Autosomal Dominant Polycystic Kidney Disease (ADPKD)Phase 3NCT02964273
Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease)
A Phase 3 study testing Tolvaptan in people with Autosomal Dominant Polycystic Kidney Disease (ADPKD), run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 20 sites in 4 countries.
Trial summary
The primary objective of the study is to assess the long term safety of treatment with tolvaptan in children and adolescents with autosomal dominant polycystic kidney disease (ADPKD). Read more about this study
- Who is it for?
- Ages 4 to 17 years
- Conditions the study is for
- Autosomal Dominant Polycystic Kidney Disease (ADPKD)
- What is being tested?
- Tolvaptan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 91 participants
- Where
- 20 sitesin 4 countries
- Study dates
- 23 Sep 2016to 17 Nov 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
20 sites in 4 countries.
20 sites in 4 countries
Germany6 sites
Study site
Cologne, 50937
Study site
Hamburg, 20246
Study site
Hanover, 30625
Study site
Heidelberg, 69120
Study site
Leipzig, 04103
Study site
Tübingen, 72076
Belgium5 sites
Study site
Brussels, 1020
Study site
Brussels, 1200
Study site
Ghent, Oost-Vlaanderen, 9000
Study site
Leuven, Vlaams Brabant, 3000
Study site
Montegnée, 4420
United Kingdom5 sites
Study site
Birmingham, B4 6NH
Study site
London, SE1 7EH
Study site
London, WC1N 3JH
Study site
Manchester, M13 9WL
Study site
Nottingham, NG7 2UH
Italy4 sites
Study site
Milan, 20122
Study site
Naples, 80129
Study site
Naples, 80131
Study site
Pavia, 27100
About this study
Official 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)
The primary objective of the study is to assess the long term safety of treatment with tolvaptan in children and adolescents with autosomal dominant polycystic kidney disease (ADPKD). The secondary objective is to assess the pharmacodynamics, pharmacokinetics, and efficacy of tolvaptan in the same participant population.
Read the detailed description
Tolvaptan has been demonstrated to delay the decline of kidney function in adults with rapidly progressing ADPKD (chronic kidney disease [CKD] stages 1 to 3) as measured by estimated glomerular filtration rate (eGFR) and Total Kidney Volume (TKV).
This trial will be the first trial of tolvaptan in children and adolescents with ADPKD.
Participants in this study will be randomly assigned to one of two groups in Phase A; tolvaptan or placebo. Participants will have an equal chance of being assigned to either treatment group and will be stratified by age and gender into the following cohorts:
- Female participant ages 12 to 14 years, inclusive
- Female participant ages 15 to 17 years, inclusive
- Male participant ages 12 to 14 years, inclusive
- Male participant ages 15 to 17 years, inclusive
Phase (A) of this study will last 12 months. After that time, all participants who qualify will be assigned tolvaptan and will be treated with tolvaptan for 24 months (Phase B).
A qualified participant is defined as one who has completed Phase A on investigational medicinal product (IMP), is willing to continue in the trial, and who does not have any adverse events (AEs), which would require IMP discontinuation.
Participants in this study will be required to make monthly visits to the study clinic and will be closely monitored over the course of the study.
- Being tested
- Tolvaptan, Tolvaptan Matching-placebo
- Keywords
- Autosomal Dominant Polycystic Kidney Disease, ADPKD, Tolvaptan, Renal cysts, Chronic Kidney Disease, Genetic Kidney Disease
- Medical subject headings
- Polycystic Kidney, Autosomal Dominant, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolvaptanDrug
Also called OPC-41061
Tolvaptan spray-dried, immediate release tablets
Tolvaptan Matching-placeboDrug
Tolvaptan matching-placebo tablets
| Study group | Role | What they receive |
|---|---|---|
| Phase A: Tolvaptan | Experimental | Participants received tolvaptan tablets, orally as a split dose (with the first dose taken upon awakening and the second dose taken approximately 8 hours later), and starting doses based on their weight as per the following specifications: ≥20 to 45 kg: 15/7.5 mg; ≥45 to ≤75 kg: 30/15 mg; >75 kg: 45/15 mg, for 1 week. The starting dose was up-titrated (≥20 to <45 kg: 30/15 mg; ≥45 to ≤75 kg: 45/15 mg; >75 kg: 60/30 mg) after 1 week based upon tolerability and thereafter participants continued the same dose for 12 months. Doses may be titrated down dependent upon participant tolerability. Receives: Drug: Tolvaptan |
| Phase A: Placebo | Placebo comparator | Participants received matching-placebo tablets, orally as a split-dose (with the first dose taken upon awakening and second dose taken approximately 8 hours later), and starting dose based on their weight as per the following specifications: ≥20 to <45 kg: 15/7.5 mg; ≥45 to ≤75 kg: 30/15 mg; >75 kg: 45/15 mg, for 1 week. The starting dose was up-titrated (≥20 to <45 kg: 30/15 mg; ≥45 to ≤75 kg: 45/15 mg; >75 kg: 60/30 mg) after 1 week based upon tolerability and thereafter participants continued the same dose for 12 months. Doses may be titrated down dependent upon participant tolerability. Receives: Drug: Tolvaptan Matching-placebo |
| Phase B: Prior Tolvaptan | Experimental | Qualified participants (defined as those who were willing to continue in the trial and who did not have any adverse events [AEs] that would require investigational medicinal product [IMP] discontinuation) who received tolvaptan and completed Phase A were enrolled in Phase B and received tolvaptan tablets, orally as a split dose (with the first dose taken upon awakening and the second dose taken approximately 8 hours later), and starting dose based on their body weight as per following specifications: ≥20 to <45 kg: 15/7.5 mg; ≥45 to ≤75 kg: 30/15 mg; >75 kg: 45/15 mg, for 1 week. The starting dose was up-titrated (≥20 to <45 kg: 30/15 mg; ≥45 to ≤75 kg: 45/15 mg; >75 kg: 60/30 mg) after 1 week based upon tolerability and thereafter participants continued the same dose for 24 months. Doses may be titrated down dependent upon participant tolerability. Receives: Drug: Tolvaptan |
| Phase B: Prior Placebo | Experimental | Qualified participants (defined as those who were willing to continue in the trial and who did not have any AEs that would require IMP discontinuation) who received matching-placebo and completed Phase A, were enrolled in Phase B and received tolvaptan tablets, orally as a split dose (with the first dose taken upon awakening and the second dose taken approximately 8 hours later), based on their current body weight as per following specifications: ≥20 to <45 kg: 15/7.5 mg; ≥45 to ≤75 kg: 30/15 mg; >75 kg: 45/15 mg, for 1 week. The starting dose was up-titrated (≥20 to <45 kg: 30/15 mg; ≥45 to ≤75 kg: 45/15 mg; >75 kg: 60/30 mg) after 1 week based upon tolerability and thereafter participants continued the same dose for 24 months. Doses may be titrated down dependent upon participant tolerability. Receives: Drug: Tolvaptan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase A: Change From Baseline in Spot Urine Osmolality (Pre-morning Dose)
Urine osmolality is a measure of urine concentration, measured by osmometer, which evaluates the freezing point depression of a solution and supplies results as milliosmoles per kilogram of water. Spot urine osmolality was determined for urine samples collected immediately prior to morning dosing for Day 1 (Baseline), and Week 1 for all participants. Sample was taken after the first morning's void and was provided as a mid-stream, clean catch sample. All participants were fasting.
Measured: Baseline, and Week 1 of Phase A
Phase A: Change From Baseline in Specific Gravity (Pre-morning Dose)
Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Spot urine sample for determination of specific gravity was collected immediately prior to morning dosing for Day 1 (Baseline), and Week 1 for all participants. Sample was taken after the first morning's void and was provided as a mid-stream, clean catch sample. All participants were fasting.
Measured: Baseline, and Week 1 of Phase A
Secondary outcomes (20)
Phase A: Percent Change From Phase A Baseline in Height-Adjusted Total Kidney Volume (htTKV) as Measured by Magnetic Resonance Imaging (MRI)
htTKV is used in participants with autosomal dominant polycystic kidney disease to predict the onset of renal insufficiency.
Measured: Baseline, and Month 12 of Phase A
Phase A and B: Mean 24-hour Fluid Balance Prior to Week 1
Participants were instructed to record all fluid taken and all urine output for the 24-hour period.
Measured: Prior to Week 1 in Phase A and B
Phase A: Change From Baseline in Renal Function (Estimated Glomerular Filtration Rate [eGFR] by Schwartz Formula) at Each Clinic Visit in Phase A
Renal function was assessed by estimated eGFR calculated by the Schwartz formula (eGFR = 0.413 × height [cm] /serum creatinine mg/dL), expressed as mean change in eGFR at the specified time points. The units for the data reported are milliliter per minute per 1.73 meter square (mL/min/1.73 m^2). The baseline was the evaluation done at Week 1 in Phase A for this outcome measure.
Measured: Phase A Baseline, Months 1, 6, and 12
Phase B: Change From Phase B Baseline in Renal Function (eGFR by Schwartz Formula) at Each Clinic Visit in Phase B
Renal function was assessed by estimated eGFR calculated by the Schwartz formula (eGFR = 0.413 × height [cm] /serum creatinine mg/dL), expressed as mean change in eGFR at the specified time points.
Measured: Phase B Baseline, Week 1, Months 1, 6, 12, 18, and 24
Phase B: Percent Change From Phase B Baseline in htTKV as Measured by MRI at Month 12 and Month 24
htTKV is used in participants with autosomal dominant polycystic kidney disease to predict the onset of renal insufficiency.
Measured: Phase B Baseline, Months 12 and 24
Phase A: 24-hour Urine Volume
Urine volume refers to the quantity of urine produced per unit of time.
Measured: 24 hours post dose after Month 1 on study medication in Phase A
Phase A: 24-hour Fluid Intake
Daily fluid intake (total water) is defined as the amount of water consumed from foods, plain drinking water, and other beverages.
Measured: 24 hours post dose after Month 1 on study medication in Phase A
Phase A: 24-hour Fluid Balance
Fluid balance is a term used to describe the balance of the input and output of fluids in the body to allow metabolic processes to function correctly.
Measured: 24 hours post dose after Month 1 on study medication in Phase A
Phase A: 24-hour Sodium Clearance
Data was categorized and reported based on the total daily dose for the given time point of 0-24 hours.
Measured: 24 hours post dose after Month 1 on study medication in Phase A
Phase A: 24-hour Creatinine Clearance
Creatinine is produced from the metabolism of protein, when muscles burn energy. Most creatinine is filtered out of the blood by the kidneys and excreted in urine. The creatinine clearance value is determined by measuring the concentration of endogenous creatinine (that which is produced by the body) in both plasma and urine. Data was categorized and reported based on the total daily dose for the given time point of 0-24 hours.
Measured: 24 hours post dose after Month 1 on study medication in Phase A
Phase A: 24-hour Free Water Clearance
Data was categorized and reported based on the total daily dose for the given time point of 0-24 hours.
Measured: 24 hours post dose after Month 1 on study medication in Phase A
Phase A: Percentage of Each Tanner Stage by Gender and Age Compared to Normative Populations
Tanner stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). Only those categories with at least one participant with event are reported.
Measured: At Baseline, Months 6 and 12 of Phase A
Phase B: Percentage of Each Tanner Stage by Gender and Age Compared to Normative Populations
Tanner stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). Only those categories with at least one participant with event are reported.
Measured: At Baseline, Months 6, 12, 18, and 24 of Phase B
Phase A: Change From Baseline in Growth Percentile by Gender and Age
The growth percentile was based on the assessment of height and weight.
Measured: At Baseline, Months 6 and 12 of Phase A
Phase B: Change From Baseline in Growth Percentile by Gender and Age
The growth percentile was based on the assessment of height and weight.
Measured: At Baseline, Months 6, 12, 18, and 24 of Phase B
Phase A: Change From Baseline in Creatinine Value
Phase A Baseline is the last pre-dose evaluation. The Last Visit is the last available post-baseline evaluation including early term. As prespecified in the protocol, data for safety is reported by the treatment group (Phase A: Tolvaptan and Phase A: Placebo)
Measured: 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 Creatinine Value
Phase B Baseline is the last evaluation prior to the first dose in Phase B. The Last Visit is the last available post-baseline evaluation including early term. As prespecified in the protocol, data for safety is reported by the treatment group (Phase B: Prior Tolvaptan and Phase B: Prior Placebo).
Measured: 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 and B: Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
Vital sign measurements included measurements of respiratory rate, blood pressure, body temperature and pulse. Any value outside the normal range was flagged for the attention of the investigator who assessed whether or not a flagged value is of clinical significance. Only those categories with at least one participant with event are reported. As prespecified in the protocol, data for safety is reported by the treatment group (Phase A: Tolvaptan, Phase A: Placebo, Phase B: Prior Tolvaptan and Phase B: Prior Placebo).
Measured: From first dose of study drug up to 14 days post last dose (up to approximately 37 months)
Phase A and B: Percentage of Participants With Potentially Clinically Significant Abnormalities in Laboratory Test Results Including Liver Function Tests (LFTs)
Laboratory parameters=haematology,chemistry,urinalysis,\& LFTs.Criteria for laboratory abnormalities along with their test result grade=Increased creatinine level: Baseline(BSL):Grade 0,>BSL-1.5xBSL:1,>1.5-3xBSL:2,>3-6xBSL:3,>6xBSL:4.Decreased glucose level: <30:-4,30-<40:-3, 40-<55:-2, 55-<65:-1,>=65:0; Increased:<=115:0,>115-160:1,>160-250:2,>250-500:3,>500:4.Decreased potassium level: <2.5:-4,2.5-<3:-3,3-<lower limit of normal(LLN):-1,LLN:0; Increased:upper limit of normal(ULN):0,>ULN-5.5:1,>5.5-6:2,>6-7:3,>7:4.Decreased sodium level: <120:-4,120-124:-3,125-129:-2,130-135:-1,>=136:0; Increased:<=145:0,146-150:1,151-155:2,156-160:3,>160:4. Increased triglyceride level:ULN:0,>ULN-2.5xULN:1,>2.5-5xULN:2,>5-6xULN:3,>6xULN:4. Decreased Neutrophils:<0.5:-4,0.5-<1:-3,1-<1.5:-2,1.5-<LLN:-1,LLN:0. Potentially clinically significant increase or decrease was defined as Baseline grade 0,1,-1 and post-baseline grade >1, <-1 or Baseline grade >1,<-1 and post-baseline grade >or<Baseline grade.
Measured: From first dose of study drug up to 14 days post last dose (up to approximately 37 months)
Phase A and B: Percentage of Participants With Aquaretic Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Aquaretic AEs included Medical Dictionary for Regulatory Activities [MedDRA] preferred terms of thirst, polyuria (production of large volumes of dilute urine), nocturia (need to wake up to urinate at night), pollakiuria (abnormally frequent urination), and polydipsia (excessive thirst). As prespecified in the protocol, data for safety is reported by the treatment group (Phase A: Tolvaptan, Phase A: Placebo, Phase B: Prior Tolvaptan and Phase B: Prior Placebo).
Measured: From first dose of study drug up to 14 days post last dose (up to approximately 37 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2016 (estimated)
- Study start23 Sep 2016
- Primary completion17 Nov 2021
- Study completion17 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Autosomal Dominant Polycystic Kidney Disease (ADPKD)Studies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Otsuka Pharmaceutical Development & Commercialization, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02964273
- Sponsor's protocol ID
- 156-12-298
- Other IDs
- 2016-000187-42, 2016
- Status last verified
- Dec 2022
- First submitted
- 15 Sep 2016
- Last updated
- 3 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
Publications
Shoaf SE, Sikes K. Tolvaptan pharmacokinetics and pharmacodynamics in adolescents with autosomal dominant polycystic kidney disease. Eur J Pediatr. 2025 Dec 18;185(1):26. doi: 10.1007/s00431-025-06689-2.
PubMed 41407907St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
PubMed 39356039Mekahli D, Guay-Woodford LM, Cadnapaphornchai MA, Greenbaum LA, Litwin M, Seeman T, Dandurand A, Shi L, Sikes K, Shoaf SE, Schaefer F. Tolvaptan for Children and Adolescents with Autosomal Dominant Polycystic Kidney Disease: Randomized Controlled Trial. Clin J Am Soc Nephrol. 2023 Jan 1;18(1):36-46. doi: 10.2215/CJN.0000000000000022.
PubMed 36719158Liu F, Feng C, Shen H, Fu H, Mao J. Tolvaptan in Pediatric Autosomal Dominant Polycystic Kidney Disease: From Here to Where? Kidney Dis (Basel). 2021 Sep;7(5):343-349. doi: 10.1159/000517186. Epub 2021 Jul 2.
PubMed 34604341
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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)
- ClinicalTrials.gov ID
- NCT02964273
- Acronym / sponsor ID
- 156-12-298
- Keywords
- Autosomal Dominant Polycystic Kidney Disease, ADPKD, Tolvaptan, Renal cysts, Chronic Kidney Disease, Genetic Kidney Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Study start
- 23 Sep 2016 (actual)
- Primary completion
- 17 Nov 2021 (actual)
- Study completion
- 17 Nov 2021 (actual)
- First posted
- 16 Nov 2016 (estimated)
- Results
- Posted 3 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of the study is to assess the long term safety of treatment with tolvaptan in children and adolescents with autosomal dominant polycystic kidney disease (ADPKD). The secondary objective is to assess the pharmacodynamics, pharmacokinetics, and efficacy of tolvaptan in the same participant population.
Detailed description
Tolvaptan has been demonstrated to delay the decline of kidney function in adults with rapidly progressing ADPKD (chronic kidney disease [CKD] stages 1 to 3) as measured by estimated glomerular filtration rate (eGFR) and Total Kidney Volume (TKV).
This trial will be the first trial of tolvaptan in children and adolescents with ADPKD.
Participants in this study will be randomly assigned to one of two groups in Phase A; tolvaptan or placebo. Participants will have an equal chance of being assigned to either treatment group and will be stratified by age and gender into the following cohorts:
- Female participant ages 12 to 14 years, inclusive
- Female participant ages 15 to 17 years, inclusive
- Male participant ages 12 to 14 years, inclusive
- Male participant ages 15 to 17 years, inclusive
Phase (A) of this study will last 12 months. After that time, all participants who qualify will be assigned tolvaptan and will be treated with tolvaptan for 24 months (Phase B).
A qualified participant is defined as one who has completed Phase A on investigational medicinal product (IMP), is willing to continue in the trial, and who does not have any adverse events (AEs), which would require IMP discontinuation.
Participants in this study will be required to make monthly visits to the study clinic and will be closely monitored over the course of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase A: Tolvaptan | Experimental | Drug: TolvaptanParticipants received tolvaptan tablets, orally as a split dose (with the first dose taken upon awakening and the second dose taken approximately 8 hours later), and starting doses based on their weight as per the following specifications: ≥20 to 45 kg: 15/7.5 mg; ≥45 to ≤75 kg: 30/15 mg; >75 kg: 45/15 mg, for 1 week. The starting dose was up-titrated (≥20 to <45 kg: 30/15 mg; ≥45 to ≤75 kg: 45/15 mg; >75 kg: 60/30 mg) after 1 week based upon tolerability and thereafter participants continued the same dose for 12 months. Doses may be titrated down dependent upon participant tolerability. |
| Phase A: Placebo | Placebo comparator | Drug: Tolvaptan Matching-placeboParticipants received matching-placebo tablets, orally as a split-dose (with the first dose taken upon awakening and second dose taken approximately 8 hours later), and starting dose based on their weight as per the following specifications: ≥20 to <45 kg: 15/7.5 mg; ≥45 to ≤75 kg: 30/15 mg; >75 kg: 45/15 mg, for 1 week. The starting dose was up-titrated (≥20 to <45 kg: 30/15 mg; ≥45 to ≤75 kg: 45/15 mg; >75 kg: 60/30 mg) after 1 week based upon tolerability and thereafter participants continued the same dose for 12 months. Doses may be titrated down dependent upon participant tolerability. |
| Phase B: Prior Tolvaptan | Experimental | Drug: TolvaptanQualified participants (defined as those who were willing to continue in the trial and who did not have any adverse events [AEs] that would require investigational medicinal product [IMP] discontinuation) who received tolvaptan and completed Phase A were enrolled in Phase B and received tolvaptan tablets, orally as a split dose (with the first dose taken upon awakening and the second dose taken approximately 8 hours later), and starting dose based on their body weight as per following specifications: ≥20 to <45 kg: 15/7.5 mg; ≥45 to ≤75 kg: 30/15 mg; >75 kg: 45/15 mg, for 1 week. The starting dose was up-titrated (≥20 to <45 kg: 30/15 mg; ≥45 to ≤75 kg: 45/15 mg; >75 kg: 60/30 mg) after 1 week based upon tolerability and thereafter participants continued the same dose for 24 months. Doses may be titrated down dependent upon participant tolerability. |
| Phase B: Prior Placebo | Experimental | Drug: TolvaptanQualified participants (defined as those who were willing to continue in the trial and who did not have any AEs that would require IMP discontinuation) who received matching-placebo and completed Phase A, were enrolled in Phase B and received tolvaptan tablets, orally as a split dose (with the first dose taken upon awakening and the second dose taken approximately 8 hours later), based on their current body weight as per following specifications: ≥20 to <45 kg: 15/7.5 mg; ≥45 to ≤75 kg: 30/15 mg; >75 kg: 45/15 mg, for 1 week. The starting dose was up-titrated (≥20 to <45 kg: 30/15 mg; ≥45 to ≤75 kg: 45/15 mg; >75 kg: 60/30 mg) after 1 week based upon tolerability and thereafter participants continued the same dose for 24 months. Doses may be titrated down dependent upon participant tolerability. |
Who may qualify
- Ages
- 4 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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 (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TolvaptanAlso: OPC-41061Tolvaptan spray-dried, immediate release tablets | Drug | Phase A: Tolvaptan, Phase B: Prior Placebo, Phase B: Prior Tolvaptan |
| Tolvaptan Matching-placeboTolvaptan matching-placebo tablets | Drug | Phase A: Placebo |
Primary outcome
Phase A: Change From Baseline in Spot Urine Osmolality (Pre-morning Dose)
Time frame: Baseline, and Week 1 of Phase A
Urine osmolality is a measure of urine concentration, measured by osmometer, which evaluates the freezing point depression of a solution and supplies results as milliosmoles per kilogram of water. Spot urine osmolality was determined for urine samples collected immediately prior to morning dosing for Day 1 (Baseline), and Week 1 for all participants. Sample was taken after the first morning's void and was provided as a mid-stream, clean catch sample. All participants were fasting.
Phase A: Change From Baseline in Specific Gravity (Pre-morning Dose)
Time frame: Baseline, and Week 1 of Phase A
Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Spot urine sample for determination of specific gravity was collected immediately prior to morning dosing for Day 1 (Baseline), and Week 1 for all participants. Sample was taken after the first morning's void and was provided as a mid-stream, clean catch sample. All participants were fasting.
20 secondary outcomes
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 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: 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 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
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 A: 24-hour Urine Volume
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: 24-hour Fluid Balance
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: 24-hour Creatinine Clearance
Time frame: 24 hours post dose after Month 1 on study medication in Phase A
Phase A: 24-hour Free Water Clearance
Time frame: 24 hours post dose after Month 1 on study medication in 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 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: Change From Baseline in Growth Percentile by Gender and Age
Time frame: At Baseline, Months 6 and 12 of Phase A
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 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 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 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 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 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41407907Shoaf SE, Sikes K. Tolvaptan pharmacokinetics and pharmacodynamics in adolescents with autosomal dominant polycystic kidney disease. Eur J Pediatr. 2025 Dec 18;185(1):26. doi: 10.1007/s00431-025-06689-2.
- Derived from this study: PubMed 39356039St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
- Derived from this study: PubMed 36719158Mekahli D, Guay-Woodford LM, Cadnapaphornchai MA, Greenbaum LA, Litwin M, Seeman T, Dandurand A, Shi L, Sikes K, Shoaf SE, Schaefer F. Tolvaptan for Children and Adolescents with Autosomal Dominant Polycystic Kidney Disease: Randomized Controlled Trial. Clin J Am Soc Nephrol. 2023 Jan 1;18(1):36-46. doi: 10.2215/CJN.0000000000000022.
- Derived from this study: PubMed 34604341Liu F, Feng C, Shen H, Fu H, Mao J. Tolvaptan in Pediatric Autosomal Dominant Polycystic Kidney Disease: From Here to Where? Kidney Dis (Basel). 2021 Sep;7(5):343-349. doi: 10.1159/000517186. Epub 2021 Jul 2.
- Individual participant dataSharing planned: Yes. Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Otsuka Pharmaceutical Development & Commercialization, Inc.
20 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tolvaptan in people with Autosomal Dominant Polycystic Kidney Disease (ADPKD), run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 20 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Germany, Belgium, United Kingdom, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase A: Change From Baseline in Spot Urine Osmolality (Pre-morning Dose) (time frame: Baseline, and Week 1 of Phase A). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02964273, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2023.