Post-Marketing Surveillance Study of Tolvaptan in Patients With ADPKD

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.

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)

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)

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.

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 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.

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.