Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Conditions
Keywords
Kidney Disease, ADPKD, Autosomal Dominant Polycystic Kidney Disease, Adult Polycystic Kidney Disease
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.
Interventions
DRUGTolvaptan
Tablets of 15 or 30 mg
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 \[either 156-04-251 (NCT00428948) or 156-04-250 (NCT00413777), 156-06-260, 156-09-284 (NCT01336972), 156-09-285 (NCT01210560), and 156-09-290 (NCT01451827)\].
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From the Baseline in Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in This Study (156-08-271) | 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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 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. |
| Annualized Slope of Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in Study 156-08-271 | 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 the participants enrolled from the previous study - 156-04-251, as pre-specified in the protocol. |
| Annualized Slope of eGFR (CKD-EPI) for Study 156-04-251 Participants Enrolled in Study 156-08-271 | 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 outcome measure was analyzed only in the participants enrolled from the previous study - 156-04-251, as pre-specified in the protocol. |
| Annualized TKV Slope for Study 156-04-251 Placebo Participants Enrolled in Study 156-08-271 | 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 placebo in the previous study, as pre-specified in the protocol. |
| Annualized Slope of Renal Function (eGFRCKD-EPI) for Study 156-04-251 Placebo Participants Enrolled in Study 156-08-271 | 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 received placebo in previous study and received tolvaptan in this study, as pre-specified in the protocol. |
Countries
Argentina, Australia, Belgium, Canada, France, Germany, Italy, Netherlands, Poland, Romania, Russia, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 106 sites in 13 countries from 26 May 2010 to 29 Feb 2016. Eligible participants with autosomal dominant polycystic kidney disease (ADPKD) or renal impairment who completed previous tolvaptan treatment in studies: 156-04-251 (NCT00428948), 156-04-250 (NCT00413777), 156-06-260, 156-09-284 (NCT01336972), 156-09-285 (NCT01210560), and 156-09-290 (NCT01451827) were enrolled in this open-label study.
Pre-assignment details
All enrolled participants received tolvaptan in this study. Data in this study was collected and reported as per the prior treatment received - tolvaptan (called as early treated) or placebo (called as delayed treated), for study 156-04-251 and all other studies combined.
Participants by arm
| Arm | Count |
|---|---|
| Tolvaptan (From Study 156-04-251: Tolvaptan, Early Treated) Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg \[AM\]/15 mg \[PM\] titrated to 60 mg \[AM\]/30 mg \[PM\], then 90 mg \[AM\]/30 mg \[PM\] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with tolvaptan in previous Study 156-04-251, hence called as Early Treated. | 557 |
| Tolvaptan (From Study 156-04-251: Placebo, Delayed Treated) Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg \[AM\]/15 mg \[PM\] titrated to 60 mg \[AM\]/30 mg \[PM\], then 90 mg \[AM\]/30 mg \[PM\] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with placebo in the previous Study 156-04-251, hence called as Delayed Treated. | 314 |
| Tolvaptan (From Other Studies: Tolvaptan, Early Treated) Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg \[AM\]/15 mg \[PM\] titrated to 60 mg \[AM\]/30 mg \[PM\], then 90 mg \[AM\]/30 mg \[PM\] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with tolvaptan in other studies (156-04-250, 156-06-260, 156-09-284, 156-09-285, and 156-09-290), hence called as Early Treated. | 181 |
| Tolvaptan (From Other Studies: Placebo, Delayed Treated) Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg \[AM\]/15 mg \[PM\] titrated to 60 mg \[AM\]/30 mg \[PM\], then 90 mg \[AM\]/30 mg \[PM\] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with placebo in other studies (156-04-250, 156-06-260, 156-09-284, 156-09-285, and 156-09-290), hence called as Delayed Treated. | 31 |
| Total | 1,083 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 16 | 35 | 14 | 3 |
| Overall Study | Lost to Follow-up | 7 | 3 | 7 | 3 |
| Overall Study | Physician Decision | 2 | 0 | 4 | 0 |
| Overall Study | Sponsor Discontinued Site | 1 | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 21 | 18 | 11 | 2 |
| Overall Study | Withdrawal Criteria Met | 3 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Tolvaptan (From Study 156-04-251: Tolvaptan, Early Treated) | Total | Tolvaptan (From Other Studies: Placebo, Delayed Treated) | Tolvaptan (From Other Studies: Tolvaptan, Early Treated) | Tolvaptan (From Study 156-04-251: Placebo, Delayed Treated) |
|---|---|---|---|---|---|
| Age, Continuous | 42.2 years STANDARD_DEVIATION 6.9 | 41.7 years STANDARD_DEVIATION 7.8 | 35.6 years STANDARD_DEVIATION 8.7 | 40.0 years STANDARD_DEVIATION 10.1 | 42.5 years STANDARD_DEVIATION 7.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants | 55 Participants | 4 Participants | 8 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 471 Participants | 919 Participants | 27 Participants | 172 Participants | 249 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 62 Participants | 109 Participants | 0 Participants | 1 Participants | 46 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 10 Participants | 0 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized Black/African American | 9 Participants | 16 Participants | 3 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 10 Participants | 23 Participants | 1 Participants | 4 Participants | 8 Participants |
| Race/Ethnicity, Customized White/Caucasian | 535 Participants | 1033 Participants | 27 Participants | 169 Participants | 302 Participants |
| Sex: Female, Male Female | 254 Participants | 516 Participants | 15 Participants | 91 Participants | 156 Participants |
| Sex: Female, Male Male | 303 Participants | 567 Participants | 16 Participants | 90 Participants | 158 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 557 | 0 / 314 | 0 / 181 | 0 / 31 |
| other Total, other adverse events | 528 / 557 | 310 / 314 | 175 / 181 | 29 / 31 |
| serious Total, serious adverse events | 143 / 557 | 79 / 314 | 34 / 181 | 5 / 31 |
Outcome results
Primary
Percent Change From the Baseline in Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in This 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 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.
Time frame: Study Baseline (Prior to Day 1 in Study 156-04-251) to Month 24 in this study (Study 156-08-271)
Population: The Efficacy Sample consisted of all enrolled participants who took at least 1 dose of study drug and completed 3 years of study drug treatment in previous Study 156-04-251. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tolvaptan, Early Treated (From Study 156-04-251: Tolvaptan) | Percent Change From the Baseline in Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in This Study (156-08-271) | 28.66 percent change | Standard Deviation 26.14 |
| Tolvaptan, Delayed Treated (From Study 156-04-251: Placebo) | Percent Change From the Baseline in Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in This Study (156-08-271) | 30.58 percent change | Standard Deviation 27.21 |
p-value: 0.35895% CI: [0.96, 1.02]Mixed Models Analysis
Secondary
Annualized Slope of eGFR (CKD-EPI) for Study 156-04-251 Participants Enrolled in 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 outcome measure was analyzed only in the participants enrolled from the previous study - 156-04-251, as pre-specified in the protocol.
Time frame: Study Baseline (Prior to Day 1 in Study 156-08-271) to Month 24 (Study 156-08-271)
Population: The Efficacy Sample consisted of all enrolled participants who took at least 1 dose of study drug and completed 3 years of study drug treatment in previous Study 156-04-251. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tolvaptan, Early Treated (From Study 156-04-251: Tolvaptan) | Annualized Slope of eGFR (CKD-EPI) for Study 156-04-251 Participants Enrolled in Study 156-08-271 | -3.255 ml/min/1.73m^2/participant-years |
| Tolvaptan, Delayed Treated (From Study 156-04-251: Placebo) | Annualized Slope of eGFR (CKD-EPI) for Study 156-04-251 Participants Enrolled in Study 156-08-271 | -3.142 ml/min/1.73m^2/participant-years |
p-value: 0.725995% CI: [-0.746, 0.52]Mixed Models Analysis
Secondary
Annualized Slope of Renal Function (eGFRCKD-EPI) for Study 156-04-251 Placebo Participants Enrolled in 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 (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.
Time frame: Tolvaptan, Delayed Treated: Baseline to Month 24 in Study 156-08-271; Placebo: Baseline to Month 36 in Study 156-04-251
Population: The Efficacy Sample consisted of all enrolled participants who took at least 1 dose of study drug and completed 3 years of study drug treatment in previous Study 156-04-251. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tolvaptan, Early Treated (From Study 156-04-251: Tolvaptan) | Annualized Slope of Renal Function (eGFRCKD-EPI) for Study 156-04-251 Placebo Participants Enrolled in Study 156-08-271 | -3.211 ml/min/1.73m^2/participant-years |
| Tolvaptan, Delayed Treated (From Study 156-04-251: Placebo) | Annualized Slope of Renal Function (eGFRCKD-EPI) for Study 156-04-251 Placebo Participants Enrolled in Study 156-08-271 | -3.572 ml/min/1.73m^2/participant-years |
p-value: 0.226595% CI: [-0.224, 0.946]Mixed Models Analysis
Secondary
Annualized Slope of Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in 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 the participants enrolled from the previous study - 156-04-251, as pre-specified in the protocol.
Time frame: Study Baseline (Prior to Day 1 in Study 156-08-271) to Month 24 in this study (Study 156-08-271)
Population: The Efficacy Sample consisted of all enrolled participants who took at least 1 dose of study drug and completed 3 years of study drug treatment in previous Study 156-04-251. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tolvaptan, Early Treated (From Study 156-04-251: Tolvaptan) | Annualized Slope of Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in Study 156-08-271 | 6.164 percent change in TKV/participant-years |
| Tolvaptan, Delayed Treated (From Study 156-04-251: Placebo) | Annualized Slope of Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in Study 156-08-271 | 4.960 percent change in TKV/participant-years |
p-value: 0.046295% CI: [1, 1.023]Mixed Models Analysis
Secondary
Annualized TKV Slope for Study 156-04-251 Placebo Participants Enrolled in 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, 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.
Time frame: Tolvaptan, Delayed Treated: Baseline to Month 24 in Study 156-08-271; Placebo: Baseline to Month 36 in Study 156-04-251
Population: The Efficacy Sample consisted of all enrolled participants who took at least 1 dose of study drug and completed 3 years of study drug treatment in previous Study 156-04-251. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tolvaptan, Early Treated (From Study 156-04-251: Tolvaptan) | Annualized TKV Slope for Study 156-04-251 Placebo Participants Enrolled in Study 156-08-271 | 4.779 percent change in TKV/participant-years |
| Tolvaptan, Delayed Treated (From Study 156-04-251: Placebo) | Annualized TKV Slope for Study 156-04-251 Placebo Participants Enrolled in Study 156-08-271 | 5.627 percent change in TKV/participant-years |
p-value: 0.10895% CI: [0.982, 1.002]Mixed Models Analysis
Secondary
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)
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 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.
Time frame: Study Baseline (Prior to Day 1 in Study 156-04-251) to Month 24 in this study (Study 156-08-271)
Population: The Efficacy Sample consisted of all enrolled participants who took at least 1 dose of study drug and completed 3 years of study drug treatment in previous Study 156-04-251. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tolvaptan, Early Treated (From Study 156-04-251: Tolvaptan) | 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) | -16.77 mL/min/1.73 square meters (m^2) | Standard Deviation 13.16 |
| Tolvaptan, Delayed Treated (From Study 156-04-251: Placebo) | 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) | -19.92 mL/min/1.73 square meters (m^2) | Standard Deviation 16.4 |
p-value: 0.000395% CI: [1.462, 4.836]Mixed Models Analysis