Post-Marketing Surveillance Study of Tolvaptan in Patients With ADPKD

Post-Marketing Surveillance Study of Tolvaptan in Patients With ADPKD in Japan

The purpose of this study is to evaluate the safety and effectiveness of tolvaptan in patients with autosomal dominant polycystic kidney disease (ADPKD) in the real world clinical setting in Japan.

Study Overview

• Status: Completed
• Conditions: Polycystic Kidney, Autosomal Dominant
• Intervention / Treatment: Drug: tolvaptan

• Study Type: Observational
• Enrollment (Actual): 1802

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

medical institutes all over Japan

Description

Inclusion Criteria:

• diagnosed ADPKD
• total kidney volume of 750 or more

Exclusion Criteria:

-

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ADPKD	Drug: tolvaptan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimated Slope of Total Kidney Volume During Pre-administration and Administration	Total Kidney Volume (TKV) was used as a biomarker to assess the progression of ADPKD. TKV was measured at each participating site based on imaging obtained via ultrasound, CT, or MRI. The Estimated Slope pre-administration was calculated for subjects who had TKV measurements both prior to and on the day of Tolvaptan initiation (baseline). The rate of change in TKV from the pre-treatment measurement date to the baseline was used to determine the Estimated Slope. Since the date of initiating tolvaptan administration is considered the start date of the study, the kidney volume measured prior to administration falls outside the study period (i.e., it is a value from before the study start date). The Estimated Slope during-treatment was calculated for subjects who had bilateral TKV measurements at baseline and during the treatment period. The rate of change in TKV from baseline to the measurement date during treatment was used to determine the Estimated Slope.	Pre-administration: From the first pre-treatment measurement (up to 12.5 years prior) to the start of tolvaptan. During-treatment: From the start of tolvaptan to the final follow-up (up to 8.0 years later).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Cases in Which ALT Never Exceeded Three Times the Upper Limit of Normal (30 IU/L)	Among cases included in the safety analysis, we counted and listed the number of patients whose ALT levels increased after starting tolvaptan but never exceeded three times the upper limit of normal (30 IU/L) at a specific time point (day) during treatment. Cases in which Tolvaptan treatment was discontinued were considered as dropouts on the day of discontinuation. The number of participants analyzed in each row of the data table is the same as the Overall Number of Participants Analyzed (n=1,672)	From the date of Tolvaptan initiation to the earlier of either the date when ALT reached three times the upper limit of normal or the date of Tolvaptan discontinuation (up to 2789 days).
The Number of Cases in Which AST Never Exceeded Three Times the Upper Limit of Normal (30 IU/L)	Among cases included in the safety analysis, we counted and listed the number of patients whose AST levels increased after starting tolvaptan but never exceeded three times the upper limit of normal (30 IU/L) at a specific time point (day) during treatment. Cases in which Tolvaptan treatment was discontinued were considered as dropouts on the day of discontinuation. The number of participants analyzed in each row of the data table is the same as the Overall Number of Participants Analyzed (n=1,672)	From the date of Tolvaptan initiation to the earlier of either the date when AST reached three times the upper limit of normal or the date of Tolvaptan discontinuation (up to 2789 days).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimated Slope of Estimated Glomerular Filtration Rate (e-GFR) During Pre-administration and Administration	e-GFR was used as a biomarker to evaluate ADPKD progression. Values recorded in the CRF were prioritized; if unavailable, e-GFR was calculated using serum creatinine levels with a gender-specific formula. Male: e-GFR=194×(serum creatinine (mg/dL))^-1.094 ×(age)^-0.287 Female: e-GFR=[194×(serum creatinine (mg/dL))^-1.094 ×(age)^-0.287]×0.739 The pre-treatment Estimated Slope was determined for subjects with e-GFR data both before and at the start of tolvaptan administration (baseline). Since the date of initiating tolvaptan administration is considered the start date of the study, the e-GFR measured prior to administration falls outside the study period. The during-treatment Estimated Slope was calculated for subjects with e-GFR measurements at baseline and during treatment, based on the rate of change from baseline to follow-up.	Pre-administration: From the first pre-treatment measurement (up to 10 years prior) to the start of tolvaptan. During-treatment: From the start of tolvaptan to the final follow-up (up to 8.0 years later).
The Number and Percentage of Adverse Events Observed in Patients Aged 65 Years and Older	The incidence rates of Adverse Drug Reactions(ADRs) were calculated for 192 elderly patients aged 65 years and older, and compared with those in non-elderly patients under 65 years of age.	Adverse events were collected during the period from the start date to the end date of tolvaptan administration for each case (max. 8 years).
Safety in Patients With Advanced ADPKD	Adverse events were summarized in patients with advanced ADPKD who had their creatinine clearance measured at the start of tolvaptan treatment. Patients with advanced ADPKD were defined as those with a pre-treatment creatinine clearance of less than 60 mL/min. The incidence rates of Adverse Drug Reactions(ADRs) were calculated for 752 patients with creatinine clearance <60 mL/min, 261 patients with clearance between 60 and <80 mL/min, and 331 patients with clearance ≥80 mL/min, and the rates were compared across the creatinine clearance groups.	Adverse events were collected during the period from the start date to the end date of tolvaptan administration for each case (max. 8 years).
Safety of Long-term Treatment for ADPKD	In the clinical trials conducted prior to approval, there were no cases in which Samsca was administered continuously for more than three years. In this post-marketing surveillance, cases exceeding the three-year (36-month) treatment period of the pre-approval clinical trials were classified as long-term treatment cases. The safety of long-term treatment was evaluated based on the incidence rate of adverse drug reactions (ADRs) according to the timing of their onset.	Adverse events were collected during the period from the start date to the end date of tolvaptan administration for each case (max. 8 years).

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.
• Investigators: Study Director: Yasuhiko Fukuta, PhD, Otsuka Pharmaceutical Co., Ltd.

Publications and helpful links

General Publications

• Mochizuki T, Muto S, Suzue K, Komaniwa S, Tanaka T, Fukuta Y, Yamashige Y. Safety and efficacy of tolvaptan in real-world Japanese patients with autosomal dominant polycystic kidney disease: final results of SLOW-PKD surveillance. Clin Exp Nephrol. 2025 Jun;29(6):807-817. doi: 10.1007/s10157-025-02634-7. Epub 2025 Feb 14.

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2014
• Primary Completion (Actual): September 20, 2022
• Study Completion (Actual): September 20, 2022

Study Registration Dates

• First Submitted: July 25, 2016
• First Submitted That Met QC Criteria: July 25, 2016
• First Posted (Estimated): July 28, 2016

Study Record Updates

• Last Update Posted (Estimated): December 10, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ciliopathies; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genetic Diseases, Inborn; Congenital Abnormalities; Abnormalities, Multiple; Kidney Diseases, Cystic; Polycystic Kidney Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Polycystic Kidney, Autosomal Dominant; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzazepines; Tolvaptan
• Other Study ID Numbers: 15600-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED