Trial Outcomes & Findings for Pilot Study to Evaluate Reparixin With Weekly Paclitaxel in Patients With HER 2 Negative Metastatic Breast Cancer (MBC) (NCT NCT02001974)
NCT ID: NCT02001974
Last Updated: 2021-09-27
Results Overview
Monitoring of AEs throughout the study till the end/off-treatment visit.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
33 participants
Primary outcome timeframe
Up to 28 days following the last dose of study drug (up to 24 months).
Results posted on
2021-09-27
Participant Flow
Pts were enrolled in a staggered way. 1 pt was enrolled; if no Dose Limiting Toxicity (DLT) was observed by Day 8, 2 further pts were enrolled simultaneously. If no DLTs were observed at the end of 1 cycle, escalation to the next dose was considered and hence, 3 further pts were enrolled simultaneously. After reviewing Cycle 1 data, escalation to the next dose level was considered. Escalation was stopped if 2 pts of the initial 3 or the expanded cohort of 6 pts developed DLTs.
Reparixin + paclitaxel were administered in 28-day cycles as long as clinical benefit was observed. Reparixin was administered in oral tablets every six to ten hours during a 3 day run-in period and for 21 consecutive days during each cycle with 7 days off treatment between each cycle. Paclitaxel 80 mg/m2/week was administered in combination with the day's first dose of reparixin as an i.v. infusion on Days 1, 8 and 15 of each 28-day cycle.
Participant milestones
| Measure |
Paclitaxel 80 mg/m2 i.v.+Reparixin Oral 400 mg t.i.d.
Paclitaxel+reparixin three weeks on one week off (three to six patients)
Paclitaxel+Reparixin: Association of Paclitaxel at fixed dosage with three increasing dosage of Reparixin
|
Paclitaxel 80 mg/m2 i.v.+Reparixin Oral 800 mg t.i.d.
Paclitaxel+reparixin three weeks on one week off (three to six patients)
Paclitaxel+Reparixin: Association of Paclitaxel at fixed dosage with three increasing dosage of Reparixin
|
Paclitaxel 80 mg/m2 i.v.+Reparixin Oral 1200 mg t.i.d.
Paclitaxel+reparixin oral three weeks on one week off (three to six patients).
Paclitaxel+Reparixin: Association of Paclitaxel at fixed dosage with three increasing dosage of Reparixin
|
|---|---|---|---|
|
Run-in Period
STARTED
|
4
|
3
|
26
|
|
Run-in Period
COMPLETED
|
4
|
3
|
26
|
|
Run-in Period
NOT COMPLETED
|
0
|
0
|
0
|
|
Reparixin + Paclitaxel (28-day Cycles)
STARTED
|
4
|
3
|
26
|
|
Reparixin + Paclitaxel (28-day Cycles)
COMPLETED
|
0
|
0
|
0
|
|
Reparixin + Paclitaxel (28-day Cycles)
NOT COMPLETED
|
4
|
3
|
26
|
Reasons for withdrawal
| Measure |
Paclitaxel 80 mg/m2 i.v.+Reparixin Oral 400 mg t.i.d.
Paclitaxel+reparixin three weeks on one week off (three to six patients)
Paclitaxel+Reparixin: Association of Paclitaxel at fixed dosage with three increasing dosage of Reparixin
|
Paclitaxel 80 mg/m2 i.v.+Reparixin Oral 800 mg t.i.d.
Paclitaxel+reparixin three weeks on one week off (three to six patients)
Paclitaxel+Reparixin: Association of Paclitaxel at fixed dosage with three increasing dosage of Reparixin
|
Paclitaxel 80 mg/m2 i.v.+Reparixin Oral 1200 mg t.i.d.
Paclitaxel+reparixin oral three weeks on one week off (three to six patients).
Paclitaxel+Reparixin: Association of Paclitaxel at fixed dosage with three increasing dosage of Reparixin
|
|---|---|---|---|
|
Reparixin + Paclitaxel (28-day Cycles)
Disease progression
|
2
|
3
|
14
|
|
Reparixin + Paclitaxel (28-day Cycles)
Adverse Event
|
1
|
0
|
4
|
|
Reparixin + Paclitaxel (28-day Cycles)
Withdrawal by Subject
|
1
|
0
|
6
|
|
Reparixin + Paclitaxel (28-day Cycles)
Physician Decision
|
0
|
0
|
2
|
Baseline Characteristics
Pilot Study to Evaluate Reparixin With Weekly Paclitaxel in Patients With HER 2 Negative Metastatic Breast Cancer (MBC)
Baseline characteristics by cohort
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=23 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
Total
n=30 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
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
Age, Continuous
|
55.0 years
STANDARD_DEVIATION 9.13 • n=5 Participants
|
55.3 years
STANDARD_DEVIATION 7.77 • n=7 Participants
|
56.2 years
STANDARD_DEVIATION 12.69 • n=5 Participants
|
55.9 years
STANDARD_DEVIATION 11.59 • n=4 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
29 Participants
n=4 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
|
|
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
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 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
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
24 Participants
n=4 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
|
|
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
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
23 participants
n=5 Participants
|
30 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Up to 28 days following the last dose of study drug (up to 24 months).Population: Safety Population: all enrolled patients who took at least one dose of study drug, reparixin.
Monitoring of AEs throughout the study till the end/off-treatment visit.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=23 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Treatment-Emergent Adverse Events (TEAEs)
|
106 adverse events
|
99 adverse events
|
506 adverse events
|
PRIMARY outcome
Timeframe: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter.
Plasma DF 1681Y concentrations are reported by time point for the PK Population. The CSR also presents: * plots of mean plasma PK concentrations versus time for DF 1681Y on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population; * plots of individual plasma PK concentrations versus time for DF 1681Y on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population; and * a plot of reparixin versus time on Day -3 and Day 21 on a linear (upper) or semi-log (lower) axis.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Plasma DF1681Y Concentrations by Time Point
Day 1 - 8 hr
|
2.185 ug/mL
Standard Deviation 0.8552
|
2.733 ug/mL
Standard Deviation 1.1838
|
17.579 ug/mL
Standard Deviation 23.5794
|
|
Plasma DF1681Y Concentrations by Time Point
Day 1 - 24 hr
|
23.667 ug/mL
Standard Deviation 31.3613
|
23.193 ug/mL
Standard Deviation 13.3628
|
19.685 ug/mL
Standard Deviation 21.7424
|
|
Plasma DF1681Y Concentrations by Time Point
Day 8 - 0 hr
|
0.785 ug/mL
Standard Deviation 1.0511
|
2.403 ug/mL
Standard Deviation 1.7784
|
3.549 ug/mL
Standard Deviation 2.0530
|
|
Plasma DF1681Y Concentrations by Time Point
Day -3 - 4 hr
|
8.233 ug/mL
Standard Deviation 4.9883
|
14.933 ug/mL
Standard Deviation 7.2954
|
20.747 ug/mL
Standard Deviation 8.4992
|
|
Plasma DF1681Y Concentrations by Time Point
Day -3 - 6 hr
|
2.838 ug/mL
Standard Deviation 2.1480
|
6.537 ug/mL
Standard Deviation 2.6240
|
9.650 ug/mL
Standard Deviation 7.3114
|
|
Plasma DF1681Y Concentrations by Time Point
Day -3 - 8 hr
|
1.538 ug/mL
Standard Deviation 0.6268
|
3.980 ug/mL
Standard Deviation 2.1701
|
8.768 ug/mL
Standard Deviation 12.3086
|
|
Plasma DF1681Y Concentrations by Time Point
Day 1 - 0 hr
|
1.050 ug/mL
Standard Deviation 0.3705
|
4.243 ug/mL
Standard Deviation 3.3862
|
5.739 ug/mL
Standard Deviation 6.7727
|
|
Plasma DF1681Y Concentrations by Time Point
Day 1 - 0.5 hr
|
21.503 ug/mL
Standard Deviation 22.1075
|
26.023 ug/mL
Standard Deviation 16.2351
|
21.407 ug/mL
Standard Deviation 23.0450
|
|
Plasma DF1681Y Concentrations by Time Point
Day 1 - 1 hr
|
19.553 ug/mL
Standard Deviation 19.5114
|
45.413 ug/mL
Standard Deviation 3.8760
|
39.378 ug/mL
Standard Deviation 31.5133
|
|
Plasma DF1681Y Concentrations by Time Point
Day 1 - 2 hr
|
22.420 ug/mL
Standard Deviation 13.4937
|
31.090 ug/mL
Standard Deviation 10.9918
|
47.519 ug/mL
Standard Deviation 21.1919
|
|
Plasma DF1681Y Concentrations by Time Point
Day 1 - 4 hr
|
9.923 ug/mL
Standard Deviation 5.3392
|
11.127 ug/mL
Standard Deviation 3.5750
|
27.033 ug/mL
Standard Deviation 14.4401
|
|
Plasma DF1681Y Concentrations by Time Point
Day -3 - 0 hr
|
0.000 ug/mL
Standard Deviation 0.000
|
0.000 ug/mL
Standard Deviation 0.000
|
0.000 ug/mL
Standard Deviation 0.000
|
|
Plasma DF1681Y Concentrations by Time Point
Day -3 - 0.5 hr
|
20.648 ug/mL
Standard Deviation 22.1597
|
25.743 ug/mL
Standard Deviation 25.4196
|
34.689 ug/mL
Standard Deviation 34.8550
|
|
Plasma DF1681Y Concentrations by Time Point
Day -3 - 1 hr
|
27.683 ug/mL
Standard Deviation 19.5342
|
26.780 ug/mL
Standard Deviation 28.4543
|
48.653 ug/mL
Standard Deviation 27.4858
|
|
Plasma DF1681Y Concentrations by Time Point
Day -3 - 1.5 hr
|
31.038 ug/mL
Standard Deviation 15.2190
|
22.180 ug/mL
Standard Deviation 14.3448
|
55.810 ug/mL
Standard Deviation 22.6579
|
|
Plasma DF1681Y Concentrations by Time Point
Day -3 - 2 hr
|
22.020 ug/mL
Standard Deviation 11.0967
|
20.253 ug/mL
Standard Deviation 12.2131
|
50.630 ug/mL
Standard Deviation 17.8120
|
|
Plasma DF1681Y Concentrations by Time Point
Day -3 - 3 hr
|
12.868 ug/mL
Standard Deviation 5.8392
|
18.650 ug/mL
Standard Deviation 8.4463
|
30.968 ug/mL
Standard Deviation 10.7100
|
|
Plasma DF1681Y Concentrations by Time Point
Day 8 - 0.5 hr
|
8.010 ug/mL
Standard Deviation 4.5690
|
5.689 ug/mL
Standard Deviation 6.7670
|
38.937 ug/mL
Standard Deviation 39.3111
|
|
Plasma DF1681Y Concentrations by Time Point
Day 8 - 1 hr
|
14.178 ug/mL
Standard Deviation 9.3500
|
21.383 ug/mL
Standard Deviation 21.5045
|
35.506 ug/mL
Standard Deviation 29.9050
|
|
Plasma DF1681Y Concentrations by Time Point
Day 8 - 2 hr
|
14.110 ug/mL
Standard Deviation 9.4066
|
30.897 ug/mL
Standard Deviation 7.7797
|
34.182 ug/mL
Standard Deviation 23.7096
|
|
Plasma DF1681Y Concentrations by Time Point
Day 8 - 4 hr
|
9.360 ug/mL
Standard Deviation 6.2105
|
24.717 ug/mL
Standard Deviation 6.1212
|
23.986 ug/mL
Standard Deviation 15.9604
|
|
Plasma DF1681Y Concentrations by Time Point
Day 8 - 8 hr
|
2.740 ug/mL
Standard Deviation 1.4252
|
7.807 ug/mL
Standard Deviation 3.7770
|
11.111 ug/mL
Standard Deviation 17.0215
|
|
Plasma DF1681Y Concentrations by Time Point
Day 8 - 24 hr
|
22.000 ug/mL
Standard Deviation 27.8459
|
14.843 ug/mL
Standard Deviation 18.6946
|
10.394 ug/mL
Standard Deviation 7.5534
|
|
Plasma DF1681Y Concentrations by Time Point
Day 21 - 0 hr
|
1.247 ug/mL
Standard Deviation 0.7580
|
6.003 ug/mL
Standard Deviation 5.5644
|
4.978 ug/mL
Standard Deviation 4.3227
|
|
Plasma DF1681Y Concentrations by Time Point
Day 21 - 0.5 hr
|
2.187 ug/mL
Standard Deviation 0.7559
|
29.380 ug/mL
Standard Deviation 31.8622
|
48.578 ug/mL
Standard Deviation 28.9433
|
|
Plasma DF1681Y Concentrations by Time Point
Day 21 - 1 hr
|
3.883 ug/mL
Standard Deviation 1.1319
|
36.397 ug/mL
Standard Deviation 33.4112
|
62.916 ug/mL
Standard Deviation 28.5967
|
|
Plasma DF1681Y Concentrations by Time Point
Day 21 - 1.5 hr
|
10.113 ug/mL
Standard Deviation 5.4962
|
33.787 ug/mL
Standard Deviation 25.5501
|
54.749 ug/mL
Standard Deviation 19.5782
|
|
Plasma DF1681Y Concentrations by Time Point
Day 21 - 2 hr
|
13.433 ug/mL
Standard Deviation 9.0774
|
29.663 ug/mL
Standard Deviation 17.0469
|
43.490 ug/mL
Standard Deviation 20.5604
|
|
Plasma DF1681Y Concentrations by Time Point
Day 21 - 3 hr
|
18.677 ug/mL
Standard Deviation 2.3019
|
24.693 ug/mL
Standard Deviation 7.9406
|
24.698 ug/mL
Standard Deviation 13.4553
|
|
Plasma DF1681Y Concentrations by Time Point
Day 21 - 4 hr
|
8.897 ug/mL
Standard Deviation 2.5150
|
17.780 ug/mL
Standard Deviation 2.4222
|
17.359 ug/mL
Standard Deviation 10.2954
|
|
Plasma DF1681Y Concentrations by Time Point
Day 21 - 6 hr
|
3.247 ug/mL
Standard Deviation 0.6596
|
12.383 ug/mL
Standard Deviation 6.9546
|
7.041 ug/mL
Standard Deviation 3.9328
|
|
Plasma DF1681Y Concentrations by Time Point
Day 21 - 8 hr
|
2.003 ug/mL
Standard Deviation 0.2380
|
5.607 ug/mL
Standard Deviation 2.1608
|
3.684 ug/mL
Standard Deviation 2.2504
|
PRIMARY outcome
Timeframe: Days -3 (1, 2 hours), 1 (1, 2 hours), 8 (1, 2 hours), and 21 (1, 2 hours) of cycle 1.Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter.
Plasma unbound DF 1681Y concentrations by time point for the PK Population are reported. CSR also presents: * plots of mean plasma PK concentrations versus time for unbound DF 1681Y on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population; and * plots of individual plasma PK concentrations versus time for unbound DF 1681Y on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Plasma Unbound DF1681Y Concentrations by Time Point
Day -3 - 1 hr
|
13.7 ng/mL
Standard Deviation 10.13
|
22.4 ng/mL
Standard Deviation 19.14
|
109.1 ng/mL
Standard Deviation 131.15
|
|
Plasma Unbound DF1681Y Concentrations by Time Point
Day -3 - 2 hr
|
13.1 ng/mL
Standard Deviation 7.27
|
37.2 ng/mL
Standard Deviation 26.35
|
74.5 ng/mL
Standard Deviation 63.82
|
|
Plasma Unbound DF1681Y Concentrations by Time Point
Day 1 - 1 hr
|
12.3 ng/mL
Standard Deviation 14.64
|
78.9 ng/mL
Standard Deviation 38.86
|
76.2 ng/mL
Standard Deviation 107.84
|
|
Plasma Unbound DF1681Y Concentrations by Time Point
Day 1 - 2 hr
|
13.2 ng/mL
Standard Deviation 7.79
|
25.0 ng/mL
Standard Deviation 11.57
|
83.9 ng/mL
Standard Deviation 97.73
|
|
Plasma Unbound DF1681Y Concentrations by Time Point
Day 8 - 1 hr
|
9.1 ng/mL
Standard Deviation 7.63
|
13.0 ng/mL
Standard Deviation 13.27
|
84.4 ng/mL
Standard Deviation 147.04
|
|
Plasma Unbound DF1681Y Concentrations by Time Point
Day 8 - 2 hr
|
9.3 ng/mL
Standard Deviation 5.00
|
21.6 ng/mL
Standard Deviation 8.37
|
30.4 ng/mL
Standard Deviation 29.46
|
|
Plasma Unbound DF1681Y Concentrations by Time Point
Day 21 - 1 hr
|
2.5 ng/mL
Standard Deviation 0.96
|
44.9 ng/mL
Standard Deviation 61.18
|
117.2 ng/mL
Standard Deviation 84.65
|
|
Plasma Unbound DF1681Y Concentrations by Time Point
Day 21 - 2 hr
|
14.9 ng/mL
Standard Deviation 16.49
|
34.1 ng/mL
Standard Deviation 21.54
|
50.8 ng/mL
Standard Deviation 42.04
|
PRIMARY outcome
Timeframe: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter.
DF2243Y, DF2188Y, methanesulfonamide and ibuprofen are the metabolites detected in human plasma and urine, with DF2243Y being the major metabolite. Plasma DF 2243Y concentrations by time point for the PK Population are reported. CSR also presents: * plots of mean plasma PK concentrations versus time for DF 2243Y on Days -3, 1, 8 and 21, respectively (linear and semi-logarithmic) for the PK Population; * plots of individual plasma PK concentrations versus time for DF 2243Y on Days -3, 1, 8 and 21 (linear and semi-logarithmic) for the PK Population; * a plot of DF 2243Y versus time on Day -3 and Day 21 on a linear (upper) or semi-log (lower) axis.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Plasma DF2243Y Concentrations by Time Point
Day 21 - 0.5 hr
|
1.373 ug/mL
Standard Deviation 1.1150
|
3.577 ug/mL
Standard Deviation 2.9258
|
5.833 ug/mL
Standard Deviation 3.6968
|
|
Plasma DF2243Y Concentrations by Time Point
Day 21 - 1 hr
|
1.593 ug/mL
Standard Deviation 1.1089
|
5.650 ug/mL
Standard Deviation 5.6922
|
11.106 ug/mL
Standard Deviation 7.6876
|
|
Plasma DF2243Y Concentrations by Time Point
Day 21 - 3 hr
|
5.650 ug/mL
Standard Deviation 2.3079
|
10.343 ug/mL
Standard Deviation 5.5662
|
18.900 ug/mL
Standard Deviation 8.1250
|
|
Plasma DF2243Y Concentrations by Time Point
Day 1 - 8 hr
|
1.555 ug/mL
Standard Deviation 0.5630
|
2.933 ug/mL
Standard Deviation 0.4864
|
11.402 ug/mL
Standard Deviation 8.7268
|
|
Plasma DF2243Y Concentrations by Time Point
Day 1 - 24 hr
|
5.507 ug/mL
Standard Deviation 4.0277
|
12.953 ug/mL
Standard Deviation 7.3222
|
12.365 ug/mL
Standard Deviation 10.8597
|
|
Plasma DF2243Y Concentrations by Time Point
Day 8 - 0 hr
|
0.768 ug/mL
Standard Deviation 0.8572
|
2.787 ug/mL
Standard Deviation 2.6405
|
6.435 ug/mL
Standard Deviation 7.0355
|
|
Plasma DF2243Y Concentrations by Time Point
Day 21 - 0 hr
|
2.090 ug/mL
Standard Deviation 2.2439
|
3.923 ug/mL
Standard Deviation 3.1708
|
5.984 ug/mL
Standard Deviation 4.0332
|
|
Plasma DF2243Y Concentrations by Time Point
Day 8 - 8 hr
|
2.080 ug/mL
Standard Deviation 0.4491
|
4.320 ug/mL
Standard Deviation 1.1801
|
8.401 ug/mL
Standard Deviation 6.9080
|
|
Plasma DF2243Y Concentrations by Time Point
Day 8 - 24 hr
|
4.205 ug/mL
Standard Deviation 1.5768
|
3.310 ug/mL
Standard Deviation 1.3343
|
10.500 ug/mL
Standard Deviation 8.1986
|
|
Plasma DF2243Y Concentrations by Time Point
Day 21 - 1.5 hr
|
1.777 ug/mL
Standard Deviation 1.0633
|
7.097 ug/mL
Standard Deviation 7.0797
|
15.220 ug/mL
Standard Deviation 7.9701
|
|
Plasma DF2243Y Concentrations by Time Point
Day 21 - 2 hr
|
2.333 ug/mL
Standard Deviation 1.4514
|
8.093 ug/mL
Standard Deviation 6.9801
|
19.603 ug/mL
Standard Deviation 9.6539
|
|
Plasma DF2243Y Concentrations by Time Point
Day 21 - 4 hr
|
7.320 ug/mL
Standard Deviation 1.7217
|
8.947 ug/mL
Standard Deviation 3.6574
|
16.361 ug/mL
Standard Deviation 6.5721
|
|
Plasma DF2243Y Concentrations by Time Point
Day 21 - 6 hr
|
4.090 ug/mL
Standard Deviation 0.9231
|
7.597 ug/mL
Standard Deviation 3.2853
|
11.146 ug/mL
Standard Deviation 5.9542
|
|
Plasma DF2243Y Concentrations by Time Point
Day 21 - 8 hr
|
2.070 ug/mL
Standard Deviation 0.3811
|
4.497 ug/mL
Standard Deviation 1.9566
|
7.086 ug/mL
Standard Deviation 5.3867
|
|
Plasma DF2243Y Concentrations by Time Point
Day -3 - 0 hr
|
0.000 ug/mL
Standard Deviation 0.0000
|
0.000 ug/mL
Standard Deviation 0.0000
|
0.000 ug/mL
Standard Deviation 0.0000
|
|
Plasma DF2243Y Concentrations by Time Point
Day -3 - 0.5 hr
|
0.188 ug/mL
Standard Deviation 0.1477
|
0.167 ug/mL
Standard Deviation 0.1943
|
0.813 ug/mL
Standard Deviation 1.2689
|
|
Plasma DF2243Y Concentrations by Time Point
Day -3 - 1 hr
|
0.905 ug/mL
Standard Deviation 0.4641
|
1.380 ug/mL
Standard Deviation 1.6229
|
4.679 ug/mL
Standard Deviation 4.8768
|
|
Plasma DF2243Y Concentrations by Time Point
Day -3 - 1.5 hr
|
2.760 ug/mL
Standard Deviation 1.5317
|
2.803 ug/mL
Standard Deviation 2.3608
|
10.339 ug/mL
Standard Deviation 7.9404
|
|
Plasma DF2243Y Concentrations by Time Point
Day -3 - 2 hr
|
4.990 ug/mL
Standard Deviation 2.2479
|
4.470 ug/mL
Standard Deviation 2.7070
|
14.382 ug/mL
Standard Deviation 7.8212
|
|
Plasma DF2243Y Concentrations by Time Point
Day -3 - 3 hr
|
5.478 ug/mL
Standard Deviation 1.6318
|
7.497 ug/mL
Standard Deviation 4.2183
|
18.168 ug/mL
Standard Deviation 7.3720
|
|
Plasma DF2243Y Concentrations by Time Point
Day -3 - 4 hr
|
4.743 ug/mL
Standard Deviation 0.1638
|
7.857 ug/mL
Standard Deviation 3.7009
|
16.806 ug/mL
Standard Deviation 5.3131
|
|
Plasma DF2243Y Concentrations by Time Point
Day -3 - 6 hr
|
2.753 ug/mL
Standard Deviation 1.1919
|
6.000 ug/mL
Standard Deviation 0.6744
|
11.187 ug/mL
Standard Deviation 4.8182
|
|
Plasma DF2243Y Concentrations by Time Point
Day -3 - 8 hr
|
1.660 ug/mL
Standard Deviation 1.1473
|
3.693 ug/mL
Standard Deviation 1.1453
|
6.935 ug/mL
Standard Deviation 4.18711
|
|
Plasma DF2243Y Concentrations by Time Point
Day 1 - 0 hr
|
1.078 ug/mL
Standard Deviation 0.5890
|
4.683 ug/mL
Standard Deviation 5.2831
|
6.524 ug/mL
Standard Deviation 7.2445
|
|
Plasma DF2243Y Concentrations by Time Point
Day 1 - 0.5 hr
|
1.008 ug/mL
Standard Deviation 0.4421
|
4.987 ug/mL
Standard Deviation 4.8793
|
5.878 ug/mL
Standard Deviation 6.5607
|
|
Plasma DF2243Y Concentrations by Time Point
Day 1 - 1 hr
|
2.023 ug/mL
Standard Deviation 0.0645
|
6.520 ug/mL
Standard Deviation 4.1584
|
7.027 ug/mL
Standard Deviation 6.0291
|
|
Plasma DF2243Y Concentrations by Time Point
Day 1 - 2 hr
|
4.218 ug/mL
Standard Deviation 2.0817
|
13.093 ug/mL
Standard Deviation 4.0594
|
14.229 ug/mL
Standard Deviation 8.7457
|
|
Plasma DF2243Y Concentrations by Time Point
Day 1 - 4 hr
|
5.228 ug/mL
Standard Deviation 2.7555
|
11.727 ug/mL
Standard Deviation 1.3886
|
19.320 ug/mL
Standard Deviation 8.1202
|
|
Plasma DF2243Y Concentrations by Time Point
Day 8 - 0.5 hr
|
0.710 ug/mL
Standard Deviation 0.7590
|
2.595 ug/mL
Standard Deviation 2.9911
|
5.927 ug/mL
Standard Deviation 4.2413
|
|
Plasma DF2243Y Concentrations by Time Point
Day 8 - 1 hr
|
1.118 ug/mL
Standard Deviation 0.8848
|
2.850 ug/mL
Standard Deviation 2.2700
|
8.123 ug/mL
Standard Deviation 5.8406
|
|
Plasma DF2243Y Concentrations by Time Point
Day 8 - 2 hr
|
3.873 ug/mL
Standard Deviation 3.7232
|
6.080 ug/mL
Standard Deviation 3.6576
|
16.459 ug/mL
Standard Deviation 10.0027
|
|
Plasma DF2243Y Concentrations by Time Point
Day 8 - 4 hr
|
6.447 ug/mL
Standard Deviation 3.9722
|
9.960 ug/mL
Standard Deviation 1.3869
|
16.595 ug/mL
Standard Deviation 6.9212
|
PRIMARY outcome
Timeframe: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter.
DF2243Y, DF2188Y, methanesulfonamide and ibuprofen are the metabolites detected in human plasma and urine, with DF2243Y being the major metabolite. Plasma DF 2188Y concentrations by time point for the PK Population are reported. CSR also presents: * a plot of mean plasma PK concentrations versus time for DF 2188Y on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population; * plots of individual plasma PK concentrations versus time for DF 2188Y on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population; * a plot of DF 2881Y versus time on Day -3 and Day 21 on a linear (upper) or semi-log (lower) axis.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Plasma DF2188Y Concentrations by Time Point
Day 1 - 1 hr
|
1.883 ug/mL
Standard Deviation 1.0503
|
7.251 ug/mL
Standard Deviation 1.4929
|
6.940 ug/mL
Standard Deviation 6.5771
|
|
Plasma DF2188Y Concentrations by Time Point
Day -3 - 0 hr
|
0.000 ug/mL
Standard Deviation 0.0000
|
0.000 ug/mL
Standard Deviation 0.0000
|
0.000 ug/mL
Standard Deviation 0.0000
|
|
Plasma DF2188Y Concentrations by Time Point
Day -3 - 0.5 hr
|
0.547 ug/mL
Standard Deviation 0.3798
|
0.717 ug/mL
Standard Deviation 0.8503
|
1.781 ug/mL
Standard Deviation 2.4828
|
|
Plasma DF2188Y Concentrations by Time Point
Day -3 - 2 hr
|
2.882 ug/mL
Standard Deviation 1.1328
|
2.693 ug/mL
Standard Deviation 1.0611
|
9.381 ug/mL
Standard Deviation 5.0573
|
|
Plasma DF2188Y Concentrations by Time Point
Day -3 - 6 hr
|
0.571 ug/mL
Standard Deviation 0.2527
|
1.732 ug/mL
Standard Deviation 0.4955
|
2.373 ug/mL
Standard Deviation 1.2315
|
|
Plasma DF2188Y Concentrations by Time Point
Day -3 - 8 hr
|
0.385 ug/mL
Standard Deviation 0.2775
|
0.891 ug/mL
Standard Deviation 0.4059
|
1.813 ug/mL
Standard Deviation 1.5823
|
|
Plasma DF2188Y Concentrations by Time Point
Day 1 - 0.5 hr
|
0.997 ug/mL
Standard Deviation 0.4469
|
2.930 ug/mL
Standard Deviation 0.9101
|
2.324 ug/mL
Standard Deviation 2.7844
|
|
Plasma DF2188Y Concentrations by Time Point
Day 1 - 2 hr
|
2.804 ug/mL
Standard Deviation 1.5570
|
6.129 ug/mL
Standard Deviation 0.5653
|
12.093 ug/mL
Standard Deviation 8.5639
|
|
Plasma DF2188Y Concentrations by Time Point
Day 1 - 4 hr
|
1.687 ug/mL
Standard Deviation 0.7018
|
3.103 ug/mL
Standard Deviation 0.6448
|
8.951 ug/mL
Standard Deviation 6.3792
|
|
Plasma DF2188Y Concentrations by Time Point
Day 1 - 8 hr
|
0.342 ug/mL
Standard Deviation 0.1840
|
0.519 ug/mL
Standard Deviation 0.2349
|
4.222 ug/mL
Standard Deviation 3.8268
|
|
Plasma DF2188Y Concentrations by Time Point
Day 1 - 24 hr
|
2.019 ug/mL
Standard Deviation 1.8027
|
4.706 ug/mL
Standard Deviation 2.4979
|
5.249 ug/mL
Standard Deviation 7.1068
|
|
Plasma DF2188Y Concentrations by Time Point
Day 8 - 0 hr
|
0.185 ug/mL
Standard Deviation 0.2617
|
0.536 ug/mL
Standard Deviation 0.4428
|
1.302 ug/mL
Standard Deviation 1.9543
|
|
Plasma DF2188Y Concentrations by Time Point
Day 8 - 24 hr
|
1.961 ug/mL
Standard Deviation 1.5761
|
1.627 ug/mL
Standard Deviation 1.1583
|
2.753 ug/mL
Standard Deviation 2.7020
|
|
Plasma DF2188Y Concentrations by Time Point
Day 21 - 0 hr
|
0.348 ug/mL
Standard Deviation 0.2480
|
0.913 ug/mL
Standard Deviation 0.7577
|
1.211 ug/mL
Standard Deviation 1.0054
|
|
Plasma DF2188Y Concentrations by Time Point
Day 21 - 1 hr
|
0.398 ug/mL
Standard Deviation 0.0494
|
3.039 ug/mL
Standard Deviation 3.1614
|
8.087 ug/mL
Standard Deviation 4.2863
|
|
Plasma DF2188Y Concentrations by Time Point
Day 21 - 1.5 hr
|
0.911 ug/mL
Standard Deviation 0.3382
|
3.522 ug/mL
Standard Deviation 2.8731
|
9.590 ug/mL
Standard Deviation 4.4184
|
|
Plasma DF2188Y Concentrations by Time Point
Day 21 - 2 hr
|
1.612 ug/mL
Standard Deviation 0.7290
|
3.647 ug/mL
Standard Deviation 2.0369
|
9.485 ug/mL
Standard Deviation 6.1568
|
|
Plasma DF2188Y Concentrations by Time Point
Day 21 - 3 hr
|
3.138 ug/mL
Standard Deviation 0.9689
|
3982 ug/mL
Standard Deviation 1.2720
|
6.382 ug/mL
Standard Deviation 4.5496
|
|
Plasma DF2188Y Concentrations by Time Point
Day 1 - 0 hr
|
0.243 ug/mL
Standard Deviation 0.1092
|
1.360 ug/mL
Standard Deviation 1.7820
|
1.433 ug/mL
Standard Deviation 2.0366
|
|
Plasma DF2188Y Concentrations by Time Point
Day -3 - 1 hr
|
1.311 ug/mL
Standard Deviation 0.6671
|
2.128 ug/mL
Standard Deviation 2.3765
|
4.986 ug/mL
Standard Deviation 3.6296
|
|
Plasma DF2188Y Concentrations by Time Point
Day -3 - 1.5 hr
|
2.337 ug/mL
Standard Deviation 0.9274
|
2.581 ug/mL
Standard Deviation 2.0086
|
8.136 ug/mL
Standard Deviation 3.7429
|
|
Plasma DF2188Y Concentrations by Time Point
Day -3 - 3 hr
|
2.024 ug/mL
Standard Deviation 0.4877
|
2.968 ug/mL
Standard Deviation 1.0848
|
8.332 ug/mL
Standard Deviation 4.3300
|
|
Plasma DF2188Y Concentrations by Time Point
Day -3 - 4 hr
|
1.455 ug/mL
Standard Deviation 0.5505
|
2.752 ug/mL
Standard Deviation 0.5639
|
5.320 ug/mL
Standard Deviation 2.8278
|
|
Plasma DF2188Y Concentrations by Time Point
Day 8 - 8 hr
|
0.614 ug/mL
Standard Deviation 0.4115
|
1.117 ug/mL
Standard Deviation 0.5547
|
2.101 ug/mL
Standard Deviation 2.1855
|
|
Plasma DF2188Y Concentrations by Time Point
Day 21 - 0.5 hr
|
0.331 ug/mL
Standard Deviation 0.0515
|
1.542 ug/mL
Standard Deviation 1.5637
|
3.707 ug/mL
Standard Deviation 2.8351
|
|
Plasma DF2188Y Concentrations by Time Point
Day 8 - 0.5 hr
|
0.381 ug/mL
Standard Deviation 0.2595
|
0.913 ug/mL
Standard Deviation 1.1455
|
7.260 ug/mL
Standard Deviation 9.2883
|
|
Plasma DF2188Y Concentrations by Time Point
Day 8 - 1 hr
|
1.360 ug/mL
Standard Deviation 1.0877
|
2.022 ug/mL
Standard Deviation 1.5295
|
9.494 ug/mL
Standard Deviation 8.6619
|
|
Plasma DF2188Y Concentrations by Time Point
Day 8 - 2 hr
|
2.159 ug/mL
Standard Deviation 0.9085
|
4.423 ug/mL
Standard Deviation 0.8932
|
10.592 ug/mL
Standard Deviation 9.1860
|
|
Plasma DF2188Y Concentrations by Time Point
Day 8 - 4 hr
|
1.966 ug/mL
Standard Deviation 1.2606
|
3.552 ug/mL
Standard Deviation 0.6505
|
6.181 ug/mL
Standard Deviation 3.1973
|
|
Plasma DF2188Y Concentrations by Time Point
Day 21 - 4 hr
|
2.389 ug/mL
Standard Deviation 0.1047
|
3.518 ug/mL
Standard Deviation 1.4208
|
4.209 ug/mL
Standard Deviation 2.0152
|
|
Plasma DF2188Y Concentrations by Time Point
Day 21 - 6 hr
|
0.949 ug/mL
Standard Deviation 0.1443
|
2.185 ug/mL
Standard Deviation 1.2816
|
2.139 ug/mL
Standard Deviation 1.9283
|
|
Plasma DF2188Y Concentrations by Time Point
Day 21 - 8 hr
|
0.482 ug/mL
Standard Deviation 0.1344
|
0.987 ug/mL
Standard Deviation 0.4603
|
1.166 ug/mL
Standard Deviation 1.4547
|
PRIMARY outcome
Timeframe: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter.
DF2243Y, DF2188Y, methanesulfonamide and ibuprofen are the metabolites detected in human plasma and urine, with DF2243Y being the major metabolite. Plasma ibuprofen concentrations are reported by time point for the PK Population. CSR describes also: * a plot of mean plasma PK concentrations versus time for ibuprofen on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population; * plots of individual plasma PK concentrations versus time for ibuprofen on Days -3, 1, 8 and 21 respectively (linear and semi-logarithmic) for the PK Population; * a plot of ibuprofen versus time on Day -3 and Day 21 on a linear (upper) or semi-log (lower) axis.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Plasma Ibuprofen Concentrations by Time Point
Day -3 - 0.5 hr
|
0.165 ug/mL
Standard Deviation 0.1401
|
0.260 ug/mL
Standard Deviation 0.3355
|
0.282 ug/mL
Standard Deviation 0.2943
|
|
Plasma Ibuprofen Concentrations by Time Point
Day -3 - 1 hr
|
0.244 ug/mL
Standard Deviation 0.3003
|
0.578 ug/mL
Standard Deviation 0.7653
|
1.141 ug/mL
Standard Deviation 0.9977
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 21 - 6 hr
|
0.404 ug/mL
Standard Deviation 0.4958
|
1.179 ug/mL
Standard Deviation 0.6063
|
1.645 ug/mL
Standard Deviation 1.2753
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 21 - 8 hr
|
0.312 ug/mL
Standard Deviation 0.227
|
0.802 ug/mL
Standard Deviation 0.3472
|
1.218 ug/mL
Standard Deviation 0.9901
|
|
Plasma Ibuprofen Concentrations by Time Point
Day -3 - 1.5 hr
|
0.430 ug/mL
Standard Deviation 0.4382
|
0.663 ug/mL
Standard Deviation 0.8429
|
2.144 ug/mL
Standard Deviation 1.6461
|
|
Plasma Ibuprofen Concentrations by Time Point
Day -3 - 2 hr
|
0.676 ug/mL
Standard Deviation 0.6193
|
0.736 ug/mL
Standard Deviation 0.7971
|
2.728 ug/mL
Standard Deviation 2.5583
|
|
Plasma Ibuprofen Concentrations by Time Point
Day -3 - 3 hr
|
0.760 ug/mL
Standard Deviation 0.6860
|
0.863 ug/mL
Standard Deviation 0.6598
|
2.979 ug/mL
Standard Deviation 2.6527
|
|
Plasma Ibuprofen Concentrations by Time Point
Day -3 - 4 hr
|
0.732 ug/mL
Standard Deviation 0.6436
|
0.930 ug/mL
Standard Deviation 0.5859
|
2.420 ug/mL
Standard Deviation 2.3095
|
|
Plasma Ibuprofen Concentrations by Time Point
Day -3 - 6 hr
|
0.564 ug/mL
Standard Deviation 0.5032
|
0.861 ug/mL
Standard Deviation 0.5131
|
1.653 ug/mL
Standard Deviation 1.3698
|
|
Plasma Ibuprofen Concentrations by Time Point
Day -3 - 8 hr
|
0.453 ug/mL
Standard Deviation 0.3960
|
0.680 ug/mL
Standard Deviation 0.4165
|
1.249 ug/mL
Standard Deviation 0.9589
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 1 - 0 hr
|
0.414 ug/mL
Standard Deviation 0.4035
|
1.245 ug/mL
Standard Deviation 1.3888
|
1.077 ug/mL
Standard Deviation 0.9690
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 1 - 0.5 hr
|
0.410 ug/mL
Standard Deviation 0.3334
|
1.2220 ug/mL
Standard Deviation 1.0325
|
0.984 ug/mL
Standard Deviation 0.8270
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 1 - 1 hr
|
0.539 ug/mL
Standard Deviation 0.5508
|
1.759 ug/mL
Standard Deviation 1.5027
|
1.319 ug/mL
Standard Deviation 1.2569
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 1 - 2 hr
|
0.798 ug/mL
Standard Deviation 0.8648
|
1.948 ug/mL
Standard Deviation 1.4572
|
2.633 ug/mL
Standard Deviation 2.2699
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 1 - 4 hr
|
0.816 ug/mL
Standard Deviation 0.8769
|
1.557 ug/mL
Standard Deviation 0.9902
|
2.575 ug/mL
Standard Deviation 2.0191
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 1 - 8 hr
|
0.440 ug/mL
Standard Deviation 0.3806
|
0.693 ug/mL
Standard Deviation 0.4651
|
1.532 ug/mL
Standard Deviation 1.0465
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 1 - 24 hr
|
0.862 ug/mL
Standard Deviation 0.4607
|
1.964 ug/mL
Standard Deviation 1.5247
|
1.667 ug/mL
Standard Deviation 1.3126
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 8 - 0 hr
|
0.125 ug/mL
Standard Deviation 0.1307
|
0.534 ug/mL
Standard Deviation 0.5566
|
1.068 ug/mL
Standard Deviation 0.7676
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 8 - 0.5 hr
|
0.140 ug/mL
Standard Deviation 0.1191
|
0.652 ug/mL
Standard Deviation 0.7177
|
2.087 ug/mL
Standard Deviation 2.0162
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 8 - 1 hr
|
0.251 ug/mL
Standard Deviation 0.2304
|
0.571 ug/mL
Standard Deviation 0.5765
|
2.683 ug/mL
Standard Deviation 2.7211
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 8 - 2 hr
|
0.312 ug/mL
Standard Deviation 0.3725
|
1.065 ug/mL
Standard Deviation 0.8626
|
2.879 ug/mL
Standard Deviation 2.7853
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 8 - 4 hr
|
0.352 ug/mL
Standard Deviation 0.3909
|
1.016 ug/mL
Standard Deviation 0.4036
|
2.553 ug/mL
Standard Deviation 2.0585
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 8 - 8 hr
|
0.213 ug/mL
Standard Deviation 0.2363
|
0.699 ug/mL
Standard Deviation 0.4269
|
1.310 ug/mL
Standard Deviation 1.0034
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 8 - 24 hr
|
0.416 ug/mL
Standard Deviation 0.4582
|
0.602 ug/mL
Standard Deviation 0.3706
|
1.448 ug/mL
Standard Deviation 0.9161
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 21 - 0 hr
|
0.300 ug/mL
Standard Deviation 0.3560
|
0.863 ug/mL
Standard Deviation 0.7528
|
1.210 ug/mL
Standard Deviation 0.8951
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 21 - 0.5 hr
|
0.226 ug/mL
Standard Deviation 0.2443
|
0.734 ug/mL
Standard Deviation 0.5966
|
1.341 ug/mL
Standard Deviation 0.7483
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 21 - 1 hr
|
0.238 ug/mL
Standard Deviation 0.2627
|
0.849 ug/mL
Standard Deviation 0.6339
|
2.381 ug/mL
Standard Deviation 1.4899
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 21 - 1.5 hr
|
0.237 ug/mL
Standard Deviation 0.2291
|
0.986 ug/mL
Standard Deviation 0.7064
|
3.222 ug/mL
Standard Deviation 2.2855
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 21 - 2 hr
|
0.342 ug/mL
Standard Deviation 0.3656
|
1.214 ug/mL
Standard Deviation 0.8686
|
3.335 ug/mL
Standard Deviation 2.4454
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 21 - 3 hr
|
0.543 ug/mL
Standard Deviation 0.5866
|
1.562 ug/mL
Standard Deviation 1.1380
|
3.327 ug/mL
Standard Deviation 2.8221
|
|
Plasma Ibuprofen Concentrations by Time Point
Day 21 - 4 hr
|
0.546 ug/mL
Standard Deviation 0.6712
|
1.970 ug/mL
Standard Deviation 1.9069
|
2.712 ug/mL
Standard Deviation 1.9665
|
|
Plasma Ibuprofen Concentrations by Time Point
Day -3 - 0 hr
|
0.040 ug/mL
Standard Deviation 0.0383
|
0.024 ug/mL
Standard Deviation 0.0172
|
0.030 ug/mL
Standard Deviation 0.0444
|
PRIMARY outcome
Timeframe: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours) and 8 (0, 0.5, 1, 2, 4, 8, 24 hours) of cycle 1.Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter.
Plasma paclitaxel concentrations are reported by time point for the PK Population. CSR describes also: * A plot of mean plasma PK concentrations versus time for paclitaxel on Days 1 and 8 respectively (linear and semi-logarithmic) for the PK Population; * plots of individual plasma PK concentrations versus time for paclitaxel on Days 1 and 8 respectively (linear and semi-logarithmic) for the PK Population; * a plot of paclitaxel versus time on Day 1 and Day 8 on a linear (upper) or semi-log (lower) axis.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Plasma Paclitaxel Concentrations by Time Point
Day 1 - 0 hr
|
0.000 ug/mL
Standard Deviation 0.0000
|
0.000 ug/mL
Standard Deviation 0.0000
|
0.070 ug/mL
Standard Deviation 0.1664
|
|
Plasma Paclitaxel Concentrations by Time Point
Day 1 - 8 hr
|
0.066 ug/mL
Standard Deviation 0.0094
|
0.060 ug/mL
Standard Deviation 0.0190
|
0.099 ug/mL
Standard Deviation 0.0622
|
|
Plasma Paclitaxel Concentrations by Time Point
Day 1 - 0.5 hr
|
1.483 ug/mL
Standard Deviation 1.0948
|
1.560 ug/mL
Standard Deviation 0.5060
|
2.275 ug/mL
Standard Deviation 1.2319
|
|
Plasma Paclitaxel Concentrations by Time Point
Day 1 - 1 hr
|
1.954 ug/mL
Standard Deviation 1.0995
|
2.438 ug/mL
Standard Deviation 0.4045
|
2.898 ug/mL
Standard Deviation 1.4819
|
|
Plasma Paclitaxel Concentrations by Time Point
Day 1 - 2 hr
|
0.733 ug/mL
Standard Deviation 0.7148
|
0.342 ug/mL
Standard Deviation 0.1071
|
0.600 ug/mL
Standard Deviation 0.4058
|
|
Plasma Paclitaxel Concentrations by Time Point
Day 1 - 4 hr
|
0.166 ug/mL
Standard Deviation 0.0560
|
0.118 ug/mL
Standard Deviation 0.0398
|
0.363 ug/mL
Standard Deviation 0.5901
|
|
Plasma Paclitaxel Concentrations by Time Point
Day 1 - 24 hr
|
0.019 ug/mL
Standard Deviation 0.0076
|
0.020 ug/mL
Standard Deviation 0.0076
|
0.030 ug/mL
Standard Deviation 0.0145
|
|
Plasma Paclitaxel Concentrations by Time Point
Day 8 - 0 hr
|
0.000 ug/mL
Standard Deviation 0.0000
|
0.004 ug/mL
Standard Deviation 0.0075
|
0.001 ug/mL
Standard Deviation 0.0022
|
|
Plasma Paclitaxel Concentrations by Time Point
Day 8 - 0.5 hr
|
1.409 ug/mL
Standard Deviation 1.0059
|
1.466 ug/mL
Standard Deviation 0.1372
|
2.426 ug/mL
Standard Deviation 1.3387
|
|
Plasma Paclitaxel Concentrations by Time Point
Day 8 - 1 hr
|
1.730 ug/mL
Standard Deviation 1.1795
|
2.554 ug/mL
Standard Deviation 0.7296
|
3.222 ug/mL
Standard Deviation 1.4919
|
|
Plasma Paclitaxel Concentrations by Time Point
Day 8 - 2 hr
|
0.318 ug/mL
Standard Deviation 0.0707
|
0.706 ug/mL
Standard Deviation 0.7383
|
0.759 ug/mL
Standard Deviation 1.0239
|
|
Plasma Paclitaxel Concentrations by Time Point
Day 8 - 4 hr
|
0.122 ug/mL
Standard Deviation 0.0294
|
0.175 ug/mL
Standard Deviation 0.1054
|
0.196 ug/mL
Standard Deviation 0.1234
|
|
Plasma Paclitaxel Concentrations by Time Point
Day 8 - 8 hr
|
0.060 ug/mL
Standard Deviation 0.0195
|
0.102 ug/mL
Standard Deviation 0.0814
|
0.095 ug/mL
Standard Deviation 0.0638
|
|
Plasma Paclitaxel Concentrations by Time Point
Day 8 - 24 hr
|
0.023 ug/mL
Standard Deviation 0.0078
|
0.047 ug/mL
Standard Deviation 0.0430
|
0.031 ug/mL
Standard Deviation 0.0190
|
PRIMARY outcome
Timeframe: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter.
PK parameters were calculated for cycle 1 only. Co is the pre-dose concentration/concentration at time zero. Cmax is the maximum plasma concentration obtained directly from the data without interpolation, expressed in concentration units.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
C0 and Cmax for DF1681Y
DF1681Y - C0 - Day -3
|
0.00 ug/mL
Standard Deviation 0
|
0.00 ug/mL
Standard Deviation 0
|
0.00 ug/mL
Standard Deviation 0
|
|
C0 and Cmax for DF1681Y
DF1681Y - C0 - Day 1
|
1.05 ug/mL
Standard Deviation 0.37
|
4.24 ug/mL
Standard Deviation 3.39
|
5.74 ug/mL
Standard Deviation 6.77
|
|
C0 and Cmax for DF1681Y
DF1681Y - C0 - Day 8
|
0.79 ug/mL
Standard Deviation 1.05
|
2.40 ug/mL
Standard Deviation 1.78
|
3.55 ug/mL
Standard Deviation 2.05
|
|
C0 and Cmax for DF1681Y
DF1681Y - C0 - Day 21
|
1.25 ug/mL
Standard Deviation 0.76
|
6.00 ug/mL
Standard Deviation 5.56
|
4.98 ug/mL
Standard Deviation 4.32
|
|
C0 and Cmax for DF1681Y
DF1681Y - Cmax - Day -3
|
37.9 ug/mL
Standard Deviation 15.2
|
35.6 ug/mL
Standard Deviation 328.6
|
65.0 ug/mL
Standard Deviation 21.1
|
|
C0 and Cmax for DF1681Y
DF1681Y - Cmax - Day 1
|
30.7 ug/mL
Standard Deviation 19.0
|
45.4 ug/mL
Standard Deviation 3.88
|
58.7 ug/mL
Standard Deviation 22.9
|
|
C0 and Cmax for DF1681Y
DF1681Y - Cmax - Day 8
|
17.9 ug/mL
Standard Deviation 7.11
|
34.4 ug/mL
Standard Deviation 11.5
|
60.2 ug/mL
Standard Deviation 26.5
|
|
C0 and Cmax for DF1681Y
DF1681Y - Cmax - Day 21
|
19.4 ug/mL
Standard Deviation 3.27
|
44.6 ug/mL
Standard Deviation 25.3
|
71.2 ug/mL
Standard Deviation 24.6
|
PRIMARY outcome
Timeframe: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter.
PK parameters were calculated for cycle 1 only. Co is the pre-dose concentration/concentration at time zero. Cmax is the maximum plasma concentration obtained directly from the data without interpolation, expressed in concentration units.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
C0 and Cmax for DF2243Y
DF2243Y - C0 - Day -3
|
0.00 ug/mL
Standard Deviation 0
|
0.00 ug/mL
Standard Deviation 0
|
0.00 ug/mL
Standard Deviation 0
|
|
C0 and Cmax for DF2243Y
DF2243Y - C0 - Day 1
|
1.08 ug/mL
Standard Deviation 0.59
|
4.68 ug/mL
Standard Deviation 5.28
|
6.52 ug/mL
Standard Deviation 7.25
|
|
C0 and Cmax for DF2243Y
DF2243Y - C0 - Day 8
|
0.77 ug/mL
Standard Deviation 0.86
|
2.79 ug/mL
Standard Deviation 2.64
|
6.44 ug/mL
Standard Deviation 7.04
|
|
C0 and Cmax for DF2243Y
DF2243Y - C0 - Day 21
|
2.09 ug/mL
Standard Deviation 2.24
|
3.92 ug/mL
Standard Deviation 3.17
|
5.98 ug/mL
Standard Deviation 4.03
|
|
C0 and Cmax for DF2243Y
DF2243Y - Cmax - Day -3
|
5.85 ug/mL
Standard Deviation 1.50
|
8.46 ug/mL
Standard Deviation 3.05
|
19.5 ug/mL
Standard Deviation 6.73
|
|
C0 and Cmax for DF2243Y
DF2243Y - Cmax - Day 1
|
5.79 ug/mL
Standard Deviation 2.84
|
13.8 ug/mL
Standard Deviation 3.51
|
20.6 ug/mL
Standard Deviation 8.35
|
|
C0 and Cmax for DF2243Y
DF2243Y - Cmax - Day 8
|
5.07 ug/mL
Standard Deviation 4.32
|
10.6 ug/mL
Standard Deviation 0.32
|
18.3 ug/mL
Standard Deviation 8.22
|
|
C0 and Cmax for DF2243Y
DF2243Y - Cmax - Day 21
|
7.71 ug/mL
Standard Deviation 1.63
|
12.6 ug/mL
Standard Deviation 3.13
|
21.4 ug/mL
Standard Deviation 8.75
|
PRIMARY outcome
Timeframe: Days -3 (pre-dose, 0.5, 1, 2, 4, 8, 24 hours), 1 (pre-dose, 0.5, 1, 2, 4, 8, 24 hours), 8 (pre-dose, 0.5, 1, 2, 4, 8, 24 hours) and 21 (pre-dose, 0.5, 1, 2, 4, 8, 24 hours)Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter.
PK parameters were calculated for cycle 1 only. Co is the pre-dose concentration/concentration at time zero. Cmax is the maximum plasma concentration obtained directly from the data without interpolation, expressed in concentration units.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
C0 and Cmax for DF2188Y
DF2188Y - Cmax - Day 8
|
2.11 ug/mL
Standard Deviation 1.25
|
4.42 ug/mL
Standard Deviation 0.89
|
14.5 ug/mL
Standard Deviation 9.30
|
|
C0 and Cmax for DF2188Y
DF2188Y - Cmax - Day 21
|
3.29 ug/mL
Standard Deviation 0.73
|
5.27 ug/mL
Standard Deviation 2.42
|
12.2 ug/mL
Standard Deviation 5.83
|
|
C0 and Cmax for DF2188Y
DF2188Y- C0 - Day -3
|
0 ug/mL
Standard Deviation 0
|
0 ug/mL
Standard Deviation 0
|
0 ug/mL
Standard Deviation 0
|
|
C0 and Cmax for DF2188Y
DF2188Y - C0 - Day 1
|
0.24 ug/mL
Standard Deviation 0.11
|
1.36 ug/mL
Standard Deviation 1.78
|
1.43 ug/mL
Standard Deviation 2.04
|
|
C0 and Cmax for DF2188Y
DF2188Y - C0 - Day 8
|
0.18 ug/mL
Standard Deviation 0.26
|
0.54 ug/mL
Standard Deviation 0.44
|
1.30 ug/mL
Standard Deviation 1.95
|
|
C0 and Cmax for DF2188Y
DF2188Y - C0 - Day 21
|
0.35 ug/mL
Standard Deviation 0.25
|
0.91 ug/mL
Standard Deviation 0.76
|
1.21 ug/mL
Standard Deviation 1.01
|
|
C0 and Cmax for DF2188Y
DF2188Y - Cmax - Day -3
|
3.01 ug/mL
Standard Deviation 0.99
|
3.67 ug/mL
Standard Deviation 1.42
|
10.5 ug/mL
Standard Deviation 4.85
|
|
C0 and Cmax for DF2188Y
DF2188Y - Cmax - Day 1
|
2.90 ug/mL
Standard Deviation 1.53
|
7.37 ug/mL
Standard Deviation 1.29
|
13.4 ug/mL
Standard Deviation 7.68
|
PRIMARY outcome
Timeframe: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter.
PK parameters were calculated for cycle 1 only. Co is the pre-dose concentration/concentration at time zero. Cmax is the maximum plasma concentration obtained directly from the data without interpolation, expressed in concentration units.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
C0 and Cmax for Ibuprofen
ibuprofen - C0 - Day -3
|
0.04 ug/mL
Standard Deviation 0.04
|
0.02 ug/mL
Standard Deviation 0.02
|
0.03 ug/mL
Standard Deviation 0.04
|
|
C0 and Cmax for Ibuprofen
ibuprofen - C0 - Day 1
|
0.41 ug/mL
Standard Deviation 0.40
|
1.25 ug/mL
Standard Deviation 1.39
|
1.08 ug/mL
Standard Deviation 0.97
|
|
C0 and Cmax for Ibuprofen
ibuprofen - C0 - Day 8
|
0.12 ug/mL
Standard Deviation 0.13
|
0.53 ug/mL
Standard Deviation 0.56
|
1.07 ug/mL
Standard Deviation 0.77
|
|
C0 and Cmax for Ibuprofen
ibuprofen - C0 - Day 21
|
0.3 ug/mL
Standard Deviation 0.36
|
0.86 ug/mL
Standard Deviation 0.75
|
1.21 ug/mL
Standard Deviation 0.90
|
|
C0 and Cmax for Ibuprofen
ibuprofen - Cmax - Day -3
|
0.77 ug/mL
Standard Deviation 0.78
|
1.02 ug/mL
Standard Deviation 0.59
|
3.11 ug/mL
Standard Deviation 2.59
|
|
C0 and Cmax for Ibuprofen
ibuprofen - Cmax - Day 1
|
0.86 ug/mL
Standard Deviation 0.86
|
1.98 ug/mL
Standard Deviation 1.46
|
2.95 ug/mL
Standard Deviation 2.10
|
|
C0 and Cmax for Ibuprofen
ibuprofen - Cmax - Day 8
|
0.34 ug/mL
Standard Deviation 0.32
|
1.24 ug/mL
Standard Deviation 0.75
|
3.69 ug/mL
Standard Deviation 2.67
|
|
C0 and Cmax for Ibuprofen
ibuprofen - Cmax - Day 21
|
0.58 ug/mL
Standard Deviation 0.64
|
2.16 ug/mL
Standard Deviation 1.74
|
3.99 ug/mL
Standard Deviation 2.74
|
PRIMARY outcome
Timeframe: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours)Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter.
PK parameters were calculated for cycle 1 only. Co is the pre-dose concentration/concentration at time zero. Cmax is the maximum plasma concentration obtained directly from the data without interpolation, expressed in concentration units.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Cmax for Paclitaxel
Paclitaxel - Cmax - Day 8
|
2.31 ug/mL
Standard Deviation 0.30
|
2.55 ug/mL
Standard Deviation 0.73
|
3.62 ug/mL
Standard Deviation 0.96
|
|
Cmax for Paclitaxel
Paclitaxel - Cmax - Day 1
|
2.35 ug/mL
Standard Deviation 0.47
|
2.44 ug/mL
Standard Deviation 0.41
|
3.10 ug/mL
Standard Deviation 1.16
|
PRIMARY outcome
Timeframe: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter
PK parameters were calculated for cycle 1 only. Tmax is the Time to reach the maximum plasma concentration obtained directly from the data without interpolation. t1/2 is the Elimination half-life, calculated as ln(2)/ Kel (where Kel is the Terminal elimination rate constant, calculated as the negative of the slope of the terminal log-linear segment of the plasma concentration time curve).
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Tmax and t1/2 for DF1681Y
DF1681Y - tmax - Day -3
|
0.90 hours
Standard Deviation 0.45
|
1.82 hours
Standard Deviation 1.25
|
1.41 hours
Standard Deviation 0.55
|
|
Tmax and t1/2 for DF1681Y
DF1681Y - tmax - Day 1
|
2.15 hours
Standard Deviation 1.44
|
1.01 hours
Standard Deviation 0.01
|
2.64 hours
Standard Deviation 4.07
|
|
Tmax and t1/2 for DF1681Y
DF1681Y - tmax - Day 8
|
1.30 hours
Standard Deviation 0.46
|
1.72 hours
Standard Deviation 0.48
|
2.45 hours
Standard Deviation 2.35
|
|
Tmax and t1/2 for DF1681Y
DF1681Y - tmax - Day 21
|
2.66 hours
Standard Deviation 0.57
|
2.32 hours
Standard Deviation 1.52
|
1.40 hours
Standard Deviation 0.35
|
|
Tmax and t1/2 for DF1681Y
DF1681Y - t1/2 - Day -3
|
1.65 hours
Standard Deviation 0.51
|
1.82 hours
Standard Deviation 0.82
|
1.91 hours
Standard Deviation 0.64
|
|
Tmax and t1/2 for DF1681Y
DF1681Y - t1/2 - Day 1
|
1.97 hours
|
1.73 hours
Standard Deviation 0.09
|
2.14 hours
Standard Deviation 0.45
|
|
Tmax and t1/2 for DF1681Y
DF1681Y - t1/2 - Day 8
|
2.00 hours
|
3.57 hours
|
1.88 hours
Standard Deviation 0.27
|
|
Tmax and t1/2 for DF1681Y
DF1681Y - t1/2 - Day 21
|
1.89 hours
Standard Deviation 0.57
|
1.97 hours
Standard Deviation 0.55
|
1.95 hours
Standard Deviation 0.56
|
PRIMARY outcome
Timeframe: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter
PK parameters were calculated for cycle 1 only. Tmax is the Time to reach the maximum plasma concentration obtained directly from the data without interpolation. t1/2 is the Elimination half-life, calculated as ln(2)/ Kel (where Kel is the Terminal elimination rate constant, calculated as the negative of the slope of the terminal log-linear segment of the plasma concentration time curve).
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Tmax and t1/2 for DF2243Y
DF2243Y - tmax - Day -3
|
3.30 hours
Standard Deviation 0.87
|
4.32 hours
Standard Deviation 1.52
|
3.41 hours
Standard Deviation 1.00
|
|
Tmax and t1/2 for DF2243Y
DF2243Y - tmax - Day 1
|
3.51 hours
Standard Deviation 0.99
|
2.67 hours
Standard Deviation 1.16
|
4.00 hours
Standard Deviation 1.57
|
|
Tmax and t1/2 for DF2243Y
DF2243Y - tmax - Day 8
|
4.29 hours
Standard Deviation 2.94
|
3.32 hours
Standard Deviation 1.15
|
3.40 hours
Standard Deviation 1.90
|
|
Tmax and t1/2 for DF2243Y
DF2243Y - tmax - Day 21
|
3.71 hours
Standard Deviation 0.62
|
3.66 hours
Standard Deviation 2.08
|
2.87 hours
Standard Deviation 0.83
|
|
Tmax and t1/2 for DF2243Y
DF2243Y - t1/2 - Day -3
|
1.34 hours
|
3.79 hours
|
2.81 hours
Standard Deviation 1.20
|
|
Tmax and t1/2 for DF2243Y
DF2243Y - t1/2 - Day 21
|
1.97 hours
|
2.46 hours
Standard Deviation 0.59
|
3.35 hours
Standard Deviation 1.63
|
PRIMARY outcome
Timeframe: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter
PK parameters were calculated for cycle 1 only. Tmax is the Time to reach the maximum plasma concentration obtained directly from the data without interpolation. t1/2 is the Elimination half-life, calculated as ln(2)/ Kel (where Kel is the Terminal elimination rate constant, calculated as the negative of the slope of the terminal log-linear segment of the plasma concentration time curve).
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Tmax and t1/2 for DF2188Y
DF2188Y - tmax - Day 8
|
2.30 hours
Standard Deviation 1.23
|
2.03 hours
Standard Deviation 0.06
|
2.20 hours
Standard Deviation 1.37
|
|
Tmax and t1/2 for DF2188Y
DF2188Y - tmax - Day -3
|
2.05 hours
Standard Deviation 0.71
|
2.81 hours
Standard Deviation 1.24
|
2.44 hours
Standard Deviation 1.08
|
|
Tmax and t1/2 for DF2188Y
DF2188Y- tmax - Day 1
|
1.78 hours
Standard Deviation 0.52
|
1.33 hours
Standard Deviation 0.58
|
2.45 hours
Standard Deviation 1.04
|
|
Tmax and t1/2 for DF2188Y
DF2188Y - tmax - Day 21
|
3.33 hours
Standard Deviation 0.57
|
2.33 hours
Standard Deviation 1.14
|
1.77 hours
Standard Deviation 0.96
|
|
Tmax and t1/2 for DF2188Y
DF2188Y - t1/2 - Day -3
|
1.63 hours
Standard Deviation 0.23
|
2.53 hours
Standard Deviation 1.53
|
1.65 hours
Standard Deviation 0.40
|
|
Tmax and t1/2 for DF2188Y
DF2188Y - t1/2 - Day 1
|
1.51 hours
|
1.48 hours
Standard Deviation 0.07
|
—
|
|
Tmax and t1/2 for DF2188Y
DF2188Y - t1/2 - Day 8
|
—
|
—
|
1.42 hours
Standard Deviation 0.15
|
|
Tmax and t1/2 for DF2188Y
DF2188Y - t1/2 - Day 21
|
1.90 hours
Standard Deviation 0.20
|
1.77 hours
Standard Deviation 0.21
|
2.18 hours
Standard Deviation 1.44
|
PRIMARY outcome
Timeframe: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter
PK parameters were calculated for cycle 1 only. Tmax is the Time to reach the maximum plasma concentration obtained directly from the data without interpolation. t1/2 is the Elimination half-life, calculated as ln(2)/ Kel (where Kel is the Terminal elimination rate constant, calculated as the negative of the slope of the terminal log-linear segment of the plasma concentration time curve).
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Tmax and t1/2 for Ibuprofen
DF2188Y - tmax - Day -3
|
3.50 hours
Standard Deviation 0.58
|
3.99 hours
Standard Deviation 1.99
|
2.86 hours
Standard Deviation 0.81
|
|
Tmax and t1/2 for Ibuprofen
DF2188Y- tmax - Day 1
|
4.02 hours
Standard Deviation 2.86
|
2.66 hours
Standard Deviation 1.16
|
4.00 hours
Standard Deviation 2.18
|
|
Tmax and t1/2 for Ibuprofen
DF2188Y - tmax - Day 8
|
4.29 hours
Standard Deviation 2.94
|
3.32 hours
Standard Deviation 1.15
|
2.15 hours
Standard Deviation 1.44
|
|
Tmax and t1/2 for Ibuprofen
DF2188Y - tmax - Day 21
|
3.37 hours
Standard Deviation 0.67
|
3.99 hours
Standard Deviation 2.00
|
2.58 hours
Standard Deviation 0.97
|
|
Tmax and t1/2 for Ibuprofen
DF2188Y - t1/2 - Day -3
|
6.76 hours
Standard Deviation 2.04
|
6.15 hours
|
3.76 hours
Standard Deviation 0.77
|
|
Tmax and t1/2 for Ibuprofen
DF2188Y - t1/2 - Day 8
|
—
|
—
|
2.15 hours
Standard Deviation 0.09
|
|
Tmax and t1/2 for Ibuprofen
DF2188Y - t1/2 - Day 21
|
3.12 hours
Standard Deviation 0.56
|
3.81 hours
|
3.15 hours
Standard Deviation 0.53
|
PRIMARY outcome
Timeframe: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours)Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter
PK parameters were calculated for cycle 1 only. Tmax is the Time to reach the maximum plasma concentration obtained directly from the data without interpolation. t1/2 is the Elimination half-life, calculated as ln(2)/ Kel (where Kel is the Terminal elimination rate constant, calculated as the negative of the slope of the terminal log-linear segment of the plasma concentration time curve).
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Tmax and t1/2 for Paclitaxel
paclitaxel - tmax - Day 1
|
1.14 hours
Standard Deviation 0.63
|
1.01 hours
Standard Deviation 0.01
|
1.22 hours
Standard Deviation 0.93
|
|
Tmax and t1/2 for Paclitaxel
paclitaxel - tmax - Day 8
|
1.06 hours
Standard Deviation 0.09
|
1.06 hours
Standard Deviation 0.10
|
1.07 hours
Standard Deviation 0.36
|
|
Tmax and t1/2 for Paclitaxel
paclitaxel - t1/2 - Day 1
|
5.95 hours
Standard Deviation 2.66
|
8.51 hours
Standard Deviation 0.43
|
8.18 hours
Standard Deviation 0.94
|
|
Tmax and t1/2 for Paclitaxel
paclitaxel - t1/2 - Day 8
|
6.57 hours
Standard Deviation 3.40
|
11.00 hours
Standard Deviation 2.21
|
8.76 hours
Standard Deviation 1.05
|
PRIMARY outcome
Timeframe: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter
PK parameters were calculated for cycle 1 only. AUC0-8 is the area under the plasma concentration-time curve from time 0 to 8 hours post-dose; calculated using the linear trapezoidal method.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
AUC0-8 for DF1681Y
DF1681Y - AUC0-8 - Day -3
|
86.7 hr*mg/mL
Standard Deviation 34.5
|
108 hr*mg/mL
Standard Deviation 58.1
|
194 hr*mg/mL
Standard Deviation 71.96
|
|
AUC0-8 for DF1681Y
DF1681Y - AUC0-8 - Day 1
|
86.5 hr*mg/mL
Standard Deviation 40.3
|
124 hr*mg/mL
Standard Deviation 32.2
|
216 hr*mg/mL
Standard Deviation 96.91
|
|
AUC0-8 for DF1681Y
DF1681Y - AUC0-8 - Day 8
|
49.8 hr*mg/mL
Standard Deviation 38.4
|
150 hr*mg/mL
Standard Deviation 44.0
|
178 hr*mg/mL
Standard Deviation 88.1
|
|
AUC0-8 for DF1681Y
DF1681Y - AUC0-8 - Day 21
|
57.6 hr*mg/mL
Standard Deviation 11.8
|
153 hr*mg/mL
Standard Deviation 47.2
|
191 hr*mg/mL
Standard Deviation 61.6
|
PRIMARY outcome
Timeframe: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter
PK parameters were calculated for cycle 1 only. AUC0-8 is The area under the plasma concentration-time curve from time 0 to 8 hours post-dose; calculated using the linear trapezoidal method.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
AUC0-8 for DF2243Y
DF2243Y - AUC0-8 - Day -3
|
25.03 hr*mg/mL
Standard Deviation 4.05
|
40.4 hr*mg/mL
Standard Deviation 11.9
|
90.21 hr*mg/mL
Standard Deviation 35.3
|
|
AUC0-8 for DF2243Y
DF2243Y - AUC0-8 - Day 1
|
25.8 hr*mg/mL
Standard Deviation 9.2
|
65.0 hr*mg/mL
Standard Deviation 13.8
|
108.7 hr*mg/mL
Standard Deviation 55.2
|
|
AUC0-8 for DF2243Y
DF2243Y - AUC0-8 - Day 8
|
21.6 hr*mg/mL
Standard Deviation 18.4
|
49.8 hr*mg/mL
Standard Deviation 7.89
|
99.0 hr*mg/mL
Standard Deviation 53.2
|
|
AUC0-8 for DF2243Y
DF2243Y - AUC0-8 - Day 21
|
31.0 hr*mg/mL
Standard Deviation 7.50
|
58.1 hr*mg/mL
Standard Deviation 17.7
|
108 hr*mg/mL
Standard Deviation 50.5
|
PRIMARY outcome
Timeframe: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter
PK parameters were calculated for cycle 1 only. AUC0-8 is the area under the plasma concentration-time curve from time 0 to 8 hours post-dose; calculated using the linear trapezoidal method.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
AUC0-8 for DF2188Y
DF2188Y - AUC0-8 - Day -3
|
9.79 hr*mg/mL
Standard Deviation 1.77
|
16.0 hr*mg/mL
Standard Deviation 4.54
|
36.3 hr*mg/mL
Standard Deviation 16.8
|
|
AUC0-8 for DF2188Y
DF2188Y - AUC0-8 - Day 1
|
11.0 hr*mg/mL
Standard Deviation 3.93
|
24.6 hr*mg/mL
Standard Deviation 0.86
|
57.2 hr*mg/mL
Standard Deviation 39.4
|
|
AUC0-8 for DF2188Y
DF2188Y - AUC0-8 - Day 8
|
8.2 hr*mg/mL
Standard Deviation 6.01
|
20.8 hr*mg/mL
Standard Deviation 2.93
|
46.5 hr*mg/mL
Standard Deviation 29.0
|
|
AUC0-8 for DF2188Y
DF2188Y - AUC0-8 - Day 21
|
11.0 hr*mg/mL
Standard Deviation 1.83
|
21.2 hr*mg/mL
Standard Deviation 3.56
|
36.6 hr*mg/mL
Standard Deviation 21.6
|
PRIMARY outcome
Timeframe: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1.Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter
PK parameters were calculated for cycle 1 only. AUC0-8 is the area under the plasma concentration-time curve from time 0 to 8 hours post-dose; calculated using the linear trapezoidal method.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
AUC0-8 for Ibuprofen
ibuprofen - AUC0-8 - Day -3
|
4.35 hr*mg/mL
Standard Deviation 3.90
|
5.97 hr*mg/mL
Standard Deviation 4.38
|
14.8 hr*mg/mL
Standard Deviation 12.7
|
|
AUC0-8 for Ibuprofen
ibuprofen - AUC0-8 - Day 1
|
5.14 hr*mg/mL
Standard Deviation 5.21
|
10.93 hr*mg/mL
Standard Deviation 7.55
|
16.17 hr*mg/mL
Standard Deviation 12.07
|
|
AUC0-8 for Ibuprofen
ibuprofen - AUC0-8 - Day 8
|
1.69 hr*mg/mL
Standard Deviation 2.29
|
6.82 hr*mg/mL
Standard Deviation 4.08
|
17.5 hr*mg/mL
Standard Deviation 13.8
|
|
AUC0-8 for Ibuprofen
ibuprofen - AUC0-8 - Day 21
|
3.17 hr*mg/mL
Standard Deviation 3.76
|
9.96 hr*mg/mL
Standard Deviation 6.75
|
19.4 hr*mg/mL
Standard Deviation 13.3
|
PRIMARY outcome
Timeframe: Days -3 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours), 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours).Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter
PK parameters were calculated for cycle 1 only. AUC0-8 is the area under the plasma concentration-time curve from time 0 to 8 hours post-dose; calculated using the linear trapezoidal method.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
AUC0-8 for Paclitaxel
paclitaxel - AUC0-8 - Day 1
|
4.05 hr*microg/mL
Standard Deviation 0.83
|
3.70 hr*microg/mL
Standard Deviation 0.89
|
5.82 hr*microg/mL
Standard Deviation 2.18
|
|
AUC0-8 for Paclitaxel
paclitaxel - AUC0-8 - Day 8
|
3.70 hr*microg/mL
Standard Deviation 0.73
|
5.17 hr*microg/mL
Standard Deviation 3.08
|
5.69 hr*microg/mL
Standard Deviation 1.58
|
PRIMARY outcome
Timeframe: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter
PK parameters were calculated for cycle 1 only. Rac AUC0-8 is the Accumulation ratio calculated as the ratio of Day 8 to Day 1 AUC0-8.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Rac0-8 for DF1681Y
DF1681Y- Rac0-8 - Day 1
|
0.97 ratio
Standard Deviation 0.14
|
1.3 ratio
Standard Deviation 0.53
|
1.21 ratio
Standard Deviation 0.41
|
|
Rac0-8 for DF1681Y
DF1681Y - Rac0-8 - Day 8
|
0.63 ratio
Standard Deviation 0.39
|
1.7 ratio
Standard Deviation 0.88
|
1.01 ratio
Standard Deviation 0.30
|
|
Rac0-8 for DF1681Y
DF1681Y- Rac0-8 - Day 21
|
0.82 ratio
Standard Deviation 0.22
|
1.61 ratio
Standard Deviation 0.63
|
1.02 ratio
Standard Deviation 0.21
|
PRIMARY outcome
Timeframe: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter
PK parameters were calculated for cycle 1 only. Rac AUC0-8 is the Accumulation ratio calculated as the ratio of Day 8 to Day 1 AUC0-8.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Rac0-8 for DF2243Y
DF2243Y- Rac0-8 - Day 1
|
1.02 ratio
Standard Deviation 0.28
|
1.82 ratio
Standard Deviation 1.06
|
1.18 ratio
Standard Deviation 0.27
|
|
Rac0-8 for DF2243Y
DF2243Y - Rac0-8 - Day 8
|
0.78 ratio
Standard Deviation 0.64
|
1.3 ratio
Standard Deviation 0.37
|
1.08 ratio
Standard Deviation 0.23
|
|
Rac0-8 for DF2243Y
DF2243Y- Rac0-8 - Day 21
|
1.15 ratio
Standard Deviation 0.19
|
1.44 ratio
Standard Deviation 0.11
|
1.16 ratio
Standard Deviation 0.17
|
PRIMARY outcome
Timeframe: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter
PK parameters were calculated for cycle 1 only. Rac AUC0-8 is the Accumulation ratio calculated as the ratio of Day 8 to Day 1 AUC0-8.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Rac0-8 for DF2188Y
DF2188Y- Rac0-8 - Day 1
|
1.12 ratio
Standard Deviation 0.34
|
1.61 ratio
Standard Deviation 0.40
|
1.52 ratio
Standard Deviation 0.51
|
|
Rac0-8 for DF2188Y
DF2188Y - Rac0-8 - Day 8
|
0.77 ratio
Standard Deviation 0.54
|
1.32 ratio
Standard Deviation 0.22
|
1.22 ratio
Standard Deviation 0.27
|
|
Rac0-8 for DF2188Y
DF2188Y- Rac0-8 - Day 21
|
1.04 ratio
Standard Deviation 0.09
|
1.35 ratio
Standard Deviation 0.15
|
0.95 ratio
Standard Deviation 0.15
|
PRIMARY outcome
Timeframe: Days 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours), and 21 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours) of cycle 1Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter
PK parameters were calculated for cycle 1 only. Rac AUC0-8 is the Accumulation ratio calculated as the ratio of Day 8 to Day 1 AUC0-8.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=12 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Rac0-8 for Ibuprofen
Ibuprofen - Rac0-8 - Day 1
|
1.09 ratio
Standard Deviation 0.22
|
1.99 ratio
Standard Deviation 1.38
|
1.18 ratio
Standard Deviation 0.43
|
|
Rac0-8 for Ibuprofen
Ibuprofen - Rac0-8 - Day 8
|
0.65 ratio
Standard Deviation 0.61
|
1.25 ratio
Standard Deviation 0.28
|
1.23 ratio
Standard Deviation 0.30
|
|
Rac0-8 for Ibuprofen
Ibuprofen - Rac0-8 - Day 21
|
1.18 ratio
Standard Deviation 0.74
|
1.89 ratio
Standard Deviation 0.86
|
1.24 ratio
Standard Deviation 0.26
|
PRIMARY outcome
Timeframe: Day 8 (0, 0.5, 1, 2, 4, 8, 24 hours)Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter
PK parameters were calculated for cycle 1 only. Rac AUC0-24 is the Accumulation ratio calculated as the ratio of Day 8 to Day 1 AUC0-24.
Outcome measures
| Measure |
Group 1
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=10 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Rac0-24 for Paclitaxel
|
0.90 ratio
Standard Deviation 0.110
|
1.59 ratio
Standard Deviation 1.325
|
1.04 ratio
Standard Deviation 0.121
|
SECONDARY outcome
Timeframe: At tumor assessments 1-11 and off-treatment visitPopulation: Safety Population: all enrolled patients who took at least one dose of study drug, reparixin.
Complete Response/Remission(CR): Disappearance of all target lesions. Partial Response/Remission (PR): At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD. Stable Disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD since the treatment started. Progression of Disease (PD): At least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=23 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 11 - PR
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 10 - CR
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 10 - PR
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 10 - SD
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 10 - PD
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 11 - CR
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 11 - SD
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 11 - PD
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Off-treatment visit - CR
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Off-treatment visit - PR
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Off-treatment visit - SD
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Off-treatment visit - PD
|
1 Participants
|
1 Participants
|
8 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 1 - CR
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 1 - PR
|
0 Participants
|
1 Participants
|
3 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 1 - SD
|
0 Participants
|
0 Participants
|
9 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 1 - PD
|
1 Participants
|
1 Participants
|
6 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 1.1 - CR
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 1.1 - PR
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 1.1 - SD
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 1.1 - PD
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 2 - CR
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 2 - PR
|
0 Participants
|
0 Participants
|
6 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 2 - SD
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 2 - PD
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 2.1 - CR
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 2.1 - PR
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 2.1 - SD
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 2.1 - PD
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 3 - CR
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 3 - PR
|
0 Participants
|
0 Participants
|
4 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 3 - SD
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 3 - PD
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 4 - CR
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 4 - PR
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 4 - SD
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 4 - PD
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 5 - CR
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 5 - PR
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 5 - SD
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 5 - PD
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 6 - CR
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 6 - PR
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 6 - SD
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 6 - PD
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 7 - CR
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 7 - PR
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 7 - SD
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 7 - PD
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 8 - CR
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 8 - PR
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 8 - SD
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 8 - PD
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 9 - CR
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 9 - PR
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 9 - SD
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit
Assessment 9 - PD
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: After 24 weeksPopulation: Safety Population: all enrolled patients who took at least one dose of study drug, reparixin.
The best overall response (BOR) was defined as the number of patients reaching complete remission (CR), partial remission (PR) or stable disease (SD) according to RECIST criteria version 1.1
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=23 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Best Overall Response (BOR)
CR
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Best Overall Response (BOR)
PR
|
0 Participants
|
0 Participants
|
5 Participants
|
|
Best Overall Response (BOR)
SD
|
0 Participants
|
1 Participants
|
7 Participants
|
|
Best Overall Response (BOR)
PD
|
2 Participants
|
2 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: After 24 weeksPopulation: Safety Population: all enrolled patients who took at least one dose of study drug, reparixin.
The clinical benefit rate (CBR) was defined as the percentage of patients reaching CR, PR or SD according to RECIST criteria version 1.1
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=23 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Clinical Benefit Rate (CBR)
|
25.0 Percentage of patients
|
33.3 Percentage of patients
|
56.5 Percentage of patients
|
SECONDARY outcome
Timeframe: After 24 weeksPopulation: Safety Population: all enrolled patients who took at least one dose of study drug, reparixin.
The 6-month progression-free survival rate (%) was defined as the percentage of patients with no mortality and at least 24-week duration of CR, PR or SD according to RECIST criteria version 1.1
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=23 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
6-month Progression-free Survival Rate
|
25.0 Percentage of patients
|
0.0 Percentage of patients
|
17.4 Percentage of patients
|
SECONDARY outcome
Timeframe: After 24 weeksPopulation: Safety Population: all enrolled patients who took at least one dose of study drug, reparixin.
The median time to tumor progression in days (TTP) was defined as the time from the date of the first administration of study drug to the date of the first documentation of progressive disease
Outcome measures
| Measure |
Group 1
n=4 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=23 Participants
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Median Time to Tumor Progression in Days (TTP)
|
58 days
Interval 44.0 to
the sample size of group 1 does not allow the calculation of the upper bound of the confidence interval
|
67 days
Interval 58.0 to
the sample size of group 2 does not allow the calculation of the upper bound of the confidence interval
|
170 days
Interval 65.0 to 229.0
|
Adverse Events
Group 1
Serious events: 2 serious events
Other events: 4 other events
Deaths: 0 deaths
Group 2
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Group 3
Serious events: 4 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group 1
n=4 participants at risk
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 participants at risk
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=23 participants at risk
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Metabolism and nutrition disorders
Dehydration
|
50.0%
2/4 • Number of events 2 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
0.00%
0/3 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
0.00%
0/23 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastasis to central nervous system
|
25.0%
1/4 • Number of events 1 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
0.00%
0/3 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
0.00%
0/23 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/4 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
33.3%
1/3 • Number of events 1 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
0.00%
0/23 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/4 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
0.00%
0/3 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
4.3%
1/23 • Number of events 1 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/4 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
0.00%
0/3 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
4.3%
1/23 • Number of events 1 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
|
Nervous system disorders
Intracranial hypotension
|
0.00%
0/4 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
0.00%
0/3 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
4.3%
1/23 • Number of events 1 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/4 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
0.00%
0/3 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
4.3%
1/23 • Number of events 1 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
|
General disorders
Disease progression
|
0.00%
0/4 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
0.00%
0/3 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
4.3%
1/23 • Number of events 1 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
25.0%
1/4 • Number of events 1 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
0.00%
0/3 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
0.00%
0/23 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal adenocarcinoma
|
0.00%
0/4 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
0.00%
0/3 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
4.3%
1/23 • Number of events 1 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
Other adverse events
| Measure |
Group 1
n=4 participants at risk
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 400 mg three times daily (t.i.d.) three weeks on one week off (three to six patients)
|
Group 2
n=3 participants at risk
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 100% increase to 800 mg t.i.d. if no toxicity in previous group (400 mg) three weeks on one week off (three to six patients)
|
Group 3
n=23 participants at risk
Paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15 of 28-day cycle) + reparixin oral 50% increase to 1200 mg t.i.d. if no toxicity in previous group (800 mg) three weeks on one week off (three to six patients).
|
|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
75.0%
3/4 • Number of events 4 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
100.0%
3/3 • Number of events 9 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
43.5%
10/23 • Number of events 12 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
|
Gastrointestinal disorders
Nausea
|
75.0%
3/4 • Number of events 5 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
100.0%
3/3 • Number of events 13 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
52.2%
12/23 • Number of events 16 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
|
Gastrointestinal disorders
Diarrhoea
|
50.0%
2/4 • Number of events 2 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
100.0%
3/3 • Number of events 3 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
34.8%
8/23 • Number of events 13 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
|
Gastrointestinal disorders
Vomiting
|
75.0%
3/4 • Number of events 7 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
66.7%
2/3 • Number of events 4 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
26.1%
6/23 • Number of events 8 • Throughout the study from run-in to off-treatment visit, up to 24 months.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place