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NCT01214421: TEMPO 4/4

Tolvaptan Extension Study in Participants With ADPKD

Completed Phase 3 Results posted Last updated 25 October 2021
What this trial tests

Phase 3 trial testing Tolvaptan in Autosomal Dominant Polycystic Kidney Disease (ADPKD) in 1,083 participants. Completed in 29 February 2016.

Timeline
26 May 2010
Primary endpoint
29 February 2016
29 February 2016

Quick facts

Lead sponsorOtsuka Pharmaceutical Development & Commercialization, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment1,083
Start date26 May 2010
Primary completion29 February 2016
Estimated completion29 February 2016
Sites97 locations across France, Italy, Netherlands, Russia, Belgium, United Kingdom, Germany, Poland

Drugs / interventions tested

Conditions studied

Sponsor

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

Who can join

18 and older, any sex, with Autosomal Dominant Polycystic Kidney Disease (ADPKD). 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.

Percent Change From the Baseline in Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in This Study (156-08-271) Primary · Study Baseline (Prior to Day 1 in Study 156-04-251) to Month 24 in this study (Study 156-08-271)

Total kidney volume is a measure of disease progression in the ADPKD participants. Kidney volume was assessed in T1-weighted magnetic resonance images collected at each study site and sent to a central reviewing facility. At the central reviewing facility, radiologists used proprietary software to measure the volume of both kidneys in participants continuing from previous study (156-04-251) at Month 24 of this study (156-08-271) comparing change in TKV for the early-treated (those previously treated with tolvaptan) to delayed-treated (those previously treated with placebo). The percent change

GroupValue95% CI
Tolvaptan, Early Treated (From Study 156-04-251: Tolvaptan)28.66± 26.14
Tolvaptan, Delayed Treated (From Study 156-04-251: Placebo)30.58± 27.21
Change From the Baseline in Estimated Glomerular Filtration Rate (eGFR) as Assessed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for Study 156-04-251 Participants Enrolled in This Study (156-08-271) Secondary · Study Baseline (Prior to Day 1 in Study 156-04-251) to Month 24 in this study (Study 156-08-271)

Estimated Glomerular Filtration Rate (eGFR) according to CKD-EPI is calculated using the CKD-EPI equation, expressed as a single equation, is GFR = 141 × min (serum creatinine \[Scr\]/κ, 1)α × max(Scr/κ, 1)\^-1.209 × 0.993 Age × 1.018 (if female) × 1.159 (if black), where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/ĸ or 1, and max indicates the maximum of Scr/κ or 1 in participants continuing from previous study (156-04-251) at Month 24 of this study (156-08-271) comparing change in eGFR for the

GroupValue95% CI
Tolvaptan, Early Treated (From Study 156-04-251: Tolvaptan)-16.77± 13.16
Tolvaptan, Delayed Treated (From Study 156-04-251: Placebo)-19.92± 16.40
Annualized Slope of Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in Study 156-08-271 Secondary · Study Baseline (Prior to Day 1 in Study 156-08-271) to Month 24 in this study (Study 156-08-271)

Annualized slope of TKV is a measure of renal function and disease progression in ADPKD participants. The annualized slope is calculated as percentage of growth in TKV (measured in mL by MRI) divided by each participant's years of participation for all participants was calculated using MMRM analysis in participants continuing from previous study (156-04-251) at Month 24 of this study (156-08-271) comparing annualized slope of TKV for the early-treated (those previously treated with tolvaptan) to delayed-treated (those previously treated with placebo). This outcome measure was analyzed only in

GroupValue95% CI
Tolvaptan, Early Treated (From Study 156-04-251: Tolvaptan)6.164
Tolvaptan, Delayed Treated (From Study 156-04-251: Placebo)4.960
Annualized Slope of eGFR (CKD-EPI) for Study 156-04-251 Participants Enrolled in Study 156-08-271 Secondary · Study Baseline (Prior to Day 1 in Study 156-08-271) to Month 24 (Study 156-08-271)

Annualized slope of eGFR (CKD-EPI) is a measure of renal function and disease progression in ADPKD participants. The annualized slope of eGFR (CKD-EPI) (divided by each participant's years of participation) for all participants was calculated using MMRM analysis in participants continuing from previous study (156-04-251) at Month 24 of this study (156-08-271) comparing change in TKV for the early-treated (those previously treated with tolvaptan) to delayed-treated (those previously treated with placebo). eGFR was calculated using the Chronic Kidney Disease-Epidemiology (CKD-EPI) formula. This

GroupValue95% CI
Tolvaptan, Early Treated (From Study 156-04-251: Tolvaptan)-3.255
Tolvaptan, Delayed Treated (From Study 156-04-251: Placebo)-3.142
Annualized TKV Slope for Study 156-04-251 Placebo Participants Enrolled in Study 156-08-271 Secondary · Tolvaptan, Delayed Treated: Baseline to Month 24 in Study 156-08-271; Placebo: Baseline to Month 36 in Study 156-04-251

Annualized slope of TKV is a measure of renal function and disease progression in ADPKD participants. The annualized slope is calculated as percentage of growth in TKV (measured in mL by MRI) divided by each participant's years of participation, using MMRM analysis to compare annualized slope of TKV for the participants who received placebo in previous study (156-04-251) to annualized slope of TKV for the same participants who received tolvaptan in this study (156-08-271). This outcome measure was analyzed only in the participants enrolled from the previous study - 156-04-251 and who received

GroupValue95% CI
Tolvaptan, Delayed Treated (In Study 156-08-271)4.779
Placebo (In Study 156-04-251)5.627
Annualized Slope of Renal Function (eGFRCKD-EPI) for Study 156-04-251 Placebo Participants Enrolled in Study 156-08-271 Secondary · Tolvaptan, Delayed Treated: Baseline to Month 24 in Study 156-08-271; Placebo: Baseline to Month 36 in Study 156-04-251

Annualized slope of eGFR (CKD-EPI) is a measure of renal function and disease progression in ADPKD participants. The annualized slope of eGFR (calculated using CKD-EPI formula) divided by each participant's years of participation, using MMRM analysis to compare annualized slope of eGFR (CKD-EPI) for the participants who received placebo in previous study (156-04-251) to the annualized slope of eGFR (CKD-EPI) for the same participants who received tolvaptan in this study (156-08-271). This outcome measure was analyzed only in the participants enrolled from the previous study - 156-04-251 who re

GroupValue95% CI
Tolvaptan, Delayed Treated (In Study 156-08-271)-3.211
Placebo (In Study 156-04-251)-3.572

Adverse events — posted to ClinicalTrials.gov

Time frame: From the signing of the informed consent form until the end of the study regardless of whether the participants were on or off active study medication (Up to approximately 5 years). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Tolvaptan (From Study 156-04-251: Tolvaptan, Early Treated)
Serious: 143/557 (26%)
Deaths: 5/557
Tolvaptan (From Study 156-04-251: Placebo, Delayed Treated)
Serious: 79/314 (25%)
Deaths: 0/314
Tolvaptan (From Other Studies: Tolvaptan, Early Treated)
Serious: 34/181 (19%)
Deaths: 0/181
Tolvaptan (From Other Studies: Placebo, Delayed Treated)
Serious: 5/31 (16%)
Deaths: 0/31

Serious adverse events (202 terms)

ReactionSystemTolvaptan (From Study 156-…Tolvaptan (From Study 156-…Tolvaptan (From Other Stud…Tolvaptan (From Other Stud…
Renal Cyst InfectionInfections and infestations
PyelonephritisInfections and infestations
Blood Creatinine IncreasedInvestigations
Renal Cyst HaemorrhageRenal and urinary disorders
Renal ImpairmentRenal and urinary disorders
Inguinal HerniaGastrointestinal disorders
Alanine Aminotransferase IncreasedInvestigations
Chronic Kidney DiseaseRenal and urinary disorders
Hepatic CystHepatobiliary disorders
Urinary Tract InfectionInfections and infestations
Myocardial InfarctionCardiac disorders
SepsisInfections and infestations
Aspartate Aminotransferase IncreasedInvestigations
Gamma-Glutamyltransferase IncreasedInvestigations
Transaminases IncreasedInvestigations
Cerebrovascular AccidentNervous system disorders
Intracranial AneurysmNervous system disorders
Acute Kidney InjuryRenal and urinary disorders
AnaemiaBlood and lymphatic system disorders
Atrial FibrillationCardiac disorders
BradycardiaCardiac disorders
PericarditisCardiac disorders
Abdominal HerniaGastrointestinal disorders
Abdominal PainGastrointestinal disorders
CholecystitisHepatobiliary disorders
Other adverse events (43 terms — click to expand)

ReactionSystemTolvaptan (From Study 156-…Tolvaptan (From Study 156-…Tolvaptan (From Other Stud…Tolvaptan (From Other Stud…
ThirstGeneral disorders
PolyuriaRenal and urinary disorders
HypertensionVascular disorders
Renal PainRenal and urinary disorders
NocturiaRenal and urinary disorders
Blood Creatinine IncreasedInvestigations
NasopharyngitisInfections and infestations
HeadacheNervous system disorders
PolydipsiaMetabolism and nutrition disorders
Upper Respiratory Tract InfectionInfections and infestations
Urinary Tract InfectionInfections and infestations
DiarrhoeaGastrointestinal disorders
Back PainMusculoskeletal and connective tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
FatigueGeneral disorders
Oedema PeripheralGeneral disorders
HaematuriaRenal and urinary disorders
Dry MouthGastrointestinal disorders
NauseaGastrointestinal disorders
InfluenzaInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
SinusitisInfections and infestations
Pain In ExtremityMusculoskeletal and connective tissue disorders
Abdominal PainGastrointestinal disorders
HyperuricaemiaMetabolism and nutrition disorders
DizzinessNervous system disorders
AnaemiaBlood and lymphatic system disorders
GoutMetabolism and nutrition disorders
Vitamin D DeficiencyMetabolism and nutrition disorders
VomitingGastrointestinal disorders
GastroenteritisInfections and infestations
BronchitisInfections and infestations
PollakiuriaRenal and urinary disorders
DyspepsiaGastrointestinal disorders
Muscle SpasmsMusculoskeletal and connective tissue disorders
ConstipationGastrointestinal disorders
Gastrooesophageal Reflux DiseaseGastrointestinal disorders
Abdominal Pain UpperGastrointestinal disorders
Aspartate Aminotransferase IncreasedInvestigations
Decreased AppetitieMetabolism and nutrition disorders

Most-reported serious reactions: Renal Cyst Infection, Pyelonephritis, Blood Creatinine Increased, Renal Cyst Haemorrhage, Renal Impairment, Inguinal Hernia, Alanine Aminotransferase Increased, Chronic Kidney Disease.

Data from ClinicalTrials.gov NCT01214421 adverse events section.

Sponsor's own description

To demonstrate whether tolvaptan modifies ADPKD progression as measured by changes from Baseline (from Study 156-04-251) in total kidney volume (TKV) and renal function.

Publications & conference data

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

  1. Clinical Pattern of Tolvaptan-Associated Liver Injury in Subjects with Autosomal Dominant Polycystic Kidney Disease: Analysis of Clinical Trials Database.
    Watkins PB, Lewis JH, Kaplowitz N, Alpers DH, et al · · 2015 · cited 150× · PMID 26188764 · DOI 10.1007/s40264-015-0327-3
  2. 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
  3. The role of the cilium in normal and abnormal cell cycles: emphasis on renal cystic pathologies.
    Pan J, Seeger-Nukpezah T, Golemis EA. · · 2013 · cited 64× · PMID 22782110 · DOI 10.1007/s00018-012-1052-z
  4. Inhibition of Human Hepatic Bile Acid Transporters by Tolvaptan and Metabolites: Contributing Factors to Drug-Induced Liver Injury?
    Slizgi JR, Lu Y, Brouwer KR, St Claire RL, et al · · 2016 · cited 40× · PMID 26507107 · DOI 10.1093/toxsci/kfv231
  5. Tolerability of Aquaretic-Related Symptoms Following Tolvaptan for Autosomal Dominant Polycystic Kidney Disease: Results From TEMPO 3:4.
    Devuyst O, Chapman AB, Shoaf SE, Czerwiec FS, et al · · 2017 · cited 37× · PMID 29270521 · DOI 10.1016/j.ekir.2017.07.004
  6. Pathophysiology of childhood polycystic kidney diseases: new insights into disease-specific therapy.
    Sweeney WE, Avner ED. · · 2014 · cited 35× · PMID 24336431 · DOI 10.1038/pr.2013.191
  7. 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
  8. Experimental Models of Polycystic Kidney Disease: Applications and Therapeutic Testing.
    Sieben CJ, Harris PC. · · 2023 · cited 23× · PMID 37418622 · DOI 10.34067/kid.0000000000000209

Verify or expand the search:

Other trials of Tolvaptan

Trials testing the same drug.

Other recruiting trials for Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Currently open trials in the same condition.

Other Otsuka Pharmaceutical Development & Commercialization, Inc. trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01214421.

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