, liver function test, safety profile, tolvaptan

Corrigendum for this paper has been published.

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