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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-019025-33 | EudraCT Number |
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The purpose of the trial was to determine the short-term effects of tolvaptan in patients with autosomal dominant polycystic kidney disease (ADPKD) at various levels of renal function.
Renal function was assessed during screening with the estimated glomerular filtration rate (eGFR), which was calculated with the 4-variable modification of diet in renal disease (MDRD) equation using a minimum of 2 creatinine measurements. The eGFR values were used to categorize participants into 1 of 3 mutually exclusive strata (> 60 [Group A], 30 to 60 [Group B], and < 30 [Group C] mL/min/1.73 m^2). Each of the 3 groups received the same tolvaptan treatment.
During the 3-week treatment period, participants were up-titrated on a weekly basis from 45/15 mg to 60/30 mg to 90/30 mg (AM and PM [8 hours later] split-dose) to the maximally tolerated dose. The 3-week treatment period was followed by a 3-week post-treatment period during which no study medication was administered.
The effects of the highest tolerated split-dose of tolvaptan on renal hemodynamics and pharmacokinetic and pharmacodynamic parameters were assessed throughout the 6 weeks of the study. The reversibility of changes during the post-treatment period after withdrawal of the drug was determined and the acute transitory effects on kidney volume were also explored.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A - eGFR > 60 ml/min/1.73m^2 | Experimental | Participants received tolvaptan for the first 3 weeks of the 6 week study. Participants were up-titrated on a weekly basis from tolvaptan 45/15 mg to 60/30 mg to 90/30 mg oral split-dose (AM and PM [8 hours later]) to the maximally tolerated dose. |
|
| Group B - eGFR 30 to 60 ml/min/1.73m^2 | Experimental | Participants received tolvaptan for the first 3 weeks of the 6 week study. Participants were up-titrated on a weekly basis from tolvaptan 45/15 mg to 60/30 mg to 90/30 mg oral split-dose (AM and PM [8 hours later]) to the maximally tolerated dose. |
|
| Group C - eGFR < 30 ml/min/1.73m^2 | Experimental | Participants received tolvaptan for the first 3 weeks of the 6 week study. Participants were up-titrated on a weekly basis from tolvaptan 45/15 mg to 60/30 mg to 90/30 mg oral split-dose (AM and PM [8 hours later]) to the maximally tolerated dose. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tolvaptan | Drug | Tolvaptan was supplied as 15 and 30 mg tablets. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in Measured Glomerular Filtration Rate (mGFR) After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment. | Renal function measurements were performed using the constant infusion method with 125I-iothalamate and 131I-hippuran. A priming solution containing 20 mL infusion solution (0.04 MBq of 125I-iothalamate and 0.03 MBq of 131I-hippuran) was given at 08:00 hours, followed by a constant infusion of 6 to 12 mL/h, with the lowest infusion rates in subjects with impaired renal function, based on previously known serum creatinine concentrations. Plasma concentrations of both tracers were allowed to stabilize during a 1.5-hour equilibration, which was followed by two 2-hour periods (09:30 to 11:30 hours and 11:30 to 13:30 hours) for simultaneous clearances of 125I-iothalamate and 131I-hippuran. Blood was drawn at 1, 2, 3, 4, and 5 hours post consumption of water/tolvaptan (08:30 hours). The mGFR was corrected for voiding errors. | After 3 weeks of treatment and 3 weeks post treatment |
| Mean Change From Baseline in Effective Renal Plasma Flow (ERPF) After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment. | Renal function measurements were performed using the constant infusion method with 125I-iothalamate and 131I-hippuran. A priming solution containing 20 mL infusion solution (0.04 MBq of 125I-iothalamate and 0.03 MBq of 131I-hippuran) was given at 08:00 hours, followed by a constant infusion of 6 to 12 mL/h, with the lowest infusion rates in subjects with impaired renal function, based on previously known serum creatinine concentrations. Plasma concentrations of both tracers were allowed to stabilize during a 1.5-hour equilibration, which was followed by two 2-hour periods (09:30 to 11:30 hours and 11:30 to 13:30 hours) for simultaneous clearances of 125I-iothalamate and 131I-hippuran. Blood was drawn at 1, 2, 3, 4, and 5 hours post consumption of water/tolvaptan (08:30 hours). | After 3 weeks of treatment and 3 weeks post treatment |
| Mean Change From Baseline in Filtration Fraction (GFR/ERFP) After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment. | Renal function measurements were performed using the constant infusion method with 125I-iothalamate and 131I-hippuran. A priming solution containing 20 mL infusion solution (0.04 MBq of 125I-iothalamate and 0.03 MBq of 131I-hippuran) was given at 08:00 hours, followed by a constant infusion of 6 to 12 mL/h, with the lowest infusion rates in subjects with impaired renal function, based on previously known serum creatinine concentrations. Plasma concentrations of both tracers were allowed to stabilize during a 1.5-hour equilibration, which was followed by two 2-hour periods (09:30 to 11:30 hours and 11:30 to 13:30 hours) for simultaneous clearances of 125I-iothalamate and 131I-hippuran. Blood was drawn at 1, 2, 3, 4, and 5 hours post consumption of water/tolvaptan (08:30 hours). |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in Free Water Clearance After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment | Renal function measurements were performed using the constant infusion method with 125I-iothalamate and 131I-hippuran. A priming solution containing 20 mL infusion solution (0.04 MBq of 125I-iothalamate and 0.03 MBq of 131I-hippuran) was given at 08:00 hours, followed by a constant infusion of 6 to 12 mL/h, with the lowest infusion rates in subjects with impaired renal function, based on previously known serum creatinine concentrations. Plasma concentrations of both tracers were allowed to stabilize during a 1.5-hour equilibration, which was followed by two 2-hour periods (09:30 to 11:30 hours and 11:30 to 13:30 hours) for simultaneous clearances of 125I-iothalamate and 131I-hippuran. Blood was drawn at 1, 2, 3, 4, and 5 hours post consumption of water/tolvaptan (08:30 hours). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Frank Czerwiec, MD, PhD | Otsuka Pharmaceutical Development & Commercialization, Inc. | Study Director |
| Ron T Gansevoort, MD | University Medical Center Groningen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Medical Center Groningen | Groningen | 9713 GZ | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23903369 | Background | Boertien WE, Meijer E, de Jong PE, Bakker SJ, Czerwiec FS, Struck J, Oberdhan D, Shoaf SE, Krasa HB, Gansevoort RT. Short-term renal hemodynamic effects of tolvaptan in subjects with autosomal dominant polycystic kidney disease at various stages of chronic kidney disease. Kidney Int. 2013 Dec;84(6):1278-86. doi: 10.1038/ki.2013.285. Epub 2013 Jul 31. | |
| 26003607 |
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The trial consisted of a 2- to 42-day screening period, a 3-week treatment period, and a 3-week post treatment period.
The trial was conducted in 29 participants at one center in The Netherlands. Participants were stratified based on their estimated glomerular filtration rate (eGFR): >60, 30-60 and <30 millilitres (mL)/minute (min)/1.73 meter squared (m2). eGFR was assessed using the 4-variable modification of diet in renal disease (MDRD).
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| ID | Title | Description |
|---|---|---|
| FG000 | eGFR > 60 mL/Min/1.73m2 | Daily split-dose of tolvaptan titrated weekly to the maximally tolerated dose. Starting daily tolvaptan dose of 45mg/15mg titrated to 60mg/30mg, then 90mg/30mg based on tolerability. |
| FG001 | eGFR 30-60 mL/Min/1.73m2 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| After 3 weeks of treatment and 3 weeks post treatment |
| After 3 weeks of treatment and 3 weeks post treatment |
| Time to Peak Plasma Concentration (Cmax) After 3 Weeks of Tolvaptan Treatment. | Blood sampling for determination of tolvaptan concentrations took place at the Baseline, Final Treatment, and the Post Treatment or Early Termination visits. At the Final Treatment visit (Day 21 [+/- 1 day)]), blood samples were collected prior to the start of infusion of study treatment and at 1, 2, 3, 4, and 5 hours postdose. At the Baseline (Day 0), and Post Treatment visit (3 weeks [+/-3 days] after last dose), a blood sample was collected prior to the start of infusion of study treatment. | Day 0: 0 hour, Day 21: (0, 1, 2, 3, 4 and 5 hours postdose), 3 Weeks after last dose: 0 hour |
| Time to Peak Plasma Concentration (Tmax) After 3 Weeks of Tolvaptan Treatment. | Blood sampling for determination of tolvaptan concentrations took place at the Baseline, Final Treatment, and the Post Treatment or Early Termination visits. At the Final Treatment visit (Day 21 [+/- 1 day)]), blood samples were collected prior to the start of infusion of study treatment and at 1, 2, 3, 4, and 5 hours postdose. At the Baseline (Day 0), and Post Treatment visit (3 weeks [+/-3 days] after last dose), a blood sample was collected prior to the start of infusion of study treatment. | Day 0: 0 hour, Day 21: (0, 1, 2, 3, 4 and 5 hours postdose), 3 Weeks after last dose: 0 hour |
| Area Under the Concentration-time Curve From 0 to 5 Hours (AUC0-5) After 3 Weeks of Tolvaptan Treatment. | Blood sampling for determination of tolvaptan concentrations took place at the Baseline, Final Treatment, and the Post Treatment or Early Termination visits. At the Final Treatment visit (Day 21 [+/- 1 day)]), blood samples were collected prior to the start of infusion of study treatment and at 1, 2, 3, 4, and 5 hours postdose. At the Baseline (Day 0), and Post Treatment visit (3 weeks [+/-3 days] after last dose), a blood sample was collected prior to the start of infusion of study treatment. | Day 0: 0 hour, Day 21: (0, 1, 2, 3, 4 and 5 hours postdose), 3 Weeks after last dose: 0 hour |
| Percentage Change From Baseline in Total Kidney Volume (TKV) After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment. | TKV was measured using magnetic resonance imaging. | After 3 weeks of treatment and 3 weeks post treatment |
| Mean Change From Baseline in 24 Hour Urine Volume After 3 Weeks Tolvaptan Treatment and at 3 Weeks Post Treatment. | A 24-hour split urine sample (approximate times: 0700 to 1700 hours, 1700 hours to bedtime, and bedtime to 0700 hours) was collected beginning the day before the Baseline, Final Treatment, and Post Treatment visits and ending at admission to the renal function ward. Individual voids in a collection interval were pooled and the total volume determined. | 24 hours |
| Mean Change From Baseline in 2 Hour Urine Volume After 3 Weeks Tolvaptan Treatment and at 3 Weeks Post Treatment. | The volume of urine from each 2-hour urine collection in the renal function tests at Baseline, Final Treatment, and Post Treatment was recorded. Individual voids in a collection interval were pooled before determination of total volume. | 2 hours |
| Reddy B, Chapman AB. Acute Response to Tolvaptan in ADPKD: A Window to Predict Long-term Efficacy? Am J Kidney Dis. 2015 Jun;65(6):811-3. doi: 10.1053/j.ajkd.2015.03.004. No abstract available. |
| 25600953 | Background | Boertien WE, Meijer E, de Jong PE, ter Horst GJ, Renken RJ, van der Jagt EJ, Kappert P, Ouyang J, Engels GE, van Oeveren W, Struck J, Czerwiec FS, Oberdhan D, Krasa HB, Gansevoort RT. Short-term Effects of Tolvaptan in Individuals With Autosomal Dominant Polycystic Kidney Disease at Various Levels of Kidney Function. Am J Kidney Dis. 2015 Jun;65(6):833-41. doi: 10.1053/j.ajkd.2014.11.010. Epub 2015 Jan 15. |
| 30578153 | Background | Kramers BJ, van Gastel MDA, Boertien WE, Meijer E, Gansevoort RT. Determinants of Urine Volume in ADPKD Patients Using the Vasopressin V2 Receptor Antagonist Tolvaptan. Am J Kidney Dis. 2019 Mar;73(3):354-362. doi: 10.1053/j.ajkd.2018.09.016. Epub 2018 Dec 19. |
| 37250503 | Derived | Chebib FT, Zhou X, Garbinsky D, Davenport E, Nunna S, Oberdhan D, Fernandes A. Tolvaptan and Kidney Function Decline in Older Individuals With Autosomal Dominant Polycystic Kidney Disease: A Pooled Analysis of Randomized Clinical Trials and Observational Studies. Kidney Med. 2023 Apr 14;5(6):100639. doi: 10.1016/j.xkme.2023.100639. eCollection 2023 Jun. |
Daily split-dose of tolvaptan titrated weekly to the maximally tolerated dose. Starting daily tolvaptan dose of 45mg/15mg titrated to 60mg/30mg, then 90mg/30mg based on tolerability. |
| FG002 | eGFR <30 ml/Min/1.73m2 | Daily split-dose of tolvaptan titrated weekly to the maximally tolerated dose. Starting daily tolvaptan dose of 45mg/15mg titrated to 60mg/30mg, then 90mg/30mg based on tolerability. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | eGFR > 60 mL/Min/1.73m2 | Daily split-dose of tolvaptan titrated weekly to the maximally tolerated dose. Starting daily tolvaptan dose of 45mg/15mg titrated to 60mg/30mg, then 90mg/30mg based on tolerability. |
| BG001 | eGFR 30-60 mL/Min/1.73m2 | Daily split-dose of tolvaptan titrated weekly to the maximally tolerated dose. Starting daily tolvaptan dose of 45mg/15mg titrated to 60mg/30mg, then 90mg/30mg based on tolerability. |
| BG002 | eGFR <30 mL/Min/1.73m2 | Daily split-dose of tolvaptan titrated weekly to the maximally tolerated dose. Starting daily tolvaptan dose of 45mg/15mg titrated to 60mg/30mg, then 90mg/30mg based on tolerability. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Mean Change From Baseline in Measured Glomerular Filtration Rate (mGFR) After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment. | Renal function measurements were performed using the constant infusion method with 125I-iothalamate and 131I-hippuran. A priming solution containing 20 mL infusion solution (0.04 MBq of 125I-iothalamate and 0.03 MBq of 131I-hippuran) was given at 08:00 hours, followed by a constant infusion of 6 to 12 mL/h, with the lowest infusion rates in subjects with impaired renal function, based on previously known serum creatinine concentrations. Plasma concentrations of both tracers were allowed to stabilize during a 1.5-hour equilibration, which was followed by two 2-hour periods (09:30 to 11:30 hours and 11:30 to 13:30 hours) for simultaneous clearances of 125I-iothalamate and 131I-hippuran. Blood was drawn at 1, 2, 3, 4, and 5 hours post consumption of water/tolvaptan (08:30 hours). The mGFR was corrected for voiding errors. | All participants who took any trial medication and had a postbaseline renal function test. | Posted | Mean | Standard Deviation | mL/min | After 3 weeks of treatment and 3 weeks post treatment |
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| Primary | Mean Change From Baseline in Effective Renal Plasma Flow (ERPF) After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment. | Renal function measurements were performed using the constant infusion method with 125I-iothalamate and 131I-hippuran. A priming solution containing 20 mL infusion solution (0.04 MBq of 125I-iothalamate and 0.03 MBq of 131I-hippuran) was given at 08:00 hours, followed by a constant infusion of 6 to 12 mL/h, with the lowest infusion rates in subjects with impaired renal function, based on previously known serum creatinine concentrations. Plasma concentrations of both tracers were allowed to stabilize during a 1.5-hour equilibration, which was followed by two 2-hour periods (09:30 to 11:30 hours and 11:30 to 13:30 hours) for simultaneous clearances of 125I-iothalamate and 131I-hippuran. Blood was drawn at 1, 2, 3, 4, and 5 hours post consumption of water/tolvaptan (08:30 hours). | All participants who took any trial medication and had a postbaseline renal function test. | Posted | Mean | Standard Deviation | mL/min | After 3 weeks of treatment and 3 weeks post treatment |
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| Primary | Mean Change From Baseline in Filtration Fraction (GFR/ERFP) After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment. | Renal function measurements were performed using the constant infusion method with 125I-iothalamate and 131I-hippuran. A priming solution containing 20 mL infusion solution (0.04 MBq of 125I-iothalamate and 0.03 MBq of 131I-hippuran) was given at 08:00 hours, followed by a constant infusion of 6 to 12 mL/h, with the lowest infusion rates in subjects with impaired renal function, based on previously known serum creatinine concentrations. Plasma concentrations of both tracers were allowed to stabilize during a 1.5-hour equilibration, which was followed by two 2-hour periods (09:30 to 11:30 hours and 11:30 to 13:30 hours) for simultaneous clearances of 125I-iothalamate and 131I-hippuran. Blood was drawn at 1, 2, 3, 4, and 5 hours post consumption of water/tolvaptan (08:30 hours). | All participants who took any trial medication and had a postbaseline renal function test. | Posted | Mean | Standard Deviation | Ratios | After 3 weeks of treatment and 3 weeks post treatment |
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| Secondary | Mean Change From Baseline in Free Water Clearance After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment | Renal function measurements were performed using the constant infusion method with 125I-iothalamate and 131I-hippuran. A priming solution containing 20 mL infusion solution (0.04 MBq of 125I-iothalamate and 0.03 MBq of 131I-hippuran) was given at 08:00 hours, followed by a constant infusion of 6 to 12 mL/h, with the lowest infusion rates in subjects with impaired renal function, based on previously known serum creatinine concentrations. Plasma concentrations of both tracers were allowed to stabilize during a 1.5-hour equilibration, which was followed by two 2-hour periods (09:30 to 11:30 hours and 11:30 to 13:30 hours) for simultaneous clearances of 125I-iothalamate and 131I-hippuran. Blood was drawn at 1, 2, 3, 4, and 5 hours post consumption of water/tolvaptan (08:30 hours). | All participants who took any trial medication and had a postbaseline renal function test. | Posted | Mean | Standard Deviation | mL/min | After 3 weeks of treatment and 3 weeks post treatment |
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| Secondary | Time to Peak Plasma Concentration (Cmax) After 3 Weeks of Tolvaptan Treatment. | Blood sampling for determination of tolvaptan concentrations took place at the Baseline, Final Treatment, and the Post Treatment or Early Termination visits. At the Final Treatment visit (Day 21 [+/- 1 day)]), blood samples were collected prior to the start of infusion of study treatment and at 1, 2, 3, 4, and 5 hours postdose. At the Baseline (Day 0), and Post Treatment visit (3 weeks [+/-3 days] after last dose), a blood sample was collected prior to the start of infusion of study treatment. | All participants who took any trial medication and had a postbaseline renal function test. | Posted | Mean | Standard Deviation | ng/mL | Day 0: 0 hour, Day 21: (0, 1, 2, 3, 4 and 5 hours postdose), 3 Weeks after last dose: 0 hour |
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| Secondary | Time to Peak Plasma Concentration (Tmax) After 3 Weeks of Tolvaptan Treatment. | Blood sampling for determination of tolvaptan concentrations took place at the Baseline, Final Treatment, and the Post Treatment or Early Termination visits. At the Final Treatment visit (Day 21 [+/- 1 day)]), blood samples were collected prior to the start of infusion of study treatment and at 1, 2, 3, 4, and 5 hours postdose. At the Baseline (Day 0), and Post Treatment visit (3 weeks [+/-3 days] after last dose), a blood sample was collected prior to the start of infusion of study treatment. | All participants who took any trial medication and had a postbaseline renal function test. | Posted | Median | Full Range | hours | Day 0: 0 hour, Day 21: (0, 1, 2, 3, 4 and 5 hours postdose), 3 Weeks after last dose: 0 hour |
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| Secondary | Area Under the Concentration-time Curve From 0 to 5 Hours (AUC0-5) After 3 Weeks of Tolvaptan Treatment. | Blood sampling for determination of tolvaptan concentrations took place at the Baseline, Final Treatment, and the Post Treatment or Early Termination visits. At the Final Treatment visit (Day 21 [+/- 1 day)]), blood samples were collected prior to the start of infusion of study treatment and at 1, 2, 3, 4, and 5 hours postdose. At the Baseline (Day 0), and Post Treatment visit (3 weeks [+/-3 days] after last dose), a blood sample was collected prior to the start of infusion of study treatment. | All participants who took any trial medication and had a postbaseline renal function test. | Posted | Mean | Standard Deviation | ng.h/mL | Day 0: 0 hour, Day 21: (0, 1, 2, 3, 4 and 5 hours postdose), 3 Weeks after last dose: 0 hour |
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| Secondary | Percentage Change From Baseline in Total Kidney Volume (TKV) After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment. | TKV was measured using magnetic resonance imaging. | All participants who took any trial medication and had a postbaseline renal function test. | Posted | Mean | Standard Deviation | Percent | After 3 weeks of treatment and 3 weeks post treatment |
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| Secondary | Mean Change From Baseline in 24 Hour Urine Volume After 3 Weeks Tolvaptan Treatment and at 3 Weeks Post Treatment. | A 24-hour split urine sample (approximate times: 0700 to 1700 hours, 1700 hours to bedtime, and bedtime to 0700 hours) was collected beginning the day before the Baseline, Final Treatment, and Post Treatment visits and ending at admission to the renal function ward. Individual voids in a collection interval were pooled and the total volume determined. | All participants who took any trial medication and had a postbaseline renal function test. | Posted | Mean | Standard Deviation | mL | 24 hours |
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| Secondary | Mean Change From Baseline in 2 Hour Urine Volume After 3 Weeks Tolvaptan Treatment and at 3 Weeks Post Treatment. | The volume of urine from each 2-hour urine collection in the renal function tests at Baseline, Final Treatment, and Post Treatment was recorded. Individual voids in a collection interval were pooled before determination of total volume. | All participants who took any trial medication and had a postbaseline renal function test. | Posted | Mean | Standard Deviation | mL | 2 hours |
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Adverse events were collected from the time of signing the informed consent to 7 days after the early termination visit or up to the 21 Day Post-Treatment Visit
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | eGFR > 60 mL/Min/1.73m2 | Daily split-dose of tolvaptan titrated weekly to the maximally tolerated dose. Starting daily tolvaptan dose of 45mg/15mg titrated to 60mg/30mg, then 90mg/30mg based on tolerability. | 1 | 10 | 10 | 10 | ||
| EG001 | eGFR 30-60 mL/Min/1.73m2 | Daily split-dose of tolvaptan titrated weekly to the maximally tolerated dose. Starting daily tolvaptan dose of 45mg/15mg titrated to 60mg/30mg, then 90mg/30mg based on tolerability. | 0 | 10 | 10 | 10 | ||
| EG002 | eGFR <30 mL/Min/1.73m2 | Daily split-dose of tolvaptan titrated weekly to the maximally tolerated dose. Starting daily tolvaptan dose of 45mg/15mg titrated to 60mg/30mg, then 90mg/30mg based on tolerability. | 1 | 9 | 9 | 9 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Polyuria | Renal and urinary disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | 14.1 | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Bradycardia | Cardiac disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Conjunctival haemorrhage | Eye disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Oedema | General disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Pyrexia | General disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Thirst | General disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 14.1 | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 14.1 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 14.1 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 14.1 | Non-systematic Assessment |
| |
| Vulvovaginal mycotic infection | Infections and infestations | MedDRA 14.1 | Non-systematic Assessment |
| |
| Wound | Injury, poisoning and procedural complications | MedDRA 14.1 | Non-systematic Assessment |
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| Skin turgor decreased | Investigations | MedDRA 14.1 | Non-systematic Assessment |
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| Weight decreased | Investigations | MedDRA 14.1 | Non-systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 14.1 | Non-systematic Assessment |
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| Hypernatraemia | Metabolism and nutrition disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Nocturia | Renal and urinary disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Polyuria | Renal and urinary disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Renal pain | Renal and urinary disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Breast pain | Reproductive system and breast disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Erectile dysfunction | Reproductive system and breast disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Family stress | Social circumstances | MedDRA 14.1 | Non-systematic Assessment |
| |
| Stress at work | Social circumstances | MedDRA 14.1 | Non-systematic Assessment |
| |
| Fushing | Vascular disorders | MedDRA 14.1 | Non-systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA 14.1 | Non-systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Medical Affairs | Otsuka Pharmaceutical Development and Commercialization, Inc. | 800 562-3974 |
| ID | Term |
|---|---|
| D016891 | Polycystic Kidney, Autosomal Dominant |
| ID | Term |
|---|---|
| D007690 | Polycystic Kidney Diseases |
| D052177 | Kidney Diseases, Cystic |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D000072661 | Ciliopathies |
| D030342 | Genetic Diseases, Inborn |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077602 | Tolvaptan |
| ID | Term |
|---|---|
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Male |
|
|
A change of 10% was chosen as representing a clinically significant change in mGFR or ERPF. For this purpose, the alpha level was set at 0.05 and the beta level (power) at 95% instead of 80%, to decrease the chance of a false-negative finding. |
| paited t-test |
| <0.05 |
Test to compare Final Treatment versus Baseline |
| 2-Sided |
| Superiority or Other |
| A change of 10% was chosen as representing a clinically significant change in mGFR or ERPF. For this purpose, the alpha level was set at 0.05 and the beta level (power) at 95% instead of 80%, to decrease the chance of a false-negative finding. | paired t-test | >0.05 | Test to compare Final Treatment versus Baseline | 2-Sided | Superiority or Other |
| A change of 10% was chosen as representing a clinically significant change in mGFR or ERPF. For this purpose, the alpha level was set at 0.05 and the beta level (power) at 95% instead of 80%, to decrease the chance of a false-negative finding. | paired t-test | >0.05 | Test to compare Post Treatment versus Baseline | 2-Sided | Superiority or Other |
| A change of 10% was chosen as representing a clinically significant change in mGFR or ERPF. For this purpose, the alpha level was set at 0.05 and the beta level (power) at 95% instead of 80%, to decrease the chance of a false-negative finding. | paired t-test | >0.05 | Test to compare Post Treatment versus Baseline | 2-Sided | Superiority or Other |
| A change of 10% was chosen as representing a clinically significant change in mGFR or ERPF. For this purpose, the alpha level was set at 0.05 and the beta level (power) at 95% instead of 80%, to decrease the chance of a false-negative finding. | paired t-test | >0.05 | Test to compare Post Treatment versus Baseline | 2-Sided | Superiority or Other |
| A change of 10% was chosen as representing a clinically significant change in mGFR or ERPF. For this purpose, the alpha level was set at 0.05 and the beta level (power) at 95% instead of 80%, to decrease the chance of a false-negative finding. | Wilcoxon (Mann-Whitney) | >0.05 | Test to compare treatment groups at Final Treatment | 2-Sided | Superiority or Other |
| A change of 10% was chosen as representing a clinically significant change in mGFR or ERPF. For this purpose, the alpha level was set at 0.05 and the beta level (power) at 95% instead of 80%, to decrease the chance of a false-negative finding. | Wilcoxon (Mann-Whitney) | >0.05 | Test to compare treatment groups at Final Treatment | 2-Sided | Superiority or Other |
| A change of 10% was chosen as representing a clinically significant change in mGFR or ERPF. For this purpose, the alpha level was set at 0.05 and the beta level (power) at 95% instead of 80%, to decrease the chance of a false-negative finding. | Wilcoxon (Mann-Whitney) | <0.05 | Test to compare treatment groups at Final Treatment | 2-Sided | Superiority or Other |
| A change of 10% was chosen as representing a clinically significant change in mGFR or ERPF. For this purpose, the alpha level was set at 0.05 and the beta level (power) at 95% instead of 80%, to decrease the chance of a false-negative finding. | Wilcoxon (Mann-Whitney) | >0.05 | Test to compare treatment groups at Post Treatment | 2-Sided | Superiority or Other |
| A change of 10% was chosen as representing a clinically significant change in mGFR or ERPF. For this purpose, the alpha level was set at 0.05 and the beta level (power) at 95% instead of 80%, to decrease the chance of a false-negative finding. | Wilcoxon (Mann-Whitney) | >0.05 | 2-Sided | Superiority or Other |
| A change of 10% was chosen as representing a clinically significant change in mGFR or ERPF. For this purpose, the alpha level was set at 0.05 and the beta level (power) at 95% instead of 80%, to decrease the chance of a false-negative finding. | Wilcoxon (Mann-Whitney) | >0.05 | 2-Sided | Superiority or Other |
| OG002 | eGFR <30 mL/Min/1.73m2 | Daily split-dose of tolvaptan titrated weekly to the maximally tolerated dose. Starting daily tolvaptan dose of 45mg/15mg titrated to 60mg/30mg, then 90mg/30mg based on tolerability. |
|
|
|
| OG002 | eGFR <30 mL/Min/1.73m2 | Daily split-dose of tolvaptan titrated weekly to the maximally tolerated dose. Starting daily tolvaptan dose of 45mg/15mg titrated to 60mg/30mg, then 90mg/30mg based on tolerability. |
|
|
|
| OG002 | eGFR <30 mL/Min/1.73m2 | Daily split-dose of tolvaptan titrated weekly to the maximally tolerated dose. Starting daily tolvaptan dose of 45mg/15mg titrated to 60mg/30mg, then 90mg/30mg based on tolerability. |
|
|
|
Daily split-dose of tolvaptan titrated weekly to the maximally tolerated dose. Starting daily tolvaptan dose of 45mg/15mg titrated to 60mg/30mg, then 90mg/30mg based on tolerability. |
|
|
Daily split-dose of tolvaptan titrated weekly to the maximally tolerated dose. Starting daily tolvaptan dose of 45mg/15mg titrated to 60mg/30mg, then 90mg/30mg based on tolerability. |
|
|
Daily split-dose of tolvaptan titrated weekly to the maximally tolerated dose. Starting daily tolvaptan dose of 45mg/15mg titrated to 60mg/30mg, then 90mg/30mg based on tolerability. |
|
|
| Units | Counts |
|---|---|
| Participants |
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