Trial Outcomes & Findings for The ELiSA Study - Evaluation of Lixivaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease (NCT NCT03487913)
NCT ID: NCT03487913
Last Updated: 2022-12-05
Results Overview
The pharmacokinetic parameter Cmax, the highest concentration of lixivaptan measured in plasma after multiple doses of drug, will be calculated from the observed concentration of lixivaptan and summarized by cohort.
COMPLETED
PHASE2
31 participants
Day 1 (am and pm) and Day 7 (am and pm)
2022-12-05
Participant Flow
Participant milestones
| Measure |
High Dose Lixivaptan / CKD1 or CKD2
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD3
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
9
|
7
|
8
|
7
|
|
Overall Study
COMPLETED
|
9
|
7
|
8
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The ELiSA Study - Evaluation of Lixivaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease
Baseline characteristics by cohort
| Measure |
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Total
n=31 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
31 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Continuous
|
40.1 years
STANDARD_DEVIATION 16.99 • n=5 Participants
|
34.9 years
STANDARD_DEVIATION 10.85 • n=7 Participants
|
54.0 years
STANDARD_DEVIATION 9.07 • n=5 Participants
|
51.6 years
STANDARD_DEVIATION 10.54 • n=4 Participants
|
45.1 years
STANDARD_DEVIATION 14.31 • n=21 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
18 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
23 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
31 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Day 1 (am and pm) and Day 7 (am and pm)Population: The PKAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan, underwent plasma PK sampling, and were evaluable for this PK outcome. Of these, all 31 subjects contributed to the PK data on Day 1 (am); 30 contributed data to Day 1 (pm); and 29 contributed data to Day 7 (am) and (pm).
The pharmacokinetic parameter Cmax, the highest concentration of lixivaptan measured in plasma after multiple doses of drug, will be calculated from the observed concentration of lixivaptan and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Lixivaptan in ADPKD Patients
Day 1 (am)
|
156.9 ng/mL
Geometric Coefficient of Variation 66.9
|
656.8 ng/mL
Geometric Coefficient of Variation 28.1
|
190.9 ng/mL
Geometric Coefficient of Variation 52.0
|
681.3 ng/mL
Geometric Coefficient of Variation 45.9
|
|
Maximum Observed Plasma Concentration (Cmax) of Lixivaptan in ADPKD Patients
Day 1 (pm)
|
159.5 ng/mL
Geometric Coefficient of Variation 51.9
|
1007 ng/mL
Geometric Coefficient of Variation 36.6
|
211.5 ng/mL
Geometric Coefficient of Variation 33.5
|
930.2 ng/mL
Geometric Coefficient of Variation 44.5
|
|
Maximum Observed Plasma Concentration (Cmax) of Lixivaptan in ADPKD Patients
Day 7 (am)
|
276.9 ng/mL
Geometric Coefficient of Variation 33.7
|
1442 ng/mL
Geometric Coefficient of Variation 34.3
|
339.5 ng/mL
Geometric Coefficient of Variation 19.5
|
1422 ng/mL
Geometric Coefficient of Variation 48.3
|
|
Maximum Observed Plasma Concentration (Cmax) of Lixivaptan in ADPKD Patients
Day 7 (pm)
|
258.8 ng/mL
Geometric Coefficient of Variation 38.4
|
1582 ng/mL
Geometric Coefficient of Variation 45.8
|
301.0 ng/mL
Geometric Coefficient of Variation 13.7
|
1211 ng/mL
Geometric Coefficient of Variation 90.5
|
PRIMARY outcome
Timeframe: Day 1 (am and pm) and Day 7 (am and pm)Population: The PKAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan, underwent plasma PK sampling, and were evaluable for this PK outcome. Missing values and substantial deviations from planned dosing interval durations meant results were excluded from subjects at various time points.
The pharmacokinetic parameter Cmax, the highest concentration of WAY-141624 measured in plasma after multiple doses of drug, will be calculated from the observed concentration of WAY-141624 and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of WAY-141624 in ADPKD Patients
Day 1 (am)
|
135.3 ng/mL
Geometric Coefficient of Variation 55.5
|
455.3 ng/mL
Geometric Coefficient of Variation 33.3
|
123.7 ng/mL
Geometric Coefficient of Variation 69.7
|
381.7 ng/mL
Geometric Coefficient of Variation 46.6
|
|
Maximum Observed Plasma Concentration (Cmax) of WAY-141624 in ADPKD Patients
Day 1 (pm)
|
142.3 ng/mL
Geometric Coefficient of Variation 28.7
|
561.7 ng/mL
Geometric Coefficient of Variation 35.4
|
160.8 ng/mL
Geometric Coefficient of Variation 56.0
|
417.8 ng/mL
Geometric Coefficient of Variation 41.4
|
|
Maximum Observed Plasma Concentration (Cmax) of WAY-141624 in ADPKD Patients
Day 7 (am)
|
233.7 ng/mL
Geometric Coefficient of Variation 50.8
|
535.8 ng/mL
Geometric Coefficient of Variation 34.4
|
213.8 ng/mL
Geometric Coefficient of Variation 75.4
|
652.1 ng/mL
Geometric Coefficient of Variation 49.0
|
|
Maximum Observed Plasma Concentration (Cmax) of WAY-141624 in ADPKD Patients
Day 7 (pm)
|
224.8 ng/mL
Geometric Coefficient of Variation 44.7
|
612.6 ng/mL
Geometric Coefficient of Variation 42.3
|
200.1 ng/mL
Geometric Coefficient of Variation 63.0
|
588.5 ng/mL
Geometric Coefficient of Variation 69.2
|
PRIMARY outcome
Timeframe: Day 1 (am and pm) and Day 7 (am and pm)Population: The PKAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan, underwent plasma PK sampling, and were evaluable for this PK outcome. Missing values, substantial deviations, and \<3 quantifiable postdose WAY-138451 concentrations meant results were excluded from subjects at various time points.
The pharmacokinetic parameter Cmax, the highest concentration of WAY-138451 measured in plasma after multiple doses of drug, will be calculated from the observed concentration of WAY-138451 and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of WAY-138451 in ADPKD Patients
Day 1 (am)
|
24.74 ng/mL
Geometric Coefficient of Variation 38.6
|
84.33 ng/mL
Geometric Coefficient of Variation 28.3
|
28.83 ng/mL
Geometric Coefficient of Variation 21.4
|
82.23 ng/mL
Geometric Coefficient of Variation 56.3
|
|
Maximum Observed Plasma Concentration (Cmax) of WAY-138451 in ADPKD Patients
Day 1 (pm)
|
20.95 ng/mL
Geometric Coefficient of Variation 35.4
|
117.1 ng/mL
Geometric Coefficient of Variation 38.1
|
25.93 ng/mL
Geometric Coefficient of Variation 25.4
|
103.3 ng/mL
Geometric Coefficient of Variation 38.3
|
|
Maximum Observed Plasma Concentration (Cmax) of WAY-138451 in ADPKD Patients
Day 7 (am)
|
33.61 ng/mL
Geometric Coefficient of Variation 36.2
|
177.4 ng/mL
Geometric Coefficient of Variation 22.8
|
40.79 ng/mL
Geometric Coefficient of Variation 27.6
|
165.4 ng/mL
Geometric Coefficient of Variation 43.1
|
|
Maximum Observed Plasma Concentration (Cmax) of WAY-138451 in ADPKD Patients
Day 7 (pm)
|
31.64 ng/mL
Geometric Coefficient of Variation 20.2
|
189.1 ng/mL
Geometric Coefficient of Variation 35.2
|
35.36 ng/mL
Geometric Coefficient of Variation 10.4
|
155.2 ng/mL
Geometric Coefficient of Variation 74.0
|
PRIMARY outcome
Timeframe: Day 1 (am and pm) and Day 7 (am and pm)Population: The PKAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan, underwent plasma PK sampling, and were evaluable for this PK outcome. Of these, all 31 subjects contributed to the PK data on Day 1 (am); 30 contributed data to Day 1 (pm); and 29 contributed data to Day 7 (am) and (pm). Substantial deviations from planned dosing interval durations meant additional results were excluded from subjects at various time points.
The pharmacokinetic parameter Cmax, the highest concentration of WAY-138758 measured in plasma after multiple doses of drug, will be calculated from the observed concentration of WAY-138758 and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of WAY-138758 in ADPKD Patients
Day 1 (am)
|
64.26 ng/mL
Geometric Coefficient of Variation 53.9
|
239.3 ng/mL
Geometric Coefficient of Variation 40.3
|
85.11 ng/mL
Geometric Coefficient of Variation 36.5
|
185.2 ng/mL
Geometric Coefficient of Variation 49.7
|
|
Maximum Observed Plasma Concentration (Cmax) of WAY-138758 in ADPKD Patients
Day 1 (pm)
|
107.1 ng/mL
Geometric Coefficient of Variation 43.5
|
354.6 ng/mL
Geometric Coefficient of Variation 32.8
|
125.5 ng/mL
Geometric Coefficient of Variation 53.8
|
275.0 ng/mL
Geometric Coefficient of Variation 26.5
|
|
Maximum Observed Plasma Concentration (Cmax) of WAY-138758 in ADPKD Patients
Day 7 (am)
|
343.9 ng/mL
Geometric Coefficient of Variation 35.8
|
822.3 ng/mL
Geometric Coefficient of Variation 54.4
|
320.4 ng/mL
Geometric Coefficient of Variation 60.4
|
833.6 ng/mL
Geometric Coefficient of Variation 25.0
|
|
Maximum Observed Plasma Concentration (Cmax) of WAY-138758 in ADPKD Patients
Day 7 (pm)
|
342.2 ng/mL
Geometric Coefficient of Variation 36.0
|
861.4 ng/mL
Geometric Coefficient of Variation 56.0
|
326.8 ng/mL
Geometric Coefficient of Variation 56.7
|
825.2 ng/mL
Geometric Coefficient of Variation 24.0
|
PRIMARY outcome
Timeframe: Day 1 (am and pm) and Day 7 (am and pm)Population: The PKAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan, underwent plasma PK sampling, and were evaluable for this PK outcome. Of these, all 31 subjects contributed to the PK data on Day 1 (am); 30 contributed data to Day 1 (pm); and 29 contributed data to Day 7 (am) and (pm). Substantial deviations from planned dosing interval durations meant results were excluded from subjects at various time points.
The pharmacokinetic parameter tmax, the time taken to reach the highest concentration of lixivaptan in plasma after multiple doses of drug, will be calculated from the observed concentration of lixivaptan and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Lixivaptan in ADPKD Patients
Day 1 (am)
|
1.020 hours
Interval 0.67 to 2.0
|
1.000 hours
Interval 1.0 to 1.0
|
1.000 hours
Interval 1.0 to 1.05
|
1.000 hours
Interval 1.0 to 2.0
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Lixivaptan in ADPKD Patients
Day 1 (pm)
|
0.980 hours
Interval 0.95 to 5.62
|
1.000 hours
Interval 0.97 to 2.0
|
1.000 hours
Interval 1.0 to 1.93
|
1.000 hours
Interval 1.0 to 5.97
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Lixivaptan in ADPKD Patients
Day 7 (am)
|
1.000 hours
Interval 0.78 to 1.05
|
1.000 hours
Interval 1.0 to 1.0
|
1.000 hours
Interval 1.0 to 1.02
|
1.000 hours
Interval 1.0 to 2.0
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Lixivaptan in ADPKD Patients
Day 7 (pm)
|
0.920 hours
Interval 0.83 to 1.67
|
1.000 hours
Interval 1.0 to 2.0
|
1.000 hours
Interval 0.95 to 1.03
|
1.000 hours
Interval 0.97 to 13.95
|
PRIMARY outcome
Timeframe: Day 1 (am and pm) and Day 7 (am and pm)Population: The PKAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan, underwent plasma PK sampling, and were evaluable for this PK outcome. Missing values and substantial deviations from planned dosing interval durations meant results were excluded from subjects at various time points.
The pharmacokinetic parameter tmax, the time taken to reach the highest concentration of WAY-141624 in plasma after multiple doses of drug, will be calculated from the observed concentration of WAY-141624 and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax) of WAY-141624 in ADPKD Patients
Day 1 (am)
|
2.000 hours
Interval 1.67 to 4.0
|
2.000 hours
Interval 1.0 to 4.0
|
2.000 hours
Interval 1.05 to 2.0
|
2.000 hours
Interval 1.0 to 4.0
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of WAY-141624 in ADPKD Patients
Day 1 (pm)
|
1.950 hours
Interval 1.92 to 13.58
|
2.000 hours
Interval 2.0 to 4.0
|
2.000 hours
Interval 1.93 to 4.03
|
2.000 hours
Interval 0.0 to 4.0
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of WAY-141624 in ADPKD Patients
Day 7 (am)
|
2.000 hours
Interval 1.83 to 2.0
|
2.000 hours
Interval 1.0 to 2.0
|
2.000 hours
Interval 2.0 to 2.03
|
2.000 hours
Interval 1.0 to 4.08
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of WAY-141624 in ADPKD Patients
Day 7 (pm)
|
1.920 hours
Interval 1.67 to 2.0
|
2.000 hours
Interval 2.0 to 4.0
|
2.010 hours
Interval 1.93 to 5.95
|
2.025 hours
Interval 0.0 to 13.95
|
PRIMARY outcome
Timeframe: Day 1 (am and pm) and Day 7 (am and pm)Population: The PKAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan, underwent plasma PK sampling, and were evaluable for this PK outcome. Missing values, substantial deviations from planned dosing interval durations, and \<3 quantifiable postdose WAY-138451 concentrations meant results were excluded from subjects at various time points.
The pharmacokinetic parameter tmax, the time taken to reach the highest concentration of WAY-138451 in plasma after multiple doses of drug, will be calculated from the observed concentration of WAY-138451 and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax) of WAY-138451 in ADPKD Patients
Day 1 (am)
|
1.020 hours
Interval 0.67 to 2.0
|
1.000 hours
Interval 1.0 to 2.0
|
1.010 hours
Interval 1.0 to 1.05
|
1.000 hours
Interval 1.0 to 2.0
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of WAY-138451 in ADPKD Patients
Day 1 (pm)
|
0.975 hours
Interval 0.95 to 1.93
|
1.000 hours
Interval 0.97 to 2.0
|
1.475 hours
Interval 1.0 to 2.0
|
2.000 hours
Interval 0.92 to 5.97
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of WAY-138451 in ADPKD Patients
Day 7 (am)
|
1.050 hours
Interval 0.95 to 2.0
|
1.000 hours
Interval 1.0 to 1.0
|
1.000 hours
Interval 1.0 to 2.0
|
2.000 hours
Interval 1.0 to 2.08
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of WAY-138451 in ADPKD Patients
Day 7 (pm)
|
1.000 hours
Interval 0.83 to 2.0
|
1.000 hours
Interval 1.0 to 2.0
|
1.015 hours
Interval 1.0 to 1.95
|
3.000 hours
Interval 1.0 to 13.95
|
PRIMARY outcome
Timeframe: Day 1 (am and pm) and Day 7 (am and pm)Population: The PKAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan, underwent plasma PK sampling, and were evaluable for this PK outcome. All 31 subjects in the PKAS contributed to the PK data on Day 1 (am); 30 contributed data to Day 1 (pm); and 29 contributed data to Day 7 (am) and (pm). Substantial deviations from planned dosing interval durations and missing values meant results were excluded from subjects at various time points.
The pharmacokinetic parameter tmax, the time taken to reach the highest concentration of WAY-138758 in plasma after multiple doses of drug, will be calculated from the observed concentration of WAY-138758 and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax) of WAY-138758 in ADPKD Patients
Day 1 (am)
|
4.020 hours
Interval 3.68 to 9.93
|
4.000 hours
Interval 2.0 to 6.0
|
4.030 hours
Interval 4.0 to 6.0
|
9.460 hours
Interval 6.0 to 10.0
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of WAY-138758 in ADPKD Patients
Day 1 (pm)
|
13.400 hours
Interval 3.98 to 13.87
|
4.000 hours
Interval 2.0 to 13.87
|
4.000 hours
Interval 2.0 to 13.83
|
4.000 hours
Interval 4.0 to 13.95
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of WAY-138758 in ADPKD Patients
Day 7 (am)
|
5.980 hours
Interval 0.0 to 9.75
|
4.000 hours
Interval 0.0 to 6.0
|
2.030 hours
Interval 2.0 to 4.0
|
3.000 hours
Interval 0.0 to 9.92
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of WAY-138758 in ADPKD Patients
Day 7 (pm)
|
3.900 hours
Interval 0.0 to 5.97
|
2.000 hours
Interval 1.0 to 13.98
|
3.010 hours
Interval 2.0 to 6.1
|
4.000 hours
Interval 0.0 to 13.95
|
PRIMARY outcome
Timeframe: Day 1 (am and pm) and Day 7 (am and pm)Population: The PKAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan, underwent plasma PK sampling, and were evaluable for this PK outcome. All 31 subjects in the PKAS contributed to the PK data on Day 1 (am); 30 contributed data to Day 1 (pm); 29 contributed data to Day 7 (am), and 27 contributed data to Day 7 (pm). Substantial deviations from planned dosing interval durations and missing values meant results were excluded from subjects at various time points.
The pharmacokinetic parameter AUC(0-last) for lixivaptan will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values, summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of Lixivaptan in ADPKD Patients
Day 1 (am)
|
428.8 ng*hour/mL
Geometric Coefficient of Variation 46.6
|
1688 ng*hour/mL
Geometric Coefficient of Variation 43.5
|
506.7 ng*hour/mL
Geometric Coefficient of Variation 45.0
|
2281 ng*hour/mL
Geometric Coefficient of Variation 37.9
|
|
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of Lixivaptan in ADPKD Patients
Day 1 (pm)
|
782.8 ng*hour/mL
Geometric Coefficient of Variation 24.7
|
3619 ng*hour/mL
Geometric Coefficient of Variation 48.5
|
782.1 ng*hour/mL
Geometric Coefficient of Variation 15.7
|
5208 ng*hour/mL
Geometric Coefficient of Variation 46.3
|
|
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of Lixivaptan in ADPKD Patients
Day 7 (am)
|
889.4 ng*hour/mL
Geometric Coefficient of Variation 29.7
|
4237 ng*hour/mL
Geometric Coefficient of Variation 36.8
|
1007 ng*hour/mL
Geometric Coefficient of Variation 27.7
|
5395 ng*hour/mL
Geometric Coefficient of Variation 35.3
|
|
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of Lixivaptan in ADPKD Patients
Day 7 (pm)
|
1666 ng*hour/mL
Geometric Coefficient of Variation 56.0
|
8467 ng*hour/mL
Geometric Coefficient of Variation 47.2
|
1958 ng*hour/mL
Geometric Coefficient of Variation 80.2
|
12870 ng*hour/mL
Geometric Coefficient of Variation 56.2
|
PRIMARY outcome
Timeframe: Day 1 (am and pm) and Day 7 (am and pm)Population: The PKAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan, underwent plasma PK sampling, and were evaluable for this PK outcome. Missing values and substantial deviations from planned dosing interval durations meant results were excluded from subjects at various time points.
The pharmacokinetic parameter AUC(0-last) for WAY-141624 will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-141624 in ADPKD Patients
Day 1 (am)
|
716.5 ng*hour/mL
Geometric Coefficient of Variation 54.2
|
2339 ng*hour/mL
Geometric Coefficient of Variation 44.1
|
669.1 ng*hour/mL
Geometric Coefficient of Variation 48.8
|
2300 ng*hour/mL
Geometric Coefficient of Variation 43.1
|
|
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-141624 in ADPKD Patients
Day 1 (pm)
|
1266 ng*hour/mL
Geometric Coefficient of Variation 45.7
|
3963 ng*hour/mL
Geometric Coefficient of Variation 48.7
|
1214 ng*hour/mL
Geometric Coefficient of Variation 49.3
|
3894 ng*hour/mL
Geometric Coefficient of Variation 29.0
|
|
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-141624 in ADPKD Patients
Day 7 (am)
|
1560 ng*hour/mL
Geometric Coefficient of Variation 56.9
|
3440 ng*hour/mL
Geometric Coefficient of Variation 40.4
|
1349 ng*hour/mL
Geometric Coefficient of Variation 58.1
|
4196 ng*hour/mL
Geometric Coefficient of Variation 37.7
|
|
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-141624 in ADPKD Patients
Day 7 (pm)
|
4731 ng*hour/mL
Geometric Coefficient of Variation 81.2
|
11330 ng*hour/mL
Geometric Coefficient of Variation 56.4
|
4174 ng*hour/mL
Geometric Coefficient of Variation 56.3
|
15160 ng*hour/mL
Geometric Coefficient of Variation 54.8
|
PRIMARY outcome
Timeframe: Day 1 (am and pm) and Day 7 (am and pm)Population: The PKAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan, underwent plasma PK sampling, and were evaluable for this PK outcome. Missing values, substantial deviations from planned dosing interval durations, and \<3 quantifiable postdose WAY-138451 concentrations meant results were excluded from subjects at various time points.
The pharmacokinetic parameter AUC(0-last) for WAY-138451 will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-138451 in ADPKD Patients
Day 1 (am)
|
70.01 ng*hour/mL
Geometric Coefficient of Variation 21.6
|
284.7 ng*hour/mL
Geometric Coefficient of Variation 50.3
|
77.23 ng*hour/mL
Geometric Coefficient of Variation 24.8
|
373.6 ng*hour/mL
Geometric Coefficient of Variation 44.9
|
|
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-138451 in ADPKD Patients
Day 1 (pm)
|
74.00 ng*hour/mL
Geometric Coefficient of Variation 26.9
|
532.8 ng*hour/mL
Geometric Coefficient of Variation 65.5
|
80.14 ng*hour/mL
Geometric Coefficient of Variation 36.1
|
764.5 ng*hour/mL
Geometric Coefficient of Variation 40.1
|
|
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-138451 in ADPKD Patients
Day 7 (am)
|
132.9 ng*hour/mL
Geometric Coefficient of Variation 42.4
|
736.8 ng*hour/mL
Geometric Coefficient of Variation 31.2
|
139.7 ng*hour/mL
Geometric Coefficient of Variation 45.1
|
919.2 ng*hour/mL
Geometric Coefficient of Variation 39.8
|
|
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-138451 in ADPKD Patients
Day 7 (pm)
|
137.3 ng*hour/mL
Geometric Coefficient of Variation 46.5
|
1444 ng*hour/mL
Geometric Coefficient of Variation 52.6
|
194.6 ng*hour/mL
Geometric Coefficient of Variation 138.3
|
1867 ng*hour/mL
Geometric Coefficient of Variation 58.8
|
PRIMARY outcome
Timeframe: Day 1 (am and pm) and Day 7 (am and pm)Population: The PKAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan, underwent plasma PK sampling, and were evaluable for this PK outcome. Missing values and substantial deviations from planned dosing interval durations meant results were excluded from subjects at various time points.
The pharmacokinetic parameter AUC(0-last) for WAY-138758 will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-138758 in ADPKD Patients
Day 1 (am)
|
485.1 ng*hour/mL
Geometric Coefficient of Variation 65.0
|
1792 ng*hour/mL
Geometric Coefficient of Variation 36.9
|
669.7 ng*hour/mL
Geometric Coefficient of Variation 37.1
|
1412 ng*hour/mL
Geometric Coefficient of Variation 51.3
|
|
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-138758 in ADPKD Patients
Day 1 (pm)
|
1212 ng*hour/mL
Geometric Coefficient of Variation 49.2
|
4281 ng*hour/mL
Geometric Coefficient of Variation 35.3
|
1449 ng*hour/mL
Geometric Coefficient of Variation 50.7
|
3418 ng*hour/mL
Geometric Coefficient of Variation 24.5
|
|
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-138758 in ADPKD Patients
Day 7 (am)
|
3162 ng*hour/mL
Geometric Coefficient of Variation 36.3
|
7471 ng*hour/mL
Geometric Coefficient of Variation 54.5
|
2919 ng*hour/mL
Geometric Coefficient of Variation 59.2
|
7660 ng*hour/mL
Geometric Coefficient of Variation 24.6
|
|
Area Under the Concentration-time Curve From Time 0 Until the Last Quantifiable Concentration (AUC[0-last]) of WAY-138758 in ADPKD Patients
Day 7 (pm)
|
23890 ng*hour/mL
Geometric Coefficient of Variation 38.1
|
46910 ng*hour/mL
Geometric Coefficient of Variation 62.8
|
18940 ng*hour/mL
Geometric Coefficient of Variation 51.9
|
52560 ng*hour/mL
Geometric Coefficient of Variation 28.0
|
PRIMARY outcome
Timeframe: Day 1 (am)Population: Upon final PK data analysis, it was evident based upon Day 7 PM profiles (sampled out to 96 hours) that lixivaptan did not appear to have concentration-time data in the terminal phase for Day 1 (AM) or Day 7 AM due to the limited time frame of the dosing intervals of 10 hours. Therefore, the terminal slope-related PK parameter of AUC(0-inf), planned in the protocol/SAP for Day 1 AM, was unable to be calculated due to insufficient sampling duration prior to the PM dose.
The pharmacokinetic parameter AUC(0-inf) for lixivaptan will be calculated using the linear trapezoidal rule for increasing values, the log trapezoidal rule for decreasing values, and extrapolated to infinity by addition of the last quantifiable observed concentration divided by the elimination rate constant and summarized by cohort.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Day 1 (am)Population: Upon final PK data analysis, it was evident based upon Day 7 PM profiles (sampled out to 96 hours) that WAY-141624 did not appear to have concentration-time data in the terminal phase for Day 1 (AM) or Day 7 AM due to the limited time frame of the dosing intervals of 10 hours. Therefore, the terminal slope-related PK parameter of AUC(0-inf), planned in the protocol/SAP for Day 1 AM, was unable to be calculated due to insufficient sampling duration prior to the PM dose.
The pharmacokinetic parameter AUC(0-inf) for WAY-141624 will be calculated using the linear trapezoidal rule for increasing values, the log trapezoidal rule for decreasing values, and extrapolated to infinity by addition of the last quantifiable observed concentration divided by the elimination rate constant and summarized by cohort.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Day 1 (am)Population: Upon final PK data analysis, it was evident based upon Day 7 PM profiles (sampled out to 96 hours) that WAY-138451 did not appear to have concentration-time data in the terminal phase for Day 1 (AM) or Day 7 AM due to the limited time frame of the dosing intervals of 10 hours. Therefore, the terminal slope-related PK parameter of AUC(0-inf), planned in the protocol/SAP for Day 1 AM, was unable to be calculated due to insufficient sampling duration prior to the PM dose.
The pharmacokinetic parameter AUC(0-inf) for WAY-138451 will be calculated using the linear trapezoidal rule for increasing values, the log trapezoidal rule for decreasing values, and extrapolated to infinity by addition of the last quantifiable observed concentration divided by the elimination rate constant and summarized by cohort.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Day 1 (am)Population: Upon final PK data analysis, it was evident based upon Day 7 PM profiles (sampled out to 96 hours) that WAY-138758 did not appear to have concentration-time data in the terminal phase for Day 1 (AM) or Day 7 AM due to the limited time frame of the dosing intervals of 10 hours. Therefore, the terminal slope-related PK parameter of AUC(0-inf), planned in the protocol/SAP for Day 1 AM, was unable to be calculated due to insufficient sampling duration prior to the PM dose.
The pharmacokinetic parameter AUC(0-inf) for WAY-138758 will be calculated using the linear trapezoidal rule for increasing values, the log trapezoidal rule for decreasing values, and extrapolated to infinity by addition of the last quantifiable observed concentration divided by the elimination rate constant and summarized by cohort.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Day 1 (am) and Day 7 (pm)Population: Upon final PK data analysis, it was evident based upon Day 7 (pm) profiles that lixivaptan did not have concentration-time data in the terminal phase for Day 1 (am) due to the limited time frame of the dosing intervals of 10 hours. Therefore, t1/2, planned for Day 1 (am), was unable to be calculated due to insufficient sampling duration prior to the PM dose. Missing values and substantial deviations meant results were excluded from subjects at various time points.
The pharmacokinetic parameter t1/2 for lixivaptan, determined as ln2/apparent terminal elimination rate constant, will be calculated and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Terminal Elimination Phase Half-life (t1/2) of Lixivaptan in ADPKD Patients
Day 7 (pm)
|
10.25 hours
Geometric Coefficient of Variation 27.4
|
9.696 hours
Geometric Coefficient of Variation 24.2
|
7.688 hours
Geometric Coefficient of Variation 51.6
|
11.39 hours
Geometric Coefficient of Variation 28.9
|
PRIMARY outcome
Timeframe: Day 1 (am) and Day 7 (pm)Population: Upon final PK data analysis, it was evident based upon Day 7 (pm) profiles that WAY-141624 did not have concentration-time data in the terminal phase for Day 1 (am) due to the limited time frame of the dosing intervals of 10 hours. Therefore, t1/2, planned for Day 1 AM, was unable to be calculated due to insufficient sampling duration prior to the PM dose. Missing values and substantial deviations meant results were excluded from subjects at various time points.
The pharmacokinetic parameter t1/2 for WAY-141624, determined as ln2/apparent terminal elimination rate constant, will be calculated and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Terminal Elimination Phase Half-life (t1/2) of WAY-141624 in ADPKD Patients
Day 7 (pm)
|
18.79 hours
Geometric Coefficient of Variation 22.2
|
20.48 hours
Geometric Coefficient of Variation 33.3
|
22.41 hours
Geometric Coefficient of Variation 56.1
|
20.81 hours
Geometric Coefficient of Variation 30.4
|
PRIMARY outcome
Timeframe: Day 1 (am) and Day 7 (pm)Population: It was evident WAY-138451 did not have concentration-time data in the terminal phase for D1(am) due to the limited time frame of the 10-hour dosing intervals. t1/2, planned for Day 1 AM, was unable to be calculated due to insufficient sampling duration prior to the PM dose. Missing values, substantial deviations and \<3 quantifiable postdose WAY-138451 concentrations meant some results were excluded; also, t1/2 could not be calculated for the 2 participants in the low dose lixivaptan/CKD3 cohort.
The pharmacokinetic parameter t1/2 for WAY-138451, determined as ln2/apparent terminal elimination rate constant, will be calculated and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Terminal Elimination Phase Half-life (t1/2) of WAY-138451 in ADPKD Patients
Day 7 (pm)
|
NA hours
Geometric Coefficient of Variation NA
Insufficient number of subjects with data to calculate the geometric mean
|
6.439 hours
Geometric Coefficient of Variation 36.7
|
—
|
9.426 hours
Geometric Coefficient of Variation 22.6
|
PRIMARY outcome
Timeframe: Day 1 (am) and Day 7 (pm)Population: Upon final PK data analysis, it was evident based upon Day 7 (pm) profiles that WAY-138758 did not appear to have concentration-time data in the terminal phase for Day 1 (am) due to the limited time frame of the dosing intervals of 10 hours. Therefore, t1/2, planned for Day 1 (am), was unable to be calculated due to insufficient sampling duration prior to the PM dose. Missing values and substantial deviations meant additional results were excluded from subjects at various time points.
The pharmacokinetic parameter t1/2 for WAY-138758, determined as ln2/apparent terminal elimination rate constant, will be calculated and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Terminal Elimination Phase Half-life (t1/2) of WAY-138758 in ADPKD Patients
Day 7 (pm)
|
65.11 hours
Geometric Coefficient of Variation 30.2
|
48.80 hours
Geometric Coefficient of Variation 25.8
|
50.70 hours
Geometric Coefficient of Variation 8.6
|
59.93 hours
Geometric Coefficient of Variation 32.8
|
PRIMARY outcome
Timeframe: Day 1 (am) and Day 7 (pm)Population: Upon final PK data analysis, it was evident based upon Day 7 (pm) profiles that lixivaptan did not appear to have concentration-time data in the terminal phase for Day 1 (am) due to the limited time frame of the dosing intervals of 10 hours. Therefore, λZ, planned for Day 1 (am), was unable to be calculated due to insufficient sampling duration prior to the PM dose. Missing values and substantial deviations meant additional results were excluded from subjects at various time points.
The pharmacokinetic parameter λZ for lixivaptan will be determined by linear regression of the terminal points of the log-linear concentration-time curve. The Best Fit method utilized by WinNonlin will be used to identify the terminal linear phase of the concentration-time profile, with visual assessment and adjustment of the selected data points by the PK scientist if warranted. A minimum of 3 data points will be used for determination. Results will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Apparent Terminal Elimination Rate Constant (λZ) of Lixivaptan in ADPKD Patients
Day 7 (pm)
|
0.06762 1/hour
Geometric Coefficient of Variation 27.4
|
0.07149 1/hour
Geometric Coefficient of Variation 24.2
|
0.09016 1/hour
Geometric Coefficient of Variation 51.6
|
0.06085 1/hour
Geometric Coefficient of Variation 28.9
|
PRIMARY outcome
Timeframe: Day 1 (am) and Day 7 (pm)Population: Upon final PK data analysis, it was evident based upon Day 7 (pm) profiles that WAY-141624 did not appear to have concentration-time data in the terminal phase for Day 1 (am) due to the limited time frame of the dosing intervals of 10 hours. Therefore, λZ, planned for Day 1 (am), was unable to be calculated due to insufficient sampling duration prior to the PM dose. Missing values and substantial deviations meant additional results were excluded from subjects at various time points.
The pharmacokinetic parameter λZ for WAY-141624 will be determined by linear regression of the terminal points of the log-linear concentration-time curve. The Best Fit method utilized by WinNonlin will be used to identify the terminal linear phase of the concentration-time profile, with visual assessment and adjustment of the selected data points by the PK scientist if warranted. A minimum of 3 data points will be used for determination. Results will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Apparent Terminal Elimination Rate Constant (λZ) of WAY-141624 in ADPKD Patients
Day 7 (pm)
|
0.03690 1/hour
Geometric Coefficient of Variation 22.2
|
0.03384 1/hour
Geometric Coefficient of Variation 33.3
|
0.03093 1/hour
Geometric Coefficient of Variation 56.1
|
0.03330 1/hour
Geometric Coefficient of Variation 30.4
|
PRIMARY outcome
Timeframe: Day 1 (am) and Day 7 (pm)Population: It was evident WAY-138451 did not appear to have concentration-time data in the terminal phase for D1(am) due to the limited time frame of the dosing intervals of 10 hours. λZ, planned for D1(am), was unable to be calculated due to insufficient sampling duration prior to the pm dose. Missing values, deviations, and \<3 quantifiable postdose WAY-138451 concentrations meant results were excluded; also, λZ could not be calculated for the 2 participants in the low dose lixivaptan/CKD3 cohort.
The pharmacokinetic parameter λZ for WAY-138451 will be determined by linear regression of the terminal points of the log-linear concentration-time curve. The Best Fit method utilized by WinNonlin will be used to identify the terminal linear phase of the concentration-time profile, with visual assessment and adjustment of the selected data points by the PK scientist if warranted. A minimum of 3 data points will be used for determination. Results will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Apparent Terminal Elimination Rate Constant (λZ) of WAY-138451 in ADPKD Patients
Day 7 (pm)
|
NA 1/hour
Geometric Coefficient of Variation NA
Insufficient number of subjects with data to calculate the geometric mean
|
0.1077 1/hour
Geometric Coefficient of Variation 36.7
|
—
|
0.07353 1/hour
Geometric Coefficient of Variation 22.6
|
PRIMARY outcome
Timeframe: Day 1 (am) and Day 7 (pm)Population: Upon final PK data analysis, it was evident based upon Day 7 (pm) profiles that WAY-138758 did not appear to have concentration-time data in the terminal phase for Day 1 (am) due to the limited time frame of the dosing intervals of 10 hours. Therefore, λZ, planned for Day 1 (am), was unable to be calculated due to insufficient sampling duration prior to the pm dose. Missing values and substantial deviations meant additional results were excluded from subjects at various time points.
The pharmacokinetic parameter λZ for WAY-138758 will be determined by linear regression of the terminal points of the log-linear concentration-time curve. The Best Fit method utilized by WinNonlin will be used to identify the terminal linear phase of the concentration-time profile, with visual assessment and adjustment of the selected data points by the PK scientist if warranted. A minimum of 3 data points will be used for determination. Results will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Apparent Terminal Elimination Rate Constant (λZ) of WAY-138758 in ADPKD Patients
Day 7 (pm)
|
0.01065 1/hour
Geometric Coefficient of Variation 30.2
|
0.01421 1/hour
Geometric Coefficient of Variation 25.8
|
0.01367 1/hour
Geometric Coefficient of Variation 8.6
|
0.01157 1/hour
Geometric Coefficient of Variation 32.8
|
PRIMARY outcome
Timeframe: Day 1 (am) and Day 7 (am)Population: Upon final PK data analysis, it was evident based upon Day 7 (pm) profiles that lixivaptan did not appear to have concentration-time data in the terminal phase for Day 1 (am) due to the limited time frame of the dosing intervals of 10 hours. Therefore, CL/F, planned for Day 1 (am), was unable to be calculated due to insufficient sampling duration prior to the pm dose. Missing values and substantial deviations meant additional results were excluded from subjects at various time points.
The pharmacokinetic parameter CL/F for lixivaptan, calculated as: Day 1 AM: dose divided by AUC(0-inf), or Day 7 AM: dose divided by AUC(0-last), will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Apparent Systemic Clearance After Extravascular Dosing (CL/F) of Lixivaptan in ADPKD Patients
Day 7 (am)
|
56.22 L/hour
Geometric Coefficient of Variation 29.7
|
47.20 L/hour
Geometric Coefficient of Variation 36.8
|
49.65 L/hour
Geometric Coefficient of Variation 27.7
|
37.07 L/hour
Geometric Coefficient of Variation 35.3
|
PRIMARY outcome
Timeframe: Day 1 (am) and Day 7 (am)Population: Upon final data analysis, it was evident based upon Day (D) 7(pm) profiles that lixivaptan did not have concentration-time data in the terminal phase for D1(am) due to the limited time frame of the 10-hour dosing intervals. Therefore, VZ/F, planned for D1(am), was unable to be calculated due to insufficient sampling duration prior to the pm dose, and values for the D7(am) time point were not presented. Instead, VZ/F24H was determined and presented as an Other Pre-specified Outcome Measure.
The pharmacokinetic parameter VZ/F for lixivaptan, calculated as CL/F divided by λZ, will be summarized by cohort.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Day 7 (am)Population: Of the 31 subjects in the PKAS, 29 contributed data to Day 7 (am).
The pharmacokinetic parameter RCmax for lixivaptan, calculated as \[Cmax on Day 7\]/\[Cmax on Day 1\], will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=8 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=6 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Accumulation Ratio for Cmax (RCmax) of Lixivaptan in ADPKD Patients
|
1.765 Ratio
Geometric Coefficient of Variation 50.1
|
2.287 Ratio
Geometric Coefficient of Variation 24.1
|
1.687 Ratio
Geometric Coefficient of Variation 68.4
|
2.087 Ratio
Geometric Coefficient of Variation 36.2
|
PRIMARY outcome
Timeframe: Day 7 (am)Population: Of the 31 subjects in the PKAS, 29 contributed data to Day 7 (am).
The pharmacokinetic parameter RAUC(0-last) for lixivaptan, calculated as \[AUC(0-last) on Day 7\]/\[AUC(0-last) on Day 1\], will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=8 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=6 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Accumulation Ratio for AUC(0-last) (RAUC[0-last]) of Lixivaptan in ADPKD Patients
|
2.074 Ratio
Geometric Coefficient of Variation 31.5
|
2.643 Ratio
Geometric Coefficient of Variation 28.6
|
1.795 Ratio
Geometric Coefficient of Variation 25.6
|
2.365 Ratio
Geometric Coefficient of Variation 28.9
|
PRIMARY outcome
Timeframe: Day 7 (pm)Population: Of the 31 subjects in the PKAS, 29 contributed data to Day 7 (pm).
The pharmacokinetic parameter AUC(0-14) for lixivaptan will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values. The actual elapsed time for the nominal 14-hour sample will be used for the calculation. Results will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=8 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=6 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of Lixivaptan in ADPKD Patients
|
1069 ng*h/mL
Geometric Coefficient of Variation 29.0
|
6530 ng*h/mL
Geometric Coefficient of Variation 44.3
|
1280 ng*h/mL
Geometric Coefficient of Variation 26.9
|
7800 ng*h/mL
Geometric Coefficient of Variation 55.2
|
PRIMARY outcome
Timeframe: Day 7 (pm)Population: Of the 31 subjects in the PKAS, 29 contributed data to Day 7 (pm).
The pharmacokinetic parameter AUC(0-14) for WAY-141624 will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values. The actual elapsed time for the nominal 14-hour sample will be used for the calculation. Results will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=8 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=6 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-141624 in ADPKD Patients
|
1959 ng*h/mL
Geometric Coefficient of Variation 54.0
|
5227 ng*h/mL
Geometric Coefficient of Variation 46.6
|
1717 ng*h/mL
Geometric Coefficient of Variation 46.6
|
5871 ng*h/mL
Geometric Coefficient of Variation 50.7
|
PRIMARY outcome
Timeframe: Day 7 (pm)Population: Of the 31 subjects in the PKAS, 29 contributed data to Day 7 (pm).
The pharmacokinetic parameter AUC(0-14) for WAY-138451 will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values. The actual elapsed time for the nominal 14-hour sample will be used for the calculation. Results will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=8 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=6 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-138451 in ADPKD Patients
|
154.4 ng*h/mL
Geometric Coefficient of Variation 37.7
|
1107 ng*h/mL
Geometric Coefficient of Variation 39.2
|
182.8 ng*h/mL
Geometric Coefficient of Variation 33.4
|
1270 ng*h/mL
Geometric Coefficient of Variation 50.8
|
PRIMARY outcome
Timeframe: Day 7 (pm)Population: Of the 31 subjects in the PKAS, 29 contributed data to Day 7 (pm).
The pharmacokinetic parameter AUC(0-14) for WAY-138758 will be calculated using the linear trapezoidal rule for increasing values and the log trapezoidal rule for decreasing values. The actual elapsed time for the nominal 14-hour sample will be used for the calculation. Results will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=8 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=6 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Area Under the Concentration-time Curve From Time 0 Until 14 Hours Postdose (AUC[0-14]) of WAY-138758 in ADPKD Patients
|
4509 ng*h/mL
Geometric Coefficient of Variation 36.2
|
10900 ng*h/mL
Geometric Coefficient of Variation 55.6
|
4121 ng*h/mL
Geometric Coefficient of Variation 56.9
|
10730 ng*h/mL
Geometric Coefficient of Variation 25.3
|
PRIMARY outcome
Timeframe: Day 7 (pm)Population: Of the 31 subjects in the PKAS, 29 contributed data to Day 7 (pm).
The pharmacokinetic parameter MRCmax for WAY-141624 will be calculated and corrected for molecular weight of WAY-141624 and parent lixivaptan as: (Cmax,m/Cmax,p)(MWp/MWm), where Cmax,m and MWm are Cmax and molecular weight of WAY-141624, respectively, and Cmax,p and MWp are Cmax and molecular weight of parent lixivaptan, respectively. The following molecular weights are to be used in all MRCmax calculations: * lixivaptan: 473.93 g/mol * WAY-141624: 505.95 g/mol Results will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=8 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=6 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Ratio of WAY-141624 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients
|
0.8137 Ratio
Geometric Coefficient of Variation 41.5
|
0.3627 Ratio
Geometric Coefficient of Variation 40.0
|
0.6225 Ratio
Geometric Coefficient of Variation 57.5
|
0.4554 Ratio
Geometric Coefficient of Variation 31.0
|
PRIMARY outcome
Timeframe: Day 7 (pm)Population: Of the 31 subjects in the PKAS, 29 contributed data to Day 7 (pm).
The pharmacokinetic parameter MRCmax for WAY-138451 will be calculated and corrected for molecular weight of WAY-138451 and parent lixivaptan as: (Cmax,m/Cmax,p)(MWp/MWm), where Cmax,m and MWm are Cmax and molecular weight of WAY-138451, respectively, and Cmax,p and MWp are Cmax and molecular weight of parent lixivaptan, respectively. The following molecular weights are to be used in all MRCmax calculations: * lixivaptan: 473.93 g/mol * WAY-138451: 488.92 g/mol Results will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=8 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=6 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Ratio of WAY-138451 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients
|
0.1185 Ratio
Geometric Coefficient of Variation 29.3
|
0.1159 Ratio
Geometric Coefficient of Variation 17.7
|
0.1139 Ratio
Geometric Coefficient of Variation 14.9
|
0.1243 Ratio
Geometric Coefficient of Variation 27.5
|
PRIMARY outcome
Timeframe: Day 7 (pm)Population: Of the 31 subjects in the PKAS, 29 contributed data to Day 7 (pm).
The pharmacokinetic parameter MRCmax for WAY-138758 will be calculated and corrected for molecular weight of WAY-138758 and parent lixivaptan as: (Cmax,m/Cmax,p)(MWp/MWm), where Cmax,m and MWm are Cmax and molecular weight of WAY-138758, respectively, and Cmax,p and MWp are Cmax and molecular weight of parent lixivaptan, respectively. The following molecular weights are to be used in all MRCmax calculations: * lixivaptan: 473.93 g/mol * WAY-138758: 426.82 g/mol Results will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=8 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=6 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Ratio of WAY-138758 Cmax to Parent Lixivaptan Cmax (MRCmax) in ADPKD Patients
|
1.468 Ratio
Geometric Coefficient of Variation 51.2
|
0.6045 Ratio
Geometric Coefficient of Variation 61.7
|
1.205 Ratio
Geometric Coefficient of Variation 56.9
|
0.7569 Ratio
Geometric Coefficient of Variation 86.0
|
PRIMARY outcome
Timeframe: Day 7 (pm)Population: Of the 31 subjects in the PKAS, 29 contributed data to Day 7 (pm).
The pharmacokinetic parameter MRAUC(0-14) for WAY-141624 will be calculated and corrected for molecular weight of WAY-141624 and parent lixivaptan as: (AUC(0-14),m/AUC(0-14),p)(MWp/MWm), where AUC(0-14),m and MWm are AUC(0-14) and molecular weight of WAY-141624, respectively, and AUC(0-14),p and MWp are AUC(0-14) and molecular weight of parent lixivaptan, respectively. The following molecular weights are to be used in all MRAUC(0-14) calculations: * lixivaptan: 473.93 g/mol * WAY-141624: 505.95 g/mol Results will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=8 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=6 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Ratio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-141624 in ADPKD Patients
|
1.717 Ratio
Geometric Coefficient of Variation 42.7
|
0.7498 Ratio
Geometric Coefficient of Variation 41.0
|
1.256 Ratio
Geometric Coefficient of Variation 69.7
|
0.7050 Ratio
Geometric Coefficient of Variation 24.1
|
PRIMARY outcome
Timeframe: Day 7 (pm)Population: Of the 31 subjects in the PKAS, 29 contributed data to Day 7 (pm).
The pharmacokinetic parameter MRAUC(0-14) for WAY-138451 will be calculated and corrected for molecular weight of WAY-138451 and parent lixivaptan as: (AUC(0-14),m/AUC(0-14),p)(MWp/MWm), where AUC(0-14),m and MWm are AUC(0-14) and molecular weight of WAY-138451, respectively, and AUC(0-14),p and MWp are AUC(0-14) and molecular weight of parent lixivaptan, respectively. The following molecular weights are to be used in all MRAUC(0-14) calculations: * lixivaptan: 473.93 g/mol * WAY-138451: 488.92 g/mol Results will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=8 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=6 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Ratio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-138451 in ADPKD Patients
|
0.1401 Ratio
Geometric Coefficient of Variation 23.9
|
0.1643 Ratio
Geometric Coefficient of Variation 10.9
|
0.1384 Ratio
Geometric Coefficient of Variation 11.3
|
0.1579 Ratio
Geometric Coefficient of Variation 17.5
|
PRIMARY outcome
Timeframe: Day 7 (pm)Population: Of the 31 subjects in the PKAS, 29 contributed data to Day 7 (pm).
The pharmacokinetic parameter MRAUC(0-14) for WAY-138758 will be calculated and corrected for molecular weight of WAY-138758 and parent lixivaptan as: (AUC(0-14),m/AUC(0-14),p)(MWp/MWm), where AUC(0-14),m and MWm are AUC(0-14) and molecular weight of WAY-138758, respectively, and AUC(0-14),p and MWp are AUC(0-14) and molecular weight of parent lixivaptan, respectively. The following molecular weights are to be used in all MRAUC(0-14) calculations: * lixivaptan: 473.93 g/mol * WAY-138758: 426.82 g/mol Results will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=8 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=6 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Ratio of Metabolite AUC(0-14) to Parent Lixivaptan AUC(0-14) (MRAUC[0-14]) of WAY-138758 in ADPKD Patients
|
4.685 Ratio
Geometric Coefficient of Variation 39.7
|
1.854 Ratio
Geometric Coefficient of Variation 64.2
|
3.573 Ratio
Geometric Coefficient of Variation 83.1
|
1.528 Ratio
Geometric Coefficient of Variation 53.7
|
PRIMARY outcome
Timeframe: 35 daysPopulation: Results are presented based on the Safety Analysis Set, which included all subjects who received at least 1 dose of study medication, and were analyzed according to treatment received. The Safety Analysis Set included all 31 subjects who were enrolled in the study.
The number of study participants who experience treatment-emergent adverse events during the study will be counted and summarized by dose level.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Number of Study Participants With Treatment-emergent Adverse Events
|
4 Participants
|
2 Participants
|
4 Participants
|
4 Participants
|
PRIMARY outcome
Timeframe: 35 daysPopulation: Results are presented based on the Safety Analysis Set, which included all subjects who received at least 1 dose of study medication, and were analyzed according to treatment received. The Safety Analysis Set included all 31 subjects who were enrolled in the study.
The number of study participants who experience clinically significant physical examination findings during the study will be counted and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Number of Study Participants With Clinically Significant Physical Examination Findings
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: 35 daysPopulation: Results are presented based on the Safety Analysis Set, which included all subjects who received at least 1 dose of study medication, and were analyzed according to treatment received. The Safety Analysis Set included all 31 subjects who were enrolled in the study.
The number of study participants who experience vital signs (systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, and body temperature) meeting the predefined markedly abnormal criteria during the study will be counted and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Number of Study Participants With Clinically Significant Vital Signs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day 1) to Day 8 (8 days)Population: Results are presented based on the Safety Analysis Set, which included all subjects who received at least 1 dose of study medication, and were analyzed according to treatment received. The Safety Analysis Set included all 31 subjects who were enrolled in the study.
The number of study participants who experience 12-lead electrocardiograms meeting the predefined markedly abnormal criteria during the study will be counted and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Number of Study Participants With Clinically Significant Changes in 12-lead Electrocardiograms
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: 35 daysPopulation: Results are presented based on the Safety Analysis Set, which included all subjects who received at least 1 dose of study medication, and were analyzed according to treatment received. The Safety Analysis Set included all 31 subjects who were enrolled in the study.
The number of study participants who experience clinically meaningful laboratory findings, relating to clinical chemistry, hematology, and urinalysis, during the study will be counted and summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Number of Study Participants With Abnormal Clinical Laboratory Findings (Including Clinical Chemistry, Hematology, and Urinalysis)
Urinalysis
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Study Participants With Abnormal Clinical Laboratory Findings (Including Clinical Chemistry, Hematology, and Urinalysis)
Clinical chemistry
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Study Participants With Abnormal Clinical Laboratory Findings (Including Clinical Chemistry, Hematology, and Urinalysis)
Hematology
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 7Population: Results are presented based on the Safety Analysis Set, which included all subjects who received at least 1 dose of study medication, and were analyzed according to treatment received. The Safety Analysis Set included all 31 subjects who were enrolled in the study.
The number of study participants who answered "yes" to the following questions at Day 7 will be counted and summarized by dose level: * Could you tolerate taking this dose of study drug for the next 12 months? * Did the study drug make you feel thirsty more often than usual? * Did the study drug make you go to the bathroom (urinate) more often than usual during the night? * Would you be comfortable recommending the study drug to another patient with your kidney condition?
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Aquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Questions 1, 2, 6, and 10
Could you tolerate taking this dose of study drug for the next 12 months?
|
7 Participants
|
7 Participants
|
6 Participants
|
7 Participants
|
|
Aquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Questions 1, 2, 6, and 10
Did the study drug make you feel thirsty more often than usual?
|
4 Participants
|
7 Participants
|
6 Participants
|
8 Participants
|
|
Aquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Questions 1, 2, 6, and 10
Did the study drug make you go to the bathroom (urinate) more often than usual during the night?
|
4 Participants
|
6 Participants
|
3 Participants
|
6 Participants
|
|
Aquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Questions 1, 2, 6, and 10
Would you be comfortable recommending the study drug to another patient with your kidney condition?
|
7 Participants
|
9 Participants
|
7 Participants
|
8 Participants
|
PRIMARY outcome
Timeframe: Day 7Population: Results are presented based on the Safety Analysis Set, which included all subjects who received at least 1 dose of study medication, and were analyzed according to treatment received. The Safety Analysis Set included all 31 subjects who were enrolled in the study. Answers were not received from all participants.
The number of study participants who answered "not at all" and "slightly" to the following question at Day 7 will be measured: • If the study drug made you feel thirsty more often than usual, were you bothered by it?
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=4 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=6 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Aquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Question 3
Answered "not at all"
|
2 Participants
|
2 Participants
|
2 Participants
|
4 Participants
|
|
Aquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Question 3
Answered "slightly"
|
0 Participants
|
4 Participants
|
2 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: Day 7Population: Results are presented based on the Safety Analysis Set, which included all subjects who received at least 1 dose of study medication, and were analyzed according to treatment received. The Safety Analysis Set included all 31 subjects who were enrolled in the study. Answers were not received from all participants.
The number of study participants who answered "not at all" and "slightly" to the following question at Day 7 will be measured: • If the study drug made you go to the bathroom (urinate) more often than usual during the night, did it bother you?
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=4 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=6 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=3 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=6 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Aquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Question 7
Answered "not at all"
|
1 Participants
|
2 Participants
|
1 Participants
|
2 Participants
|
|
Aquaretic Tolerability of Lixivaptan Measured by a Tolerability Questionnaire Relating to the Symptom Burden of Nocturia, Urgency, and Frequency at Day 7: Question 7
Answered "slightly"
|
1 Participants
|
3 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: At time of dose, and at 1, 2, 4, 6, 9, 10, 11, 12, 14, and 24 hours after the Day 1 and Day 7 dosesPopulation: The Pharmacodynamic Analysis Set (PDAS) consisted of all 31 subjects in the Safety analysis set who received lixivaptan. Overall, all 31 subjects contributed PD endpoints to the Day 1/2 assessment; 30 subjects contributed data to the Day 7/8 PD endpoints and scheduled EOS assessments; however, values were not available for all participants at each time point.
Changes from baseline in spot urine measurements for samples taken at 0, 1, 2, 4, 6, 9, 10, 11, 12, 14, and 24 hours after the Day 1 and Day 7 doses will be summarized by cohort. The baseline value for each time point after first administration of study drug is the value observed at the corresponding time point on Day -1 (or Day 1 for the AM predose assessment only).
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Change From Baseline in Spot Urine Osmolality
Time of Day 1 dose
|
-167.3 mOsm/kg
Standard Deviation 63.4
|
-27.7 mOsm/kg
Standard Deviation 253.8
|
-28.4 mOsm/kg
Standard Deviation 183.5
|
-52.3 mOsm/kg
Standard Deviation 56.1
|
|
Change From Baseline in Spot Urine Osmolality
1 hour post Day 1 dose
|
-114.7 mOsm/kg
Standard Deviation 95.0
|
-101.9 mOsm/kg
Standard Deviation 150.2
|
6.1 mOsm/kg
Standard Deviation 60.1
|
-44.2 mOsm/kg
Standard Deviation 68.7
|
|
Change From Baseline in Spot Urine Osmolality
2 hours post Day 1 dose
|
-68.1 mOsm/kg
Standard Deviation 69.8
|
-10.1 mOsm/kg
Standard Deviation 25.1
|
-41.6 mOsm/kg
Standard Deviation 64.3
|
-86.0 mOsm/kg
Standard Deviation 147.1
|
|
Change From Baseline in Spot Urine Osmolality
4 hours post Day 1 dose
|
-48.7 mOsm/kg
Standard Deviation 77.5
|
-64.9 mOsm/kg
Standard Deviation 124.3
|
-43.7 mOsm/kg
Standard Deviation 36.1
|
-26.6 mOsm/kg
Standard Deviation 16.6
|
|
Change From Baseline in Spot Urine Osmolality
6 hours post Day 1 dose
|
-40.7 mOsm/kg
Standard Deviation 87.0
|
-68.8 mOsm/kg
Standard Deviation 80.5
|
-6.0 mOsm/kg
Standard Deviation 73.5
|
-72.9 mOsm/kg
Standard Deviation 89.6
|
|
Change From Baseline in Spot Urine Osmolality
9 hours post Day 1 dose
|
-54.1 mOsm/kg
Standard Deviation 93.2
|
-62.8 mOsm/kg
Standard Deviation 85.3
|
-46.6 mOsm/kg
Standard Deviation 240.7
|
-84.6 mOsm/kg
Standard Deviation 78.6
|
|
Change From Baseline in Spot Urine Osmolality
10 hours post Day 1 dose
|
-5.7 mOsm/kg
Standard Deviation 127.9
|
-7.7 mOsm/kg
Standard Deviation 99.4
|
-8.4 mOsm/kg
Standard Deviation 114.7
|
-45.0 mOsm/kg
Standard Deviation 73.2
|
|
Change From Baseline in Spot Urine Osmolality
11 hours post Day 1 dose
|
-55.0 mOsm/kg
Standard Deviation 113.8
|
-35.6 mOsm/kg
Standard Deviation 60.9
|
-41.1 mOsm/kg
Standard Deviation 84.5
|
-70.3 mOsm/kg
Standard Deviation 58.3
|
|
Change From Baseline in Spot Urine Osmolality
12 hours post Day 1 dose
|
-76.6 mOsm/kg
Standard Deviation 90.3
|
-49.6 mOsm/kg
Standard Deviation 48.1
|
-61.9 mOsm/kg
Standard Deviation 88.1
|
-112.1 mOsm/kg
Standard Deviation 144.6
|
|
Change From Baseline in Spot Urine Osmolality
14 hours post Day 1 dose
|
-67.3 mOsm/kg
Standard Deviation 63.7
|
-139.0 mOsm/kg
Standard Deviation 248.4
|
-60.9 mOsm/kg
Standard Deviation 124.3
|
-99.7 mOsm/kg
Standard Deviation 82.1
|
|
Change From Baseline in Spot Urine Osmolality
24 hours post Day 1 dose
|
-37.9 mOsm/kg
Standard Deviation 104.5
|
-115.2 mOsm/kg
Standard Deviation 118.8
|
20.4 mOsm/kg
Standard Deviation 252.6
|
-110.4 mOsm/kg
Standard Deviation 111.7
|
|
Change From Baseline in Spot Urine Osmolality
Time of Day 7 dose
|
-97.4 mOsm/kg
Standard Deviation 176.7
|
-173.1 mOsm/kg
Standard Deviation 306.8
|
-23.7 mOsm/kg
Standard Deviation 296.2
|
-150.7 mOsm/kg
Standard Deviation 91.2
|
|
Change From Baseline in Spot Urine Osmolality
1 hour post Day 7 dose
|
-100.7 mOsm/kg
Standard Deviation 135.0
|
-101.1 mOsm/kg
Standard Deviation 169.1
|
-22.6 mOsm/kg
Standard Deviation 63.4
|
-114.7 mOsm/kg
Standard Deviation 173.3
|
|
Change From Baseline in Spot Urine Osmolality
2 hours post Day 7 dose
|
-63.1 mOsm/kg
Standard Deviation 86.7
|
-2.9 mOsm/kg
Standard Deviation 20.6
|
-13.0 mOsm/kg
Standard Deviation 69.7
|
-88.1 mOsm/kg
Standard Deviation 158.9
|
|
Change From Baseline in Spot Urine Osmolality
4 hours post Day 7 dose
|
-31.1 mOsm/kg
Standard Deviation 77.4
|
-78.3 mOsm/kg
Standard Deviation 185.0
|
-5.3 mOsm/kg
Standard Deviation 98.8
|
-13.4 mOsm/kg
Standard Deviation 33.7
|
|
Change From Baseline in Spot Urine Osmolality
6 hours post Day 7 dose
|
-6.9 mOsm/kg
Standard Deviation 122.6
|
-86.4 mOsm/kg
Standard Deviation 122.3
|
16.6 mOsm/kg
Standard Deviation 167.4
|
-57.6 mOsm/kg
Standard Deviation 96.7
|
|
Change From Baseline in Spot Urine Osmolality
9 hours post Day 7 dose
|
-36.3 mOsm/kg
Standard Deviation 137.6
|
-100.4 mOsm/kg
Standard Deviation 152.3
|
-80.6 mOsm/kg
Standard Deviation 211.5
|
-44.3 mOsm/kg
Standard Deviation 71.7
|
|
Change From Baseline in Spot Urine Osmolality
10 hours post Day 7 dose
|
30.4 mOsm/kg
Standard Deviation 176.4
|
-54.9 mOsm/kg
Standard Deviation 238.4
|
-8.6 mOsm/kg
Standard Deviation 189.4
|
-7.0 mOsm/kg
Standard Deviation 72.1
|
|
Change From Baseline in Spot Urine Osmolality
11 hours post Day 7 dose
|
-48.7 mOsm/kg
Standard Deviation 118.8
|
-37.0 mOsm/kg
Standard Deviation 49.1
|
-51.3 mOsm/kg
Standard Deviation 106.2
|
-63.0 mOsm/kg
Standard Deviation 48.7
|
|
Change From Baseline in Spot Urine Osmolality
12 hours post Day 7 dose
|
-80.3 mOsm/kg
Standard Deviation 97.3
|
-52.3 mOsm/kg
Standard Deviation 42.6
|
-67.0 mOsm/kg
Standard Deviation 55.5
|
-128.7 mOsm/kg
Standard Deviation 141.0
|
|
Change From Baseline in Spot Urine Osmolality
14 hours post Day 7 dose
|
-47.3 mOsm/kg
Standard Deviation 51.2
|
-141.4 mOsm/kg
Standard Deviation 271.8
|
-25.0 mOsm/kg
Standard Deviation 21.5
|
-83.0 mOsm/kg
Standard Deviation 100.9
|
|
Change From Baseline in Spot Urine Osmolality
24 hours post Day 7 dose
|
35.4 mOsm/kg
Standard Deviation 66.4
|
-219.8 mOsm/kg
Standard Deviation 202.5
|
104.3 mOsm/kg
Standard Deviation 257.0
|
-199.4 mOsm/kg
Standard Deviation 135.5
|
SECONDARY outcome
Timeframe: Baseline (Day -1), Day 1, and Day 7Population: The PDAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan. Values were not available for all participants in the PDAS at each time point.
Changes from baseline in 24-hour urine output for samples taken on Day 1 and Day 7 will be summarized by cohort. The baseline value was the last value observed prior to first administration of study drug on Day -1.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Change From Baseline in 24-hour Urine Output
Day 1
|
1329.9 mL
Standard Deviation 916.7
|
2175.3 mL
Standard Deviation 2629.2
|
1794.4 mL
Standard Deviation 1697.0
|
3041.1 mL
Standard Deviation 889.2
|
|
Change From Baseline in 24-hour Urine Output
Day 7
|
458.4 mL
Standard Deviation 2233.7
|
1995.6 mL
Standard Deviation 2294.0
|
1744.6 mL
Standard Deviation 1658.7
|
1843.6 mL
Standard Deviation 1027.7
|
SECONDARY outcome
Timeframe: Baseline (Day 1) to end of study (35 days)Population: The PDAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan. Of these, all 31 subjects contributed PD endpoints to the Day 1/2 assessment; 30 subjects contributed data to the Day 7/8 PD endpoints and scheduled EOS assessments.
Changes from baseline of eGFR derived from the serum creatinine concentrations for samples taken at Day 1 (postdose), Day 2, Day 7, Day 8, and Day 35 will summarized by cohort
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Change From Baseline of the Estimated Glomerular Filtration Rate (eGFR)
Day 2
|
-1.9 mL/min/1.73 m²
Standard Deviation 3.1
|
-7.4 mL/min/1.73 m²
Standard Deviation 7.2
|
-3.9 mL/min/1.73 m²
Standard Deviation 8.8
|
-2.1 mL/min/1.73 m²
Standard Deviation 4.3
|
|
Change From Baseline of the Estimated Glomerular Filtration Rate (eGFR)
Day 7
|
-3.4 mL/min/1.73 m²
Standard Deviation 4.1
|
-11.9 mL/min/1.73 m²
Standard Deviation 10.0
|
-3.0 mL/min/1.73 m²
Standard Deviation 3.7
|
-5.3 mL/min/1.73 m²
Standard Deviation 3.7
|
|
Change From Baseline of the Estimated Glomerular Filtration Rate (eGFR)
Day 8
|
-3.4 mL/min/1.73 m²
Standard Deviation 3.5
|
-9.1 mL/min/1.73 m²
Standard Deviation 12.5
|
-2.9 mL/min/1.73 m²
Standard Deviation 3.3
|
-5.5 mL/min/1.73 m²
Standard Deviation 4.8
|
|
Change From Baseline of the Estimated Glomerular Filtration Rate (eGFR)
Day 35
|
-3.7 mL/min/1.73 m²
Standard Deviation 3.2
|
-0.9 mL/min/1.73 m²
Standard Deviation 8.4
|
0.0 mL/min/1.73 m²
Standard Deviation 8.3
|
2.1 mL/min/1.73 m²
Standard Deviation 4.3
|
SECONDARY outcome
Timeframe: Baseline (Day -1) to end of study (36 days)Population: The PDAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan. Overall, all 31 subjects contributed PD endpoints to the Day 1/2 assessment; 30 subjects contributed data to the Day 7/8 PD endpoints and scheduled EOS assessments; however, values were not available for all participants at each time point.
Changes from baseline (Day -1) in total kidney volume, measured by abdominal MRI on Day 7 and Day 35, will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Change From Baseline in Total Kidney Volume
Day 7
|
23.58 mL
Standard Deviation 33.69
|
-8.75 mL
Standard Deviation 42.47
|
4.97 mL
Standard Deviation 30.84
|
-66.19 mL
Standard Deviation 141.47
|
|
Change From Baseline in Total Kidney Volume
Day 35
|
28.88 mL
Standard Deviation 68.16
|
-26.63 mL
Standard Deviation 77.84
|
-3.78 mL
Standard Deviation 26.06
|
-4.29 mL
Standard Deviation 81.27
|
SECONDARY outcome
Timeframe: Baseline (Day -1) to end of study (36 days)Population: The PDAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan. Values were not available for all participants in the PDAS at each time point.
Changes from baseline (Day -1) in liver volume, measured by abdominal MRI on Day 7 and Day 35, will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Change From Baseline in Liver Volume
Day 7
|
-0.03 mL
Standard Deviation 40.98
|
53.04 mL
Standard Deviation 125.51
|
43.02 mL
Standard Deviation 92.15
|
104.01 mL
Standard Deviation 131.21
|
|
Change From Baseline in Liver Volume
Day 35
|
-11.00 mL
Standard Deviation 109.04
|
-6.70 mL
Standard Deviation 86.74
|
28.66 mL
Standard Deviation 99.77
|
53.51 mL
Standard Deviation 82.52
|
SECONDARY outcome
Timeframe: Baseline (Day -1) to end of study (36 days)Population: The PDAS consisted of all 31 subjects in the Safety analysis set who received lixivaptan. Of these, all 31 subjects contributed PD endpoints to the Day 1/2 assessment; 30 subjects contributed data to the Day 7/8 PD endpoints and scheduled EOS assessments.
Changes from baseline (Day -1) in plasma copeptin, a marker for circulating vasopressin, at Day 2, Day 7, and Day 35 will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Change From Baseline of Plasma Copeptin
Day 2
|
-1.986 pmol/L
Standard Deviation 10.893
|
5.072 pmol/L
Standard Deviation 4.798
|
1.986 pmol/L
Standard Deviation 3.286
|
12.655 pmol/L
Standard Deviation 15.527
|
|
Change From Baseline of Plasma Copeptin
Day 7
|
34.519 pmol/L
Standard Deviation 89.262
|
9.745 pmol/L
Standard Deviation 4.910
|
3.016 pmol/L
Standard Deviation 3.392
|
17.906 pmol/L
Standard Deviation 10.321
|
|
Change From Baseline of Plasma Copeptin
Day 35
|
-3.337 pmol/L
Standard Deviation 13.993
|
2.111 pmol/L
Standard Deviation 2.829
|
2.786 pmol/L
Standard Deviation 5.498
|
-0.943 pmol/L
Standard Deviation 8.435
|
SECONDARY outcome
Timeframe: Baseline (Day 1, predose) to end of study (35 days)Population: Results are presented based on the Safety Analysis Set, which included all subjects who received at least 1 dose of study medication, and were analyzed according to treatment received. The Safety Analysis Set included all 31 subjects who were enrolled in the study.
Changes from baseline in serum creatinine for samples taken at Day 2, Day 7, Day 8, and Day 35 will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Change From Baseline in Serum Creatinine
Day 2
|
4.5714 umol/L
Standard Deviation 5.62308
|
6.7778 umol/L
Standard Deviation 6.13958
|
4.1429 umol/L
Standard Deviation 7.17469
|
4.7500 umol/L
Standard Deviation 13.49868
|
|
Change From Baseline in Serum Creatinine
Day 7
|
6.5714 umol/L
Standard Deviation 8.86674
|
12.6667 umol/L
Standard Deviation 9.73396
|
2.7143 umol/L
Standard Deviation 3.45033
|
19.2500 umol/L
Standard Deviation 16.88406
|
|
Change From Baseline in Serum Creatinine
Day 8
|
7.5714 umol/L
Standard Deviation 7.48013
|
11.1111 umol/L
Standard Deviation 11.94199
|
2.2857 umol/L
Standard Deviation 3.14718
|
17.6250 umol/L
Standard Deviation 12.81670
|
|
Change From Baseline in Serum Creatinine
Day 35
|
7.5714 umol/L
Standard Deviation 5.12696
|
2.4004 umol/L
Standard Deviation 6.87657
|
0.8571 umol/L
Standard Deviation 6.59365
|
-8.5000 umol/L
Standard Deviation 14.04076
|
SECONDARY outcome
Timeframe: Baseline (Day 1, predose) to end of study (35 days)Population: Results are presented based on the Safety Analysis Set, which included all subjects who received at least 1 dose of study medication, and were analyzed according to treatment received. The Safety Analysis Set included all 31 subjects who were enrolled in the study.
Changes from baseline in BUN for samples taken at Day 2, Day 7, Day 8, and Day 35 will be summarized by cohort.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=7 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=9 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Change From Baseline in Blood Urea Nitrogen (BUN)
Day 7
|
0.2014 mmol/L
Standard Deviation 1.59194
|
-0.2000 mmol/L
Standard Deviation 1.17573
|
-0.0614 mmol/L
Standard Deviation 1.29029
|
-0.7488 mmol/L
Standard Deviation 1.66207
|
|
Change From Baseline in Blood Urea Nitrogen (BUN)
Day 2
|
-0.1300 mmol/L
Standard Deviation 1.16973
|
0.0644 mmol/L
Standard Deviation 0.82257
|
-0.1743 mmol/L
Standard Deviation 0.43535
|
-0.1563 mmol/L
Standard Deviation 1.15821
|
|
Change From Baseline in Blood Urea Nitrogen (BUN)
Day 8
|
-0.1229 mmol/L
Standard Deviation 0.99856
|
-0.5711 mmol/L
Standard Deviation 1.14740
|
-0.1043 mmol/L
Standard Deviation 1.22296
|
-0.2338 mmol/L
Standard Deviation 1.43097
|
|
Change From Baseline in Blood Urea Nitrogen (BUN)
Day 35
|
0.2286 mmol/L
Standard Deviation 1.94233
|
0.0008 mmol/L
Standard Deviation 1.61696
|
-0.1886 mmol/L
Standard Deviation 1.36772
|
-0.2338 mmol/L
Standard Deviation 2.08729
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 7 (am)Population: Of the 31 subjects in the PKAS, 29 contributed data to Day 7 (am). Data were excluded for 1 subject in the low dose/CKD1 or 2 cohort from Day 1 (pm) onwards due to substantial deviations from planned dosing interval durations. Missing values and substantial deviations meant additional results were excluded from subjects at various time points.
The pharmacokinetic parameter VZ/F24H for lixivaptan, calculated as CL/F24H divided by Day 7 PM λZ, will be summarized by cohort. VZ/F24H was not specified in the statistical analysis plan and was calculated for the combined 24-hour period including AM and PM dosing intervals on Day 7. This parameter replaces VZ/F initially planned for the Day 7 AM dose.
Outcome measures
| Measure |
Low Dose Lixivaptan / CKD3
n=6 Participants
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD1 or CKD2
n=6 Participants
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=4 Participants
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=7 Participants
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Volume of Distribution Over 24 Hours After Extravascular Dosing (VZ/F24H) of Lixivaptan in ADPKD Patients
|
731.8 L
Geometric Coefficient of Variation 38.4
|
547.4 L
Geometric Coefficient of Variation 57.4
|
546.0 L
Geometric Coefficient of Variation 48.2
|
515.1 L
Geometric Coefficient of Variation 50.7
|
Adverse Events
High Dose Lixivaptan / CKD1 or CKD2
Low Dose Lixivaptan / CKD1 or CKD2
High Dose Lixivaptan / CKD3
Low Dose Lixivaptan / CKD3
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
High Dose Lixivaptan / CKD1 or CKD2
n=9 participants at risk
Oral high dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD1 or CKD2
n=7 participants at risk
Oral low dose lixivaptan in participants with CKD1 or CKD2
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
High Dose Lixivaptan / CKD3
n=8 participants at risk
Oral high dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
Low Dose Lixivaptan / CKD3
n=7 participants at risk
Oral low dose lixivaptan in participants with CKD3
Lixivaptan: Oral vasopressin V2 receptor antagonist
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/9 • 35 days
|
28.6%
2/7 • Number of events 2 • 35 days
|
12.5%
1/8 • Number of events 1 • 35 days
|
0.00%
0/7 • 35 days
|
|
Gastrointestinal disorders
Nausea
|
11.1%
1/9 • Number of events 1 • 35 days
|
0.00%
0/7 • 35 days
|
0.00%
0/8 • 35 days
|
28.6%
2/7 • Number of events 2 • 35 days
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/9 • 35 days
|
0.00%
0/7 • 35 days
|
0.00%
0/8 • 35 days
|
28.6%
2/7 • Number of events 2 • 35 days
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/9 • 35 days
|
14.3%
1/7 • Number of events 1 • 35 days
|
0.00%
0/8 • 35 days
|
0.00%
0/7 • 35 days
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/9 • 35 days
|
0.00%
0/7 • 35 days
|
0.00%
0/8 • 35 days
|
14.3%
1/7 • Number of events 1 • 35 days
|
|
General disorders
Thirst
|
0.00%
0/9 • 35 days
|
14.3%
1/7 • Number of events 1 • 35 days
|
12.5%
1/8 • Number of events 1 • 35 days
|
0.00%
0/7 • 35 days
|
|
General disorders
Oedema peripheral
|
0.00%
0/9 • 35 days
|
0.00%
0/7 • 35 days
|
12.5%
1/8 • Number of events 1 • 35 days
|
0.00%
0/7 • 35 days
|
|
Infections and infestations
Impetigo
|
0.00%
0/9 • 35 days
|
14.3%
1/7 • Number of events 1 • 35 days
|
0.00%
0/8 • 35 days
|
0.00%
0/7 • 35 days
|
|
Infections and infestations
Urinary tract infection
|
11.1%
1/9 • Number of events 1 • 35 days
|
0.00%
0/7 • 35 days
|
0.00%
0/8 • 35 days
|
0.00%
0/7 • 35 days
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
11.1%
1/9 • Number of events 1 • 35 days
|
0.00%
0/7 • 35 days
|
12.5%
1/8 • Number of events 1 • 35 days
|
0.00%
0/7 • 35 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/9 • 35 days
|
0.00%
0/7 • 35 days
|
0.00%
0/8 • 35 days
|
14.3%
1/7 • Number of events 1 • 35 days
|
|
Musculoskeletal and connective tissue disorders
Muscle fatigue
|
0.00%
0/9 • 35 days
|
0.00%
0/7 • 35 days
|
0.00%
0/8 • 35 days
|
14.3%
1/7 • Number of events 1 • 35 days
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/9 • 35 days
|
0.00%
0/7 • 35 days
|
0.00%
0/8 • 35 days
|
14.3%
1/7 • Number of events 1 • 35 days
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/9 • 35 days
|
0.00%
0/7 • 35 days
|
12.5%
1/8 • Number of events 1 • 35 days
|
0.00%
0/7 • 35 days
|
|
Nervous system disorders
Headache
|
0.00%
0/9 • 35 days
|
42.9%
3/7 • Number of events 3 • 35 days
|
0.00%
0/8 • 35 days
|
0.00%
0/7 • 35 days
|
|
Nervous system disorders
Paraesthesia
|
11.1%
1/9 • Number of events 1 • 35 days
|
0.00%
0/7 • 35 days
|
12.5%
1/8 • Number of events 1 • 35 days
|
0.00%
0/7 • 35 days
|
|
Nervous system disorders
Syncope
|
0.00%
0/9 • 35 days
|
0.00%
0/7 • 35 days
|
0.00%
0/8 • 35 days
|
28.6%
2/7 • Number of events 2 • 35 days
|
|
Nervous system disorders
Dizziness
|
0.00%
0/9 • 35 days
|
14.3%
1/7 • Number of events 1 • 35 days
|
0.00%
0/8 • 35 days
|
0.00%
0/7 • 35 days
|
|
Nervous system disorders
Somnolence
|
0.00%
0/9 • 35 days
|
0.00%
0/7 • 35 days
|
12.5%
1/8 • Number of events 1 • 35 days
|
0.00%
0/7 • 35 days
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/9 • 35 days
|
0.00%
0/7 • 35 days
|
12.5%
1/8 • Number of events 1 • 35 days
|
0.00%
0/7 • 35 days
|
|
Renal and urinary disorders
Polyuria
|
0.00%
0/9 • 35 days
|
0.00%
0/7 • 35 days
|
0.00%
0/8 • 35 days
|
14.3%
1/7 • Number of events 1 • 35 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/9 • 35 days
|
0.00%
0/7 • 35 days
|
0.00%
0/8 • 35 days
|
14.3%
1/7 • Number of events 1 • 35 days
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/9 • 35 days
|
0.00%
0/7 • 35 days
|
0.00%
0/8 • 35 days
|
14.3%
1/7 • Number of events 1 • 35 days
|
Additional Information
Milena Kanova, MD, Vice President, Clinical Operations
Centessa Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place