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Long Term Safety of Immediate-release Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease

Phase 3
Completed
Conditions
Polycystic Kidney, Autosomal Dominant
Interventions
Registration Number
NCT02251275
Lead Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Brief Summary

The purpose of the trial was to evaluate and describe the long term safety of tolvaptan in participants with autosomal dominant polycystic kidney disease (ADPKD).

Detailed Description

This was a Phase 3b trial to evaluate and describe the long term safety of tolvaptan treatment in ADPKD participants with chronic kidney disease (CKD). Eligible participants could enroll into Trial 156-13-211 after completing the follow-up visit(s) of their previous trial (156-13-210, 156-08-271, 156-04-251, or 156-09-290). Renal function was assessed during screening by using historical laboratory values for serum creatinine levels to calculate the estimated glomerular filtration rate (eGFR).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1803
Inclusion Criteria
  • Male and female participants ≥ 18 years with confirmed diagnosis of ADPKD (during participation in prior tolvaptan trials) who have completed and transferred from the double-blind Trial 156-13-210 (12-month period including post treatment follow-up, regardless of whether this was on-treatment or off-treatment), or completed Trial 156-08-271 or a prior tolvaptan trial, or interrupted or discontinued treatment in a prior tolvaptan ADPKD trial other than Trial 156-13-210. Participants may be enrolled with the medical monitor approval, and additional close monitoring may be required at the beginning of the trial.
  • eGFR ≥ 20 milliliter (mL)/minute (min)/1.73 meter squared (m^2) within 3 months prior to the baseline visit. Participants who have an eGFR ≤ 20 mL/min/1.73 m^2 may be enrolled with medical monitor approval.
Exclusion Criteria
  • Need for chronic diuretic use
  • Hepatic impairment based on liver function abnormalities other than that expected for ADPKD with cystic liver disease
  • Women of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose of investigational medicinal product (IMP)
  • Women who are breast-feeding and/or who have a positive pregnancy test result prior to receiving IMP.
  • Participants with contraindications to required trial assessments (contraindications to optional assessments, for example, magnetic resonance imaging [MRI] are not a limitation).
  • Participants who in the opinion of the investigator or the medical monitor, have a medical history or medical finding inconsistent with safety or trial compliance

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TolvaptanTolvaptanTolvaptan was self-administered orally as split-dose regimens. The dose regimens used in this trial were 15/15 milligram (mg), 30/15 mg, 45/15 mg, 60/30 mg, or 90/30 mg. Starting doses were dependent upon the participant's previous trial as follows: * Trial 156-13-210: initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability. * Trial 156-08-271: retained the last dose level of tolvaptan received in the trial (45/15 mg, 60/30 mg, or 90/30 mg) and started at that same dose in Trial 156-13-211. * Other Trials (156-04-251 and 156-09-290): initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.
Primary Outcome Measures
NameTimeMethod
Number Of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment(+ 7 days)

An adverse event (AE) was as any untoward medical occurrence associated with the use of an investigational medicinal product (IMP), whether or not considered IMP related. A TEAE was an AE that started after trial drug treatment; or if the event was continuous from baseline and was serious, related to IMP, or resulted in death, discontinuation, interruption or reduction of trial therapy. A serious TEAE included any event that resulted in: death, life-threatening, persistent or significant incapacity, substantial disruption of ability to conduct normal life functions, required inpatient hospitalization, prolonged hospitalization, congenital anomaly/birth defect, or other medically significant events as per medical judgment, that jeopardized the participant and that required medical or surgical intervention. A severe TEAE was an inability to work or perform normal daily activity. A summary of serious and all other non-serious TEAEs, regardless of causality, is located in the AE section.

Secondary Outcome Measures
NameTimeMethod
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