Dose-finding Study of New Tolvaptan Formulation in Subjects With ADPKD
Condition: Autosomal Dominant Polycystic Kidney Disease
MeSH terms: Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant
Study type: Interventional
Phase: Phase 2

Summary: 
      To establish pharmacokinetics (PK), pharmacodynamics (PD), and adverse event (AE) profile of
      tolvaptan administered as the modified-release (MR) formulation in ADPKD subjects. The goals
      of this trial are two-fold:

        1. To directly compare the immediate release (IR) and MR formulations

        2. To determine the dose range and dose regimen for MR (dose finding)
    

Detailed description: 
      Group 1 will have 12 subjects enrolled in a 3-period, randomized, crossover to compare
      multiple doses of a 90-30 mg split-dose of the tolvaptan IR formulation, a 120 mg once daily
      (QD) dose of the tolvaptan MR formulation, and, in an incomplete block randomization,
      multiple doses of either 20 mg QD, 60 mg QD, or 20 mg twice daily (BID) tolvaptan MR
      formulation. All dose regimens will be administered for 7 days. Placebo doses will be
      administered in order to mask QD vs BID treatments.

      Group 2 will have 12 subjects enrolled in a 3-period, randomized, crossover to compare
      multiple oral doses of the tolvaptan MR formulation administered for 7 days as 20 mg QD, 60
      mg QD, and 20 mg BID. Placebo capsules will be administered in order to mask QD vs BID
      treatments.

      Subjects will have in-clinic assessments on 12 days to obtain 24-hour PK and PD data.
      Subjects will visit the clinic from the afternoon of Day -1 through the morning of Day 1.
      They will return at the end of each dosing period for a similar inpatient period (ie, from
      the afternoon of Day 6 through the morning of Day 8, from the afternoon of Day 13 through the
      morning of Day 15, from the afternoon of Day 20 through the morning of Day 22). Except for
      the first dose of each period and the doses taken in the clinic on the last day of each
      regimen and the afternoon of Days 6, 13 and 20, all other doses will be taken by the subject
      as an outpatient.
    

Intervention name(s): Tolvaptan MR; Tolvaptan MR; Tolvaptan MR; Tolvaptan IR; Tolvaptan MR
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): 20 mg Tolvaptan MR capsule(morning); Placebo capsules/tablets (morning and afternoon) for 7 days; 20 mg Tolvaptan MR capsule(morning and afternoon); Placebo capsules/tablets (morning and afternoon) for 7 days; 60 mg Tolvaptan MR capsule(morning); Placebo capsules/tablets (morning and afternoon) for 7 days; 90 mg Tolvaptan IR tablet(morning); 30 mg Tolvaptan IR tablet (afternoon); Placebo capsules (morning and afternoon) for 7 days; 120 mg Tolvaptan MR capsule(morning); Placebo capsules/tablets (morning and afternoon) for 7 days
Other intervention name(s): OPC-41061; OPC-41061; OPC-41061; OPC-41061; OPC-41061
Intervention MeSH terms: Tolvaptan
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Kidney Disease; Polycystic Kidney Disease