Short-term Renal Hemodynamic Effects of Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Otsuka

Status and phase: Completed; Phase 2

Conditions: Autosomal Dominant Polycystic Kidney Disease

Treatments: Drug: Tolvaptan

Study type: Interventional

Funder types: Industry

Identifiers

NCT01336972

156-09-284

2010-019025-33 (EudraCT Number)

Details and patient eligibility

About

The purpose of the trial was to determine the short-term effects of tolvaptan in patients with autosomal dominant polycystic kidney disease (ADPKD) at various levels of renal function.

Full description

Renal function was assessed during screening with the estimated glomerular filtration rate (eGFR), which was calculated with the 4-variable modification of diet in renal disease (MDRD) equation using a minimum of 2 creatinine measurements. The eGFR values were used to categorize participants into 1 of 3 mutually exclusive strata (> 60 [Group A], 30 to 60 [Group B], and < 30 [Group C] mL/min/1.73 m^2). Each of the 3 groups received the same tolvaptan treatment.

During the 3-week treatment period, participants were up-titrated on a weekly basis from 45/15 mg to 60/30 mg to 90/30 mg (AM and PM [8 hours later] split-dose) to the maximally tolerated dose. The 3-week treatment period was followed by a 3-week post-treatment period during which no study medication was administered.

The effects of the highest tolerated split-dose of tolvaptan on renal hemodynamics and pharmacokinetic and pharmacodynamic parameters were assessed throughout the 6 weeks of the study. The reversibility of changes during the post-treatment period after withdrawal of the drug was determined and the acute transitory effects on kidney volume were also explored.

Enrollment: 29 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of autosomal dominant polycystic kidney disease (ADPKD) by Ravine criteria.

Exclusion criteria

• Renal replacement therapy.
• Use of therapies for the purpose of affecting polycystic kidney disease (PKD) cysts.
• Evidence of significant renal disease, eg, active glomerular nephritides, renal cancer, single kidney.
• Significant risk-factors for renal impairment, eg, chronic use of diuretics, advanced diabetes, use of nephrotoxic drugs.
• History of significant coagulation defects or hemorrhagic diathesis.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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29 participants in 3 patient groups

Group A - eGFR > 60 ml/min/1.73m^2

Experimental group

Description:

Participants received tolvaptan for the first 3 weeks of the 6 week study. Participants were up-titrated on a weekly basis from tolvaptan 45/15 mg to 60/30 mg to 90/30 mg oral split-dose (AM and PM \[8 hours later\]) to the maximally tolerated dose.

Treatment:

Drug: Tolvaptan

Group B - eGFR 30 to 60 ml/min/1.73m^2

Experimental group

Description:

Participants received tolvaptan for the first 3 weeks of the 6 week study. Participants were up-titrated on a weekly basis from tolvaptan 45/15 mg to 60/30 mg to 90/30 mg oral split-dose (AM and PM \[8 hours later\]) to the maximally tolerated dose.

Treatment:

Drug: Tolvaptan

Group C - eGFR < 30 ml/min/1.73m^2

Experimental group

Description:

Participants received tolvaptan for the first 3 weeks of the 6 week study. Participants were up-titrated on a weekly basis from tolvaptan 45/15 mg to 60/30 mg to 90/30 mg oral split-dose (AM and PM \[8 hours later\]) to the maximally tolerated dose.

Treatment:

Drug: Tolvaptan