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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01214421
Registration number
NCT01214421
Ethics application status
Date submitted
26/09/2010
Date registered
5/10/2010
Date last updated
25/10/2021
Titles & IDs
Public title
Tolvaptan Extension Study in Participants With ADPKD
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Scientific title
Multi-center, Open-label, Extension Study to Evaluate the Long-term Efficacy and Safety of Oral Tolvaptan Tablet Regimens in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
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Secondary ID [1]
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2010-018401-10
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Secondary ID [2]
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156-08-271
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Universal Trial Number (UTN)
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Trial acronym
TEMPO 4/4
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
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Condition category
Condition code
Musculoskeletal
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Other muscular and skeletal disorders
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Renal and Urogenital
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Kidney disease
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Renal and Urogenital
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0
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Other renal and urogenital disorders
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Human Genetics and Inherited Disorders
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0
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Other human genetics and inherited disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Tolvaptan
Experimental: Tolvaptan - Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 milligrams (mg) in the morning [AM]/15 mg in the evening [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily until the last participant originating from prior studies (either 156-04-251 or 156-04-250, 156-06-260, 156-09-284, 156-09-285, and 156-09-290) who was eligible for efficacy analysis completed the Month 24.
Treatment: Drugs: Tolvaptan
Tablets of 15 or 30 mg
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Percent Change From the Baseline in Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in This Study (156-08-271)
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Assessment method [1]
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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 in the volume of both kidneys combined was analysed using mixed-effect model repeated measures (MMRM) analysis and reported. This outcome measure was analyzed only in the participants enrolled from the previous study - 156-04-251, as pre-specified in the protocol.
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Timepoint [1]
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Study Baseline (Prior to Day 1 in Study 156-04-251) to Month 24 in this study (Study 156-08-271)
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Secondary outcome [1]
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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)
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Assessment method [1]
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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]/?, 1)a × max(Scr/?, 1)^-1.209 × 0.993 Age × 1.018 (if female) × 1.159 (if black), where Scr is serum creatinine, ? is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/? or 1, and max indicates the maximum of Scr/? 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 early-treated (those previously treated with tolvaptan) to delayed-treated (those previously treated with placebo). MMRM was used for the analysis. This outcome measure was analyzed only in the participants enrolled from the previous - 156-04-251, as pre-specified in the protocol.
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Timepoint [1]
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Study Baseline (Prior to Day 1 in Study 156-04-251) to Month 24 in this study (Study 156-08-271)
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Secondary outcome [2]
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Annualized Slope of Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in Study 156-08-271
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Assessment method [2]
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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 the participants enrolled from the previous study - 156-04-251, as pre-specified in the protocol.
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Timepoint [2]
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Study Baseline (Prior to Day 1 in Study 156-08-271) to Month 24 in this study (Study 156-08-271)
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Secondary outcome [3]
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Annualized Slope of eGFR (CKD-EPI) for Study 156-04-251 Participants Enrolled in Study 156-08-271
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Assessment method [3]
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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 outcome measure was analyzed only in the participants enrolled from the previous study - 156-04-251, as pre-specified in the protocol.
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Timepoint [3]
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Study Baseline (Prior to Day 1 in Study 156-08-271) to Month 24 (Study 156-08-271)
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Secondary outcome [4]
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Annualized TKV Slope for Study 156-04-251 Placebo Participants Enrolled in Study 156-08-271
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Assessment method [4]
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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 placebo in the previous study, as pre-specified in the protocol.
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Timepoint [4]
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Tolvaptan, Delayed Treated: Baseline to Month 24 in Study 156-08-271; Placebo: Baseline to Month 36 in Study 156-04-251
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Secondary outcome [5]
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Annualized Slope of Renal Function (eGFRCKD-EPI) for Study 156-04-251 Placebo Participants Enrolled in Study 156-08-271
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Assessment method [5]
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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 received placebo in previous study and received tolvaptan in this study, as pre-specified in the protocol.
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Timepoint [5]
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Tolvaptan, Delayed Treated: Baseline to Month 24 in Study 156-08-271; Placebo: Baseline to Month 36 in Study 156-04-251
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Eligibility
Key inclusion criteria
- Participants who had successfully completed a Phase 1, 2, or 3 tolvaptan ADPKD or renal
impairment study, with a confirmed diagnosis of ADPKD from prior studies [either 156-04-251
(NCT00428948) or 156-04-250 (NCT00413777), 156-06-260, 156-09-284 (NCT01336972), 156-09-285
(NCT01210560), and 156-09-290 (NCT01451827)].
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- Participants unable to provide written informed consent.
- Participants (men or women) would not adhere to the reproductive precautions as
outlined in the Informed Consent Form.
- Participants (women only) with a positive urine pregnancy test.
- Participants who were pregnant or breast-feeding.
- Participants unable to take oral medications.
- Participants who had allergic reactions to tolvaptan or chemically related structures
such as benzazepines (benzazepril, conivaptan, fenoldopam mesylate, or mirtazapine).
- Participants with disorders in thirst recognition or an 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 significant anemia, as determined by investigator.
- Participants with a history of substance abuse (within the last 3 years).
- Participants who were taking other experimental (that is, non-marketed) therapies or
were participating in another clinical drug or device study; participating in the
off-drug follow-up period of another ADPKD trial with tolvaptan was permitted.
- Participants unable to complete magnetic resonance imaging (MRI) assessments (for
example, participants with ferro-magnetic prostheses, aneurysm clips, severe
claustrophobia).
- Participants who had taken a vasopressin antagonist (outside of previous participation
in a tolvaptan study).
- Participants unable to comply with anti-hypertensive or other important medical
therapy.
- Participants with advanced diabetes.
- Participants who were taking medications or had an illness that could confound
endpoint assessments (including taking approved therapies for the purpose of affecting
polycystic kidney disease [PKD] cysts).
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Study design
Purpose of the study
Treatment
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
26/05/2010
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
29/02/2016
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Sample size
Target
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Accrual to date
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Final
1083
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
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Recruitment hospital [1]
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Otsuka Investigational Site - St. Leonards
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Otsuka Investigational Site - Westmead
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Otsuka Investigational Site - Woolloongabba
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Otsuka Investigational Site - Parkville
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Otsuka Investigational Site - Perth
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Recruitment postcode(s) [1]
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2065 - St. Leonards
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2145 - Westmead
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4102 - Woolloongabba
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5000 - Adelaide
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3050 - Parkville
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Recruitment postcode(s) [6]
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6000 - Perth
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Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Otsuka Pharmaceutical Development & Commercialization, Inc.
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT01214421
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Study Director
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Address
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Otsuka Pharmaceutical Development & Commercialization, Inc.
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01214421
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