Short-term Renal Hemodynamic Effects of Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01336972
Collaborator
(none)
29
1
3
13
2.2
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
29 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2a, Single-center Study Investigating the Short-term Renal Hemodynamic Effects, Safety and Pharmacokinetics/ Pharmacodynamics of Oral Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease at Various Stages of Renal Function
Study Start Date
:
Oct 1, 2010
Actual Primary Completion Date
:
Nov 1, 2011
Actual Study Completion Date
:
Nov 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group A - eGFR > 60 ml/min/1.73m^2 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. |
Drug: Tolvaptan
Tolvaptan was supplied as 15 and 30 mg tablets.
Other Names:
|
| Experimental: Group B - eGFR 30 to 60 ml/min/1.73m^2 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. |
Drug: Tolvaptan
Tolvaptan was supplied as 15 and 30 mg tablets.
Other Names:
|
| Experimental: Group C - eGFR < 30 ml/min/1.73m^2 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. |
Drug: Tolvaptan
Tolvaptan was supplied as 15 and 30 mg tablets.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Mean Change From Baseline in Measured Glomerular Filtration Rate (mGFR) After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment. [After 3 weeks of treatment and 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.
- Mean Change From Baseline in Effective Renal Plasma Flow (ERPF) After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment. [After 3 weeks of treatment and 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).
- Mean Change From Baseline in Filtration Fraction (GFR/ERFP) After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment. [After 3 weeks of treatment and 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).
Secondary Outcome Measures
- Mean Change From Baseline in Free Water Clearance After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment [After 3 weeks of treatment and 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).
- Time to Peak Plasma Concentration (Cmax) After 3 Weeks of Tolvaptan Treatment. [Day 0: 0 hour, Day 21: (0, 1, 2, 3, 4 and 5 hours postdose), 3 Weeks after last dose: 0 hour]
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.
- Time to Peak Plasma Concentration (Tmax) After 3 Weeks of Tolvaptan Treatment. [Day 0: 0 hour, Day 21: (0, 1, 2, 3, 4 and 5 hours postdose), 3 Weeks after last dose: 0 hour]
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.
- Area Under the Concentration-time Curve From 0 to 5 Hours (AUC0-5) After 3 Weeks of Tolvaptan Treatment. [Day 0: 0 hour, Day 21: (0, 1, 2, 3, 4 and 5 hours postdose), 3 Weeks after last dose: 0 hour]
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.
- Percentage Change From Baseline in Total Kidney Volume (TKV) After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment. [After 3 weeks of treatment and 3 weeks post treatment]
TKV was measured using magnetic resonance imaging.
- Mean Change From Baseline in 24 Hour Urine Volume After 3 Weeks Tolvaptan Treatment and at 3 Weeks Post Treatment. [24 hours]
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.
- Mean Change From Baseline in 2 Hour Urine Volume After 3 Weeks Tolvaptan Treatment and at 3 Weeks Post Treatment. [2 hours]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
- Diagnosis of autosomal dominant polycystic kidney disease (ADPKD) by Ravine criteria.
Exclusion Criteria:
-
Renal replacement therapy.
-
Use of therapies for the purpose of affecting polycystic kidney disease (PKD) cysts.
-
Evidence of significant renal disease, eg, active glomerular nephritides, renal cancer, single kidney.
-
Significant risk-factors for renal impairment, eg, chronic use of diuretics, advanced diabetes, use of nephrotoxic drugs.
-
History of significant coagulation defects or hemorrhagic diathesis.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Medical Center Groningen | Groningen | Netherlands | 9713 GZ |
Sponsors and Collaborators
- Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
- Study Director: Frank Czerwiec, MD, PhD, Otsuka Pharmaceutical Development & Commercialization, Inc.
- Principal Investigator: Ron T Gansevoort, MD, University Medical Center Groningen
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- 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.
Responsible Party:
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01336972
Other Study ID Numbers:
- 156-09-284
- 2010-019025-33
First Posted:
Apr 18, 2011
Last Update Posted:
Mar 5, 2019
Last Verified:
Feb 1, 2019
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | 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). |
|---|---|
| Pre-assignment Detail | The trial consisted of a 2- to 42-day screening period, a 3-week treatment period, and a 3-week post treatment period. |
| Arm/Group Title | eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 ml/Min/1.73m2 |
|---|---|---|---|
| Arm/Group Description | 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. |
| Period Title: Overall Study | |||
| STARTED | 10 | 10 | 9 |
| COMPLETED | 9 | 9 | 9 |
| NOT COMPLETED | 1 | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 mL/Min/1.73m2 | Total |
|---|---|---|---|---|
| Arm/Group Description | 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. | Total of all reporting groups |
| Overall Participants | 10 | 10 | 9 | 29 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
38.7
(7.1)
|
47.8
(12.9)
|
52.1
(6.7)
|
46.0
(10.7)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
6
60%
|
6
60%
|
2
22.2%
|
14
48.3%
|
| Male |
4
40%
|
4
40%
|
7
77.8%
|
15
51.7%
|
Outcome Measures
| Title | Mean Change From Baseline in Measured Glomerular Filtration Rate (mGFR) After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment. |
|---|---|
| Description | 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. |
| Time Frame | After 3 weeks of treatment and 3 weeks post treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who took any trial medication and had a postbaseline renal function test. |
| Arm/Group Title | eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 mL/Min/1.73m2 |
|---|---|---|---|
| Arm/Group Description | 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 |
| Measure Participants | 9 | 9 | 9 |
| Final treatment change from Baseline |
-8.0
(9.1)
|
-6.2
(6.2)
|
-0.7
(1.5)
|
| Post treatment change from Baseline |
0.1
(4.9)
|
-1.5
(4.0)
|
-1.2
(3.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | Test to compare Final Treatment versus Baseline | |
| Method | paired t-test | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | eGFR 30-60 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | Test to compare Final Treatment versus Baseline | |
| Method | paited t-test | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare Final Treatment versus Baseline | |
| Method | paired t-test | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare Post Treatment versus Baseline | |
| Method | paired t-test | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | eGFR 30-60 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare Post Treatment versus Baseline | |
| Method | paired t-test | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare Post Treatment versus Baseline | |
| Method | paired t-test | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare treatment groups at Final Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare treatment groups at Final Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | Test to compare treatment groups at Final Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare treatment groups at Post Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Mean Change From Baseline in Effective Renal Plasma Flow (ERPF) After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment. |
|---|---|
| Description | 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). |
| Time Frame | After 3 weeks of treatment and 3 weeks post treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who took any trial medication and had a postbaseline renal function test. |
| Arm/Group Title | eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 mL/Min/1.73m2 |
|---|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 9 | 9 | 9 |
| Final treatment change from Baseline |
-16.9
(36.4)
|
-11.1
(18.4)
|
-1.7
(5.1)
|
| Post treatment change from Baseline |
4.3
(30.2)
|
-8.4
(17.7)
|
-1.3
(10.3)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare Final Treatment versus Baseline for all treatment groups | |
| Method | paired t-test | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare Post Treatment versus Baseline for all treatment groups | |
| Method | paired t-test | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare treatment groups at Final Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare treatment groups at Final Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare treatment groups at Post Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare treatment groups at Post Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare treatment groups at Post Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Mean Change From Baseline in Filtration Fraction (GFR/ERFP) After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment. |
|---|---|
| Description | 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). |
| Time Frame | After 3 weeks of treatment and 3 weeks post treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who took any trial medication and had a postbaseline renal function test. |
| Arm/Group Title | eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 mL/Min/1.73m2 |
|---|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 9 | 9 | 9 |
| Final treatment change from Baseline |
-0.005
(0.017)
|
-0.013
(0.016)
|
-0.010
(0.014)
|
| Post treatment change from Baseline |
-0.003
(0.018)
|
0.005
(0.015)
|
-0.016
(0.023)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare Final Treatment versus Baseline | |
| Method | paired t-test | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare Post Treatment versus Baseline for all treatment groups | |
| Method | paired t-test | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare treatment groups at Final Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare treatment groups at Final Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare treatment groups at Final Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare treatment groups at Post Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | Test to compare treatment groups at Post Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare treatment groups at Post Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Mean Change From Baseline in Free Water Clearance After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment |
|---|---|
| Description | 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). |
| Time Frame | After 3 weeks of treatment and 3 weeks post treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who took any trial medication and had a postbaseline renal function test. |
| Arm/Group Title | eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 mL/Min/1.73m2 |
|---|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 9 | 9 | 9 |
| Final treatment change from Baseline |
4.334
(3.268)
|
2.822
(1.715)
|
1.701
(1.225)
|
| Post treatment change from Baseline |
-0.675
(1.475)
|
-0.195
(1.124)
|
0.382
(0.543)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare Final Treatment versus Baseline for all treatment groups | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | paired t-test | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare Post Treatment versus Baseline | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | paired t-test | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | eGFR 30-60 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare Post Treatment versus Baseline | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | paired t-test | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare Post Treatment versus Baseline | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | paired t-test | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | Test to compare treatment groups at Final Treatment | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare treatment groups at Final Treatment | |
| Method | paired t-test | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare treatment groups at Final Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare treatment groups at Post Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | Test to compare treatment groups at Post Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | Test to compare treatment groups at Post Treatment | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Time to Peak Plasma Concentration (Cmax) After 3 Weeks of Tolvaptan Treatment. |
|---|---|
| Description | 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. |
| Time Frame | Day 0: 0 hour, Day 21: (0, 1, 2, 3, 4 and 5 hours postdose), 3 Weeks after last dose: 0 hour |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who took any trial medication and had a postbaseline renal function test. |
| Arm/Group Title | eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 mL/Min/1.73m2 |
|---|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 | 9 | 9 |
| Mean (Standard Deviation) [ng/mL] |
828
(297)
|
591
(235)
|
840
(355)
|
| Title | Time to Peak Plasma Concentration (Tmax) After 3 Weeks of Tolvaptan Treatment. |
|---|---|
| Description | 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. |
| Time Frame | Day 0: 0 hour, Day 21: (0, 1, 2, 3, 4 and 5 hours postdose), 3 Weeks after last dose: 0 hour |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who took any trial medication and had a postbaseline renal function test. |
| Arm/Group Title | eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 mL/Min/1.73m2 |
|---|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 | 9 | 9 |
| Median (Full Range) [hours] |
2.0
|
2.0
|
2.0
|
| Title | Area Under the Concentration-time Curve From 0 to 5 Hours (AUC0-5) After 3 Weeks of Tolvaptan Treatment. |
|---|---|
| Description | 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. |
| Time Frame | Day 0: 0 hour, Day 21: (0, 1, 2, 3, 4 and 5 hours postdose), 3 Weeks after last dose: 0 hour |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who took any trial medication and had a postbaseline renal function test. |
| Arm/Group Title | eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 mL/Min/1.73m2 |
|---|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 8 | 9 | 9 |
| Mean (Standard Deviation) [ng.h/mL] |
2850
(774)
|
2140
(863)
|
3100
(1060)
|
| Title | Percentage Change From Baseline in Total Kidney Volume (TKV) After 3 Weeks of Tolvaptan Treatment and at 3 Weeks Post Treatment. |
|---|---|
| Description | TKV was measured using magnetic resonance imaging. |
| Time Frame | After 3 weeks of treatment and 3 weeks post treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who took any trial medication and had a postbaseline renal function test. |
| Arm/Group Title | eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 mL/Min/1.73m2 |
|---|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 9 | 9 | 9 |
| Final treatment change from Baseline |
-4.5
(3.7)
|
-4.6
(2.7)
|
-1.9
(1.9)
|
| Post treatment change from Baseline |
-1.5
(2.3)
|
-2.4
(3.8)
|
-0.7
(2.5)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Comparison of all treatment groups versus Baseline at Final Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | paired t-test | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Comparison of all treatment groups versus Baseline at Post Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | paired t-test | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare treatment groups at Final Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare treatment groups at Final Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare treatment groups at Final Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare treatment groups at Post Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare treatment groups at Post Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare treatment groups at Post Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Mean Change From Baseline in 24 Hour Urine Volume After 3 Weeks Tolvaptan Treatment and at 3 Weeks Post Treatment. |
|---|---|
| Description | 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. |
| Time Frame | 24 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who took any trial medication and had a postbaseline renal function test. |
| Arm/Group Title | eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 mL/Min/1.73m2 |
|---|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 9 | 9 | 9 |
| Final treatment change from Baseline |
4551.1
(1792.7)
|
3274.4
(1293.3)
|
2215.0
(1142.0)
|
| Post treatment change from Baseline |
-312.2
(468.2)
|
-287.2
(744.7)
|
143.1
(390.4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare Final Treatment versus Baseline for all treatment groups | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | Paired t-test | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare treatment groups at Final Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare treatment groups at Final Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare treatment groups at Final Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare PostTreatment versus Baseline for all treatment groups | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Paired t-test | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare treatment groups at Post Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare treatment groups at Post Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare treatment groups at Post Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Mean Change From Baseline in 2 Hour Urine Volume After 3 Weeks Tolvaptan Treatment and at 3 Weeks Post Treatment. |
|---|---|
| Description | 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. |
| Time Frame | 2 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who took any trial medication and had a postbaseline renal function test. |
| Arm/Group Title | eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 mL/Min/1.73m2 |
|---|---|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 9 | 9 | 9 |
| Final treatment change from Baseline |
888.9
(730.3)
|
625.6
(478.5)
|
356.7
(283.2)
|
| Post treatment change from Baseline |
-187.8
(218.2)
|
-10.0
(335.1)
|
27.5
(155.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare Final Treatment versus Baseline for all treatment groups | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | paired te-test | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare treatment groups at Final Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare treatment groups at Final Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare treatment groups at Final Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare Post Treatment versus Baseline | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | ||
| Method | paired t-test | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | eGFR 30-60 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare Post Treatment versus Baseline | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | paired t-test | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare Post Treatment versus Baseline | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Paired t-test | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR 30-60 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare treatment groups at Post Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | eGFR 30-60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare treatment groups at Post Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | eGFR > 60 mL/Min/1.73m2, eGFR <30 mL/Min/1.73m2 |
|---|---|---|
| Comments | Test to compare treatment groups at Post Treatment | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | >0.05 |
| Comments | ||
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Adverse Events
| Time Frame | 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 | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 mL/Min/1.73m2 | |||
| Arm/Group Description | 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. | |||
All Cause Mortality |
||||||
| eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 mL/Min/1.73m2 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 mL/Min/1.73m2 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/10 (10%) | 0/10 (0%) | 1/9 (11.1%) | |||
| Cardiac disorders | ||||||
| Angina pectoris | 0/10 (0%) | 0/10 (0%) | 1/9 (11.1%) | |||
| Renal and urinary disorders | ||||||
| Polyuria | 1/10 (10%) | 0/10 (0%) | 0/9 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| eGFR > 60 mL/Min/1.73m2 | eGFR 30-60 mL/Min/1.73m2 | eGFR <30 mL/Min/1.73m2 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/10 (100%) | 10/10 (100%) | 9/9 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 1/10 (10%) | 0/10 (0%) | 1/9 (11.1%) | |||
| Lymphadenopathy | 0/10 (0%) | 1/10 (10%) | 0/9 (0%) | |||
| Cardiac disorders | ||||||
| Angina pectoris | 0/10 (0%) | 0/10 (0%) | 1/9 (11.1%) | |||
| Bradycardia | 0/10 (0%) | 1/10 (10%) | 0/9 (0%) | |||
| Palpitations | 1/10 (10%) | 0/10 (0%) | 0/9 (0%) | |||
| Eye disorders | ||||||
| Conjunctival haemorrhage | 1/10 (10%) | 0/10 (0%) | 0/9 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 1/10 (10%) | 0/10 (0%) | 0/9 (0%) | |||
| Abdominal distension | 2/10 (20%) | 0/10 (0%) | 0/9 (0%) | |||
| Abdominal pain | 2/10 (20%) | 0/10 (0%) | 0/9 (0%) | |||
| Abdominal pain upper | 1/10 (10%) | 0/10 (0%) | 0/9 (0%) | |||
| Constipation | 0/10 (0%) | 1/10 (10%) | 0/9 (0%) | |||
| Diarrhoea | 1/10 (10%) | 1/10 (10%) | 0/9 (0%) | |||
| Dry mouth | 6/10 (60%) | 5/10 (50%) | 5/9 (55.6%) | |||
| Nausea | 1/10 (10%) | 1/10 (10%) | 2/9 (22.2%) | |||
| Toothache | 1/10 (10%) | 0/10 (0%) | 0/9 (0%) | |||
| General disorders | ||||||
| Fatigue | 2/10 (20%) | 1/10 (10%) | 3/9 (33.3%) | |||
| Malaise | 1/10 (10%) | 0/10 (0%) | 0/9 (0%) | |||
| Oedema | 0/10 (0%) | 0/10 (0%) | 2/9 (22.2%) | |||
| Pyrexia | 2/10 (20%) | 0/10 (0%) | 0/9 (0%) | |||
| Thirst | 10/10 (100%) | 10/10 (100%) | 8/9 (88.9%) | |||
| Infections and infestations | ||||||
| Gastroenteritis | 1/10 (10%) | 0/10 (0%) | 0/9 (0%) | |||
| Influenza | 1/10 (10%) | 0/10 (0%) | 0/9 (0%) | |||
| Nasopharyngitis | 1/10 (10%) | 0/10 (0%) | 0/9 (0%) | |||
| Urinary tract infection | 0/10 (0%) | 0/10 (0%) | 1/9 (11.1%) | |||
| Vulvovaginal mycotic infection | 0/10 (0%) | 1/10 (10%) | 0/9 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Wound | 0/10 (0%) | 1/10 (10%) | 0/9 (0%) | |||
| Investigations | ||||||
| Skin turgor decreased | 0/10 (0%) | 1/10 (10%) | 0/9 (0%) | |||
| Weight decreased | 0/10 (0%) | 0/10 (0%) | 1/9 (11.1%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 2/10 (20%) | 3/10 (30%) | 2/9 (22.2%) | |||
| Hypernatraemia | 0/10 (0%) | 1/10 (10%) | 1/9 (11.1%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 0/10 (0%) | 0/10 (0%) | 1/9 (11.1%) | |||
| Myalgia | 0/10 (0%) | 0/10 (0%) | 1/9 (11.1%) | |||
| Nervous system disorders | ||||||
| Dizziness | 1/10 (10%) | 2/10 (20%) | 1/9 (11.1%) | |||
| Dysgeusia | 0/10 (0%) | 0/10 (0%) | 1/9 (11.1%) | |||
| Headache | 2/10 (20%) | 2/10 (20%) | 2/9 (22.2%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 0/10 (0%) | 0/10 (0%) | 2/9 (22.2%) | |||
| Renal and urinary disorders | ||||||
| Dysuria | 0/10 (0%) | 0/10 (0%) | 1/9 (11.1%) | |||
| Nocturia | 8/10 (80%) | 6/10 (60%) | 6/9 (66.7%) | |||
| Polyuria | 9/10 (90%) | 9/10 (90%) | 7/9 (77.8%) | |||
| Renal pain | 3/10 (30%) | 0/10 (0%) | 1/9 (11.1%) | |||
| Reproductive system and breast disorders | ||||||
| Breast pain | 0/10 (0%) | 0/10 (0%) | 1/9 (11.1%) | |||
| Erectile dysfunction | 0/10 (0%) | 1/10 (10%) | 0/9 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 1/10 (10%) | 0/10 (0%) | 1/9 (11.1%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Dry skin | 0/10 (0%) | 1/10 (10%) | 0/9 (0%) | |||
| Pruritus | 1/10 (10%) | 0/10 (0%) | 0/9 (0%) | |||
| Skin irritation | 0/10 (0%) | 1/10 (10%) | 0/9 (0%) | |||
| Social circumstances | ||||||
| Family stress | 0/10 (0%) | 1/10 (10%) | 0/9 (0%) | |||
| Stress at work | 1/10 (10%) | 0/10 (0%) | 0/9 (0%) | |||
| Vascular disorders | ||||||
| Fushing | 1/10 (10%) | 0/10 (0%) | 1/9 (11.1%) | |||
| Hot flush | 1/10 (10%) | 0/10 (0%) | 0/9 (0%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Global Medical Affairs |
|---|---|
| Organization | Otsuka Pharmaceutical Development and Commercialization, Inc. |
| Phone | 800 562-3974 |
Responsible Party:
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01336972
Other Study ID Numbers:
- 156-09-284
- 2010-019025-33
First Posted:
Apr 18, 2011
Last Update Posted:
Mar 5, 2019
Last Verified:
Feb 1, 2019