Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease)

• Register: ClinicalTrials.gov
• Last refreshed on: 9 January 2023
• Main ID: NCT02964273
• Date of registration: 15/09/2016
• Prospective Registration: Yes
• Primary sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Public title: Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease)
• Scientific title: A Phase 3b, Two-part, Multicenter, One Year Randomized, Double-blind, Placebo-controlled Trial of the Safety, Pharmacokinetics, Tolerability, and Efficacy of Tolvaptan Followed by a Two Year Open-label Extension in Children and Adolescent Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
• Date of first enrolment: September 23, 2016
• Target sample size: 91
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02964273
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 3

Countries of recruitment

Belgium, Germany, Italy, United Kingdom

Contacts

• Name: Study Director
• Affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.

Key inclusion & exclusion criteria

Key Inclusion Criteria:

- Male and female participants aged 4 to 17 years (inclusive) with a diagnosis of ADPKD
as defined by the presence of family history and/or genetic criteria AND who have at
least 10 renal cysts, each of which measure at least 0.5 cm, confirmed upon magnetic
resonance imaging (MRI) inspection; participants under the age of 12 years must have
at least 4 cysts that are at least 1 cm in size, confirmed by ultrasound.

- Weight =20 kg.

- Participants with estimated glomerular filtration rate (eGFR) = 60 mL/min/1.73m^2
within 31 days prior to randomization (using the Schwartz formula, eGFR = 0.413 ×
height [cm]/serum creatinine milligrams per deciliter [mg/dL]).

- Independent in toileting.

- Ability to swallow a tablet.

Key Exclusion Criteria:

- Liver function tests including aspartate aminotransferase (AST), alanine
aminotransferase (ALT) > 1.5 × the upper limit of normal (ULN).

- Nocturnal enuresis.

- Need for chronic diuretic use.

- Participants with advanced diabetes (e.g., glycosylated hemoglobin >7.5, and/or
glycosuria by dipstick, significant proteinuria, retinopathy), evidence of additional
significant renal disease(s) (i.e., currently active glomerular nephritides), renal
cancer, single kidney, or recent (within 6 months of screening) renal surgery or acute
kidney injury.

- Participants having disorders in thirst recognition or inability to access fluids.

- Participants with critical electrolyte imbalances, as determined by the investigator.

- Participants with, or at risk of, significant hypovolemia as determined by
investigator.

- Participants with clinically significant anemia, as determined by investigator.

- Participants 12 years of age and older having contraindications to, or interference
with MRI assessments (e.g., ferro-magnetic prostheses, aneurysm clips, severe
claustrophobia).

- Participants with a history of taking a vasopressin agonist/antagonist.

- Participants taking medications or having concomitant illnesses likely to confound
endpoint assessments, including taking approved (i.e., marketed) therapies for the
purpose of affecting polycystic kidney disease (PKD) cysts such as tolvaptan,
vasopressin antagonists, anti-sense ribonucleic acid (RNA) therapies, rapamycin,
sirolimus, everolimus, or somatostatin analogs (i.e., octreotide, sandostatin).

- Participants who have had cyst reduction surgery within 6 weeks of the screening
visit.



Age minimum: 4 Years
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Intervention(s)

Drug: Tolvaptan

Drug: Tolvaptan Matching-placebo

Primary Outcome(s)

Phase A: Change From Baseline in Spot Urine Osmolality (Pre-morning Dose) [Time Frame: Baseline, and Week 1 of Phase A]

Phase A: Change From Baseline in Specific Gravity (Pre-morning Dose) [Time Frame: Baseline, and Week 1 of Phase A]

Secondary Outcome(s)

Phase A and B: Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs [Time Frame: From first dose of study drug up to 14 days post last dose (up to approximately 37 months)]

Phase A: Change From Baseline in Growth Percentile by Gender and Age [Time Frame: At Baseline, Months 6 and 12 of Phase A]

Phase A: Percentage of Each Tanner Stage by Gender and Age Compared to Normative Populations [Time Frame: At Baseline, Months 6 and 12 of Phase A]

Phase A and B: Percentage of Participants With Aquaretic Adverse Events (AEs) [Time Frame: From first dose of study drug up to 14 days post last dose (up to approximately 37 months)]

Phase B: Percent Change From Phase B Baseline in htTKV as Measured by MRI at Month 12 and Month 24 [Time Frame: Phase B Baseline, Months 12 and 24]

Phase B: Percentage of Each Tanner Stage by Gender and Age Compared to Normative Populations [Time Frame: At Baseline, Months 6, 12, 18, and 24 of Phase B]

Phase A: 24-hour Creatinine Clearance [Time Frame: 24 hours post dose after Month 1 on study medication in Phase A]

Phase A: 24-hour Fluid Intake [Time Frame: 24 hours post dose after Month 1 on study medication in Phase A]

Phase A and B: Mean 24-hour Fluid Balance Prior to Week 1 [Time Frame: Prior to Week 1 in Phase A and B]

Phase A and B: Percentage of Participants With Potentially Clinically Significant Abnormalities in Laboratory Test Results Including Liver Function Tests (LFTs) [Time Frame: From first dose of study drug up to 14 days post last dose (up to approximately 37 months)]

Phase A: 24-hour Fluid Balance [Time Frame: 24 hours post dose after Month 1 on study medication in Phase A]

Phase A: 24-hour Urine Volume [Time Frame: 24 hours post dose after Month 1 on study medication in Phase A]

Phase A: 24-hour Sodium Clearance [Time Frame: 24 hours post dose after Month 1 on study medication in Phase A]

Phase A: Change From Baseline in Creatinine Value [Time Frame: Baseline, Week 1, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, Follow Up Day 7, End of Treatment, and Last Visit]

Phase B: Change From Baseline in Growth Percentile by Gender and Age [Time Frame: At Baseline, Months 6, 12, 18, and 24 of Phase B]

Phase A: Change From Baseline in Renal Function (Estimated Glomerular Filtration Rate [eGFR] by Schwartz Formula) at Each Clinic Visit in Phase A [Time Frame: Phase A Baseline, Months 1, 6, and 12]

Phase B: Change From Baseline in Creatinine Value [Time Frame: Baseline, Week 1, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, Follow Up Day 7, End of Treatment, and Last Visit]

Phase A: 24-hour Free Water Clearance [Time Frame: 24 hours post dose after Month 1 on study medication in Phase A]

Phase A: Percent Change From Phase A Baseline in Height-Adjusted Total Kidney Volume (htTKV) as Measured by Magnetic Resonance Imaging (MRI) [Time Frame: Baseline, and Month 12 of Phase A]

Phase B: Change From Phase B Baseline in Renal Function (eGFR by Schwartz Formula) at Each Clinic Visit in Phase B [Time Frame: Phase B Baseline, Week 1, Months 1, 6, 12, 18, and 24]

Secondary ID(s)

156-12-298

2016-000187-42

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 03/01/2023
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02964273