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

• Register: ClinicalTrials.gov
• Last refreshed on: 27 June 2022
• Main ID: NCT03949894
• Date of registration: 16/04/2019
• Prospective Registration: Yes
• Primary sponsor: Korea Otsuka Pharmaceutical Co., Ltd.
• Public title: Evaluating the Safety and effectivenesS in Adult KorEaN Patients Treated With Tolvaptan for Management of Autosomal domInAnt poLycystic Kidney Disease ESSENTIAL
• Scientific title: Evaluating the Safety and effectivenesS in Adult KorEaN Patients Treated With Tolvaptan for Management of Autosomal domInAnt poLycystic Kidney Disease
• Date of first enrolment: July 1, 2019
• Target sample size: 118
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03949894
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

Korea, Republic of

Key inclusion & exclusion criteria

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



Age minimum: 19 Years
Age maximum: 50 Years
Gender: All

Health Condition(s) or Problem(s) studied

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Intervention(s)

Drug: Tolvaptan

Primary Outcome(s)

The incidences of TEAEs [Time Frame: 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. [Time Frame: during the tolvaptan treatment period and up to 7 days after the date of last dosing]

Secondary Outcome(s)

Total kidney volume (TKV) annual mean percent change rate [%/year] [Time Frame: from baseline to End of Treatment (Visit 25, Month 24)]

eGFR CKD-EPI annual mean change [mL/min/1.73m^2] (on-treatment) [Time Frame: from Completion of Tolvaptan Titration Period (Visit 6, Week 4) to End of Treatment (Visit 25, Month 24)]

eGFR CKD-EPI annual mean change [mL/min/1.73m^2] (off-treatment) [Time Frame: from baseline to the Follow-up visit (Visit 26, 7 days after End of Treatment(Visit 25, Month 24))]

Secondary ID(s)

156-402-00144

Source(s) of Monetary Support

Please refer to primary and secondary sponsors