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

Autosomal Dominant Polycystic Kidney Disease (ADPKD) Clinical Trial

— ESSENTIAL  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03949894
• Other study ID #: 156-402-00144
• Status: Completed
• Phase: Phase 4
• Start date: July 1, 2019
• Est. completion date: May 25, 2022

Study information

• Verified date: June 2022
• Source: Korea Otsuka Pharmaceutical Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: May 25, 2022
• Est. primary completion date: May 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 50 Years

Eligibility

Inclusion Criteria:

1. Subjects who voluntarily participate by giving written informed consent on this trial

2. Male and female patients aged = 19 to = 50 years

3. Subjects diagnosed with ADPKD based on the Unified Criteria for Ultrasonographic diagnosis of ADPKD (Pei-Ravine Criteria)

4. Subjects with confirmed CKD stages 1-3 at the screening visit

5. 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 ? PRO-PKD score > 6 ? 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)

Exclusion Criteria:

1. Patients with hyponatremia or hypernatremia

2. Patients with anuria

3. Patients with volume depletion

4. Patients who are unable to sense or appropriately respond to thirst

5. Patients with contraindications to MRI assessment [e.g., ferromagnetic metal prosthesis, aneurysm clips, severe claustrophobia, large tattoo on the abdomen or back, etc.]

6. 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.]

7. 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.]

8. 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.)

9. Patients with a history of hypersensitivity and/or specific reactions to benzazepine or benzazepine derivatives (such as Benazepril), or tolvaptan

10. Patients with hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption, etc.

11. Patients who need chronic diuretic use

12. 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)]

13. Patients who have received cyst decompression or sclerotherapy within 3 years from the screening visit

14. Patients with a history of taking tolvaptan within 6 months from the screening visit

15. Patients who received any investigational medicinal product in another trial within 30 days from the screening visit

16. Fertile women who are currently pregnant or breat feeding, or not willing to use or capable of using acceptable contraceptive methods (abstinence, oral, implanted or injected hormonal methods of contraception, intrauterine device or barrier methods of contraception, such as condom, contraceptive diaphragm and spermicidal agents) to avoid pregnancy until completion of the trial

17. Patients who are, in the opinion of the investigator, unable to comply with the administration of the Investigational Medicinal Product(IMP) or the trial procedures

Related Conditions & MeSH terms

• Arthrogryposis
• Autosomal Dominant Polycystic Kidney Disease (ADPKD)
• Kidney Diseases
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Intervention

Drug:
• Tolvaptan
30mg and 15mg of Tolvaptan Tablet

Locations

Country	Name	City	State
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Kosin University Gospel Hospital	Busan
Korea, Republic of	Hallym University Chuncheon Sacred Heart Hospital	Chuncheon
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Hallym University Medical Center	Pyeongchon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Hallym University Kangnam Sacred Heart Hospital	Seoul
Korea, Republic of	Hanyang University Seoul Hospital	Seoul
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	SMG-SNU Boramae Medical Center	Seoul
Korea, Republic of	The Catholic University of Korea Seoul St. Mary's Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Korea Otsuka Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidences of TEAEs	The incidences of TEAEs	during the tolvaptan treatment period and up to 7 days after the date of last dosing
Primary	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	Total kidney volume (TKV) annual mean percent change rate [%/year]	Baseline TKV refers to the value measured during the screening period	from baseline to End of Treatment (Visit 25, Month 24)
Secondary	eGFR CKD-EPI annual mean change [mL/min/1.73m^2] (off-treatment)	(off-treatment)	from baseline to the Follow-up visit (Visit 26, 7 days after End of Treatment(Visit 25, Month 24))
Secondary	eGFR CKD-EPI annual mean change [mL/min/1.73m^2] (on-treatment)	(on-treatment)	from Completion of Tolvaptan Titration Period (Visit 6, Week 4) to End of Treatment (Visit 25, Month 24)