Resumen

The purpose of the study is to determine whether tolvaptan is effective and safe for the treatment of late-stage chronic kidney disease due to autosomal dominant polycystic kidney disease (ADPKD)

Descripción detallada

The protocol will extend the understanding of the efficacy and safety of tolvaptan treatment in ADPKD patients with late stage 2 to early stage 4 CKD (chronic kidney disease). This trial will compare the efficacy of tolvaptan treatment in reducing the annualized change in estimated glomerular filtration rate (eGFR) from pre-treatment baseline to post-treatment follow-up, as compared with placebo, in subjects who tolerate tolvaptan during an initial run-in period. The change in eGFR, calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) formula, will provide kidney function data that are complementary to the data demonstrating the benefits previously observed primarily in ADPKD subjects with earlier stages of disease. Also, it will compare the efficacy of tolvaptan treatment in reducing the decline of annualized eGFR slope, as compared with placebo, in this type of subjects. Finally, it will compare the overall and hepatic safety profile of tolvaptan with placebo and to compare incidence of ADPKD complications (outcomes) during the trial

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 65 YearsSexo: ALL

Criterios de inclusión

Male and female subjects with eGFR between 25-65 mL/min/1.73m2 (if aged 18 to55) or eGFR between 25-44 mL/min/1.73m2 (if aged 56 to \<66)
Tolvaptan naïve
Diagnosis of ADPKD by modified pei-Ravine criteria 1) 3 cysts per kidney by sonography or 5 cysts by CT or MRI with family history of ADPKD or 2) 10 cysts per kidney by any radiologic method and exclusion of other cystic kidney diseases if without family history

Criterios de exclusión

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 prior to receiving IMP
Need for chronic diuretic use
Hepatic impairment or liver function abnormalities other than that expected for ADPKD with typical cystic liver disease
Advanced diabetes, evidence of additional significant renal disease, renal cancer, single kidney, recent renal surgery or acute kidney injury
Contraindications to required trial assessments
Medical history or medical findings inconsistent with safety or compliance with trial assessments

Intervenciones

drug

Tolvaptan (OPC-41061)

Tolvaptan tablets (15 or 30 mg) will be self-administered orally as split-dose regimens, once upon awakening and another approximately 8 to 9 hours later.

drug

Placebo

Matching placebo tablets will be self-administered orally as split-dose regimens, once upon awakening and another approximately 8 to 9 hours later

Ubicaciones

Bahía Blanca, Buenos Aires, Argentina

Ciudad Autonoma, Buenos Aires, Argentina

Junín, Buenos Aires, Argentina

Pergamino, Buenos Aires, Argentina

Pilar, Buenos Aires, Argentina

Sarandí, Buenos Aires, Argentina

Córdoba, Argentina