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NCT02251275

Long Term Safety of Immediate-release Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease

Completed Phase 3 Results posted Last updated 27 November 2019
What this trial tests

Phase 3 trial testing Tolvaptan in Polycystic Kidney, Autosomal Dominant in 1,803 participants. Completed in 9 November 2018.

Timeline
17 October 2014
Primary endpoint
9 November 2018
9 November 2018

Quick facts

Lead sponsorOtsuka Pharmaceutical Development & Commercialization, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment1,803
Start date17 October 2014
Primary completion9 November 2018
Estimated completion9 November 2018
Sites210 locations across Italy, Poland, Denmark, Netherlands, Russia, Belgium, Sweden, United States

Drugs / interventions tested

Conditions studied

Sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc. — full company profile →

Who can join

18 and older, any sex, with Polycystic Kidney, Autosomal Dominant. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number Of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) Primary · Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment(+ 7 days)

An adverse event (AE) was as any untoward medical occurrence associated with the use of an investigational medicinal product (IMP), whether or not considered IMP related. A TEAE was an AE that started after trial drug treatment; or if the event was continuous from baseline and was serious, related to IMP, or resulted in death, discontinuation, interruption or reduction of trial therapy. A serious TEAE included any event that resulted in: death, life-threatening, persistent or significant incapacity, substantial disruption of ability to conduct normal life functions, required inpatient hospital

Participants with TEAEs
GroupValue95% CI
Tolvaptan (From 156-13-210: Tolvaptan)473
Tolvaptan (From 156-13-210: Placebo)531
Tolvaptan (From 156-08-271: Tolvaptan)640
Tolvaptan (From Other: Tolvaptan)6
Tolvaptan (From Other: Placebo)3
Participants with serious TEAEs
GroupValue95% CI
Tolvaptan (From 156-13-210: Tolvaptan)87
Tolvaptan (From 156-13-210: Placebo)96
Tolvaptan (From 156-08-271: Tolvaptan)103
Tolvaptan (From Other: Tolvaptan)1
Tolvaptan (From Other: Placebo)2
Participants with severe TEAEs
GroupValue95% CI
Tolvaptan (From 156-13-210: Tolvaptan)74
Tolvaptan (From 156-13-210: Placebo)78
Tolvaptan (From 156-08-271: Tolvaptan)83
Tolvaptan (From Other: Tolvaptan)2
Tolvaptan (From Other: Placebo)1
Discontinued due to TEAEs
GroupValue95% CI
Tolvaptan (From 156-13-210: Tolvaptan)33
Tolvaptan (From 156-13-210: Placebo)65
Tolvaptan (From 156-08-271: Tolvaptan)38
Tolvaptan (From Other: Tolvaptan)0
Tolvaptan (From Other: Placebo)1
Deaths
GroupValue95% CI
Tolvaptan (From 156-13-210: Tolvaptan)1
Tolvaptan (From 156-13-210: Placebo)5
Tolvaptan (From 156-08-271: Tolvaptan)3
Tolvaptan (From Other: Tolvaptan)0
Tolvaptan (From Other: Placebo)0

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment (+ 7 days). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Tolvaptan (From 156-13-210: Tolvaptan)
Serious: 87/505 (17%)
Deaths: 1/505
Tolvaptan (From 156-13-210: Placebo)
Serious: 96/569 (17%)
Deaths: 5/569
Tolvaptan (From 156-08-271: Tolvaptan)
Serious: 103/717 (14%)
Deaths: 3/717
Tolvaptan (From Other: Tolvaptan)
Serious: 1/6 (17%)
Deaths: 0/6
Tolvaptan (From Other: Placebo)
Serious: 2/3 (67%)
Deaths: 0/3

Serious adverse events (254 terms)

ReactionSystemTolvaptan (From 156-13-210…Tolvaptan (From 156-13-210…Tolvaptan (From 156-08-271…Tolvaptan (From Other: Tol…Tolvaptan (From Other: Pla…
Renal Cyst InfectionInfections and infestations
Acute Kidney InjuryRenal and urinary disorders
End Stage Renal DiseaseRenal and urinary disorders
Renal ImpairmentRenal and urinary disorders
Urinary Tract InfectionInfections and infestations
PneumoniaInfections and infestations
Alanine Aminotransferase IncreasedInvestigations
Blood Creatinine IncreasedInvestigations
Renal PainRenal and urinary disorders
Renal Cyst HaemorrhageRenal and urinary disorders
Atrial FibrillationCardiac disorders
Umbilical HerniaGastrointestinal disorders
IleusGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Abdominal PainGastrointestinal disorders
PyelonephritisInfections and infestations
GastroenteritisInfections and infestations
Liver Function Test IncreasedInvestigations
Hepatic Enzyme IncreasedInvestigations
Glomerular Filtration Rate DecreasedInvestigations
HypertensionVascular disorders
AnaemiaBlood and lymphatic system disorders
Angina PectorisCardiac disorders
Retinal DetachmentEye disorders
Intestinal ObstructionGastrointestinal disorders
Other adverse events (67 terms — click to expand)

ReactionSystemTolvaptan (From 156-13-210…Tolvaptan (From 156-13-210…Tolvaptan (From 156-08-271…Tolvaptan (From Other: Tol…Tolvaptan (From Other: Pla…
ThirstGeneral disorders
PolyuriaRenal and urinary disorders
Renal PainRenal and urinary disorders
HypertensionVascular disorders
NocturiaRenal and urinary disorders
NasopharyngitisInfections and infestations
Blood Creatinine IncreasedInvestigations
Upper Respiratory Tract InfectionInfections and infestations
FatigueGeneral disorders
HeadacheNervous system disorders
Urinary Tract InfectionInfections and infestations
Back PainMusculoskeletal and connective tissue disorders
PolydipsiaMetabolism and nutrition disorders
HaematuriaRenal and urinary disorders
NauseaGastrointestinal disorders
InfluenzaInfections and infestations
Oedema PeripheralGeneral disorders
GastroenteritisInfections and infestations
DiarrhoeaGastrointestinal disorders
Dry MouthGastrointestinal disorders
VomitingGastrointestinal disorders
SinusitisInfections and infestations
PollakiuriaRenal and urinary disorders
ArthralgiaMusculoskeletal and connective tissue disorders
BronchitisInfections and infestations
DizzinessNervous system disorders
GoutMetabolism and nutrition disorders
Renal ImpairmentRenal and urinary disorders
ConstipationGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspepsiaGastrointestinal disorders
Abdominal Pain UpperGastrointestinal disorders
Gastrooesophageal Reflux DiseaseGastrointestinal disorders
Alanine Aminotransferase IncreasedInvestigations
Decreased AppetiteMetabolism and nutrition disorders
PalpitationsCardiac disorders
Abdominal DiscomfortGastrointestinal disorders
AnxietyPsychiatric disorders
FallInjury, poisoning and procedural complications
Ear InfectionInfections and infestations

Most-reported serious reactions: Renal Cyst Infection, Acute Kidney Injury, End Stage Renal Disease, Renal Impairment, Urinary Tract Infection, Pneumonia, Alanine Aminotransferase Increased, Blood Creatinine Increased.

Data from ClinicalTrials.gov NCT02251275 adverse events section.

Sponsor's own description

The purpose of the trial was to evaluate and describe the long term safety of tolvaptan in participants with autosomal dominant polycystic kidney disease (ADPKD).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Long-Term Administration of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease.
    Edwards ME, Chebib FT, Irazabal MV, Ofstie TG, et al · · 2018 · cited 64× · PMID 30026287 · DOI 10.2215/cjn.01520218
  2. Multicenter Study of Long-Term Safety of Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease.
    Torres VE, Chapman AB, Devuyst O, Gansevoort RT, et al · · 2020 · cited 34× · PMID 33376102 · DOI 10.2215/cjn.10250620
  3. Experimental Models of Polycystic Kidney Disease: Applications and Therapeutic Testing.
    Sieben CJ, Harris PC. · · 2023 · cited 23× · PMID 37418622 · DOI 10.34067/kid.0000000000000209
  4. Clinical Pattern of Tolvaptan-Associated Liver Injury in Trial Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD): An Analysis of Pivotal Clinical Trials.
    Alpers DH, Lewis JH, Hunt CM, Freston JW, et al · · 2023 · cited 22× · PMID 36191725 · DOI 10.1053/j.ajkd.2022.08.012
  5. Tolvaptan in ADPKD Patients With Very Low Kidney Function.
    Torres VE, Gansevoort RT, Perrone RD, Chapman AB, et al · · 2021 · cited 19× · PMID 34386666 · DOI 10.1016/j.ekir.2021.05.037
  6. Research and Nonresearch Industry Payments to Nephrologists in the United States between 2014 and 2021.
    Murayama A, Kamamoto S, Kugo H, Saito H, et al · · 2023 · cited 18× · PMID 37488676 · DOI 10.1681/asn.0000000000000172
  7. Targeting and therapeutic peptide-based strategies for polycystic kidney disease.
    Wang J, Tripathy N, Chung EJ. · · 2020 · cited 14× · PMID 32866560 · DOI 10.1016/j.addr.2020.08.011
  8. Pooled Data Analysis of the Long-Term Treatment Effects of Tolvaptan in ADPKD.
    Zhou X, Davenport E, Ouyang J, Hoke ME, et al · · 2022 · cited 13× · PMID 35570988 · DOI 10.1016/j.ekir.2022.02.009

Verify or expand the search:

Other trials of Tolvaptan

Trials testing the same drug.

Other recruiting trials for Polycystic Kidney, Autosomal Dominant

Currently open trials in the same condition.

Other Otsuka Pharmaceutical Development & Commercialization, Inc. trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing