Evaluating the Safety and effectivenesS in Adult KorEaN Patients Treated With Tolvaptan for Management of Autosomal domInAnt poLycystic Kidney Disease

NCT03949894 | Completed Phase 4

• 1 other identifier: 156-402-00144
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 18

Brief Summary

To evaluate the safety and therapeutic effectiveness of tolvaptan when administered to slow the progression of cyst development and renal function insufficiency in adult Korean patients diagnosed with rapidly progressive ADPKD who have chronic kidney disease (CKD) stages 1-3 at initiation of treatment.

Conditions

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Outcome Measures

Primary Outcomes (2)

• The incidences of TEAEs

  The incidences of TEAEs

  during the tolvaptan treatment period and up to 7 days after the date of last dosing

• The incidences of TEAEs meeting any of the followings will be summarized.

  Liver injury \[ALT or AST elevation (\>3 x ULN) or Total Bilirubin elevation (\>2 x ULN), etc.\], AEs leading to death, Serious AEs, AEs leading to treatment discontinuation, AEs whose causal relationship with the IMP cannot be ruled out, Severe AEs, Dehydration, Effects on Sodium, Creatinine

  during the tolvaptan treatment period and up to 7 days after the date of last dosing

Secondary Outcomes (3)

• Total kidney volume (TKV) annual mean percent change rate [%/year]

  from baseline to End of Treatment (Visit 25, Month 24)

• eGFR CKD-EPI annual mean change [mL/min/1.73m^2] (off-treatment)

  from baseline to the Follow-up visit (Visit 26, 7 days after End of Treatment(Visit 25, Month 24))

• eGFR CKD-EPI annual mean change [mL/min/1.73m^2] (on-treatment)

  from Completion of Tolvaptan Titration Period (Visit 6, Week 4) to End of Treatment (Visit 25, Month 24)

Study Arms (1)

tolvaptan

EXPERIMENTAL

Drug: Tolvaptan

Interventions

Tolvaptan DRUG

30mg and 15mg of Tolvaptan Tablet

Also known as: Samsca

tolvaptan

Eligibility Criteria

• Age: 19 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects who voluntarily participate by giving written informed consent on this trial
• Male and female patients aged ≥ 19 to ≤ 50 years
• Subjects diagnosed with ADPKD based on the Unified Criteria for Ultrasonographic diagnosis of ADPKD (Pei-Ravine Criteria)
• Subjects with confirmed CKD stages 1-3 at the screening visit
• Subjects with confirmed rapidly progressive typical ADPKD 'Typical ADPKD'
• refers to bilateral and diffuse distribution, with mild, moderate or severe replacement of kidney tissue by cysts, where all cysts contribute similarly to TKV.
• 'rapidly progressive ADPKD'
• Patients will be defined as 'rapidly progressive ADPKD' if they meet any of the following criteria:
• Mayo class 1C, 1D or 1E
• Truncating PKD1 mutation confirmed by genetic testing before participating this trial ③ PRO-PKD score \> 6 ④ Patients with ADPKD with a decline in Estimated glomerular filtration rate(eGFR) ≥ 5 mL/min/1.73 m2 within 1 year from the screening visit or with an average annual decline in eGFR ≥ 2.5 mL/min/1.73 m2 over a period of 5 years (excluding patients with an eGFR decline due to factors other than ADPKD, such as uncontrolled type 2 diabetes, early diabetic glomerular disease or immune-mediated glomerulonephritis)

You may not qualify if:

• Patients with hyponatremia or hypernatremia
• Patients with anuria
• Patients with volume depletion
• Patients who are unable to sense or appropriately respond to thirst
• Patients with contraindications to MRI assessment \[e.g., ferromagnetic metal prosthesis, aneurysm clips, severe claustrophobia, large tattoo on the abdomen or back, etc.\]
• Patients with severe renal impairment \[e.g., patients with currently active glomerulonephritis, kidney cancer, having a single kidney, history of renal surgery within the last 3 years, etc.\]
• Patients with severe hepatic impairment \[e.g., cirrhosis, viral hepatitis, unspecified liver function test abnormalities (ALT or Aspartate aminotransferase(AST)) \> 3 x ULN or Total Bilirubin \> 2 x ULN), etc.\]
• Patients with eGFR decline due to factors other than ADPKD (e.g., uncontrolled type 2 diabetes, early diabetic glomerular disease or immune-mediated glomerulonephritis, etc.)
• Patients with a history of hypersensitivity and/or specific reactions to benzazepine or benzazepine derivatives (such as Benazepril), or tolvaptan
• Patients with hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption, etc.
• Patients who need chronic diuretic use
• Patients who are receiving any experimental (not marketed) or approved therapies that may affect the treatment of ADPKD within 6 months from the screening visit \[e.g., anti-sense RNA therapy, rapamycin, sirolimus, everolimus and somatostatin analogs (octreotide, sandostatin), vasopressin antagonist (mozavaptan, conivaptan), vasopressin agonist (desmopressin)\]
• Patients who have received cyst decompression or sclerotherapy within 3 years from the screening visit
• Patients with a history of taking tolvaptan within 6 months from the screening visit
• Patients who received any investigational medicinal product in another trial within 30 days from the screening visit

Sponsors & Collaborators

• Korea Otsuka Pharmaceutical Co., Ltd.: lead

Study Sites (18)

Inje University Busan Paik Hospital

Busan, South Korea

Location

Kosin University Gospel Hospital

Busan, South Korea

Location

Hallym University Chuncheon Sacred Heart Hospital

Chuncheon, South Korea

Location

Keimyung University Dongsan Medical Center

Daegu, South Korea

Location

Kyungpook National University Hospital

Daegu, South Korea

Location

Chungnam National University Hospital

Daejeon, South Korea

Location

Chonnam National University Hospital

Gwangju, South Korea

Location

Gachon University Gil Medical Center

Incheon, South Korea

Location

Hallym University Medical Center

Pyeongchon, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Gangnam Severance Hospital

Seoul, South Korea

Location

Hallym University Kangnam Sacred Heart Hospital

Seoul, South Korea

Location

Hanyang University Seoul Hospital

Seoul, South Korea

Location

Kangbuk Samsung Hospital

Seoul, South Korea

Location

Severance Hospital

Seoul, South Korea

Location

SMG-SNU Boramae Medical Center

Seoul, South Korea

Location

The Catholic University of Korea Seoul St. Mary's Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant

Interventions

Tolvaptan

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2019
• First Posted: May 14, 2019
• Study Start: July 1, 2019
• Primary Completion: May 25, 2022
• Study Completion: May 25, 2022
• Last Updated: June 16, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

KR (18)