Trial Outcomes & Findings for Dose-finding Study of New Tolvaptan Formulation in Subjects With ADPKD (NCT NCT01210560)
NCT ID: NCT01210560
Last Updated: 2018-06-14
Results Overview
Blood samples (6 mL) for determination of tolvaptan PK parameters were collected on Day 1 predose, and on Days 7, 14 and 21 at predose, and 1, 2, 4, 6, 8, 9, 10, 12, 16, and 24 hours postdose. If a sample was not drawn at the designated time, a window of ± 3 minutes for each blood draw was acceptable. Maximum and minimum plasma concentration of the drug was calculated.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
25 participants
Primary outcome timeframe
Day 7
Results posted on
2018-06-14
Participant Flow
Study was conducted at 6 centers in the United States. 25 participants were randomized (12+13) to Group 1 \& 2 with 5 \& 3 treatment sequences, respectively; received tolvaptan Modified-release \[MR\] capsules \& Immediate-release \[IR\] tablets in Group 1 \& MR in Group 2 over 3 therapy periods (each 7 days) in parallel-group, crossover design
Screening visit, baseline visit, 3 periods - each with 3 treatments in Group 1 \& 2 in one of the sequences DAE, DBE, DCE, EAD, EBD / ECD \& FGH, HFG / GHF (2 \& 4 participants per sequence) respectively; (MR: A\&F= 20mg, B\&G = 20+20mg, C\&H = 60mg, D = 120mg; IR: E = 90+30mg) and 7 Day follow-up. All doses were taken orally once/twice(B\&G) daily.
Participant milestones
| Measure |
Group 1: DAE
D = participants received MR tolvaptan 120 mg QD A = participants received MR tolvaptan 20 mg QD E = participants received IR tolvaptan 90 + 30 mg QD
|
Group 1: DBE
D = participants received MR tolvaptan 120 mg QD B = participants received MR tolvaptan 20 mg BID E = participants received IR tolvaptan 90 + 30 mg QD
|
Group 1: DCE
D = participants received MR tolvaptan 120 mg QD C = participants received MR tolvaptan 60 mg QD E = participants received IR tolvaptan 90 + 30 mg QD
|
Group 1: EAD
E = participants received IR tolvaptan 90 + 30 mg QD A = participants received MR tolvaptan 20 mg QD D = participants received MR tolvaptan 120 mg QD
|
Group 1: EBD
E = participants received IR tolvaptan 90 + 30 mg QD B = participants received MR tolvaptan 20 mg BID D = participants received MR tolvaptan 120 mg QD
|
Group 1: ECD
E = participants received IR tolvaptan 90 + 30 mg QD C = participants received MR tolvaptan 60 mg QD D = participants received MR tolvaptan 120 mg QD
|
Group 2: FGH
F = participants received MR tolvaptan 20 mg QD G = participants received MR tolvaptan 20 + 20 mg BID H = participants received MR tolvaptan 60 mg QD
|
Group 2: HFG
H = participants received MR tolvaptan 60 mg QD F = participants received MR tolvaptan 20 mg QD G = participants received MR tolvaptan 20 + 20 mg BID
|
Group 2: GHF
G = participants received MR tolvaptan 20 + 20 mg BID H = participants received MR tolvaptan 60 mg QD F = participants received MR tolvaptan 20 mg QD
|
|---|---|---|---|---|---|---|---|---|---|
|
Intervention 1 (7 Days)
STARTED
|
2
|
2
|
2
|
2
|
2
|
2
|
4
|
4
|
5
|
|
Intervention 1 (7 Days)
COMPLETED
|
2
|
2
|
2
|
2
|
2
|
2
|
4
|
4
|
5
|
|
Intervention 1 (7 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Intervention 2 (7 Days)
STARTED
|
2
|
2
|
2
|
2
|
2
|
2
|
4
|
4
|
5
|
|
Intervention 2 (7 Days)
COMPLETED
|
2
|
2
|
2
|
2
|
2
|
2
|
4
|
4
|
5
|
|
Intervention 2 (7 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Intervention 3 (7 Days)
STARTED
|
2
|
2
|
2
|
2
|
2
|
2
|
4
|
4
|
5
|
|
Intervention 3 (7 Days)
COMPLETED
|
2
|
2
|
2
|
2
|
2
|
2
|
4
|
4
|
5
|
|
Intervention 3 (7 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Dose-finding Study of New Tolvaptan Formulation in Subjects With ADPKD
Baseline characteristics by cohort
| Measure |
Group 1
n=12 Participants
Group 1 participants enrolled in a 3-period, randomized, crossover design to compare multiple doses of a 90+30 mg split-dose of the tolvaptan IR formulation, a 120 mg QD dose of the tolvaptan MR formulation, and, in an incomplete block randomization, multiple doses of either 20 mg QD, 60 mg QD, or 20 mg BID tolvaptan MR formulation. All dose regimens were administered for 7 days. Placebo doses were administered in order to mask formulation and dosing regimen.
|
Group 2
n=13 Participants
Group 2 participants enrolled in a 3-period, randomized, crossover design to compare multiple oral doses of the tolvaptan MR formulation administered for 7 days as 20 mg QD, 60 mg QD, and 20 mg BID. Placebo capsules were administered in order to mask dosing regimen.
|
Total
n=25 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
39.4 Years
STANDARD_DEVIATION 4.3 • n=5 Participants
|
36.8 Years
STANDARD_DEVIATION 9.0 • n=7 Participants
|
38.0 Years
STANDARD_DEVIATION 7.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 7Population: Participants having valid measurements (per clinical pharmacology) were included.
Blood samples (6 mL) for determination of tolvaptan PK parameters were collected on Day 1 predose, and on Days 7, 14 and 21 at predose, and 1, 2, 4, 6, 8, 9, 10, 12, 16, and 24 hours postdose. If a sample was not drawn at the designated time, a window of ± 3 minutes for each blood draw was acceptable. Maximum and minimum plasma concentration of the drug was calculated.
Outcome measures
| Measure |
MR 20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg QD.
|
MR 20+20 mg
n=16 Participants
Participants received MR tolvaptan 20 mg BID.
|
MR 60 mg
n=17 Participants
Participants received MR tolvaptan 60 mg QD.
|
MR 120 mg
n=12 Participants
Participants received MR tolvaptan 120 mg QD.
|
IR 90+30 mg
n=12 Participants
Participants received IR tolvaptan 90+30 mg QD.
|
|---|---|---|---|---|---|
|
Maximum (Peak) Plasma Concentration of the Drug [Cmax] and Minimum (Trough) Plasma Concentration of the Drug [Cmin] After Tolvaptan Treatment on Day 7.
Cmax
|
140 ng/mL
Standard Deviation 68.4
|
175 ng/mL
Standard Deviation 60.1
|
350 ng/mL
Standard Deviation 156
|
669 ng/mL
Standard Deviation 370
|
716 ng/mL
Standard Deviation 344
|
|
Maximum (Peak) Plasma Concentration of the Drug [Cmax] and Minimum (Trough) Plasma Concentration of the Drug [Cmin] After Tolvaptan Treatment on Day 7.
Cmin
|
14.7 ng/mL
Standard Deviation 9.95
|
50.8 ng/mL
Standard Deviation 24.0
|
51.1 ng/mL
Standard Deviation 32.3
|
139 ng/mL
Standard Deviation 75.5
|
57.5 ng/mL
Standard Deviation 41.8
|
PRIMARY outcome
Timeframe: Day 7Population: Participants having valid measurements (per clinical pharmacology) were included.
Blood samples (6 mL) for determination of tolvaptan PK parameters were collected on Day 1 predose, and on Days 7, 14 and 21 at predose, and 1, 2, 4, 6, 8, 9, 10, 12, 16, and 24 hours postdose. If a sample was not drawn at the designated time, a window of ± 3 minutes for each blood draw was acceptable. Time to maximum plasma concentration was calculated.
Outcome measures
| Measure |
MR 20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg QD.
|
MR 20+20 mg
n=16 Participants
Participants received MR tolvaptan 20 mg BID.
|
MR 60 mg
n=17 Participants
Participants received MR tolvaptan 60 mg QD.
|
MR 120 mg
n=12 Participants
Participants received MR tolvaptan 120 mg QD.
|
IR 90+30 mg
n=12 Participants
Participants received IR tolvaptan 90+30 mg QD.
|
|---|---|---|---|---|---|
|
Time to Maximum (Peak) Plasma Concentration (Tmax) After Tolvaptan Treatment on Day 7.
|
6.00 Hours
Interval 3.97 to 10.0
|
6.00 Hours
Interval 3.97 to 16.0
|
6.00 Hours
Interval 3.98 to 9.0
|
5.98 Hours
Interval 3.97 to 6.0
|
2.00 Hours
Interval 1.0 to 9.0
|
PRIMARY outcome
Timeframe: Day 7Population: Participants having valid measurements (per clinical pharmacology) were included.
Blood samples (6 mL) for determination of tolvaptan PK parameters were collected on Day 1 predose, and on Days 7, 14 and 21 at predose, and 1, 2, 4, 6, 8, 9, 10, 12, 16, and 24 hours postdose. If a sample was not drawn at the designated time, a window of ± 3 minutes for each blood draw was acceptable. Hence, both AUCT and AUC0-24h values were calculated.
Outcome measures
| Measure |
MR 20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg QD.
|
MR 20+20 mg
n=16 Participants
Participants received MR tolvaptan 20 mg BID.
|
MR 60 mg
n=17 Participants
Participants received MR tolvaptan 60 mg QD.
|
MR 120 mg
n=12 Participants
Participants received MR tolvaptan 120 mg QD.
|
IR 90+30 mg
n=12 Participants
Participants received IR tolvaptan 90+30 mg QD.
|
|---|---|---|---|---|---|
|
Area Under the Concentration-time Curve During the Dosing Interval at Steady State and Area Under the Concentration-time Curve From Time 0 to 24 Hours Postdose (AUCT & AUC0-24h) After Tolvaptan Treatment on Day 7.
|
1260 ng·h/mL
Standard Deviation 654
|
2310 ng·h/mL
Standard Deviation 704
|
3600 ng·h/mL
Standard Deviation 1670
|
7740 ng·h/mL
Standard Deviation 3650
|
6570 ng·h/mL
Standard Deviation 3230
|
SECONDARY outcome
Timeframe: 23.5 hours post-dosePopulation: All participants who had taken study drug and had measurements of the pharmacodynamic endpoint were included.
For determination of duration of urine osmolality \<300 mOsm/kg, the value was the end time of the last collection interval in which urine osmolality was \<300 mOsm/kg. Day 8 in the table below was defined as Day 8 of Period 1, Day 15 of Period 2, and Day 22 of period 3.
Outcome measures
| Measure |
MR 20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg QD.
|
MR 20+20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg BID.
|
MR 60 mg
n=17 Participants
Participants received MR tolvaptan 60 mg QD.
|
MR 120 mg
n=12 Participants
Participants received MR tolvaptan 120 mg QD.
|
IR 90+30 mg
n=12 Participants
Participants received IR tolvaptan 90+30 mg QD.
|
|---|---|---|---|---|---|
|
Number of Participants With Urine Osmolality < 300 mOsm/kg at 23.5 Hours Postdose.
Baseline
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Urine Osmolality < 300 mOsm/kg at 23.5 Hours Postdose.
Day 8
|
5 Participants
|
11 Participants
|
9 Participants
|
11 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Day 7Population: All participants who had taken study drug and had measurements of the pharmacodynamic endpoint were included.
The AUC0-24h for urine osmolality was determined by multiplying the concentration by the collection interval duration for each collection interval and summing all the intervals in the 24-hour period. If the urine volume for an interval is zero, the duration of that interval will be added to the next collection interval. Day 7 was defined as Day 7 of Period 1, Day 14 of Period 2 and Day 21 of Period 3.
Outcome measures
| Measure |
MR 20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg QD.
|
MR 20+20 mg
n=16 Participants
Participants received MR tolvaptan 20 mg BID.
|
MR 60 mg
n=17 Participants
Participants received MR tolvaptan 60 mg QD.
|
MR 120 mg
n=12 Participants
Participants received MR tolvaptan 120 mg QD.
|
IR 90+30 mg
n=11 Participants
Participants received IR tolvaptan 90+30 mg QD.
|
|---|---|---|---|---|---|
|
Change From Baseline in Urine Osmolality Area Under the Concentration-time Curve From Time 0 to 24 Hours Postdose (AUC0-24h) at Day 7.
|
-2546 mOsm/kg*Hour
Standard Deviation 1743
|
-3438 mOsm/kg*Hour
Standard Deviation 2277
|
-4209 mOsm/kg*Hour
Standard Deviation 2569
|
-4325 mOsm/kg*Hour
Standard Deviation 2237
|
-4620 mOsm/kg*Hour
Standard Deviation 2419
|
SECONDARY outcome
Timeframe: 0-4, 4-8, 8-12, 12-16, 16-24 Hours at Day 7Population: All participants who had taken study drug and have measurements of the pharmacodynamic endpoint were included.
To determine the tolerability and nighttime urinary suppression of osmolality. The urine osmolality was summarized by collection interval (0 to 4, 4 to 8, 8 to 12, 12 to 16, and 16 to 24 hours)
Outcome measures
| Measure |
MR 20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg QD.
|
MR 20+20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg BID.
|
MR 60 mg
n=17 Participants
Participants received MR tolvaptan 60 mg QD.
|
MR 120 mg
n=12 Participants
Participants received MR tolvaptan 120 mg QD.
|
IR 90+30 mg
n=12 Participants
Participants received IR tolvaptan 90+30 mg QD.
|
|---|---|---|---|---|---|
|
Change From Baseline in Urine Osmolality at Day 7.
0-4 Hour
|
2.6 mOsm/kg
Standard Deviation 132.1
|
-0.7 mOsm/kg
Standard Deviation 111.9
|
-88.9 mOsm/kg
Standard Deviation 130.9
|
-59.5 mOsm/kg
Standard Deviation 169.2
|
-123.3 mOsm/kg
Standard Deviation 139.5
|
|
Change From Baseline in Urine Osmolality at Day 7.
4-8 Hour
|
-140.9 mOsm/kg
Standard Deviation 127.1
|
-128.3 mOsm/kg
Standard Deviation 127.2
|
-188.2 mOsm/kg
Standard Deviation 140.5
|
-186.1 mOsm/kg
Standard Deviation 161.1
|
-191.8 mOsm/kg
Standard Deviation 155.1
|
|
Change From Baseline in Urine Osmolality at Day 7.
8-12 Hour
|
-123.1 mOsm/kg
Standard Deviation 115.9
|
-172.1 mOsm/kg
Standard Deviation 129.8
|
-201.8 mOsm/kg
Standard Deviation 158.8
|
-167.1 mOsm/kg
Standard Deviation 148.7
|
-166.9 mOsm/kg
Standard Deviation 131.7
|
|
Change From Baseline in Urine Osmolality at Day 7.
12-16 Hour
|
-128.3 mOsm/kg
Standard Deviation 142.9
|
-193.6 mOsm/kg
Standard Deviation 152.5
|
-195.8 mOsm/kg
Standard Deviation 151.6
|
-176.3 mOsm/kg
Standard Deviation 121.8
|
-178.3 mOsm/kg
Standard Deviation 128.9
|
|
Change From Baseline in Urine Osmolality at Day 7.
16-24 Hour
|
-123.4 mOsm/kg
Standard Deviation 102.6
|
-182.4 mOsm/kg
Standard Deviation 145.6
|
-188.8 mOsm/kg
Standard Deviation 160.0
|
-246.1 mOsm/kg
Standard Deviation 108.9
|
-239.8 mOsm/kg
Standard Deviation 117.8
|
SECONDARY outcome
Timeframe: Day 7Population: All participants who had taken study drug and have measurements of the pharmacodynamic endpoint were included.
Urine volume was collected by 0 to 24-hour interval at Day 7. Day 7 was defined as Day 7 of Period 1, Day 14 of Period 2 and Day 21 of Period 3.
Outcome measures
| Measure |
MR 20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg QD.
|
MR 20+20 mg
n=16 Participants
Participants received MR tolvaptan 20 mg BID.
|
MR 60 mg
n=16 Participants
Participants received MR tolvaptan 60 mg QD.
|
MR 120 mg
n=12 Participants
Participants received MR tolvaptan 120 mg QD.
|
IR 90+30 mg
n=12 Participants
Participants received IR tolvaptan 90+30 mg QD.
|
|---|---|---|---|---|---|
|
Change From Baseline in Urine Volume at 24 Hours at Day 7.
|
1111 mL
Standard Deviation 919
|
2066 mL
Standard Deviation 1237
|
2396 mL
Standard Deviation 1022
|
3722 mL
Standard Deviation 1776
|
3820 mL
Standard Deviation 1759
|
SECONDARY outcome
Timeframe: 0-4, 4-8, 8-12, 12-16, 16-24 Hours at Day 7Population: All participants who had taken study drug and have measurements of the pharmacodynamic endpoint were included.
Urine volume collected was by interval (0-4, 4-8, 8-12, 12-16, 16-24 hours). Day 7 was defined as Day 7 of Period 1, Day 14 of Period 2 and Day 21 of Period 3.
Outcome measures
| Measure |
MR 20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg QD.
|
MR 20+20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg BID.
|
MR 60 mg
n=17 Participants
Participants received MR tolvaptan 60 mg QD.
|
MR 120 mg
n=12 Participants
Participants received MR tolvaptan 120 mg QD.
|
IR 90+30 mg
n=12 Participants
Participants received IR tolvaptan 90+30 mg QD.
|
|---|---|---|---|---|---|
|
Change From Baseline in Urine Volume by Interval at Day 7.
0-4 Hour
|
-87 mL
Standard Deviation 348
|
-118 mL
Standard Deviation 391
|
56 mL
Standard Deviation 345
|
87 mL
Standard Deviation 449
|
241 mL
Standard Deviation 412
|
|
Change From Baseline in Urine Volume by Interval at Day 7.
4-8 Hour
|
326 mL
Standard Deviation 531
|
423 mL
Standard Deviation 439
|
636 mL
Standard Deviation 382
|
785 mL
Standard Deviation 605
|
825 mL
Standard Deviation 472
|
|
Change From Baseline in Urine Volume by Interval at Day 7.
8-12 Hour
|
301 mL
Standard Deviation 317
|
529 mL
Standard Deviation 349
|
689 mL
Standard Deviation 603
|
887 mL
Standard Deviation 558
|
801 mL
Standard Deviation 494
|
|
Change From Baseline in Urine Volume by Interval at Day 7.
12-16 Hour
|
314 mL
Standard Deviation 328
|
635 mL
Standard Deviation 473
|
667 mL
Standard Deviation 337
|
926 mL
Standard Deviation 459
|
910 mL
Standard Deviation 738
|
|
Change From Baseline in Urine Volume by Interval at Day 7.
16-24 Hour
|
257 mL
Standard Deviation 407
|
598 mL
Standard Deviation 482
|
286 mL
Standard Deviation 421
|
1038 mL
Standard Deviation 642
|
1044 mL
Standard Deviation 421
|
SECONDARY outcome
Timeframe: Baseline and Day 7Population: The duration that urine osmolality remained \< 300 mOsm/kg was not calculated. Instead was calculated as the sum where urine osmolality was \< 300 mOsm/kg in the 24-hour postdose period. The change was made because low doses of the MR formulation frequently do not produce suppression of urine osmolality in the 0- to 4-hour period.
Duration of urine osmolality remains below 300 mOsm/kg was the sum of the durations (nominal times) of all intervals where the urine concentration was \< 300 mOsm/kg. Day 7 was defined as Day 7 of Period 1, Day 14 of Period 2, and Day 21 of Period 3.
Outcome measures
| Measure |
MR 20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg QD.
|
MR 20+20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg BID.
|
MR 60 mg
n=17 Participants
Participants received MR tolvaptan 60 mg QD.
|
MR 120 mg
n=12 Participants
Participants received MR tolvaptan 120 mg QD.
|
IR 90+30 mg
n=12 Participants
Participants received IR tolvaptan 90+30 mg QD.
|
|---|---|---|---|---|---|
|
Duration of Urine Osmolality Less Than 300 mOsm/kg at Baseline and Day 7.
Day 7
|
16.0 Hours
Interval 4.0 to 24.0
|
24.0 Hours
Interval 4.0 to 24.0
|
24.0 Hours
Interval 8.0 to 24.0
|
24.0 Hours
Interval 20.0 to 24.0
|
24.0 Hours
Interval 24.0 to 24.0
|
|
Duration of Urine Osmolality Less Than 300 mOsm/kg at Baseline and Day 7.
Baseline
|
8.0 Hours
Interval 0.0 to 24.0
|
8.0 Hours
Interval 0.0 to 24.0
|
8.0 Hours
Interval 0.0 to 24.0
|
14.0 Hours
Interval 0.0 to 24.0
|
14.0 Hours
Interval 0.0 to 24.0
|
SECONDARY outcome
Timeframe: Days 1, 2, 3, 4, 5, 6 and 7Population: All participants who had taken study drug and had measurements of the pharmacodynamic endpoint were included.
Average number of daily urine voids during awake periods for each dose group. Day 1 was defined as Day1 of Period 1, Day 8 of Period 2 adn Day 15 of Period 3; Day 7 was defined as Day 7 of Period 1, Day 14 of Period 2 and Day 21 of Period 3; Same rule applied to Day 2 and Day 6.
Outcome measures
| Measure |
MR 20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg QD.
|
MR 20+20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg BID.
|
MR 60 mg
n=17 Participants
Participants received MR tolvaptan 60 mg QD.
|
MR 120 mg
n=12 Participants
Participants received MR tolvaptan 120 mg QD.
|
IR 90+30 mg
n=12 Participants
Participants received IR tolvaptan 90+30 mg QD.
|
|---|---|---|---|---|---|
|
Change From Baseline in Number of Urine Voids During Awake Periods.
Day 1
|
1.7 Number of urine voids
Standard Deviation 4.1
|
1.5 Number of urine voids
Standard Deviation 3.1
|
3.5 Number of urine voids
Standard Deviation 4.3
|
5.6 Number of urine voids
Standard Deviation 5.6
|
4.8 Number of urine voids
Standard Deviation 4.1
|
|
Change From Baseline in Number of Urine Voids During Awake Periods.
Day 2
|
-0.4 Number of urine voids
Standard Deviation 2.9
|
1.2 Number of urine voids
Standard Deviation 4.0
|
1.8 Number of urine voids
Standard Deviation 4.1
|
4.8 Number of urine voids
Standard Deviation 7.8
|
3.8 Number of urine voids
Standard Deviation 4.2
|
|
Change From Baseline in Number of Urine Voids During Awake Periods.
Day 3
|
-0.8 Number of urine voids
Standard Deviation 2.4
|
0.9 Number of urine voids
Standard Deviation 2.4
|
2.4 Number of urine voids
Standard Deviation 3.9
|
3.1 Number of urine voids
Standard Deviation 4.6
|
3.3 Number of urine voids
Standard Deviation 5.2
|
|
Change From Baseline in Number of Urine Voids During Awake Periods.
Day 4
|
-1.4 Number of urine voids
Standard Deviation 2.3
|
1.5 Number of urine voids
Standard Deviation 3.8
|
0.4 Number of urine voids
Standard Deviation 5.0
|
2.8 Number of urine voids
Standard Deviation 5.0
|
3.7 Number of urine voids
Standard Deviation 5.9
|
|
Change From Baseline in Number of Urine Voids During Awake Periods.
Day 5
|
-0.5 Number of urine voids
Standard Deviation 2.9
|
0.6 Number of urine voids
Standard Deviation 3.5
|
-0.4 Number of urine voids
Standard Deviation 4.2
|
3.3 Number of urine voids
Standard Deviation 5.6
|
4.0 Number of urine voids
Standard Deviation 4.9
|
|
Change From Baseline in Number of Urine Voids During Awake Periods.
Day 6
|
0.0 Number of urine voids
Standard Deviation 3.3
|
2.9 Number of urine voids
Standard Deviation 4.1
|
5.8 Number of urine voids
Standard Deviation 10.6
|
2.3 Number of urine voids
Standard Deviation 6.8
|
4.8 Number of urine voids
Standard Deviation 5.2
|
|
Change From Baseline in Number of Urine Voids During Awake Periods.
Day 7
|
2.0 Number of urine voids
Standard Deviation 3.0
|
3.5 Number of urine voids
Standard Deviation 2.4
|
3.5 Number of urine voids
Standard Deviation 3.8
|
2.8 Number of urine voids
Standard Deviation 6.4
|
4.3 Number of urine voids
Standard Deviation 4.5
|
SECONDARY outcome
Timeframe: Days 1, 2, 3, 4, 5, 6 and 7Population: All participants who had taken study drug and have measurements of the pharmacodynamic endpoint were included.
Average number of daily urine voids during sleep periods for each dose group. Day 1 was defined as Day 1 of Period 1, Day 8 of Period 2, Day 15 of Period 3; Day 7 was defined as Day 7 of Period 1, Day 14 of Period 2 and Day 21 of Period 3; Same rule applied to Day 2 to 6.
Outcome measures
| Measure |
MR 20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg QD.
|
MR 20+20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg BID.
|
MR 60 mg
n=17 Participants
Participants received MR tolvaptan 60 mg QD.
|
MR 120 mg
n=12 Participants
Participants received MR tolvaptan 120 mg QD.
|
IR 90+30 mg
n=12 Participants
Participants received IR tolvaptan 90+30 mg QD.
|
|---|---|---|---|---|---|
|
Change From Baseline in Number of Urine Voids During Sleep Periods.
Day 1
|
0.6 Number of urine voids
Standard Deviation 1.6
|
1.1 Number of urine voids
Standard Deviation 2.0
|
0.4 Number of urine voids
Standard Deviation 2.2
|
2.5 Number of urine voids
Standard Deviation 1.7
|
1.5 Number of urine voids
Standard Deviation 1.6
|
|
Change From Baseline in Number of Urine Voids During Sleep Periods.
Day 2
|
-0.2 Number of urine voids
Standard Deviation 1.7
|
0.8 Number of urine voids
Standard Deviation 1.6
|
0.8 Number of urine voids
Standard Deviation 1.9
|
1.8 Number of urine voids
Standard Deviation 1.4
|
1.7 Number of urine voids
Standard Deviation 1.2
|
|
Change From Baseline in Number of Urine Voids During Sleep Periods.
Day 3
|
0.1 Number of urine voids
Standard Deviation 1.0
|
1.4 Number of urine voids
Standard Deviation 2.4
|
0.8 Number of urine voids
Standard Deviation 1.7
|
1.9 Number of urine voids
Standard Deviation 1.5
|
1.9 Number of urine voids
Standard Deviation 1.7
|
|
Change From Baseline in Number of Urine Voids During Sleep Periods.
Day 4
|
0.6 Number of urine voids
Standard Deviation 2.3
|
0.7 Number of urine voids
Standard Deviation 1.6
|
0.5 Number of urine voids
Standard Deviation 1.7
|
1.7 Number of urine voids
Standard Deviation 1.3
|
1.8 Number of urine voids
Standard Deviation 1.9
|
|
Change From Baseline in Number of Urine Voids During Sleep Periods.
Day 5
|
0.3 Number of urine voids
Standard Deviation 1.3
|
0.9 Number of urine voids
Standard Deviation 2.0
|
0.2 Number of urine voids
Standard Deviation 1.4
|
1.0 Number of urine voids
Standard Deviation 2.0
|
0.9 Number of urine voids
Standard Deviation 1.7
|
|
Change From Baseline in Number of Urine Voids During Sleep Periods.
Day 6
|
1.2 Number of urine voids
Standard Deviation 3.3
|
1.3 Number of urine voids
Standard Deviation 2.0
|
0.4 Number of urine voids
Standard Deviation 1.6
|
1.1 Number of urine voids
Standard Deviation 2.1
|
1.7 Number of urine voids
Standard Deviation 1.7
|
|
Change From Baseline in Number of Urine Voids During Sleep Periods.
Day 7
|
0.1 Number of urine voids
Standard Deviation 1.3
|
1.0 Number of urine voids
Standard Deviation 1.7
|
0.9 Number of urine voids
Standard Deviation 1.8
|
1.8 Number of urine voids
Standard Deviation 2.4
|
2.1 Number of urine voids
Standard Deviation 1.9
|
SECONDARY outcome
Timeframe: Day 6Population: All participants who had taken study drug and have measurements of the pharmacodynamic endpoint were included.
In ADPKD Nocturia Quality of Life Questionnaire, questions 1 to 11 (with possible scores ranging from 0 to 4 and higher scores indicating better quality of life) were pooled to provide a total score (maximum of 44 points). Response scores of Question 12 (with possible scores ranging from 1 to 10, with higher scores indicating more interference (worse quality of life) with everyday life due to urination at night) were pooled separately. Day 6 was defined as Day 6 of Period 1, Day 13 of Period 2 and Day 20 of Period 3.
Outcome measures
| Measure |
MR 20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg QD.
|
MR 20+20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg BID.
|
MR 60 mg
n=17 Participants
Participants received MR tolvaptan 60 mg QD.
|
MR 120 mg
n=12 Participants
Participants received MR tolvaptan 120 mg QD.
|
IR 90+30 mg
n=12 Participants
Participants received IR tolvaptan 90+30 mg QD.
|
|---|---|---|---|---|---|
|
Change From Baseline in Symptom Burden by Autosomal Dominant Polycystic Kidney Disease (ADPKD) Nocturia Quality of Life Questionnaire at Day 6.
Nocturia Quality of life Question (Q) 1 To Q 11
|
-1.5 Units on a scale
Standard Deviation 4.3
|
-6.9 Units on a scale
Standard Deviation 9.9
|
-5.1 Units on a scale
Standard Deviation 7.6
|
-15.0 Units on a scale
Standard Deviation 13.3
|
-13.1 Units on a scale
Standard Deviation 12.3
|
|
Change From Baseline in Symptom Burden by Autosomal Dominant Polycystic Kidney Disease (ADPKD) Nocturia Quality of Life Questionnaire at Day 6.
Nocturia Quality of life Q 12
|
0.6 Units on a scale
Standard Deviation 1.3
|
1.9 Units on a scale
Standard Deviation 2.7
|
1.4 Units on a scale
Standard Deviation 2.5
|
4.2 Units on a scale
Standard Deviation 3.6
|
3.7 Units on a scale
Standard Deviation 3.5
|
SECONDARY outcome
Timeframe: Baseline and Day 6Population: All participants who had taken study drug and have measurements of the pharmacodynamic endpoint were included.
For the ADPKD Urinary Urgency Questionnaire, Question 1 (currently experiencing urgency?) was assigned 'Yes' or 'No' to measure current urine urgency status. Baseline was defined as last pre-dose evaluation; Day 6 was defined as Day 6 of Period 1, Day 13 of Period 2 and Day 20 of Period 3.
Outcome measures
| Measure |
MR 20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg QD.
|
MR 20+20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg BID.
|
MR 60 mg
n=17 Participants
Participants received MR tolvaptan 60 mg QD.
|
MR 120 mg
n=12 Participants
Participants received MR tolvaptan 120 mg QD.
|
IR 90+30 mg
n=12 Participants
Participants received IR tolvaptan 90+30 mg QD.
|
|---|---|---|---|---|---|
|
Number of Participants Experiencing Urinary Urgency Based on Urinary Urgency Questionnaire (Question 1) at Baseline and Day 6.
Baseline
|
5 Participants
|
3 Participants
|
3 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants Experiencing Urinary Urgency Based on Urinary Urgency Questionnaire (Question 1) at Baseline and Day 6.
Day 6
|
8 Participants
|
13 Participants
|
12 Participants
|
10 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Day 6Population: All participants who had taken study drug and have measurements of the pharmacodynamic endpoint were included.
Question 2 to Question 6 were assigned scores of 0 to 4 with higher scores indicating worse cases in experience of urinary urgency. Scores for Question 2 to Question 5 were pooled, with a maximum possible score of 16. Question 6 was excluded from the analysis since it was only asked at screening. Question 7 to Question 14 were also assigned scores of 0 to 4 with higher scores indicating worse cases in impact of urinary urgency on life; scores for these questions were pooled, with a maximum possible score of 32. Baseline was defined as last pre-dose evaluation; Day 6 was defined as Day 6 of Period 1, Day 13 of Period 2 and Day 20 of Period 3.
Outcome measures
| Measure |
MR 20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg QD.
|
MR 20+20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg BID.
|
MR 60 mg
n=17 Participants
Participants received MR tolvaptan 60 mg QD.
|
MR 120 mg
n=12 Participants
Participants received MR tolvaptan 120 mg QD.
|
IR 90+30 mg
n=12 Participants
Participants received IR tolvaptan 90+30 mg QD.
|
|---|---|---|---|---|---|
|
Change From Baseline in Urinary Urgency Questionnaire (Questions 2 to 5 and Questions 7 to 14) at Day 6.
Urinary urgency questionnaire-Question (Q) 2 to Q5
|
1.4 Units on a scale
Standard Deviation 2.1
|
3.2 Units on a scale
Standard Deviation 2.4
|
3.2 Units on a scale
Standard Deviation 3.1
|
4.6 Units on a scale
Standard Deviation 3.9
|
4.7 Units on a scale
Standard Deviation 3.0
|
|
Change From Baseline in Urinary Urgency Questionnaire (Questions 2 to 5 and Questions 7 to 14) at Day 6.
Urinary urgency questionnaire-Q 7 to Q 14
|
0.9 Units on a scale
Standard Deviation 1.2
|
4.2 Units on a scale
Standard Deviation 5.5
|
3.5 Units on a scale
Standard Deviation 5.0
|
10.9 Units on a scale
Standard Deviation 10.9
|
8.8 Units on a scale
Standard Deviation 9.8
|
SECONDARY outcome
Timeframe: Baseline and Day 6Population: All participants who had taken study drug and have measurements of the pharmacodynamic endpoint were included.
The ADPKD Urinary Frequency Questionnaire: Question 1 (currently experiencing frequency) was assigned 'Yes' or 'No' to measure current urine frequency status. Baseline was defined as last pre-dose evaluation; Day 6 was defined as Day 6 of Period 1, Day 13 of Period 2 and Day 20 of Period 3.
Outcome measures
| Measure |
MR 20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg QD.
|
MR 20+20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg BID.
|
MR 60 mg
n=17 Participants
Participants received MR tolvaptan 60 mg QD.
|
MR 120 mg
n=12 Participants
Participants received MR tolvaptan 120 mg QD.
|
IR 90+30 mg
n=12 Participants
Participants received IR tolvaptan 90+30 mg QD.
|
|---|---|---|---|---|---|
|
Number of Participants Experiencing Urinary Frequency Based on Urinary Frequency Questionnaire (Question 1) at Baseline and Day 6.
Baseline
|
5 Participants
|
4 Participants
|
4 Participants
|
4 Participants
|
4 Participants
|
|
Number of Participants Experiencing Urinary Frequency Based on Urinary Frequency Questionnaire (Question 1) at Baseline and Day 6.
Day 6
|
10 Participants
|
15 Participants
|
16 Participants
|
12 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: Day 6Population: All participants who had taken study drug and have measurements of the pharmacodynamic endpoint were included.
Question 2 asked, "During the last 5 days, how much has urinary frequency bothered you?" In order to score the response, the written answers were assigned values from 0 to 4 as follows: 0) Not at all, 1) Somewhat, 2) Moderately, 3) Quite a bit, and 4) Constantly. Question 3 to Question 10 were assigned scores of 0 to 4 with higher scores indicating worse cases in impact of urinary frequency on life; scores for these questions were pooled, with a maximum possible score of 32. Baseline was defined as last pre-dose evaluation; Day 6 was defined as Day 6 of Period 1, Day 13 of Period 2 and Day 20 of Period 3.
Outcome measures
| Measure |
MR 20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg QD.
|
MR 20+20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg BID.
|
MR 60 mg
n=17 Participants
Participants received MR tolvaptan 60 mg QD.
|
MR 120 mg
n=12 Participants
Participants received MR tolvaptan 120 mg QD.
|
IR 90+30 mg
n=12 Participants
Participants received IR tolvaptan 90+30 mg QD.
|
|---|---|---|---|---|---|
|
Change From Baseline in Urinary Frequency Questionnaire (Question 2 and Questions 3 to 10) at Day 6.
Urinary frequency questionnaire-Question (Q) 2
|
0.4 Units on a scale
Standard Deviation 0.6
|
1.1 Units on a scale
Standard Deviation 1.1
|
0.9 Units on a scale
Standard Deviation 0.9
|
1.7 Units on a scale
Standard Deviation 1.4
|
1.5 Units on a scale
Standard Deviation 1.1
|
|
Change From Baseline in Urinary Frequency Questionnaire (Question 2 and Questions 3 to 10) at Day 6.
Urinary frequency questionnaire-Q 3 to Q 10
|
1.4 Units on a scale
Standard Deviation 2.1
|
4.6 Units on a scale
Standard Deviation 6.9
|
4.1 Units on a scale
Standard Deviation 5.7
|
12.2 Units on a scale
Standard Deviation 11.0
|
9.1 Units on a scale
Standard Deviation 10.5
|
SECONDARY outcome
Timeframe: Day 22/Early TerminationPopulation: All participants who had taken study drug and have measurements of the pharmacodynamic endpoint were included.
Ranking of treatment tolerability was evaluated based on a questionnaire. At Day 22, participants were asked the following questions and their responses recorded on the eCRF: "Which treatment period did you find most tolerable?" and "Which treatment period did you find the least tolerable?".
Outcome measures
| Measure |
MR 20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg QD.
|
MR 20+20 mg
n=17 Participants
Participants received MR tolvaptan 20 mg BID.
|
MR 60 mg
n=17 Participants
Participants received MR tolvaptan 60 mg QD.
|
MR 120 mg
n=12 Participants
Participants received MR tolvaptan 120 mg QD.
|
IR 90+30 mg
n=12 Participants
Participants received IR tolvaptan 90+30 mg QD.
|
|---|---|---|---|---|---|
|
Ranking of Treatment Tolerability.
Most tolerable Group 1
|
3 Participants
|
2 Participants
|
3 Participants
|
1 Participants
|
1 Participants
|
|
Ranking of Treatment Tolerability.
Most tolerable Group 2
|
10 Participants
|
—
|
3 Participants
|
—
|
—
|
|
Ranking of Treatment Tolerability.
Least tolerable Group 1
|
0 Participants
|
—
|
—
|
4 Participants
|
6 Participants
|
|
Ranking of Treatment Tolerability.
Least tolerable Group 2
|
0 Participants
|
7 Participants
|
6 Participants
|
—
|
—
|
Adverse Events
MR 20 mg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
MR 20+20 mg
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
MR 60 mg
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
MR 120 mg
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
IR 90+30 mg
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
MR 20 mg
n=17 participants at risk
Participants received MR tolvaptan 20 mg QD.
|
MR 20+20 mg
n=17 participants at risk
Participants received MR tolvaptan 20 mg BID.
|
MR 60 mg
n=17 participants at risk
Participants received MR tolvaptan 60 mg QD.
|
MR 120 mg
n=12 participants at risk
Participants received MR tolvaptan 120 mg QD.
|
IR 90+30 mg
n=12 participants at risk
Participants received IR tolvaptan 90+30 mg QD.
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
8.3%
1/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Gastrointestinal disorders
Abdominal pain lower
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
8.3%
1/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Gastrointestinal disorders
Dry mouth
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Gastrointestinal disorders
Lip dry
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
16.7%
2/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
8.3%
1/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
8.3%
1/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
General disorders
Chest discomfort
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
General disorders
Feeling cold
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
8.3%
1/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
General disorders
Feeling hot
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
General disorders
Mucosal dryness
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
8.3%
1/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
General disorders
Thirst
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
17.6%
3/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
11.8%
2/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
16.7%
2/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
8.3%
1/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
8.3%
1/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Investigations
Blood creatinine increased
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
8.3%
1/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
8.3%
1/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Metabolism and nutrition disorders
Polydipsia
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
11.8%
2/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
16.7%
2/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
25.0%
3/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
8.3%
1/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Nervous system disorders
Headache
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
11.8%
2/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
8.3%
1/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Nervous system disorders
Somnolence
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Psychiatric disorders
Nervousness
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
8.3%
1/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
8.3%
1/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Renal and urinary disorders
Micturition urgency
|
11.8%
2/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
11.8%
2/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
8.3%
1/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Renal and urinary disorders
Nocturia
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
11.8%
2/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
8.3%
1/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
25.0%
3/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Renal and urinary disorders
Pollakiuria
|
11.8%
2/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
11.8%
2/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
16.7%
2/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Renal and urinary disorders
Polyuria
|
11.8%
2/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
29.4%
5/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
33.3%
4/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
41.7%
5/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Renal and urinary disorders
Renal pain
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
8.3%
1/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Skin and subcutaneous tissue disorders
Acne
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
8.3%
1/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
|
Vascular disorders
Hypertension
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
5.9%
1/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/17 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
0.00%
0/12 • Screening to seven days (+ 1 day) after the last dose of study medication.
In safety analysis, all participants who had taken at least one dose of study medication were included.
|
Additional Information
Global Medical Affairs
Otsuka Pharmaceutical Development & Commercialization, Inc
Phone: 800 562-3974
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place