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Pilot Study to Evaluate Reparixin With Weekly Paclitaxel in Patients With HER 2 Negative Metastatic Breast Cancer (MBC)

Phase Ib Pilot Study to Evaluate Reparixin in Combination With Chemotherapy With Weekly Paclitaxel in Patients With HER 2 Negative Metastatic Breast Cancer (MBC)

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02001974
Enrollment
33
Registered
2013-12-05
Start date
2012-02-27
Completion date
2015-01-15
Last updated
2021-09-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Metastatic Breast Cancer

Keywords

HER 2 negative, metastatic breast cancer, Cancer Stem Cells

Brief summary

This is a phase I study to evaluate the safety and define the pharmacokinetic (PK) profile of orally administered reparixin in combination with paclitaxel in HER 2 (Human epidermal growth factor receptor-2) negative metastatic breast cancer patients. The primary objective of this study was to evaluate the safety and define the pharmacokinetic (PK) profile of orally administered reparixin in combination with paclitaxel in HER-2 negative MBC patients. The secondary objectives were to: 1. Evaluate the effects of orally administered reparixin on cancer stem cell (CSC) markers, the tumoral microenvironment and markers of cytokine inflammation; 2. Evaluate peripheral blood samples for enumeration of circulating tumor cells (CTCs), molecular characterization as CSCs and perform epithelial-mesenchymal transition (EMT) biomarker profiling; 3. Assess disease response for indication of efficacy.

Detailed description

The CSC (Cancer stem cell) concept has important implications for understanding carcinogenesis as well as for the development of cancer therapeutics. According to this concept, tumors are initiated and maintained by a cellular subcomponent that displays stem cell properties. These properties include self-renewal, which drives tumorigenesis, and differentiation (albeit aberrant), which contributes to tumor cellular heterogeneity. The existence of CSCs has been described in a variety of hematologic and solid tumors including those of the breast, brain, colon, pancreas, lung, liver, and head and neck. In addition to driving tumorigenesis, CSCs may contribute to tumor metastasis as well as to tumor recurrence after treatment. One of the therapeutic strategies being pursued to target CSCs involves inhibition of self renewal or survival pathways in these cells. These pathways include NOTCH (Notch signaling pathway), Hedgehog, and WNT (Wnt signaling pathway). Such strategies may be limited by the role of these pathways in normal stem cell function, which could result in systemic toxicities from pathway inhibition. In addition to intrinsic pathways regulating stem cell functions, normal and malignant stem cells are regulated by extrinsic signals generated in the microenvironment or CSC niche. In the breast, this niche is composed of immune cells, mesenchymal elements that include fibroblasts, endothelial cells, adipocytes, and extracellular matrix components. These components play an important role in normal breast development and carcinogenesis. If the cellular microenvironment plays an important role in the regulation of CSC growth and survival, then strategies aimed at interfering with these interactions represent a rational approach to target breast CSCs. There are limited data on the impact of treatment tailoring based on CSCs detection. Gene profiling of CSCs could lead to identification of therapeutic targets on CSCs (e.g. hormone receptors, HER-2 \[Human epidermal growth factor receptor-2\] expression, EGFR \[Epidermal growth factor receptor\] expression), and could represent tumor biopsy in real time. Several groups showed frequent discordance of HER-2 status between primary tumor and CSCs, and case reports showed clinical utility to use of trastuzumab-based therapy based on HER-2 CSCs status. Similarly, the hormonal status of CSCs could be different from that of the primary tumor, which could lead to increase the number of patients suitable for endocrine therapy, but also could explain why endocrine therapy fails in a subset of hormone receptor-positive patients. The study provided the in vivo demonstration that CXCR-1 (Chemokine receptor 1) targeting with specific blocking antibodies or reparixin is associated with reduced systemic metastases. The experimental data provides another therapeutic target in metastatic disease and warrants a pilot study investigation in humans to further explore effects of reparixin on breast CSCs and the tumoral microenvironment. Reparixin seems to be a good candidate for use in breast cancer patients because of its very acceptable toxicity profile shown in the Phase I and II clinical trials conducted so far, along with its observed activity in vitro against breast cancer cell lines and in vivo in tumor xenografts in mice. It potentially addresses another therapeutic target in metastatic disease. The current pilot study thus aims at exploring the safety and PK profile of orally administered reparixin in HER-2 negative metastatic breast cancer patients and its effects on breast CSC markers.

Interventions

DRUGPaclitaxel+Reparixin

Association of Paclitaxel at fixed dosage with three increasing dosage of Reparixin

Sponsors

PRA Health Sciences
CollaboratorINDUSTRY
Dompé Farmaceutici S.p.A
Lead SponsorINDUSTRY

Study design

Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
No

Inclusion criteria

1. Female aged ≥ 18 years. 2. Patients with histologic or cytologic diagnosis of breast cancer with evidence of metastatic disease with documented HER-2 negative status and eligible for treatment with paclitaxel. 3. Patients with at least one baseline measurable lesion according to RECIST version 1.1 criteria. 4. Zubrod (Eastern Co-operative Oncology Group \[ECOG\]) Performance Status (PS) of 0-1. 5. An electrocardiogram (ECG) with no clinically significant abnormalities indicative of myocardial ischemia. 6. Ongoing toxicity associated with prior anticancer therapy ≤ grade 1 Common Terminology Criteria for Adverse Events (CTCAE version 4.03) with the exception of alopecia. 7. Maximum of three prior chemotherapy lines for advanced breast cancer (not including neo/adjuvant chemotherapy). If prior treatment with paclitaxel, PD must have occurred \> 12 months from the end of previous adjuvant treatment or for previous metastatic treatment no PD must have occurred during treatment or within 3 months of the end of treatment 8. Life expectancy of at least three months. 9. Patients must be able to swallow and retain oral medication (intact tablet). 10. Able to undergo all screening assessments outlined in the protocol following written informed consent. 11. Adequate organ function (defined by the following parameters): 1. Serum creatinine \< 140 µmol/L or creatinine clearance \> 60 mL/min. 2. Serum hemoglobin ≥ 9 g/dL; absolute neutrophil count ≥ 1.5 x 10\*\*9/L; platelets ≥ 100 x 10\*\*9/L. 3. Serum bilirubin ≤ 1.5 x upper normal limit (UNL). 4. Serum ALT, AST ≤ 2.5 x UNL but ≤ 5.0 x UNL in case of liver metastases; ALP ≤ UNL but ≤ 1.5 x ULN in case of liver metastases; albumin within normal limits. If ALP is greater than 1.5 x UNL (in the presence of liver metastases) the liver isoenzyme fraction will be measured. Liver isoenzyme fraction (absolute value) must be ≤ 1.5 x UNL. 12. No known hepatitis B virus (not due to immunization), hepatitis C virus, human immunodeficiency virus Ι and -ΙΙ positive status.

Exclusion criteria

1. Male. 2. Pregnancy or lactation or unwillingness to use adequate method of birth control. 3. HER-2 positive disease status. 4. Less than four weeks since last chemotherapy, radiotherapy or prior investigational therapy. Less than two weeks since last hormone or immunotherapy or signal transduction therapy. 5. Neurological or psychiatric disorders which may influence understanding of study and informed consent procedures. 6. Active or uncontrolled infection. 7. Malabsorption syndrome, disease significantly affecting gastrointestinal function. 8. Hypersensitivity to: 1. paclitaxel 2. ibuprofen or to more than one non-steroidal anti-inflammatory drug. 3. medications belonging to the class of sulfonamides, such as sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib. 9. Presence of brain metastases (this does not include primary brain tumors) or leptomeningeal disease.

Design outcomes

Primary

MeasureTime frameDescription
Rac0-24 for PaclitaxelDay 8 (0, 0.5, 1, 2, 4, 8, 24 hours)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.
AUC0-8 for PaclitaxelDays -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).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.
Rac0-8 for DF1681YDays 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 1PK 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.
Rac0-8 for DF2243YDays 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 1PK 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.
Rac0-8 for DF2188YDays 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 1PK 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.
Rac0-8 for IbuprofenDays 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 1PK 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.
Treatment-Emergent Adverse Events (TEAEs)Up to 28 days following the last dose of study drug (up to 24 months).Monitoring of AEs throughout the study till the end/off-treatment visit.
Plasma DF1681Y Concentrations by Time PointDays -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.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.
Plasma Unbound DF1681Y Concentrations by Time PointDays -3 (1, 2 hours), 1 (1, 2 hours), 8 (1, 2 hours), and 21 (1, 2 hours) of cycle 1.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.
Plasma DF2243Y Concentrations by Time PointDays -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.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.
Plasma DF2188Y Concentrations by Time PointDays -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.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.
Plasma Ibuprofen Concentrations by Time PointDays -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.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.
Plasma Paclitaxel Concentrations by Time PointDays 1 (0, 0.5, 1, 2, 4, 8, 24 hours) and 8 (0, 0.5, 1, 2, 4, 8, 24 hours) of cycle 1.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.
C0 and Cmax for DF1681YDays -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 1PK 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.
C0 and Cmax for DF2243YDays -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 1PK 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.
C0 and Cmax for DF2188YDays -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)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.
C0 and Cmax for IbuprofenDays -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 1PK 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.
Cmax for PaclitaxelDays 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours)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.
Tmax and t1/2 for DF1681YDays -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 1PK 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).
Tmax and t1/2 for DF2243YDays -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 1PK 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).
Tmax and t1/2 for DF2188YDays -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 1PK 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).
AUC0-8 for IbuprofenDays -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.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.
Tmax and t1/2 for IbuprofenDays -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 1PK 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).
Tmax and t1/2 for PaclitaxelDays 1 (0, 0.5, 1, 2, 4, 8, 24 hours), 8 (0, 0.5, 1, 2, 4, 8, 24 hours)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).
AUC0-8 for DF1681YDays -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.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.
AUC0-8 for DF2243YDays -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.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.
AUC0-8 for DF2188YDays -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.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.

Secondary

MeasureTime frameDescription
Best Overall Response (BOR)After 24 weeksThe 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
Clinical Benefit Rate (CBR)After 24 weeksThe clinical benefit rate (CBR) was defined as the percentage of patients reaching CR, PR or SD according to RECIST criteria version 1.1
6-month Progression-free Survival RateAfter 24 weeksThe 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
Median Time to Tumor Progression in Days (TTP)After 24 weeksThe 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
Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAt tumor assessments 1-11 and off-treatment visitComplete 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.

Countries

United States

Participant flow

Recruitment details

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.

Pre-assignment details

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.

Participants by arm

ArmCount
Group 1
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)
4
Group 2
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)
3
Group 3
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).
23
Total30

Withdrawals & dropouts

PeriodReasonFG000FG001FG002
Reparixin + Paclitaxel (28-day Cycles)Adverse Event104
Reparixin + Paclitaxel (28-day Cycles)Disease progression2314
Reparixin + Paclitaxel (28-day Cycles)Physician Decision002
Reparixin + Paclitaxel (28-day Cycles)Withdrawal by Subject106

Baseline characteristics

CharacteristicGroup 1Group 2Group 3Total
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
1 Participants0 Participants7 Participants8 Participants
Age, Categorical
Between 18 and 65 years
3 Participants3 Participants16 Participants22 Participants
Age, Continuous55.0 years
STANDARD_DEVIATION 9.13
55.3 years
STANDARD_DEVIATION 7.77
56.2 years
STANDARD_DEVIATION 12.69
55.9 years
STANDARD_DEVIATION 11.59
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants0 Participants1 Participants1 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
4 Participants3 Participants22 Participants29 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
1 Participants0 Participants0 Participants1 Participants
Race (NIH/OMB)
Black or African American
0 Participants2 Participants3 Participants5 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
3 Participants1 Participants20 Participants24 Participants
Region of Enrollment
United States
4 participants3 participants23 participants30 participants
Sex: Female, Male
Female
4 Participants3 Participants23 Participants30 Participants
Sex: Female, Male
Male
0 Participants0 Participants0 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
0 / 40 / 30 / 23
other
Total, other adverse events
4 / 43 / 323 / 23
serious
Total, serious adverse events
2 / 41 / 34 / 23

Outcome results

Primary

AUC0-8 for DF1681Y

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.

Time frame: 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

ArmMeasureGroupValue (MEAN)Dispersion
Group 1AUC0-8 for DF1681YDF1681Y - AUC0-8 - Day -386.7 hr*mg/mLStandard Deviation 34.5
Group 1AUC0-8 for DF1681YDF1681Y - AUC0-8 - Day 186.5 hr*mg/mLStandard Deviation 40.3
Group 1AUC0-8 for DF1681YDF1681Y - AUC0-8 - Day 849.8 hr*mg/mLStandard Deviation 38.4
Group 1AUC0-8 for DF1681YDF1681Y - AUC0-8 - Day 2157.6 hr*mg/mLStandard Deviation 11.8
Group 2AUC0-8 for DF1681YDF1681Y - AUC0-8 - Day 21153 hr*mg/mLStandard Deviation 47.2
Group 2AUC0-8 for DF1681YDF1681Y - AUC0-8 - Day -3108 hr*mg/mLStandard Deviation 58.1
Group 2AUC0-8 for DF1681YDF1681Y - AUC0-8 - Day 8150 hr*mg/mLStandard Deviation 44
Group 2AUC0-8 for DF1681YDF1681Y - AUC0-8 - Day 1124 hr*mg/mLStandard Deviation 32.2
Group 3AUC0-8 for DF1681YDF1681Y - AUC0-8 - Day 21191 hr*mg/mLStandard Deviation 61.6
Group 3AUC0-8 for DF1681YDF1681Y - AUC0-8 - Day 1216 hr*mg/mLStandard Deviation 96.91
Group 3AUC0-8 for DF1681YDF1681Y - AUC0-8 - Day 8178 hr*mg/mLStandard Deviation 88.1
Group 3AUC0-8 for DF1681YDF1681Y - AUC0-8 - Day -3194 hr*mg/mLStandard Deviation 71.96
Comparison: DF1681Y, AUC0-8, Day -3p-value: 0.0799ANOVA
Comparison: DF1681Y, AUC0-8, Day -3p-value: 0.0134ANOVA
Comparison: DF1681Y, AUC0-8, Day 1p-value: 0.0241ANOVA
Comparison: DF1681Y, AUC0-8, Day 1p-value: 0.01384ANOVA
Comparison: DF1681Y, AUC0-8, Day 8p-value: 0.0091ANOVA
Comparison: DF1681Y, AUC0-8, Day 8p-value: 0.5687ANOVA
Comparison: DF1681Y, AUC0-8, Day 21p-value: 0.0058ANOVA
Comparison: DF1681Y, AUC0-8, Day 21p-value: 0.3667ANOVA
Primary

AUC0-8 for DF2188Y

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.

Time frame: 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

ArmMeasureGroupValue (MEAN)Dispersion
Group 1AUC0-8 for DF2188YDF2188Y - AUC0-8 - Day -39.79 hr*mg/mLStandard Deviation 1.77
Group 1AUC0-8 for DF2188YDF2188Y - AUC0-8 - Day 111.0 hr*mg/mLStandard Deviation 3.93
Group 1AUC0-8 for DF2188YDF2188Y - AUC0-8 - Day 88.2 hr*mg/mLStandard Deviation 6.01
Group 1AUC0-8 for DF2188YDF2188Y - AUC0-8 - Day 2111.0 hr*mg/mLStandard Deviation 1.83
Group 2AUC0-8 for DF2188YDF2188Y - AUC0-8 - Day 2121.2 hr*mg/mLStandard Deviation 3.56
Group 2AUC0-8 for DF2188YDF2188Y - AUC0-8 - Day -316.0 hr*mg/mLStandard Deviation 4.54
Group 2AUC0-8 for DF2188YDF2188Y - AUC0-8 - Day 820.8 hr*mg/mLStandard Deviation 2.93
Group 2AUC0-8 for DF2188YDF2188Y - AUC0-8 - Day 124.6 hr*mg/mLStandard Deviation 0.86
Group 3AUC0-8 for DF2188YDF2188Y - AUC0-8 - Day 2136.6 hr*mg/mLStandard Deviation 21.6
Group 3AUC0-8 for DF2188YDF2188Y - AUC0-8 - Day 157.2 hr*mg/mLStandard Deviation 39.4
Group 3AUC0-8 for DF2188YDF2188Y - AUC0-8 - Day 846.5 hr*mg/mLStandard Deviation 29
Group 3AUC0-8 for DF2188YDF2188Y - AUC0-8 - Day -336.3 hr*mg/mLStandard Deviation 16.8
Comparison: AUC0-8 for DF2188Y, Day -3p-value: 0.0081ANOVA
Comparison: AUC0-8 for DF2188Y, Day -3p-value: 0.064ANOVA
Comparison: AUC0-8 for DF2188Y, Day 1p-value: 0.0397ANOVA
Comparison: AUC0-8 for DF2188Y, Day 1p-value: 0.1898ANOVA
Comparison: AUC0-8 for DF2188Y, Day 8p-value: 0.025ANOVA
Comparison: AUC0-8 for DF2188Y, Day 8p-value: 0.1605ANOVA
Comparison: AUC0-8 for DF2188Y, Day 21p-value: 0.0786ANOVA
Comparison: AUC0-8 for DF2188Y, Day 21p-value: 0.2652ANOVA
Primary

AUC0-8 for DF2243Y

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.

Time frame: 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

ArmMeasureGroupValue (MEAN)Dispersion
Group 1AUC0-8 for DF2243YDF2243Y - AUC0-8 - Day -325.03 hr*mg/mLStandard Deviation 4.05
Group 1AUC0-8 for DF2243YDF2243Y - AUC0-8 - Day 125.8 hr*mg/mLStandard Deviation 9.2
Group 1AUC0-8 for DF2243YDF2243Y - AUC0-8 - Day 821.6 hr*mg/mLStandard Deviation 18.4
Group 1AUC0-8 for DF2243YDF2243Y - AUC0-8 - Day 2131.0 hr*mg/mLStandard Deviation 7.5
Group 2AUC0-8 for DF2243YDF2243Y - AUC0-8 - Day 2158.1 hr*mg/mLStandard Deviation 17.7
Group 2AUC0-8 for DF2243YDF2243Y - AUC0-8 - Day -340.4 hr*mg/mLStandard Deviation 11.9
Group 2AUC0-8 for DF2243YDF2243Y - AUC0-8 - Day 849.8 hr*mg/mLStandard Deviation 7.89
Group 2AUC0-8 for DF2243YDF2243Y - AUC0-8 - Day 165.0 hr*mg/mLStandard Deviation 13.8
Group 3AUC0-8 for DF2243YDF2243Y - AUC0-8 - Day 21108 hr*mg/mLStandard Deviation 50.5
Group 3AUC0-8 for DF2243YDF2243Y - AUC0-8 - Day 1108.7 hr*mg/mLStandard Deviation 55.2
Group 3AUC0-8 for DF2243YDF2243Y - AUC0-8 - Day 899.0 hr*mg/mLStandard Deviation 53.2
Group 3AUC0-8 for DF2243YDF2243Y - AUC0-8 - Day -390.21 hr*mg/mLStandard Deviation 35.3
Comparison: DF2243Y - AUC0-8 - Day -3p-value: 0.0029ANOVA
Comparison: DF2243Y - AUC0-8 - Day -3p-value: 0.0349ANOVA
Comparison: DF2243Y - AUC0-8 - Day 1p-value: 0.0119ANOVA
Comparison: DF2243Y - AUC0-8 - Day 1p-value: 0.21ANOVA
Comparison: DF2243Y - AUC0-8 - Day 8p-value: 0.0165ANOVA
Comparison: DF2243Y - AUC0-8 - Day 8p-value: 0.1496ANOVA
Comparison: DF2243Y - AUC0-8 - Day 21p-value: 0.0321ANOVA
Comparison: DF2243Y - AUC0-8 - Day 21p-value: 0.1404ANOVA
Primary

AUC0-8 for Ibuprofen

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.

Time frame: 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

ArmMeasureGroupValue (MEAN)Dispersion
Group 1AUC0-8 for Ibuprofenibuprofen - AUC0-8 - Day -34.35 hr*mg/mLStandard Deviation 3.9
Group 1AUC0-8 for Ibuprofenibuprofen - AUC0-8 - Day 15.14 hr*mg/mLStandard Deviation 5.21
Group 1AUC0-8 for Ibuprofenibuprofen - AUC0-8 - Day 81.69 hr*mg/mLStandard Deviation 2.29
Group 1AUC0-8 for Ibuprofenibuprofen - AUC0-8 - Day 213.17 hr*mg/mLStandard Deviation 3.76
Group 2AUC0-8 for Ibuprofenibuprofen - AUC0-8 - Day 219.96 hr*mg/mLStandard Deviation 6.75
Group 2AUC0-8 for Ibuprofenibuprofen - AUC0-8 - Day -35.97 hr*mg/mLStandard Deviation 4.38
Group 2AUC0-8 for Ibuprofenibuprofen - AUC0-8 - Day 86.82 hr*mg/mLStandard Deviation 4.08
Group 2AUC0-8 for Ibuprofenibuprofen - AUC0-8 - Day 110.93 hr*mg/mLStandard Deviation 7.55
Group 3AUC0-8 for Ibuprofenibuprofen - AUC0-8 - Day 2119.4 hr*mg/mLStandard Deviation 13.3
Group 3AUC0-8 for Ibuprofenibuprofen - AUC0-8 - Day 116.17 hr*mg/mLStandard Deviation 12.07
Group 3AUC0-8 for Ibuprofenibuprofen - AUC0-8 - Day 817.5 hr*mg/mLStandard Deviation 13.8
Group 3AUC0-8 for Ibuprofenibuprofen - AUC0-8 - Day -314.8 hr*mg/mLStandard Deviation 12.7
Comparison: Ibuprofen, AUC0-8, Day -3p-value: 0.1335ANOVA
Comparison: Ibuprofen, AUC0-8, Day -3p-value: 0.2658ANOVA
Comparison: Ibuprofen, AUC0-8, Day 1p-value: 0.1063ANOVA
Comparison: Ibuprofen, AUC0-8, Day 1p-value: 0.4959ANOVA
Comparison: Ibuprofen, AUC0-8, Day 8p-value: 0.0452ANOVA
Comparison: Ibuprofen, AUC0-8, Day 8p-value: 0.2223ANOVA
Comparison: Ibuprofen, AUC0-8, Day 21p-value: 0.0737ANOVA
Comparison: Ibuprofen, AUC0-8, Day21p-value: 0.2804ANOVA
Primary

AUC0-8 for Paclitaxel

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.

Time frame: 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

ArmMeasureGroupValue (MEAN)Dispersion
Group 1AUC0-8 for Paclitaxelpaclitaxel - AUC0-8 - Day 14.05 hr*microg/mLStandard Deviation 0.83
Group 1AUC0-8 for Paclitaxelpaclitaxel - AUC0-8 - Day 83.70 hr*microg/mLStandard Deviation 0.73
Group 2AUC0-8 for Paclitaxelpaclitaxel - AUC0-8 - Day 13.70 hr*microg/mLStandard Deviation 0.89
Group 2AUC0-8 for Paclitaxelpaclitaxel - AUC0-8 - Day 85.17 hr*microg/mLStandard Deviation 3.08
Group 3AUC0-8 for Paclitaxelpaclitaxel - AUC0-8 - Day 15.82 hr*microg/mLStandard Deviation 2.18
Group 3AUC0-8 for Paclitaxelpaclitaxel - AUC0-8 - Day 85.69 hr*microg/mLStandard Deviation 1.58
Comparison: Paclitaxel, AUC0-8, Day 1p-value: 0.1449ANOVA
Comparison: Ibuprofen, AUC0-8, Day 1p-value: 0.1338ANOVA
Comparison: Ibuprofen, AUC0-8, Day 8p-value: 0.0633ANOVA
Comparison: Ibuprofen, AUC0-8, Day 8p-value: 0.6939ANOVA
Primary

C0 and Cmax for DF1681Y

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.

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
Group 1C0 and Cmax for DF1681YDF1681Y - C0 - Day -30.00 ug/mLStandard Deviation 0
Group 1C0 and Cmax for DF1681YDF1681Y - C0 - Day 11.05 ug/mLStandard Deviation 0.37
Group 1C0 and Cmax for DF1681YDF1681Y - C0 - Day 80.79 ug/mLStandard Deviation 1.05
Group 1C0 and Cmax for DF1681YDF1681Y - C0 - Day 211.25 ug/mLStandard Deviation 0.76
Group 1C0 and Cmax for DF1681YDF1681Y - Cmax - Day -337.9 ug/mLStandard Deviation 15.2
Group 1C0 and Cmax for DF1681YDF1681Y - Cmax - Day 130.7 ug/mLStandard Deviation 19
Group 1C0 and Cmax for DF1681YDF1681Y - Cmax - Day 817.9 ug/mLStandard Deviation 7.11
Group 1C0 and Cmax for DF1681YDF1681Y - Cmax - Day 2119.4 ug/mLStandard Deviation 3.27
Group 2C0 and Cmax for DF1681YDF1681Y - C0 - Day 82.40 ug/mLStandard Deviation 1.78
Group 2C0 and Cmax for DF1681YDF1681Y - Cmax - Day 834.4 ug/mLStandard Deviation 11.5
Group 2C0 and Cmax for DF1681YDF1681Y - C0 - Day 216.00 ug/mLStandard Deviation 5.56
Group 2C0 and Cmax for DF1681YDF1681Y - Cmax - Day -335.6 ug/mLStandard Deviation 328.6
Group 2C0 and Cmax for DF1681YDF1681Y - Cmax - Day 145.4 ug/mLStandard Deviation 3.88
Group 2C0 and Cmax for DF1681YDF1681Y - C0 - Day -30.00 ug/mLStandard Deviation 0
Group 2C0 and Cmax for DF1681YDF1681Y - C0 - Day 14.24 ug/mLStandard Deviation 3.39
Group 2C0 and Cmax for DF1681YDF1681Y - Cmax - Day 2144.6 ug/mLStandard Deviation 25.3
Group 3C0 and Cmax for DF1681YDF1681Y - C0 - Day 83.55 ug/mLStandard Deviation 2.05
Group 3C0 and Cmax for DF1681YDF1681Y - C0 - Day 15.74 ug/mLStandard Deviation 6.77
Group 3C0 and Cmax for DF1681YDF1681Y - C0 - Day -30.00 ug/mLStandard Deviation 0
Group 3C0 and Cmax for DF1681YDF1681Y - C0 - Day 214.98 ug/mLStandard Deviation 4.32
Group 3C0 and Cmax for DF1681YDF1681Y - Cmax - Day 860.2 ug/mLStandard Deviation 26.5
Group 3C0 and Cmax for DF1681YDF1681Y - Cmax - Day 158.7 ug/mLStandard Deviation 22.9
Group 3C0 and Cmax for DF1681YDF1681Y - Cmax - Day -365.0 ug/mLStandard Deviation 21.1
Group 3C0 and Cmax for DF1681YDF1681Y - Cmax - Day 2171.2 ug/mLStandard Deviation 24.6
Comparison: DF1681Y Cmax at Day -3p-value: 0.0341ANOVA
Comparison: DF1681Y Cmax at Day -3p-value: 0.0636ANOVA
Comparison: DF1681Y Cmax at Day 1p-value: 0.0487ANOVA
Comparison: DF1681Y Cmax at Day 1p-value: 0.3498ANOVA
Comparison: DF1681Y Cmax at Day 8p-value: 0.0096ANOVA
Comparison: DF1681Y Cmax at Day 8p-value: 0.1374ANOVA
Comparison: DF1681Y Cmax at Day 21p-value: 0.0065ANOVA
Comparison: DF1681Y Cmax at Day 21p-value: 0.147ANOVA
Primary

C0 and Cmax for DF2188Y

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.

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
Group 1C0 and Cmax for DF2188YDF2188Y- C0 - Day -30 ug/mLStandard Deviation 0
Group 1C0 and Cmax for DF2188YDF2188Y - C0 - Day 10.24 ug/mLStandard Deviation 0.11
Group 1C0 and Cmax for DF2188YDF2188Y - C0 - Day 80.18 ug/mLStandard Deviation 0.26
Group 1C0 and Cmax for DF2188YDF2188Y - C0 - Day 210.35 ug/mLStandard Deviation 0.25
Group 1C0 and Cmax for DF2188YDF2188Y - Cmax - Day -33.01 ug/mLStandard Deviation 0.99
Group 1C0 and Cmax for DF2188YDF2188Y - Cmax - Day 12.90 ug/mLStandard Deviation 1.53
Group 1C0 and Cmax for DF2188YDF2188Y - Cmax - Day 82.11 ug/mLStandard Deviation 1.25
Group 1C0 and Cmax for DF2188YDF2188Y - Cmax - Day 213.29 ug/mLStandard Deviation 0.73
Group 2C0 and Cmax for DF2188YDF2188Y - C0 - Day 80.54 ug/mLStandard Deviation 0.44
Group 2C0 and Cmax for DF2188YDF2188Y - Cmax - Day 84.42 ug/mLStandard Deviation 0.89
Group 2C0 and Cmax for DF2188YDF2188Y - C0 - Day 210.91 ug/mLStandard Deviation 0.76
Group 2C0 and Cmax for DF2188YDF2188Y - Cmax - Day -33.67 ug/mLStandard Deviation 1.42
Group 2C0 and Cmax for DF2188YDF2188Y - Cmax - Day 17.37 ug/mLStandard Deviation 1.29
Group 2C0 and Cmax for DF2188YDF2188Y- C0 - Day -30 ug/mLStandard Deviation 0
Group 2C0 and Cmax for DF2188YDF2188Y - C0 - Day 11.36 ug/mLStandard Deviation 1.78
Group 2C0 and Cmax for DF2188YDF2188Y - Cmax - Day 215.27 ug/mLStandard Deviation 2.42
Group 3C0 and Cmax for DF2188YDF2188Y - C0 - Day 81.30 ug/mLStandard Deviation 1.95
Group 3C0 and Cmax for DF2188YDF2188Y - C0 - Day 11.43 ug/mLStandard Deviation 2.04
Group 3C0 and Cmax for DF2188YDF2188Y- C0 - Day -30 ug/mLStandard Deviation 0
Group 3C0 and Cmax for DF2188YDF2188Y - C0 - Day 211.21 ug/mLStandard Deviation 1.01
Group 3C0 and Cmax for DF2188YDF2188Y - Cmax - Day 814.5 ug/mLStandard Deviation 9.3
Group 3C0 and Cmax for DF2188YDF2188Y - Cmax - Day 113.4 ug/mLStandard Deviation 7.68
Group 3C0 and Cmax for DF2188YDF2188Y - Cmax - Day -310.5 ug/mLStandard Deviation 4.85
Group 3C0 and Cmax for DF2188YDF2188Y - Cmax - Day 2112.2 ug/mLStandard Deviation 5.83
Comparison: DF2188Y, Cmax, Day -3p-value: 0.0097ANOVA
Comparison: DF2188Y, Cmax, Day -3p-value: 0.0354ANOVA
Comparison: DF2188Y, Cmax, Day 1p-value: 0.02ANOVA
Comparison: DF2188Y, Cmax, Day 1p-value: 0.2134ANOVA
Comparison: DF2188Y, Cmax, Day 8p-value: 0.0235ANOVA
Comparison: DF2188Y, Cmax, Day 8p-value: 0.0964ANOVA
Comparison: DF2188Y, Cmax, Day 21p-value: 0.0314ANOVA
Comparison: DF2188Y, Cmax, Day 21p-value: 0.0773ANOVA
Primary

C0 and Cmax for DF2243Y

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.

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
Group 1C0 and Cmax for DF2243YDF2243Y - C0 - Day -30.00 ug/mLStandard Deviation 0
Group 1C0 and Cmax for DF2243YDF2243Y - C0 - Day 212.09 ug/mLStandard Deviation 2.24
Group 1C0 and Cmax for DF2243YDF2243Y - C0 - Day 11.08 ug/mLStandard Deviation 0.59
Group 1C0 and Cmax for DF2243YDF2243Y - C0 - Day 80.77 ug/mLStandard Deviation 0.86
Group 1C0 and Cmax for DF2243YDF2243Y - Cmax - Day -35.85 ug/mLStandard Deviation 1.5
Group 1C0 and Cmax for DF2243YDF2243Y - Cmax - Day 15.79 ug/mLStandard Deviation 2.84
Group 1C0 and Cmax for DF2243YDF2243Y - Cmax - Day 85.07 ug/mLStandard Deviation 4.32
Group 1C0 and Cmax for DF2243YDF2243Y - Cmax - Day 217.71 ug/mLStandard Deviation 1.63
Group 2C0 and Cmax for DF2243YDF2243Y - Cmax - Day 810.6 ug/mLStandard Deviation 0.32
Group 2C0 and Cmax for DF2243YDF2243Y - C0 - Day 82.79 ug/mLStandard Deviation 2.64
Group 2C0 and Cmax for DF2243YDF2243Y - C0 - Day 213.92 ug/mLStandard Deviation 3.17
Group 2C0 and Cmax for DF2243YDF2243Y - Cmax - Day -38.46 ug/mLStandard Deviation 3.05
Group 2C0 and Cmax for DF2243YDF2243Y - Cmax - Day 113.8 ug/mLStandard Deviation 3.51
Group 2C0 and Cmax for DF2243YDF2243Y - C0 - Day -30.00 ug/mLStandard Deviation 0
Group 2C0 and Cmax for DF2243YDF2243Y - Cmax - Day 2112.6 ug/mLStandard Deviation 3.13
Group 2C0 and Cmax for DF2243YDF2243Y - C0 - Day 14.68 ug/mLStandard Deviation 5.28
Group 3C0 and Cmax for DF2243YDF2243Y - C0 - Day -30.00 ug/mLStandard Deviation 0
Group 3C0 and Cmax for DF2243YDF2243Y - C0 - Day 86.44 ug/mLStandard Deviation 7.04
Group 3C0 and Cmax for DF2243YDF2243Y - Cmax - Day 120.6 ug/mLStandard Deviation 8.35
Group 3C0 and Cmax for DF2243YDF2243Y - C0 - Day 215.98 ug/mLStandard Deviation 4.03
Group 3C0 and Cmax for DF2243YDF2243Y - Cmax - Day 818.3 ug/mLStandard Deviation 8.22
Group 3C0 and Cmax for DF2243YDF2243Y - C0 - Day 16.52 ug/mLStandard Deviation 7.25
Group 3C0 and Cmax for DF2243YDF2243Y - Cmax - Day -319.5 ug/mLStandard Deviation 6.73
Group 3C0 and Cmax for DF2243YDF2243Y - Cmax - Day 2121.4 ug/mLStandard Deviation 8.75
Comparison: DF2243 Cmax at Day -3p-value: 0.0015ANOVA
Comparison: DF2243 Cmax at Day -3p-value: 0.0176ANOVA
Comparison: DF2243 Cmax at Day 1p-value: 0.0048ANOVA
Comparison: DF2243 Cmax at Day 1p-value: 0.2083ANOVA
Comparison: DF2243 Cmax at Day 8p-value: 0.0111ANOVA
Comparison: DF2243 Cmax at Day 8p-value: 0.1441ANOVA
Comparison: DF2243 Cmax at Day 21p-value: 0.0283ANOVA
Comparison: DF2243 Cmax at Day 21p-value: 0.1331ANOVA
Primary

C0 and Cmax for Ibuprofen

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.

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
Group 1C0 and Cmax for Ibuprofenibuprofen - C0 - Day -30.04 ug/mLStandard Deviation 0.04
Group 1C0 and Cmax for Ibuprofenibuprofen - C0 - Day 10.41 ug/mLStandard Deviation 0.4
Group 1C0 and Cmax for Ibuprofenibuprofen - C0 - Day 80.12 ug/mLStandard Deviation 0.13
Group 1C0 and Cmax for Ibuprofenibuprofen - C0 - Day 210.3 ug/mLStandard Deviation 0.36
Group 1C0 and Cmax for Ibuprofenibuprofen - Cmax - Day -30.77 ug/mLStandard Deviation 0.78
Group 1C0 and Cmax for Ibuprofenibuprofen - Cmax - Day 10.86 ug/mLStandard Deviation 0.86
Group 1C0 and Cmax for Ibuprofenibuprofen - Cmax - Day 80.34 ug/mLStandard Deviation 0.32
Group 1C0 and Cmax for Ibuprofenibuprofen - Cmax - Day 210.58 ug/mLStandard Deviation 0.64
Group 2C0 and Cmax for Ibuprofenibuprofen - C0 - Day 80.53 ug/mLStandard Deviation 0.56
Group 2C0 and Cmax for Ibuprofenibuprofen - Cmax - Day 81.24 ug/mLStandard Deviation 0.75
Group 2C0 and Cmax for Ibuprofenibuprofen - C0 - Day 210.86 ug/mLStandard Deviation 0.75
Group 2C0 and Cmax for Ibuprofenibuprofen - Cmax - Day -31.02 ug/mLStandard Deviation 0.59
Group 2C0 and Cmax for Ibuprofenibuprofen - Cmax - Day 11.98 ug/mLStandard Deviation 1.46
Group 2C0 and Cmax for Ibuprofenibuprofen - C0 - Day -30.02 ug/mLStandard Deviation 0.02
Group 2C0 and Cmax for Ibuprofenibuprofen - C0 - Day 11.25 ug/mLStandard Deviation 1.39
Group 2C0 and Cmax for Ibuprofenibuprofen - Cmax - Day 212.16 ug/mLStandard Deviation 1.74
Group 3C0 and Cmax for Ibuprofenibuprofen - C0 - Day 81.07 ug/mLStandard Deviation 0.77
Group 3C0 and Cmax for Ibuprofenibuprofen - C0 - Day 11.08 ug/mLStandard Deviation 0.97
Group 3C0 and Cmax for Ibuprofenibuprofen - C0 - Day -30.03 ug/mLStandard Deviation 0.04
Group 3C0 and Cmax for Ibuprofenibuprofen - C0 - Day 211.21 ug/mLStandard Deviation 0.9
Group 3C0 and Cmax for Ibuprofenibuprofen - Cmax - Day 83.69 ug/mLStandard Deviation 2.67
Group 3C0 and Cmax for Ibuprofenibuprofen - Cmax - Day 12.95 ug/mLStandard Deviation 2.1
Group 3C0 and Cmax for Ibuprofenibuprofen - Cmax - Day -33.11 ug/mLStandard Deviation 2.59
Group 3C0 and Cmax for Ibuprofenibuprofen - Cmax - Day 213.99 ug/mLStandard Deviation 2.74
Comparison: Cmax, ibuprofen, Day -3p-value: 0.1016ANOVA
Comparison: Cmax, ibuprofen, Day -3p-value: 0.2001ANOVA
Comparison: Cmax, ibuprofen, Day 1p-value: 0.0802ANOVA
Comparison: Cmax, ibuprofen, Day 1p-value: 0.4728ANOVA
Comparison: Cmax, ibuprofen, Day 8p-value: 0.0355ANOVA
Comparison: Cmax, ibuprofen, Day 8p-value: 0.1709ANOVA
Comparison: Cmax, ibuprofen, Day 21p-value: 0.0685ANOVA
Comparison: Cmax, ibuprofen, Day 21p-value: 0.3189ANOVA
Primary

Cmax for Paclitaxel

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.

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
Group 1Cmax for PaclitaxelPaclitaxel - Cmax - Day 12.35 ug/mLStandard Deviation 0.47
Group 1Cmax for PaclitaxelPaclitaxel - Cmax - Day 82.31 ug/mLStandard Deviation 0.3
Group 2Cmax for PaclitaxelPaclitaxel - Cmax - Day 12.44 ug/mLStandard Deviation 0.41
Group 2Cmax for PaclitaxelPaclitaxel - Cmax - Day 82.55 ug/mLStandard Deviation 0.73
Group 3Cmax for PaclitaxelPaclitaxel - Cmax - Day 13.10 ug/mLStandard Deviation 1.16
Group 3Cmax for PaclitaxelPaclitaxel - Cmax - Day 83.62 ug/mLStandard Deviation 0.96
Comparison: Paclitaxel, Cmax, Day 1p-value: 0.2375ANOVA
Comparison: Cmax, ibuprofen, Day 1p-value: 0.3608ANOVA
Comparison: Cmax, ibuprofen, Day 8p-value: 0.0442ANOVA
Comparison: Cmax, ibuprofen, Day 8p-value: 0.1067ANOVA
Primary

Plasma DF1681Y Concentrations by Time Point

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.

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
Group 1Plasma DF1681Y Concentrations by Time PointDay -3 - 8 hr1.538 ug/mLStandard Deviation 0.6268
Group 1Plasma DF1681Y Concentrations by Time PointDay -3 - 0.5 hr20.648 ug/mLStandard Deviation 22.1597
Group 1Plasma DF1681Y Concentrations by Time PointDay -3 - 1 hr27.683 ug/mLStandard Deviation 19.5342
Group 1Plasma DF1681Y Concentrations by Time PointDay -3 - 1.5 hr31.038 ug/mLStandard Deviation 15.219
Group 1Plasma DF1681Y Concentrations by Time PointDay -3 - 2 hr22.020 ug/mLStandard Deviation 11.0967
Group 1Plasma DF1681Y Concentrations by Time PointDay -3 - 3 hr12.868 ug/mLStandard Deviation 5.8392
Group 1Plasma DF1681Y Concentrations by Time PointDay -3 - 4 hr8.233 ug/mLStandard Deviation 4.9883
Group 1Plasma DF1681Y Concentrations by Time PointDay -3 - 6 hr2.838 ug/mLStandard Deviation 2.148
Group 1Plasma DF1681Y Concentrations by Time PointDay -3 - 0 hr0.000 ug/mLStandard Deviation 0
Group 1Plasma DF1681Y Concentrations by Time PointDay 1 - 0 hr1.050 ug/mLStandard Deviation 0.3705
Group 1Plasma DF1681Y Concentrations by Time PointDay 1 - 0.5 hr21.503 ug/mLStandard Deviation 22.1075
Group 1Plasma DF1681Y Concentrations by Time PointDay 1 - 1 hr19.553 ug/mLStandard Deviation 19.5114
Group 1Plasma DF1681Y Concentrations by Time PointDay 1 - 2 hr22.420 ug/mLStandard Deviation 13.4937
Group 1Plasma DF1681Y Concentrations by Time PointDay 8 - 0 hr0.785 ug/mLStandard Deviation 1.0511
Group 1Plasma DF1681Y Concentrations by Time PointDay 1 - 4 hr9.923 ug/mLStandard Deviation 5.3392
Group 1Plasma DF1681Y Concentrations by Time PointDay 1 - 8 hr2.185 ug/mLStandard Deviation 0.8552
Group 1Plasma DF1681Y Concentrations by Time PointDay 8 - 0.5 hr8.010 ug/mLStandard Deviation 4.569
Group 1Plasma DF1681Y Concentrations by Time PointDay 8 - 1 hr14.178 ug/mLStandard Deviation 9.35
Group 1Plasma DF1681Y Concentrations by Time PointDay 8 - 2 hr14.110 ug/mLStandard Deviation 9.4066
Group 1Plasma DF1681Y Concentrations by Time PointDay 8 - 4 hr9.360 ug/mLStandard Deviation 6.2105
Group 1Plasma DF1681Y Concentrations by Time PointDay 8 - 8 hr2.740 ug/mLStandard Deviation 1.4252
Group 1Plasma DF1681Y Concentrations by Time PointDay 8 - 24 hr22.000 ug/mLStandard Deviation 27.8459
Group 1Plasma DF1681Y Concentrations by Time PointDay 21 - 0 hr1.247 ug/mLStandard Deviation 0.758
Group 1Plasma DF1681Y Concentrations by Time PointDay 21 - 0.5 hr2.187 ug/mLStandard Deviation 0.7559
Group 1Plasma DF1681Y Concentrations by Time PointDay 21 - 1 hr3.883 ug/mLStandard Deviation 1.1319
Group 1Plasma DF1681Y Concentrations by Time PointDay 21 - 1.5 hr10.113 ug/mLStandard Deviation 5.4962
Group 1Plasma DF1681Y Concentrations by Time PointDay 21 - 2 hr13.433 ug/mLStandard Deviation 9.0774
Group 1Plasma DF1681Y Concentrations by Time PointDay 21 - 3 hr18.677 ug/mLStandard Deviation 2.3019
Group 1Plasma DF1681Y Concentrations by Time PointDay 21 - 4 hr8.897 ug/mLStandard Deviation 2.515
Group 1Plasma DF1681Y Concentrations by Time PointDay 21 - 6 hr3.247 ug/mLStandard Deviation 0.6596
Group 1Plasma DF1681Y Concentrations by Time PointDay 21 - 8 hr2.003 ug/mLStandard Deviation 0.238
Group 1Plasma DF1681Y Concentrations by Time PointDay 1 - 24 hr23.667 ug/mLStandard Deviation 31.3613
Group 2Plasma DF1681Y Concentrations by Time PointDay 8 - 0 hr2.403 ug/mLStandard Deviation 1.7784
Group 2Plasma DF1681Y Concentrations by Time PointDay 21 - 1 hr36.397 ug/mLStandard Deviation 33.4112
Group 2Plasma DF1681Y Concentrations by Time PointDay 1 - 1 hr45.413 ug/mLStandard Deviation 3.876
Group 2Plasma DF1681Y Concentrations by Time PointDay 1 - 2 hr31.090 ug/mLStandard Deviation 10.9918
Group 2Plasma DF1681Y Concentrations by Time PointDay 21 - 8 hr5.607 ug/mLStandard Deviation 2.1608
Group 2Plasma DF1681Y Concentrations by Time PointDay 21 - 1.5 hr33.787 ug/mLStandard Deviation 25.5501
Group 2Plasma DF1681Y Concentrations by Time PointDay 1 - 4 hr11.127 ug/mLStandard Deviation 3.575
Group 2Plasma DF1681Y Concentrations by Time PointDay 1 - 8 hr2.733 ug/mLStandard Deviation 1.1838
Group 2Plasma DF1681Y Concentrations by Time PointDay 1 - 24 hr23.193 ug/mLStandard Deviation 13.3628
Group 2Plasma DF1681Y Concentrations by Time PointDay 21 - 6 hr12.383 ug/mLStandard Deviation 6.9546
Group 2Plasma DF1681Y Concentrations by Time PointDay 8 - 0.5 hr5.689 ug/mLStandard Deviation 6.767
Group 2Plasma DF1681Y Concentrations by Time PointDay 21 - 2 hr29.663 ug/mLStandard Deviation 17.0469
Group 2Plasma DF1681Y Concentrations by Time PointDay 8 - 1 hr21.383 ug/mLStandard Deviation 21.5045
Group 2Plasma DF1681Y Concentrations by Time PointDay 8 - 2 hr30.897 ug/mLStandard Deviation 7.7797
Group 2Plasma DF1681Y Concentrations by Time PointDay 8 - 4 hr24.717 ug/mLStandard Deviation 6.1212
Group 2Plasma DF1681Y Concentrations by Time PointDay 21 - 3 hr24.693 ug/mLStandard Deviation 7.9406
Group 2Plasma DF1681Y Concentrations by Time PointDay 8 - 8 hr7.807 ug/mLStandard Deviation 3.777
Group 2Plasma DF1681Y Concentrations by Time PointDay -3 - 0 hr0.000 ug/mLStandard Deviation 0
Group 2Plasma DF1681Y Concentrations by Time PointDay -3 - 0.5 hr25.743 ug/mLStandard Deviation 25.4196
Group 2Plasma DF1681Y Concentrations by Time PointDay 8 - 24 hr14.843 ug/mLStandard Deviation 18.6946
Group 2Plasma DF1681Y Concentrations by Time PointDay -3 - 1 hr26.780 ug/mLStandard Deviation 28.4543
Group 2Plasma DF1681Y Concentrations by Time PointDay -3 - 1.5 hr22.180 ug/mLStandard Deviation 14.3448
Group 2Plasma DF1681Y Concentrations by Time PointDay -3 - 2 hr20.253 ug/mLStandard Deviation 12.2131
Group 2Plasma DF1681Y Concentrations by Time PointDay 21 - 0 hr6.003 ug/mLStandard Deviation 5.5644
Group 2Plasma DF1681Y Concentrations by Time PointDay -3 - 3 hr18.650 ug/mLStandard Deviation 8.4463
Group 2Plasma DF1681Y Concentrations by Time PointDay -3 - 4 hr14.933 ug/mLStandard Deviation 7.2954
Group 2Plasma DF1681Y Concentrations by Time PointDay 21 - 4 hr17.780 ug/mLStandard Deviation 2.4222
Group 2Plasma DF1681Y Concentrations by Time PointDay -3 - 6 hr6.537 ug/mLStandard Deviation 2.624
Group 2Plasma DF1681Y Concentrations by Time PointDay 21 - 0.5 hr29.380 ug/mLStandard Deviation 31.8622
Group 2Plasma DF1681Y Concentrations by Time PointDay -3 - 8 hr3.980 ug/mLStandard Deviation 2.1701
Group 2Plasma DF1681Y Concentrations by Time PointDay 1 - 0 hr4.243 ug/mLStandard Deviation 3.3862
Group 2Plasma DF1681Y Concentrations by Time PointDay 1 - 0.5 hr26.023 ug/mLStandard Deviation 16.2351
Group 3Plasma DF1681Y Concentrations by Time PointDay 8 - 8 hr11.111 ug/mLStandard Deviation 17.0215
Group 3Plasma DF1681Y Concentrations by Time PointDay -3 - 3 hr30.968 ug/mLStandard Deviation 10.71
Group 3Plasma DF1681Y Concentrations by Time PointDay -3 - 0 hr0.000 ug/mLStandard Deviation 0
Group 3Plasma DF1681Y Concentrations by Time PointDay 1 - 1 hr39.378 ug/mLStandard Deviation 31.5133
Group 3Plasma DF1681Y Concentrations by Time PointDay 21 - 1 hr62.916 ug/mLStandard Deviation 28.5967
Group 3Plasma DF1681Y Concentrations by Time PointDay 21 - 3 hr24.698 ug/mLStandard Deviation 13.4553
Group 3Plasma DF1681Y Concentrations by Time PointDay 21 - 0 hr4.978 ug/mLStandard Deviation 4.3227
Group 3Plasma DF1681Y Concentrations by Time PointDay 1 - 2 hr47.519 ug/mLStandard Deviation 21.1919
Group 3Plasma DF1681Y Concentrations by Time PointDay -3 - 0.5 hr34.689 ug/mLStandard Deviation 34.855
Group 3Plasma DF1681Y Concentrations by Time PointDay 1 - 0 hr5.739 ug/mLStandard Deviation 6.7727
Group 3Plasma DF1681Y Concentrations by Time PointDay 1 - 4 hr27.033 ug/mLStandard Deviation 14.4401
Group 3Plasma DF1681Y Concentrations by Time PointDay 21 - 1.5 hr54.749 ug/mLStandard Deviation 19.5782
Group 3Plasma DF1681Y Concentrations by Time PointDay -3 - 4 hr20.747 ug/mLStandard Deviation 8.4992
Group 3Plasma DF1681Y Concentrations by Time PointDay 1 - 8 hr17.579 ug/mLStandard Deviation 23.5794
Group 3Plasma DF1681Y Concentrations by Time PointDay -3 - 1 hr48.653 ug/mLStandard Deviation 27.4858
Group 3Plasma DF1681Y Concentrations by Time PointDay 1 - 24 hr19.685 ug/mLStandard Deviation 21.7424
Group 3Plasma DF1681Y Concentrations by Time PointDay 1 - 0.5 hr21.407 ug/mLStandard Deviation 23.045
Group 3Plasma DF1681Y Concentrations by Time PointDay 8 - 0 hr3.549 ug/mLStandard Deviation 2.053
Group 3Plasma DF1681Y Concentrations by Time PointDay 8 - 24 hr10.394 ug/mLStandard Deviation 7.5534
Group 3Plasma DF1681Y Concentrations by Time PointDay 21 - 4 hr17.359 ug/mLStandard Deviation 10.2954
Group 3Plasma DF1681Y Concentrations by Time PointDay 8 - 0.5 hr38.937 ug/mLStandard Deviation 39.3111
Group 3Plasma DF1681Y Concentrations by Time PointDay -3 - 1.5 hr55.810 ug/mLStandard Deviation 22.6579
Group 3Plasma DF1681Y Concentrations by Time PointDay 21 - 8 hr3.684 ug/mLStandard Deviation 2.2504
Group 3Plasma DF1681Y Concentrations by Time PointDay 8 - 1 hr35.506 ug/mLStandard Deviation 29.905
Group 3Plasma DF1681Y Concentrations by Time PointDay 21 - 2 hr43.490 ug/mLStandard Deviation 20.5604
Group 3Plasma DF1681Y Concentrations by Time PointDay -3 - 8 hr8.768 ug/mLStandard Deviation 12.3086
Group 3Plasma DF1681Y Concentrations by Time PointDay 8 - 2 hr34.182 ug/mLStandard Deviation 23.7096
Group 3Plasma DF1681Y Concentrations by Time PointDay 21 - 6 hr7.041 ug/mLStandard Deviation 3.9328
Group 3Plasma DF1681Y Concentrations by Time PointDay -3 - 2 hr50.630 ug/mLStandard Deviation 17.812
Group 3Plasma DF1681Y Concentrations by Time PointDay 8 - 4 hr23.986 ug/mLStandard Deviation 15.9604
Group 3Plasma DF1681Y Concentrations by Time PointDay -3 - 6 hr9.650 ug/mLStandard Deviation 7.3114
Group 3Plasma DF1681Y Concentrations by Time PointDay 21 - 0.5 hr48.578 ug/mLStandard Deviation 28.9433
Primary

Plasma DF2188Y Concentrations by Time Point

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.

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
Group 1Plasma DF2188Y Concentrations by Time PointDay -3 - 8 hr0.385 ug/mLStandard Deviation 0.2775
Group 1Plasma DF2188Y Concentrations by Time PointDay -3 - 0.5 hr0.547 ug/mLStandard Deviation 0.3798
Group 1Plasma DF2188Y Concentrations by Time PointDay -3 - 1 hr1.311 ug/mLStandard Deviation 0.6671
Group 1Plasma DF2188Y Concentrations by Time PointDay -3 - 1.5 hr2.337 ug/mLStandard Deviation 0.9274
Group 1Plasma DF2188Y Concentrations by Time PointDay -3 - 2 hr2.882 ug/mLStandard Deviation 1.1328
Group 1Plasma DF2188Y Concentrations by Time PointDay -3 - 3 hr2.024 ug/mLStandard Deviation 0.4877
Group 1Plasma DF2188Y Concentrations by Time PointDay -3 - 4 hr1.455 ug/mLStandard Deviation 0.5505
Group 1Plasma DF2188Y Concentrations by Time PointDay -3 - 6 hr0.571 ug/mLStandard Deviation 0.2527
Group 1Plasma DF2188Y Concentrations by Time PointDay -3 - 0 hr0.000 ug/mLStandard Deviation 0
Group 1Plasma DF2188Y Concentrations by Time PointDay 1 - 0 hr0.243 ug/mLStandard Deviation 0.1092
Group 1Plasma DF2188Y Concentrations by Time PointDay 1 - 0.5 hr0.997 ug/mLStandard Deviation 0.4469
Group 1Plasma DF2188Y Concentrations by Time PointDay 1 - 1 hr1.883 ug/mLStandard Deviation 1.0503
Group 1Plasma DF2188Y Concentrations by Time PointDay 1 - 2 hr2.804 ug/mLStandard Deviation 1.557
Group 1Plasma DF2188Y Concentrations by Time PointDay 1 - 4 hr1.687 ug/mLStandard Deviation 0.7018
Group 1Plasma DF2188Y Concentrations by Time PointDay 1 - 8 hr0.342 ug/mLStandard Deviation 0.184
Group 1Plasma DF2188Y Concentrations by Time PointDay 1 - 24 hr2.019 ug/mLStandard Deviation 1.8027
Group 1Plasma DF2188Y Concentrations by Time PointDay 8 - 0 hr0.185 ug/mLStandard Deviation 0.2617
Group 1Plasma DF2188Y Concentrations by Time PointDay 8 - 0.5 hr0.381 ug/mLStandard Deviation 0.2595
Group 1Plasma DF2188Y Concentrations by Time PointDay 8 - 1 hr1.360 ug/mLStandard Deviation 1.0877
Group 1Plasma DF2188Y Concentrations by Time PointDay 8 - 2 hr2.159 ug/mLStandard Deviation 0.9085
Group 1Plasma DF2188Y Concentrations by Time PointDay 8 - 4 hr1.966 ug/mLStandard Deviation 1.2606
Group 1Plasma DF2188Y Concentrations by Time PointDay 8 - 8 hr0.614 ug/mLStandard Deviation 0.4115
Group 1Plasma DF2188Y Concentrations by Time PointDay 8 - 24 hr1.961 ug/mLStandard Deviation 1.5761
Group 1Plasma DF2188Y Concentrations by Time PointDay 21 - 0 hr0.348 ug/mLStandard Deviation 0.248
Group 1Plasma DF2188Y Concentrations by Time PointDay 21 - 0.5 hr0.331 ug/mLStandard Deviation 0.0515
Group 1Plasma DF2188Y Concentrations by Time PointDay 21 - 1 hr0.398 ug/mLStandard Deviation 0.0494
Group 1Plasma DF2188Y Concentrations by Time PointDay 21 - 1.5 hr0.911 ug/mLStandard Deviation 0.3382
Group 1Plasma DF2188Y Concentrations by Time PointDay 21 - 2 hr1.612 ug/mLStandard Deviation 0.729
Group 1Plasma DF2188Y Concentrations by Time PointDay 21 - 3 hr3.138 ug/mLStandard Deviation 0.9689
Group 1Plasma DF2188Y Concentrations by Time PointDay 21 - 4 hr2.389 ug/mLStandard Deviation 0.1047
Group 1Plasma DF2188Y Concentrations by Time PointDay 21 - 6 hr0.949 ug/mLStandard Deviation 0.1443
Group 1Plasma DF2188Y Concentrations by Time PointDay 21 - 8 hr0.482 ug/mLStandard Deviation 0.1344
Group 2Plasma DF2188Y Concentrations by Time PointDay 8 - 8 hr1.117 ug/mLStandard Deviation 0.5547
Group 2Plasma DF2188Y Concentrations by Time PointDay -3 - 0 hr0.000 ug/mLStandard Deviation 0
Group 2Plasma DF2188Y Concentrations by Time PointDay 1 - 4 hr3.103 ug/mLStandard Deviation 0.6448
Group 2Plasma DF2188Y Concentrations by Time PointDay 8 - 0 hr0.536 ug/mLStandard Deviation 0.4428
Group 2Plasma DF2188Y Concentrations by Time PointDay -3 - 0.5 hr0.717 ug/mLStandard Deviation 0.8503
Group 2Plasma DF2188Y Concentrations by Time PointDay 1 - 2 hr6.129 ug/mLStandard Deviation 0.5653
Group 2Plasma DF2188Y Concentrations by Time PointDay 21 - 6 hr2.185 ug/mLStandard Deviation 1.2816
Group 2Plasma DF2188Y Concentrations by Time PointDay -3 - 1 hr2.128 ug/mLStandard Deviation 2.3765
Group 2Plasma DF2188Y Concentrations by Time PointDay 8 - 0.5 hr0.913 ug/mLStandard Deviation 1.1455
Group 2Plasma DF2188Y Concentrations by Time PointDay 8 - 24 hr1.627 ug/mLStandard Deviation 1.1583
Group 2Plasma DF2188Y Concentrations by Time PointDay -3 - 1.5 hr2.581 ug/mLStandard Deviation 2.0086
Group 2Plasma DF2188Y Concentrations by Time PointDay 21 - 8 hr0.987 ug/mLStandard Deviation 0.4603
Group 2Plasma DF2188Y Concentrations by Time PointDay 21 - 2 hr3.647 ug/mLStandard Deviation 2.0369
Group 2Plasma DF2188Y Concentrations by Time PointDay -3 - 2 hr2.693 ug/mLStandard Deviation 1.0611
Group 2Plasma DF2188Y Concentrations by Time PointDay 8 - 1 hr2.022 ug/mLStandard Deviation 1.5295
Group 2Plasma DF2188Y Concentrations by Time PointDay 1 - 8 hr0.519 ug/mLStandard Deviation 0.2349
Group 2Plasma DF2188Y Concentrations by Time PointDay -3 - 3 hr2.968 ug/mLStandard Deviation 1.0848
Group 2Plasma DF2188Y Concentrations by Time PointDay 1 - 1 hr7.251 ug/mLStandard Deviation 1.4929
Group 2Plasma DF2188Y Concentrations by Time PointDay 21 - 0 hr0.913 ug/mLStandard Deviation 0.7577
Group 2Plasma DF2188Y Concentrations by Time PointDay -3 - 4 hr2.752 ug/mLStandard Deviation 0.5639
Group 2Plasma DF2188Y Concentrations by Time PointDay 8 - 2 hr4.423 ug/mLStandard Deviation 0.8932
Group 2Plasma DF2188Y Concentrations by Time PointDay 21 - 1.5 hr3.522 ug/mLStandard Deviation 2.8731
Group 2Plasma DF2188Y Concentrations by Time PointDay -3 - 6 hr1.732 ug/mLStandard Deviation 0.4955
Group 2Plasma DF2188Y Concentrations by Time PointDay 1 - 24 hr4.706 ug/mLStandard Deviation 2.4979
Group 2Plasma DF2188Y Concentrations by Time PointDay 21 - 4 hr3.518 ug/mLStandard Deviation 1.4208
Group 2Plasma DF2188Y Concentrations by Time PointDay -3 - 8 hr0.891 ug/mLStandard Deviation 0.4059
Group 2Plasma DF2188Y Concentrations by Time PointDay 8 - 4 hr3.552 ug/mLStandard Deviation 0.6505
Group 2Plasma DF2188Y Concentrations by Time PointDay 21 - 0.5 hr1.542 ug/mLStandard Deviation 1.5637
Group 2Plasma DF2188Y Concentrations by Time PointDay 21 - 1 hr3.039 ug/mLStandard Deviation 3.1614
Group 2Plasma DF2188Y Concentrations by Time PointDay 1 - 0 hr1.360 ug/mLStandard Deviation 1.782
Group 2Plasma DF2188Y Concentrations by Time PointDay 21 - 3 hr3982 ug/mLStandard Deviation 1.272
Group 2Plasma DF2188Y Concentrations by Time PointDay 1 - 0.5 hr2.930 ug/mLStandard Deviation 0.9101
Group 3Plasma DF2188Y Concentrations by Time PointDay 21 - 0.5 hr3.707 ug/mLStandard Deviation 2.8351
Group 3Plasma DF2188Y Concentrations by Time PointDay 1 - 0.5 hr2.324 ug/mLStandard Deviation 2.7844
Group 3Plasma DF2188Y Concentrations by Time PointDay 21 - 4 hr4.209 ug/mLStandard Deviation 2.0152
Group 3Plasma DF2188Y Concentrations by Time PointDay 1 - 2 hr12.093 ug/mLStandard Deviation 8.5639
Group 3Plasma DF2188Y Concentrations by Time PointDay 21 - 1 hr8.087 ug/mLStandard Deviation 4.2863
Group 3Plasma DF2188Y Concentrations by Time PointDay 1 - 4 hr8.951 ug/mLStandard Deviation 6.3792
Group 3Plasma DF2188Y Concentrations by Time PointDay 1 - 8 hr4.222 ug/mLStandard Deviation 3.8268
Group 3Plasma DF2188Y Concentrations by Time PointDay 1 - 24 hr5.249 ug/mLStandard Deviation 7.1068
Group 3Plasma DF2188Y Concentrations by Time PointDay 21 - 1.5 hr9.590 ug/mLStandard Deviation 4.4184
Group 3Plasma DF2188Y Concentrations by Time PointDay 8 - 0 hr1.302 ug/mLStandard Deviation 1.9543
Group 3Plasma DF2188Y Concentrations by Time PointDay 8 - 0.5 hr7.260 ug/mLStandard Deviation 9.2883
Group 3Plasma DF2188Y Concentrations by Time PointDay 8 - 1 hr9.494 ug/mLStandard Deviation 8.6619
Group 3Plasma DF2188Y Concentrations by Time PointDay 21 - 2 hr9.485 ug/mLStandard Deviation 6.1568
Group 3Plasma DF2188Y Concentrations by Time PointDay 8 - 2 hr10.592 ug/mLStandard Deviation 9.186
Group 3Plasma DF2188Y Concentrations by Time PointDay 21 - 6 hr2.139 ug/mLStandard Deviation 1.9283
Group 3Plasma DF2188Y Concentrations by Time PointDay 8 - 4 hr6.181 ug/mLStandard Deviation 3.1973
Group 3Plasma DF2188Y Concentrations by Time PointDay -3 - 0 hr0.000 ug/mLStandard Deviation 0
Group 3Plasma DF2188Y Concentrations by Time PointDay 8 - 8 hr2.101 ug/mLStandard Deviation 2.1855
Group 3Plasma DF2188Y Concentrations by Time PointDay -3 - 0.5 hr1.781 ug/mLStandard Deviation 2.4828
Group 3Plasma DF2188Y Concentrations by Time PointDay 21 - 3 hr6.382 ug/mLStandard Deviation 4.5496
Group 3Plasma DF2188Y Concentrations by Time PointDay -3 - 1 hr4.986 ug/mLStandard Deviation 3.6296
Group 3Plasma DF2188Y Concentrations by Time PointDay -3 - 1.5 hr8.136 ug/mLStandard Deviation 3.7429
Group 3Plasma DF2188Y Concentrations by Time PointDay 8 - 24 hr2.753 ug/mLStandard Deviation 2.702
Group 3Plasma DF2188Y Concentrations by Time PointDay -3 - 2 hr9.381 ug/mLStandard Deviation 5.0573
Group 3Plasma DF2188Y Concentrations by Time PointDay 21 - 8 hr1.166 ug/mLStandard Deviation 1.4547
Group 3Plasma DF2188Y Concentrations by Time PointDay -3 - 3 hr8.332 ug/mLStandard Deviation 4.33
Group 3Plasma DF2188Y Concentrations by Time PointDay -3 - 4 hr5.320 ug/mLStandard Deviation 2.8278
Group 3Plasma DF2188Y Concentrations by Time PointDay 21 - 0 hr1.211 ug/mLStandard Deviation 1.0054
Group 3Plasma DF2188Y Concentrations by Time PointDay -3 - 6 hr2.373 ug/mLStandard Deviation 1.2315
Group 3Plasma DF2188Y Concentrations by Time PointDay -3 - 8 hr1.813 ug/mLStandard Deviation 1.5823
Group 3Plasma DF2188Y Concentrations by Time PointDay 1 - 1 hr6.940 ug/mLStandard Deviation 6.5771
Group 3Plasma DF2188Y Concentrations by Time PointDay 1 - 0 hr1.433 ug/mLStandard Deviation 2.0366
Primary

Plasma DF2243Y Concentrations by Time Point

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.

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
Group 1Plasma DF2243Y Concentrations by Time PointDay 1 - 1 hr2.023 ug/mLStandard Deviation 0.0645
Group 1Plasma DF2243Y Concentrations by Time PointDay 21 - 8 hr2.070 ug/mLStandard Deviation 0.3811
Group 1Plasma DF2243Y Concentrations by Time PointDay 1 - 2 hr4.218 ug/mLStandard Deviation 2.0817
Group 1Plasma DF2243Y Concentrations by Time PointDay 21 - 3 hr5.650 ug/mLStandard Deviation 2.3079
Group 1Plasma DF2243Y Concentrations by Time PointDay 8 - 8 hr2.080 ug/mLStandard Deviation 0.4491
Group 1Plasma DF2243Y Concentrations by Time PointDay 1 - 4 hr5.228 ug/mLStandard Deviation 2.7555
Group 1Plasma DF2243Y Concentrations by Time PointDay -3 - 2 hr4.990 ug/mLStandard Deviation 2.2479
Group 1Plasma DF2243Y Concentrations by Time PointDay 8 - 4 hr6.447 ug/mLStandard Deviation 3.9722
Group 1Plasma DF2243Y Concentrations by Time PointDay 1 - 8 hr1.555 ug/mLStandard Deviation 0.563
Group 1Plasma DF2243Y Concentrations by Time PointDay 21 - 6 hr4.090 ug/mLStandard Deviation 0.9231
Group 1Plasma DF2243Y Concentrations by Time PointDay 8 - 2 hr3.873 ug/mLStandard Deviation 3.7232
Group 1Plasma DF2243Y Concentrations by Time PointDay 1 - 24 hr5.507 ug/mLStandard Deviation 4.0277
Group 1Plasma DF2243Y Concentrations by Time PointDay 21 - 2 hr2.333 ug/mLStandard Deviation 1.4514
Group 1Plasma DF2243Y Concentrations by Time PointDay 8 - 1 hr1.118 ug/mLStandard Deviation 0.8848
Group 1Plasma DF2243Y Concentrations by Time PointDay 8 - 0.5 hr0.710 ug/mLStandard Deviation 0.759
Group 1Plasma DF2243Y Concentrations by Time PointDay 8 - 0 hr0.768 ug/mLStandard Deviation 0.8572
Group 1Plasma DF2243Y Concentrations by Time PointDay -3 - 3 hr5.478 ug/mLStandard Deviation 1.6318
Group 1Plasma DF2243Y Concentrations by Time PointDay -3 - 4 hr4.743 ug/mLStandard Deviation 0.1638
Group 1Plasma DF2243Y Concentrations by Time PointDay 21 - 4 hr7.320 ug/mLStandard Deviation 1.7217
Group 1Plasma DF2243Y Concentrations by Time PointDay 21 - 1.5 hr1.777 ug/mLStandard Deviation 1.0633
Group 1Plasma DF2243Y Concentrations by Time PointDay -3 - 6 hr2.753 ug/mLStandard Deviation 1.1919
Group 1Plasma DF2243Y Concentrations by Time PointDay -3 - 1 hr0.905 ug/mLStandard Deviation 0.4641
Group 1Plasma DF2243Y Concentrations by Time PointDay 21 - 1 hr1.593 ug/mLStandard Deviation 1.1089
Group 1Plasma DF2243Y Concentrations by Time PointDay -3 - 8 hr1.660 ug/mLStandard Deviation 1.1473
Group 1Plasma DF2243Y Concentrations by Time PointDay -3 - 0 hr0.000 ug/mLStandard Deviation 0
Group 1Plasma DF2243Y Concentrations by Time PointDay 21 - 0.5 hr1.373 ug/mLStandard Deviation 1.115
Group 1Plasma DF2243Y Concentrations by Time PointDay 1 - 0 hr1.078 ug/mLStandard Deviation 0.589
Group 1Plasma DF2243Y Concentrations by Time PointDay -3 - 0.5 hr0.188 ug/mLStandard Deviation 0.1477
Group 1Plasma DF2243Y Concentrations by Time PointDay 21 - 0 hr2.090 ug/mLStandard Deviation 2.2439
Group 1Plasma DF2243Y Concentrations by Time PointDay 1 - 0.5 hr1.008 ug/mLStandard Deviation 0.4421
Group 1Plasma DF2243Y Concentrations by Time PointDay -3 - 1.5 hr2.760 ug/mLStandard Deviation 1.5317
Group 1Plasma DF2243Y Concentrations by Time PointDay 8 - 24 hr4.205 ug/mLStandard Deviation 1.5768
Group 2Plasma DF2243Y Concentrations by Time PointDay -3 - 8 hr3.693 ug/mLStandard Deviation 1.1453
Group 2Plasma DF2243Y Concentrations by Time PointDay -3 - 0 hr0.000 ug/mLStandard Deviation 0
Group 2Plasma DF2243Y Concentrations by Time PointDay -3 - 0.5 hr0.167 ug/mLStandard Deviation 0.1943
Group 2Plasma DF2243Y Concentrations by Time PointDay -3 - 1 hr1.380 ug/mLStandard Deviation 1.6229
Group 2Plasma DF2243Y Concentrations by Time PointDay -3 - 1.5 hr2.803 ug/mLStandard Deviation 2.3608
Group 2Plasma DF2243Y Concentrations by Time PointDay -3 - 2 hr4.470 ug/mLStandard Deviation 2.707
Group 2Plasma DF2243Y Concentrations by Time PointDay -3 - 3 hr7.497 ug/mLStandard Deviation 4.2183
Group 2Plasma DF2243Y Concentrations by Time PointDay -3 - 4 hr7.857 ug/mLStandard Deviation 3.7009
Group 2Plasma DF2243Y Concentrations by Time PointDay -3 - 6 hr6.000 ug/mLStandard Deviation 0.6744
Group 2Plasma DF2243Y Concentrations by Time PointDay 1 - 0 hr4.683 ug/mLStandard Deviation 5.2831
Group 2Plasma DF2243Y Concentrations by Time PointDay 1 - 0.5 hr4.987 ug/mLStandard Deviation 4.8793
Group 2Plasma DF2243Y Concentrations by Time PointDay 1 - 1 hr6.520 ug/mLStandard Deviation 4.1584
Group 2Plasma DF2243Y Concentrations by Time PointDay 1 - 2 hr13.093 ug/mLStandard Deviation 4.0594
Group 2Plasma DF2243Y Concentrations by Time PointDay 1 - 4 hr11.727 ug/mLStandard Deviation 1.3886
Group 2Plasma DF2243Y Concentrations by Time PointDay 1 - 8 hr2.933 ug/mLStandard Deviation 0.4864
Group 2Plasma DF2243Y Concentrations by Time PointDay 1 - 24 hr12.953 ug/mLStandard Deviation 7.3222
Group 2Plasma DF2243Y Concentrations by Time PointDay 8 - 0 hr2.787 ug/mLStandard Deviation 2.6405
Group 2Plasma DF2243Y Concentrations by Time PointDay 8 - 0.5 hr2.595 ug/mLStandard Deviation 2.9911
Group 2Plasma DF2243Y Concentrations by Time PointDay 8 - 1 hr2.850 ug/mLStandard Deviation 2.27
Group 2Plasma DF2243Y Concentrations by Time PointDay 8 - 2 hr6.080 ug/mLStandard Deviation 3.6576
Group 2Plasma DF2243Y Concentrations by Time PointDay 8 - 4 hr9.960 ug/mLStandard Deviation 1.3869
Group 2Plasma DF2243Y Concentrations by Time PointDay 8 - 8 hr4.320 ug/mLStandard Deviation 1.1801
Group 2Plasma DF2243Y Concentrations by Time PointDay 8 - 24 hr3.310 ug/mLStandard Deviation 1.3343
Group 2Plasma DF2243Y Concentrations by Time PointDay 21 - 0 hr3.923 ug/mLStandard Deviation 3.1708
Group 2Plasma DF2243Y Concentrations by Time PointDay 21 - 0.5 hr3.577 ug/mLStandard Deviation 2.9258
Group 2Plasma DF2243Y Concentrations by Time PointDay 21 - 1 hr5.650 ug/mLStandard Deviation 5.6922
Group 2Plasma DF2243Y Concentrations by Time PointDay 21 - 1.5 hr7.097 ug/mLStandard Deviation 7.0797
Group 2Plasma DF2243Y Concentrations by Time PointDay 21 - 2 hr8.093 ug/mLStandard Deviation 6.9801
Group 2Plasma DF2243Y Concentrations by Time PointDay 21 - 3 hr10.343 ug/mLStandard Deviation 5.5662
Group 2Plasma DF2243Y Concentrations by Time PointDay 21 - 4 hr8.947 ug/mLStandard Deviation 3.6574
Group 2Plasma DF2243Y Concentrations by Time PointDay 21 - 6 hr7.597 ug/mLStandard Deviation 3.2853
Group 2Plasma DF2243Y Concentrations by Time PointDay 21 - 8 hr4.497 ug/mLStandard Deviation 1.9566
Group 3Plasma DF2243Y Concentrations by Time PointDay 1 - 0.5 hr5.878 ug/mLStandard Deviation 6.5607
Group 3Plasma DF2243Y Concentrations by Time PointDay 21 - 8 hr7.086 ug/mLStandard Deviation 5.3867
Group 3Plasma DF2243Y Concentrations by Time PointDay 8 - 24 hr10.500 ug/mLStandard Deviation 8.1986
Group 3Plasma DF2243Y Concentrations by Time PointDay 1 - 0 hr6.524 ug/mLStandard Deviation 7.2445
Group 3Plasma DF2243Y Concentrations by Time PointDay 21 - 4 hr16.361 ug/mLStandard Deviation 6.5721
Group 3Plasma DF2243Y Concentrations by Time PointDay 21 - 0 hr5.984 ug/mLStandard Deviation 4.0332
Group 3Plasma DF2243Y Concentrations by Time PointDay -3 - 8 hr6.935 ug/mLStandard Deviation 4.18711
Group 3Plasma DF2243Y Concentrations by Time PointDay -3 - 3 hr18.168 ug/mLStandard Deviation 7.372
Group 3Plasma DF2243Y Concentrations by Time PointDay 21 - 0.5 hr5.833 ug/mLStandard Deviation 3.6968
Group 3Plasma DF2243Y Concentrations by Time PointDay -3 - 6 hr11.187 ug/mLStandard Deviation 4.8182
Group 3Plasma DF2243Y Concentrations by Time PointDay -3 - 1 hr4.679 ug/mLStandard Deviation 4.8768
Group 3Plasma DF2243Y Concentrations by Time PointDay 21 - 1 hr11.106 ug/mLStandard Deviation 7.6876
Group 3Plasma DF2243Y Concentrations by Time PointDay -3 - 4 hr16.806 ug/mLStandard Deviation 5.3131
Group 3Plasma DF2243Y Concentrations by Time PointDay 21 - 6 hr11.146 ug/mLStandard Deviation 5.9542
Group 3Plasma DF2243Y Concentrations by Time PointDay 21 - 1.5 hr15.220 ug/mLStandard Deviation 7.9701
Group 3Plasma DF2243Y Concentrations by Time PointDay -3 - 2 hr14.382 ug/mLStandard Deviation 7.8212
Group 3Plasma DF2243Y Concentrations by Time PointDay -3 - 0 hr0.000 ug/mLStandard Deviation 0
Group 3Plasma DF2243Y Concentrations by Time PointDay 8 - 0 hr6.435 ug/mLStandard Deviation 7.0355
Group 3Plasma DF2243Y Concentrations by Time PointDay 8 - 0.5 hr5.927 ug/mLStandard Deviation 4.2413
Group 3Plasma DF2243Y Concentrations by Time PointDay 21 - 2 hr19.603 ug/mLStandard Deviation 9.6539
Group 3Plasma DF2243Y Concentrations by Time PointDay 1 - 24 hr12.365 ug/mLStandard Deviation 10.8597
Group 3Plasma DF2243Y Concentrations by Time PointDay -3 - 1.5 hr10.339 ug/mLStandard Deviation 7.9404
Group 3Plasma DF2243Y Concentrations by Time PointDay 8 - 1 hr8.123 ug/mLStandard Deviation 5.8406
Group 3Plasma DF2243Y Concentrations by Time PointDay 1 - 8 hr11.402 ug/mLStandard Deviation 8.7268
Group 3Plasma DF2243Y Concentrations by Time PointDay 1 - 1 hr7.027 ug/mLStandard Deviation 6.0291
Group 3Plasma DF2243Y Concentrations by Time PointDay 8 - 2 hr16.459 ug/mLStandard Deviation 10.0027
Group 3Plasma DF2243Y Concentrations by Time PointDay 1 - 4 hr19.320 ug/mLStandard Deviation 8.1202
Group 3Plasma DF2243Y Concentrations by Time PointDay 21 - 3 hr18.900 ug/mLStandard Deviation 8.125
Group 3Plasma DF2243Y Concentrations by Time PointDay 8 - 4 hr16.595 ug/mLStandard Deviation 6.9212
Group 3Plasma DF2243Y Concentrations by Time PointDay 1 - 2 hr14.229 ug/mLStandard Deviation 8.7457
Group 3Plasma DF2243Y Concentrations by Time PointDay -3 - 0.5 hr0.813 ug/mLStandard Deviation 1.2689
Group 3Plasma DF2243Y Concentrations by Time PointDay 8 - 8 hr8.401 ug/mLStandard Deviation 6.908
Primary

Plasma Ibuprofen Concentrations by Time Point

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.

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
Group 1Plasma Ibuprofen Concentrations by Time PointDay -3 - 2 hr0.676 ug/mLStandard Deviation 0.6193
Group 1Plasma Ibuprofen Concentrations by Time PointDay 8 - 2 hr0.312 ug/mLStandard Deviation 0.3725
Group 1Plasma Ibuprofen Concentrations by Time PointDay 8 - 4 hr0.352 ug/mLStandard Deviation 0.3909
Group 1Plasma Ibuprofen Concentrations by Time PointDay 8 - 8 hr0.213 ug/mLStandard Deviation 0.2363
Group 1Plasma Ibuprofen Concentrations by Time PointDay -3 - 0 hr0.040 ug/mLStandard Deviation 0.0383
Group 1Plasma Ibuprofen Concentrations by Time PointDay -3 - 0.5 hr0.165 ug/mLStandard Deviation 0.1401
Group 1Plasma Ibuprofen Concentrations by Time PointDay -3 - 1 hr0.244 ug/mLStandard Deviation 0.3003
Group 1Plasma Ibuprofen Concentrations by Time PointDay -3 - 1.5 hr0.430 ug/mLStandard Deviation 0.4382
Group 1Plasma Ibuprofen Concentrations by Time PointDay 8 - 1 hr0.251 ug/mLStandard Deviation 0.2304
Group 1Plasma Ibuprofen Concentrations by Time PointDay -3 - 3 hr0.760 ug/mLStandard Deviation 0.686
Group 1Plasma Ibuprofen Concentrations by Time PointDay -3 - 4 hr0.732 ug/mLStandard Deviation 0.6436
Group 1Plasma Ibuprofen Concentrations by Time PointDay -3 - 6 hr0.564 ug/mLStandard Deviation 0.5032
Group 1Plasma Ibuprofen Concentrations by Time PointDay -3 - 8 hr0.453 ug/mLStandard Deviation 0.396
Group 1Plasma Ibuprofen Concentrations by Time PointDay 1 - 0 hr0.414 ug/mLStandard Deviation 0.4035
Group 1Plasma Ibuprofen Concentrations by Time PointDay 1 - 0.5 hr0.410 ug/mLStandard Deviation 0.3334
Group 1Plasma Ibuprofen Concentrations by Time PointDay 1 - 1 hr0.539 ug/mLStandard Deviation 0.5508
Group 1Plasma Ibuprofen Concentrations by Time PointDay 1 - 2 hr0.798 ug/mLStandard Deviation 0.8648
Group 1Plasma Ibuprofen Concentrations by Time PointDay 1 - 4 hr0.816 ug/mLStandard Deviation 0.8769
Group 1Plasma Ibuprofen Concentrations by Time PointDay 1 - 8 hr0.440 ug/mLStandard Deviation 0.3806
Group 1Plasma Ibuprofen Concentrations by Time PointDay 1 - 24 hr0.862 ug/mLStandard Deviation 0.4607
Group 1Plasma Ibuprofen Concentrations by Time PointDay 8 - 0 hr0.125 ug/mLStandard Deviation 0.1307
Group 1Plasma Ibuprofen Concentrations by Time PointDay 8 - 0.5 hr0.140 ug/mLStandard Deviation 0.1191
Group 1Plasma Ibuprofen Concentrations by Time PointDay 8 - 24 hr0.416 ug/mLStandard Deviation 0.4582
Group 1Plasma Ibuprofen Concentrations by Time PointDay 21 - 0 hr0.300 ug/mLStandard Deviation 0.356
Group 1Plasma Ibuprofen Concentrations by Time PointDay 21 - 0.5 hr0.226 ug/mLStandard Deviation 0.2443
Group 1Plasma Ibuprofen Concentrations by Time PointDay 21 - 1 hr0.238 ug/mLStandard Deviation 0.2627
Group 1Plasma Ibuprofen Concentrations by Time PointDay 21 - 1.5 hr0.237 ug/mLStandard Deviation 0.2291
Group 1Plasma Ibuprofen Concentrations by Time PointDay 21 - 2 hr0.342 ug/mLStandard Deviation 0.3656
Group 1Plasma Ibuprofen Concentrations by Time PointDay 21 - 3 hr0.543 ug/mLStandard Deviation 0.5866
Group 1Plasma Ibuprofen Concentrations by Time PointDay 21 - 4 hr0.546 ug/mLStandard Deviation 0.6712
Group 1Plasma Ibuprofen Concentrations by Time PointDay 21 - 6 hr0.404 ug/mLStandard Deviation 0.4958
Group 1Plasma Ibuprofen Concentrations by Time PointDay 21 - 8 hr0.312 ug/mLStandard Deviation 0.227
Group 2Plasma Ibuprofen Concentrations by Time PointDay 8 - 0.5 hr0.652 ug/mLStandard Deviation 0.7177
Group 2Plasma Ibuprofen Concentrations by Time PointDay 8 - 1 hr0.571 ug/mLStandard Deviation 0.5765
Group 2Plasma Ibuprofen Concentrations by Time PointDay 1 - 0 hr1.245 ug/mLStandard Deviation 1.3888
Group 2Plasma Ibuprofen Concentrations by Time PointDay 1 - 2 hr1.948 ug/mLStandard Deviation 1.4572
Group 2Plasma Ibuprofen Concentrations by Time PointDay 8 - 2 hr1.065 ug/mLStandard Deviation 0.8626
Group 2Plasma Ibuprofen Concentrations by Time PointDay -3 - 8 hr0.680 ug/mLStandard Deviation 0.4165
Group 2Plasma Ibuprofen Concentrations by Time PointDay 21 - 6 hr1.179 ug/mLStandard Deviation 0.6063
Group 2Plasma Ibuprofen Concentrations by Time PointDay 8 - 4 hr1.016 ug/mLStandard Deviation 0.4036
Group 2Plasma Ibuprofen Concentrations by Time PointDay 1 - 4 hr1.557 ug/mLStandard Deviation 0.9902
Group 2Plasma Ibuprofen Concentrations by Time PointDay 21 - 8 hr0.802 ug/mLStandard Deviation 0.3472
Group 2Plasma Ibuprofen Concentrations by Time PointDay 8 - 8 hr0.699 ug/mLStandard Deviation 0.4269
Group 2Plasma Ibuprofen Concentrations by Time PointDay 21 - 2 hr1.214 ug/mLStandard Deviation 0.8686
Group 2Plasma Ibuprofen Concentrations by Time PointDay 8 - 24 hr0.602 ug/mLStandard Deviation 0.3706
Group 2Plasma Ibuprofen Concentrations by Time PointDay -3 - 0 hr0.024 ug/mLStandard Deviation 0.0172
Group 2Plasma Ibuprofen Concentrations by Time PointDay 1 - 8 hr0.693 ug/mLStandard Deviation 0.4651
Group 2Plasma Ibuprofen Concentrations by Time PointDay 1 - 0.5 hr1.2220 ug/mLStandard Deviation 1.0325
Group 2Plasma Ibuprofen Concentrations by Time PointDay -3 - 0.5 hr0.260 ug/mLStandard Deviation 0.3355
Group 2Plasma Ibuprofen Concentrations by Time PointDay -3 - 6 hr0.861 ug/mLStandard Deviation 0.5131
Group 2Plasma Ibuprofen Concentrations by Time PointDay 1 - 24 hr1.964 ug/mLStandard Deviation 1.5247
Group 2Plasma Ibuprofen Concentrations by Time PointDay -3 - 1 hr0.578 ug/mLStandard Deviation 0.7653
Group 2Plasma Ibuprofen Concentrations by Time PointDay 21 - 1.5 hr0.986 ug/mLStandard Deviation 0.7064
Group 2Plasma Ibuprofen Concentrations by Time PointDay 21 - 0 hr0.863 ug/mLStandard Deviation 0.7528
Group 2Plasma Ibuprofen Concentrations by Time PointDay -3 - 1.5 hr0.663 ug/mLStandard Deviation 0.8429
Group 2Plasma Ibuprofen Concentrations by Time PointDay 1 - 1 hr1.759 ug/mLStandard Deviation 1.5027
Group 2Plasma Ibuprofen Concentrations by Time PointDay 8 - 0 hr0.534 ug/mLStandard Deviation 0.5566
Group 2Plasma Ibuprofen Concentrations by Time PointDay -3 - 2 hr0.736 ug/mLStandard Deviation 0.7971
Group 2Plasma Ibuprofen Concentrations by Time PointDay 21 - 1 hr0.849 ug/mLStandard Deviation 0.6339
Group 2Plasma Ibuprofen Concentrations by Time PointDay 21 - 4 hr1.970 ug/mLStandard Deviation 1.9069
Group 2Plasma Ibuprofen Concentrations by Time PointDay -3 - 3 hr0.863 ug/mLStandard Deviation 0.6598
Group 2Plasma Ibuprofen Concentrations by Time PointDay 21 - 3 hr1.562 ug/mLStandard Deviation 1.138
Group 2Plasma Ibuprofen Concentrations by Time PointDay 21 - 0.5 hr0.734 ug/mLStandard Deviation 0.5966
Group 2Plasma Ibuprofen Concentrations by Time PointDay -3 - 4 hr0.930 ug/mLStandard Deviation 0.5859
Group 3Plasma Ibuprofen Concentrations by Time PointDay -3 - 1.5 hr2.144 ug/mLStandard Deviation 1.6461
Group 3Plasma Ibuprofen Concentrations by Time PointDay 21 - 0.5 hr1.341 ug/mLStandard Deviation 0.7483
Group 3Plasma Ibuprofen Concentrations by Time PointDay -3 - 6 hr1.653 ug/mLStandard Deviation 1.3698
Group 3Plasma Ibuprofen Concentrations by Time PointDay 21 - 4 hr2.712 ug/mLStandard Deviation 1.9665
Group 3Plasma Ibuprofen Concentrations by Time PointDay -3 - 8 hr1.249 ug/mLStandard Deviation 0.9589
Group 3Plasma Ibuprofen Concentrations by Time PointDay 1 - 0 hr1.077 ug/mLStandard Deviation 0.969
Group 3Plasma Ibuprofen Concentrations by Time PointDay 1 - 0.5 hr0.984 ug/mLStandard Deviation 0.827
Group 3Plasma Ibuprofen Concentrations by Time PointDay 1 - 1 hr1.319 ug/mLStandard Deviation 1.2569
Group 3Plasma Ibuprofen Concentrations by Time PointDay 21 - 1.5 hr3.222 ug/mLStandard Deviation 2.2855
Group 3Plasma Ibuprofen Concentrations by Time PointDay 1 - 2 hr2.633 ug/mLStandard Deviation 2.2699
Group 3Plasma Ibuprofen Concentrations by Time PointDay 1 - 4 hr2.575 ug/mLStandard Deviation 2.0191
Group 3Plasma Ibuprofen Concentrations by Time PointDay 1 - 8 hr1.532 ug/mLStandard Deviation 1.0465
Group 3Plasma Ibuprofen Concentrations by Time PointDay 21 - 2 hr3.335 ug/mLStandard Deviation 2.4454
Group 3Plasma Ibuprofen Concentrations by Time PointDay 1 - 24 hr1.667 ug/mLStandard Deviation 1.3126
Group 3Plasma Ibuprofen Concentrations by Time PointDay 21 - 6 hr1.645 ug/mLStandard Deviation 1.2753
Group 3Plasma Ibuprofen Concentrations by Time PointDay 8 - 0 hr1.068 ug/mLStandard Deviation 0.7676
Group 3Plasma Ibuprofen Concentrations by Time PointDay 8 - 1 hr2.683 ug/mLStandard Deviation 2.7211
Group 3Plasma Ibuprofen Concentrations by Time PointDay 8 - 0.5 hr2.087 ug/mLStandard Deviation 2.0162
Group 3Plasma Ibuprofen Concentrations by Time PointDay 8 - 2 hr2.879 ug/mLStandard Deviation 2.7853
Group 3Plasma Ibuprofen Concentrations by Time PointDay 21 - 1 hr2.381 ug/mLStandard Deviation 1.4899
Group 3Plasma Ibuprofen Concentrations by Time PointDay 8 - 4 hr2.553 ug/mLStandard Deviation 2.0585
Group 3Plasma Ibuprofen Concentrations by Time PointDay 21 - 3 hr3.327 ug/mLStandard Deviation 2.8221
Group 3Plasma Ibuprofen Concentrations by Time PointDay 8 - 8 hr1.310 ug/mLStandard Deviation 1.0034
Group 3Plasma Ibuprofen Concentrations by Time PointDay -3 - 0 hr0.030 ug/mLStandard Deviation 0.0444
Group 3Plasma Ibuprofen Concentrations by Time PointDay 8 - 24 hr1.448 ug/mLStandard Deviation 0.9161
Group 3Plasma Ibuprofen Concentrations by Time PointDay -3 - 0.5 hr0.282 ug/mLStandard Deviation 0.2943
Group 3Plasma Ibuprofen Concentrations by Time PointDay 21 - 8 hr1.218 ug/mLStandard Deviation 0.9901
Group 3Plasma Ibuprofen Concentrations by Time PointDay -3 - 1 hr1.141 ug/mLStandard Deviation 0.9977
Group 3Plasma Ibuprofen Concentrations by Time PointDay -3 - 4 hr2.420 ug/mLStandard Deviation 2.3095
Group 3Plasma Ibuprofen Concentrations by Time PointDay 21 - 0 hr1.210 ug/mLStandard Deviation 0.8951
Group 3Plasma Ibuprofen Concentrations by Time PointDay -3 - 2 hr2.728 ug/mLStandard Deviation 2.5583
Group 3Plasma Ibuprofen Concentrations by Time PointDay -3 - 3 hr2.979 ug/mLStandard Deviation 2.6527
Primary

Plasma Paclitaxel Concentrations by Time Point

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.

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
Group 1Plasma Paclitaxel Concentrations by Time PointDay 8 - 2 hr0.318 ug/mLStandard Deviation 0.0707
Group 1Plasma Paclitaxel Concentrations by Time PointDay 1 - 8 hr0.066 ug/mLStandard Deviation 0.0094
Group 1Plasma Paclitaxel Concentrations by Time PointDay 1 - 1 hr1.954 ug/mLStandard Deviation 1.0995
Group 1Plasma Paclitaxel Concentrations by Time PointDay 8 - 1 hr1.730 ug/mLStandard Deviation 1.1795
Group 1Plasma Paclitaxel Concentrations by Time PointDay 1 - 24 hr0.019 ug/mLStandard Deviation 0.0076
Group 1Plasma Paclitaxel Concentrations by Time PointDay 1 - 0.5 hr1.483 ug/mLStandard Deviation 1.0948
Group 1Plasma Paclitaxel Concentrations by Time PointDay 8 - 0.5 hr1.409 ug/mLStandard Deviation 1.0059
Group 1Plasma Paclitaxel Concentrations by Time PointDay 8 - 0 hr0.000 ug/mLStandard Deviation 0
Group 1Plasma Paclitaxel Concentrations by Time PointDay 8 - 4 hr0.122 ug/mLStandard Deviation 0.0294
Group 1Plasma Paclitaxel Concentrations by Time PointDay 1 - 2 hr0.733 ug/mLStandard Deviation 0.7148
Group 1Plasma Paclitaxel Concentrations by Time PointDay 8 - 24 hr0.023 ug/mLStandard Deviation 0.0078
Group 1Plasma Paclitaxel Concentrations by Time PointDay 1 - 0 hr0.000 ug/mLStandard Deviation 0
Group 1Plasma Paclitaxel Concentrations by Time PointDay 1 - 4 hr0.166 ug/mLStandard Deviation 0.056
Group 1Plasma Paclitaxel Concentrations by Time PointDay 8 - 8 hr0.060 ug/mLStandard Deviation 0.0195
Group 2Plasma Paclitaxel Concentrations by Time PointDay 8 - 2 hr0.706 ug/mLStandard Deviation 0.7383
Group 2Plasma Paclitaxel Concentrations by Time PointDay 1 - 0 hr0.000 ug/mLStandard Deviation 0
Group 2Plasma Paclitaxel Concentrations by Time PointDay 1 - 0.5 hr1.560 ug/mLStandard Deviation 0.506
Group 2Plasma Paclitaxel Concentrations by Time PointDay 1 - 1 hr2.438 ug/mLStandard Deviation 0.4045
Group 2Plasma Paclitaxel Concentrations by Time PointDay 1 - 2 hr0.342 ug/mLStandard Deviation 0.1071
Group 2Plasma Paclitaxel Concentrations by Time PointDay 1 - 4 hr0.118 ug/mLStandard Deviation 0.0398
Group 2Plasma Paclitaxel Concentrations by Time PointDay 1 - 8 hr0.060 ug/mLStandard Deviation 0.019
Group 2Plasma Paclitaxel Concentrations by Time PointDay 1 - 24 hr0.020 ug/mLStandard Deviation 0.0076
Group 2Plasma Paclitaxel Concentrations by Time PointDay 8 - 0 hr0.004 ug/mLStandard Deviation 0.0075
Group 2Plasma Paclitaxel Concentrations by Time PointDay 8 - 0.5 hr1.466 ug/mLStandard Deviation 0.1372
Group 2Plasma Paclitaxel Concentrations by Time PointDay 8 - 1 hr2.554 ug/mLStandard Deviation 0.7296
Group 2Plasma Paclitaxel Concentrations by Time PointDay 8 - 4 hr0.175 ug/mLStandard Deviation 0.1054
Group 2Plasma Paclitaxel Concentrations by Time PointDay 8 - 8 hr0.102 ug/mLStandard Deviation 0.0814
Group 2Plasma Paclitaxel Concentrations by Time PointDay 8 - 24 hr0.047 ug/mLStandard Deviation 0.043
Group 3Plasma Paclitaxel Concentrations by Time PointDay 8 - 8 hr0.095 ug/mLStandard Deviation 0.0638
Group 3Plasma Paclitaxel Concentrations by Time PointDay 8 - 1 hr3.222 ug/mLStandard Deviation 1.4919
Group 3Plasma Paclitaxel Concentrations by Time PointDay 1 - 4 hr0.363 ug/mLStandard Deviation 0.5901
Group 3Plasma Paclitaxel Concentrations by Time PointDay 1 - 2 hr0.600 ug/mLStandard Deviation 0.4058
Group 3Plasma Paclitaxel Concentrations by Time PointDay 8 - 2 hr0.759 ug/mLStandard Deviation 1.0239
Group 3Plasma Paclitaxel Concentrations by Time PointDay 1 - 1 hr2.898 ug/mLStandard Deviation 1.4819
Group 3Plasma Paclitaxel Concentrations by Time PointDay 1 - 0 hr0.070 ug/mLStandard Deviation 0.1664
Group 3Plasma Paclitaxel Concentrations by Time PointDay 8 - 4 hr0.196 ug/mLStandard Deviation 0.1234
Group 3Plasma Paclitaxel Concentrations by Time PointDay 1 - 0.5 hr2.275 ug/mLStandard Deviation 1.2319
Group 3Plasma Paclitaxel Concentrations by Time PointDay 8 - 0 hr0.001 ug/mLStandard Deviation 0.0022
Group 3Plasma Paclitaxel Concentrations by Time PointDay 1 - 24 hr0.030 ug/mLStandard Deviation 0.0145
Group 3Plasma Paclitaxel Concentrations by Time PointDay 8 - 24 hr0.031 ug/mLStandard Deviation 0.019
Group 3Plasma Paclitaxel Concentrations by Time PointDay 8 - 0.5 hr2.426 ug/mLStandard Deviation 1.3387
Group 3Plasma Paclitaxel Concentrations by Time PointDay 1 - 8 hr0.099 ug/mLStandard Deviation 0.0622
Primary

Plasma Unbound DF1681Y Concentrations by Time Point

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.

Time frame: 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.

ArmMeasureGroupValue (MEAN)Dispersion
Group 1Plasma Unbound DF1681Y Concentrations by Time PointDay -3 - 1 hr13.7 ng/mLStandard Deviation 10.13
Group 1Plasma Unbound DF1681Y Concentrations by Time PointDay -3 - 2 hr13.1 ng/mLStandard Deviation 7.27
Group 1Plasma Unbound DF1681Y Concentrations by Time PointDay 1 - 1 hr12.3 ng/mLStandard Deviation 14.64
Group 1Plasma Unbound DF1681Y Concentrations by Time PointDay 1 - 2 hr13.2 ng/mLStandard Deviation 7.79
Group 1Plasma Unbound DF1681Y Concentrations by Time PointDay 8 - 1 hr9.1 ng/mLStandard Deviation 7.63
Group 1Plasma Unbound DF1681Y Concentrations by Time PointDay 8 - 2 hr9.3 ng/mLStandard Deviation 5
Group 1Plasma Unbound DF1681Y Concentrations by Time PointDay 21 - 1 hr2.5 ng/mLStandard Deviation 0.96
Group 1Plasma Unbound DF1681Y Concentrations by Time PointDay 21 - 2 hr14.9 ng/mLStandard Deviation 16.49
Group 2Plasma Unbound DF1681Y Concentrations by Time PointDay 1 - 2 hr25.0 ng/mLStandard Deviation 11.57
Group 2Plasma Unbound DF1681Y Concentrations by Time PointDay 8 - 1 hr13.0 ng/mLStandard Deviation 13.27
Group 2Plasma Unbound DF1681Y Concentrations by Time PointDay -3 - 1 hr22.4 ng/mLStandard Deviation 19.14
Group 2Plasma Unbound DF1681Y Concentrations by Time PointDay 8 - 2 hr21.6 ng/mLStandard Deviation 8.37
Group 2Plasma Unbound DF1681Y Concentrations by Time PointDay 21 - 1 hr44.9 ng/mLStandard Deviation 61.18
Group 2Plasma Unbound DF1681Y Concentrations by Time PointDay -3 - 2 hr37.2 ng/mLStandard Deviation 26.35
Group 2Plasma Unbound DF1681Y Concentrations by Time PointDay 1 - 1 hr78.9 ng/mLStandard Deviation 38.86
Group 2Plasma Unbound DF1681Y Concentrations by Time PointDay 21 - 2 hr34.1 ng/mLStandard Deviation 21.54
Group 3Plasma Unbound DF1681Y Concentrations by Time PointDay -3 - 1 hr109.1 ng/mLStandard Deviation 131.15
Group 3Plasma Unbound DF1681Y Concentrations by Time PointDay 1 - 2 hr83.9 ng/mLStandard Deviation 97.73
Group 3Plasma Unbound DF1681Y Concentrations by Time PointDay 21 - 2 hr50.8 ng/mLStandard Deviation 42.04
Group 3Plasma Unbound DF1681Y Concentrations by Time PointDay 21 - 1 hr117.2 ng/mLStandard Deviation 84.65
Group 3Plasma Unbound DF1681Y Concentrations by Time PointDay 8 - 1 hr84.4 ng/mLStandard Deviation 147.04
Group 3Plasma Unbound DF1681Y Concentrations by Time PointDay 1 - 1 hr76.2 ng/mLStandard Deviation 107.84
Group 3Plasma Unbound DF1681Y Concentrations by Time PointDay -3 - 2 hr74.5 ng/mLStandard Deviation 63.82
Group 3Plasma Unbound DF1681Y Concentrations by Time PointDay 8 - 2 hr30.4 ng/mLStandard Deviation 29.46
Primary

Rac0-24 for Paclitaxel

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.

Time frame: 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

ArmMeasureValue (MEAN)Dispersion
Group 1Rac0-24 for Paclitaxel0.90 ratioStandard Deviation 0.11
Group 2Rac0-24 for Paclitaxel1.59 ratioStandard Deviation 1.325
Group 3Rac0-24 for Paclitaxel1.04 ratioStandard Deviation 0.121
Primary

Rac0-8 for DF1681Y

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.

Time frame: 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 1

Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter

ArmMeasureGroupValue (MEAN)Dispersion
Group 1Rac0-8 for DF1681YDF1681Y - Rac0-8 - Day 80.63 ratioStandard Deviation 0.39
Group 1Rac0-8 for DF1681YDF1681Y- Rac0-8 - Day 10.97 ratioStandard Deviation 0.14
Group 1Rac0-8 for DF1681YDF1681Y- Rac0-8 - Day 210.82 ratioStandard Deviation 0.22
Group 2Rac0-8 for DF1681YDF1681Y - Rac0-8 - Day 81.7 ratioStandard Deviation 0.88
Group 2Rac0-8 for DF1681YDF1681Y- Rac0-8 - Day 11.3 ratioStandard Deviation 0.53
Group 2Rac0-8 for DF1681YDF1681Y- Rac0-8 - Day 211.61 ratioStandard Deviation 0.63
Group 3Rac0-8 for DF1681YDF1681Y- Rac0-8 - Day 11.21 ratioStandard Deviation 0.41
Group 3Rac0-8 for DF1681YDF1681Y- Rac0-8 - Day 211.02 ratioStandard Deviation 0.21
Group 3Rac0-8 for DF1681YDF1681Y - Rac0-8 - Day 81.01 ratioStandard Deviation 0.3
Primary

Rac0-8 for DF2188Y

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.

Time frame: 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 1

Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter

ArmMeasureGroupValue (MEAN)Dispersion
Group 1Rac0-8 for DF2188YDF2188Y - Rac0-8 - Day 80.77 ratioStandard Deviation 0.54
Group 1Rac0-8 for DF2188YDF2188Y- Rac0-8 - Day 11.12 ratioStandard Deviation 0.34
Group 1Rac0-8 for DF2188YDF2188Y- Rac0-8 - Day 211.04 ratioStandard Deviation 0.09
Group 2Rac0-8 for DF2188YDF2188Y - Rac0-8 - Day 81.32 ratioStandard Deviation 0.22
Group 2Rac0-8 for DF2188YDF2188Y- Rac0-8 - Day 11.61 ratioStandard Deviation 0.4
Group 2Rac0-8 for DF2188YDF2188Y- Rac0-8 - Day 211.35 ratioStandard Deviation 0.15
Group 3Rac0-8 for DF2188YDF2188Y- Rac0-8 - Day 11.52 ratioStandard Deviation 0.51
Group 3Rac0-8 for DF2188YDF2188Y- Rac0-8 - Day 210.95 ratioStandard Deviation 0.15
Group 3Rac0-8 for DF2188YDF2188Y - Rac0-8 - Day 81.22 ratioStandard Deviation 0.27
Primary

Rac0-8 for DF2243Y

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.

Time frame: 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 1

Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter

ArmMeasureGroupValue (MEAN)Dispersion
Group 1Rac0-8 for DF2243YDF2243Y - Rac0-8 - Day 80.78 ratioStandard Deviation 0.64
Group 1Rac0-8 for DF2243YDF2243Y- Rac0-8 - Day 11.02 ratioStandard Deviation 0.28
Group 1Rac0-8 for DF2243YDF2243Y- Rac0-8 - Day 211.15 ratioStandard Deviation 0.19
Group 2Rac0-8 for DF2243YDF2243Y - Rac0-8 - Day 81.3 ratioStandard Deviation 0.37
Group 2Rac0-8 for DF2243YDF2243Y- Rac0-8 - Day 11.82 ratioStandard Deviation 1.06
Group 2Rac0-8 for DF2243YDF2243Y- Rac0-8 - Day 211.44 ratioStandard Deviation 0.11
Group 3Rac0-8 for DF2243YDF2243Y- Rac0-8 - Day 11.18 ratioStandard Deviation 0.27
Group 3Rac0-8 for DF2243YDF2243Y- Rac0-8 - Day 211.16 ratioStandard Deviation 0.17
Group 3Rac0-8 for DF2243YDF2243Y - Rac0-8 - Day 81.08 ratioStandard Deviation 0.23
Primary

Rac0-8 for Ibuprofen

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.

Time frame: 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 1

Population: PK Population: patients who received one dose of reparixin and had at least one valid, quantifiable PK parameter

ArmMeasureGroupValue (MEAN)Dispersion
Group 1Rac0-8 for IbuprofenIbuprofen - Rac0-8 - Day 80.65 ratioStandard Deviation 0.61
Group 1Rac0-8 for IbuprofenIbuprofen - Rac0-8 - Day 11.09 ratioStandard Deviation 0.22
Group 1Rac0-8 for IbuprofenIbuprofen - Rac0-8 - Day 211.18 ratioStandard Deviation 0.74
Group 2Rac0-8 for IbuprofenIbuprofen - Rac0-8 - Day 81.25 ratioStandard Deviation 0.28
Group 2Rac0-8 for IbuprofenIbuprofen - Rac0-8 - Day 11.99 ratioStandard Deviation 1.38
Group 2Rac0-8 for IbuprofenIbuprofen - Rac0-8 - Day 211.89 ratioStandard Deviation 0.86
Group 3Rac0-8 for IbuprofenIbuprofen - Rac0-8 - Day 11.18 ratioStandard Deviation 0.43
Group 3Rac0-8 for IbuprofenIbuprofen - Rac0-8 - Day 211.24 ratioStandard Deviation 0.26
Group 3Rac0-8 for IbuprofenIbuprofen - Rac0-8 - Day 81.23 ratioStandard Deviation 0.3
Primary

Tmax and t1/2 for DF1681Y

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).

Time frame: 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

ArmMeasureGroupValue (MEAN)Dispersion
Group 1Tmax and t1/2 for DF1681YDF1681Y - tmax - Day -30.90 hoursStandard Deviation 0.45
Group 1Tmax and t1/2 for DF1681YDF1681Y - tmax - Day 12.15 hoursStandard Deviation 1.44
Group 1Tmax and t1/2 for DF1681YDF1681Y - tmax - Day 81.30 hoursStandard Deviation 0.46
Group 1Tmax and t1/2 for DF1681YDF1681Y - tmax - Day 212.66 hoursStandard Deviation 0.57
Group 1Tmax and t1/2 for DF1681YDF1681Y - t1/2 - Day -31.65 hoursStandard Deviation 0.51
Group 1Tmax and t1/2 for DF1681YDF1681Y - t1/2 - Day 11.97 hours—
Group 1Tmax and t1/2 for DF1681YDF1681Y - t1/2 - Day 82.00 hours—
Group 1Tmax and t1/2 for DF1681YDF1681Y - t1/2 - Day 211.89 hoursStandard Deviation 0.57
Group 2Tmax and t1/2 for DF1681YDF1681Y - tmax - Day 81.72 hoursStandard Deviation 0.48
Group 2Tmax and t1/2 for DF1681YDF1681Y - t1/2 - Day 83.57 hours—
Group 2Tmax and t1/2 for DF1681YDF1681Y - tmax - Day 212.32 hoursStandard Deviation 1.52
Group 2Tmax and t1/2 for DF1681YDF1681Y - t1/2 - Day -31.82 hoursStandard Deviation 0.82
Group 2Tmax and t1/2 for DF1681YDF1681Y - t1/2 - Day 11.73 hoursStandard Deviation 0.09
Group 2Tmax and t1/2 for DF1681YDF1681Y - tmax - Day -31.82 hoursStandard Deviation 1.25
Group 2Tmax and t1/2 for DF1681YDF1681Y - tmax - Day 11.01 hoursStandard Deviation 0.01
Group 2Tmax and t1/2 for DF1681YDF1681Y - t1/2 - Day 211.97 hoursStandard Deviation 0.55
Group 3Tmax and t1/2 for DF1681YDF1681Y - tmax - Day 82.45 hoursStandard Deviation 2.35
Group 3Tmax and t1/2 for DF1681YDF1681Y - tmax - Day 12.64 hoursStandard Deviation 4.07
Group 3Tmax and t1/2 for DF1681YDF1681Y - tmax - Day -31.41 hoursStandard Deviation 0.55
Group 3Tmax and t1/2 for DF1681YDF1681Y - tmax - Day 211.40 hoursStandard Deviation 0.35
Group 3Tmax and t1/2 for DF1681YDF1681Y - t1/2 - Day 81.88 hoursStandard Deviation 0.27
Group 3Tmax and t1/2 for DF1681YDF1681Y - t1/2 - Day 12.14 hoursStandard Deviation 0.45
Group 3Tmax and t1/2 for DF1681YDF1681Y - t1/2 - Day -31.91 hoursStandard Deviation 0.64
Group 3Tmax and t1/2 for DF1681YDF1681Y - t1/2 - Day 211.95 hoursStandard Deviation 0.56
Primary

Tmax and t1/2 for DF2188Y

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).

Time frame: 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

ArmMeasureGroupValue (MEAN)Dispersion
Group 1Tmax and t1/2 for DF2188YDF2188Y- tmax - Day 11.78 hoursStandard Deviation 0.52
Group 1Tmax and t1/2 for DF2188YDF2188Y - t1/2 - Day -31.63 hoursStandard Deviation 0.23
Group 1Tmax and t1/2 for DF2188YDF2188Y - tmax - Day 213.33 hoursStandard Deviation 0.57
Group 1Tmax and t1/2 for DF2188YDF2188Y - tmax - Day -32.05 hoursStandard Deviation 0.71
Group 1Tmax and t1/2 for DF2188YDF2188Y - t1/2 - Day 211.90 hoursStandard Deviation 0.2
Group 1Tmax and t1/2 for DF2188YDF2188Y - t1/2 - Day 11.51 hours—
Group 1Tmax and t1/2 for DF2188YDF2188Y - tmax - Day 82.30 hoursStandard Deviation 1.23
Group 2Tmax and t1/2 for DF2188YDF2188Y - tmax - Day 212.33 hoursStandard Deviation 1.14
Group 2Tmax and t1/2 for DF2188YDF2188Y - tmax - Day -32.81 hoursStandard Deviation 1.24
Group 2Tmax and t1/2 for DF2188YDF2188Y- tmax - Day 11.33 hoursStandard Deviation 0.58
Group 2Tmax and t1/2 for DF2188YDF2188Y - tmax - Day 82.03 hoursStandard Deviation 0.06
Group 2Tmax and t1/2 for DF2188YDF2188Y - t1/2 - Day -32.53 hoursStandard Deviation 1.53
Group 2Tmax and t1/2 for DF2188YDF2188Y - t1/2 - Day 11.48 hoursStandard Deviation 0.07
Group 2Tmax and t1/2 for DF2188YDF2188Y - t1/2 - Day 211.77 hoursStandard Deviation 0.21
Group 3Tmax and t1/2 for DF2188YDF2188Y - t1/2 - Day -31.65 hoursStandard Deviation 0.4
Group 3Tmax and t1/2 for DF2188YDF2188Y- tmax - Day 12.45 hoursStandard Deviation 1.04
Group 3Tmax and t1/2 for DF2188YDF2188Y - t1/2 - Day 212.18 hoursStandard Deviation 1.44
Group 3Tmax and t1/2 for DF2188YDF2188Y - t1/2 - Day 81.42 hoursStandard Deviation 0.15
Group 3Tmax and t1/2 for DF2188YDF2188Y - tmax - Day 211.77 hoursStandard Deviation 0.96
Group 3Tmax and t1/2 for DF2188YDF2188Y - tmax - Day 82.20 hoursStandard Deviation 1.37
Group 3Tmax and t1/2 for DF2188YDF2188Y - tmax - Day -32.44 hoursStandard Deviation 1.08
Primary

Tmax and t1/2 for DF2243Y

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).

Time frame: 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

ArmMeasureGroupValue (MEAN)Dispersion
Group 1Tmax and t1/2 for DF2243YDF2243Y - tmax - Day -33.30 hoursStandard Deviation 0.87
Group 1Tmax and t1/2 for DF2243YDF2243Y - tmax - Day 13.51 hoursStandard Deviation 0.99
Group 1Tmax and t1/2 for DF2243YDF2243Y - tmax - Day 84.29 hoursStandard Deviation 2.94
Group 1Tmax and t1/2 for DF2243YDF2243Y - tmax - Day 213.71 hoursStandard Deviation 0.62
Group 1Tmax and t1/2 for DF2243YDF2243Y - t1/2 - Day -31.34 hours—
Group 1Tmax and t1/2 for DF2243YDF2243Y - t1/2 - Day 211.97 hours—
Group 2Tmax and t1/2 for DF2243YDF2243Y - t1/2 - Day 212.46 hoursStandard Deviation 0.59
Group 2Tmax and t1/2 for DF2243YDF2243Y - tmax - Day -34.32 hoursStandard Deviation 1.52
Group 2Tmax and t1/2 for DF2243YDF2243Y - tmax - Day 213.66 hoursStandard Deviation 2.08
Group 2Tmax and t1/2 for DF2243YDF2243Y - t1/2 - Day -33.79 hours—
Group 2Tmax and t1/2 for DF2243YDF2243Y - tmax - Day 12.67 hoursStandard Deviation 1.16
Group 2Tmax and t1/2 for DF2243YDF2243Y - tmax - Day 83.32 hoursStandard Deviation 1.15
Group 3Tmax and t1/2 for DF2243YDF2243Y - tmax - Day 14.00 hoursStandard Deviation 1.57
Group 3Tmax and t1/2 for DF2243YDF2243Y - tmax - Day 83.40 hoursStandard Deviation 1.9
Group 3Tmax and t1/2 for DF2243YDF2243Y - t1/2 - Day 213.35 hoursStandard Deviation 1.63
Group 3Tmax and t1/2 for DF2243YDF2243Y - tmax - Day 212.87 hoursStandard Deviation 0.83
Group 3Tmax and t1/2 for DF2243YDF2243Y - tmax - Day -33.41 hoursStandard Deviation 1
Group 3Tmax and t1/2 for DF2243YDF2243Y - t1/2 - Day -32.81 hoursStandard Deviation 1.2
Primary

Tmax and t1/2 for Ibuprofen

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).

Time frame: 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

ArmMeasureGroupValue (MEAN)Dispersion
Group 1Tmax and t1/2 for IbuprofenDF2188Y - tmax - Day -33.50 hoursStandard Deviation 0.58
Group 1Tmax and t1/2 for IbuprofenDF2188Y- tmax - Day 14.02 hoursStandard Deviation 2.86
Group 1Tmax and t1/2 for IbuprofenDF2188Y - tmax - Day 84.29 hoursStandard Deviation 2.94
Group 1Tmax and t1/2 for IbuprofenDF2188Y - tmax - Day 213.37 hoursStandard Deviation 0.67
Group 1Tmax and t1/2 for IbuprofenDF2188Y - t1/2 - Day -36.76 hoursStandard Deviation 2.04
Group 1Tmax and t1/2 for IbuprofenDF2188Y - t1/2 - Day 213.12 hoursStandard Deviation 0.56
Group 2Tmax and t1/2 for IbuprofenDF2188Y - t1/2 - Day -36.15 hours—
Group 2Tmax and t1/2 for IbuprofenDF2188Y - tmax - Day -33.99 hoursStandard Deviation 1.99
Group 2Tmax and t1/2 for IbuprofenDF2188Y - tmax - Day 213.99 hoursStandard Deviation 2
Group 2Tmax and t1/2 for IbuprofenDF2188Y - tmax - Day 83.32 hoursStandard Deviation 1.15
Group 2Tmax and t1/2 for IbuprofenDF2188Y- tmax - Day 12.66 hoursStandard Deviation 1.16
Group 2Tmax and t1/2 for IbuprofenDF2188Y - t1/2 - Day 213.81 hours—
Group 3Tmax and t1/2 for IbuprofenDF2188Y - t1/2 - Day 82.15 hoursStandard Deviation 0.09
Group 3Tmax and t1/2 for IbuprofenDF2188Y- tmax - Day 14.00 hoursStandard Deviation 2.18
Group 3Tmax and t1/2 for IbuprofenDF2188Y - tmax - Day 82.15 hoursStandard Deviation 1.44
Group 3Tmax and t1/2 for IbuprofenDF2188Y - t1/2 - Day 213.15 hoursStandard Deviation 0.53
Group 3Tmax and t1/2 for IbuprofenDF2188Y - tmax - Day 212.58 hoursStandard Deviation 0.97
Group 3Tmax and t1/2 for IbuprofenDF2188Y - tmax - Day -32.86 hoursStandard Deviation 0.81
Group 3Tmax and t1/2 for IbuprofenDF2188Y - t1/2 - Day -33.76 hoursStandard Deviation 0.77
Primary

Tmax and t1/2 for Paclitaxel

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).

Time frame: 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

ArmMeasureGroupValue (MEAN)Dispersion
Group 1Tmax and t1/2 for Paclitaxelpaclitaxel - tmax - Day 11.14 hoursStandard Deviation 0.63
Group 1Tmax and t1/2 for Paclitaxelpaclitaxel - tmax - Day 81.06 hoursStandard Deviation 0.09
Group 1Tmax and t1/2 for Paclitaxelpaclitaxel - t1/2 - Day 15.95 hoursStandard Deviation 2.66
Group 1Tmax and t1/2 for Paclitaxelpaclitaxel - t1/2 - Day 86.57 hoursStandard Deviation 3.4
Group 2Tmax and t1/2 for Paclitaxelpaclitaxel - t1/2 - Day 811.00 hoursStandard Deviation 2.21
Group 2Tmax and t1/2 for Paclitaxelpaclitaxel - tmax - Day 11.01 hoursStandard Deviation 0.01
Group 2Tmax and t1/2 for Paclitaxelpaclitaxel - t1/2 - Day 18.51 hoursStandard Deviation 0.43
Group 2Tmax and t1/2 for Paclitaxelpaclitaxel - tmax - Day 81.06 hoursStandard Deviation 0.1
Group 3Tmax and t1/2 for Paclitaxelpaclitaxel - t1/2 - Day 88.76 hoursStandard Deviation 1.05
Group 3Tmax and t1/2 for Paclitaxelpaclitaxel - tmax - Day 81.07 hoursStandard Deviation 0.36
Group 3Tmax and t1/2 for Paclitaxelpaclitaxel - t1/2 - Day 18.18 hoursStandard Deviation 0.94
Group 3Tmax and t1/2 for Paclitaxelpaclitaxel - tmax - Day 11.22 hoursStandard Deviation 0.93
Primary

Treatment-Emergent Adverse Events (TEAEs)

Monitoring of AEs throughout the study till the end/off-treatment visit.

Time frame: 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.

ArmMeasureValue (NUMBER)
Group 1Treatment-Emergent Adverse Events (TEAEs)106 adverse events
Group 2Treatment-Emergent Adverse Events (TEAEs)99 adverse events
Group 3Treatment-Emergent Adverse Events (TEAEs)506 adverse events
Secondary

6-month Progression-free Survival Rate

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

Time frame: After 24 weeks

Population: Safety Population: all enrolled patients who took at least one dose of study drug, reparixin.

ArmMeasureValue (NUMBER)
Group 16-month Progression-free Survival Rate25.0 Percentage of patients
Group 26-month Progression-free Survival Rate0.0 Percentage of patients
Group 36-month Progression-free Survival Rate17.4 Percentage of patients
Secondary

Best Overall Response (BOR)

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

Time frame: After 24 weeks

Population: Safety Population: all enrolled patients who took at least one dose of study drug, reparixin.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Group 1Best Overall Response (BOR)CR1 Participants
Group 1Best Overall Response (BOR)PR0 Participants
Group 1Best Overall Response (BOR)SD0 Participants
Group 1Best Overall Response (BOR)PD2 Participants
Group 2Best Overall Response (BOR)PD2 Participants
Group 2Best Overall Response (BOR)CR0 Participants
Group 2Best Overall Response (BOR)SD1 Participants
Group 2Best Overall Response (BOR)PR0 Participants
Group 3Best Overall Response (BOR)PD7 Participants
Group 3Best Overall Response (BOR)PR5 Participants
Group 3Best Overall Response (BOR)SD7 Participants
Group 3Best Overall Response (BOR)CR1 Participants
Secondary

Clinical Benefit Rate (CBR)

The clinical benefit rate (CBR) was defined as the percentage of patients reaching CR, PR or SD according to RECIST criteria version 1.1

Time frame: After 24 weeks

Population: Safety Population: all enrolled patients who took at least one dose of study drug, reparixin.

ArmMeasureValue (NUMBER)
Group 1Clinical Benefit Rate (CBR)25.0 Percentage of patients
Group 2Clinical Benefit Rate (CBR)33.3 Percentage of patients
Group 3Clinical Benefit Rate (CBR)56.5 Percentage of patients
Secondary

Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment Visit

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.

Time frame: At tumor assessments 1-11 and off-treatment visit

Population: Safety Population: all enrolled patients who took at least one dose of study drug, reparixin.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2.1 - SD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1 - PR0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1 - SD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1 - PD1 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1.1 - CR0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1.1 - PR0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1.1 - SD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1.1 - PD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2 - CR1 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2 - PR0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2 - SD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2 - PD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2.1 - CR0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2.1 - PR0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1 - CR1 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2.1 - PD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 3 - CR1 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 3 - PR0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 3 - SD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 3 - PD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 4 - CR1 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 4 - PR0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 4 - SD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 4 - PD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 5 - CR1 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 5 - PR0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 5 - SD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 5 - PD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 6 - CR1 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 6 - PR0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 6 - SD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 6 - PD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 7 - CR1 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 7 - PR0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 7 - SD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 7 - PD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 8 - CR1 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 8 - PR0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 8 - SD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 8 - PD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 9 - CR1 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 9 - PR0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 9 - SD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 9 - PD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 10 - CR1 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 10 - PR0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 10 - SD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 10 - PD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 11 - CR1 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 11 - PR0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 11 - SD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 11 - PD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitOff-treatment visit - CR1 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitOff-treatment visit - PR0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitOff-treatment visit - SD0 Participants
Group 1Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitOff-treatment visit - PD1 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 8 - PR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1 - CR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 10 - PR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 5 - CR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1 - PR1 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 6 - PR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitOff-treatment visit - PD1 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1 - SD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 4 - CR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 8 - SD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1 - PD1 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 10 - PD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 6 - SD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1.1 - CR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 3 - PD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 11 - SD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1.1 - PR1 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 5 - PR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 8 - PD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1.1 - SD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 6 - PD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 4 - SD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1.1 - PD1 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitOff-treatment visit - PR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 7 - CR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2 - CR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 10 - CR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 9 - CR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2 - PR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 11 - CR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 7 - PR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2 - SD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 5 - SD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitOff-treatment visit - SD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2 - PD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitOff-treatment visit - CR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 9 - PR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2.1 - CR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 7 - SD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 10 - SD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2.1 - PR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 5 - PD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 11 - PD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2.1 - SD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 7 - PD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 9 - SD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2.1 - PD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 4 - PD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 11 - PR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 3 - CR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 8 - CR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 4 - PR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 3 - PR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 6 - CR0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 9 - PD0 Participants
Group 2Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 3 - SD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1.1 - CR0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 9 - PD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 3 - PD1 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitOff-treatment visit - SD1 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 4 - CR1 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 4 - PR2 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 10 - CR0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 4 - SD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 4 - PD1 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 5 - CR1 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 10 - PR0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 5 - PR1 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitOff-treatment visit - CR1 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 5 - SD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 5 - PD1 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 10 - SD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 6 - CR1 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitOff-treatment visit - PD8 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 6 - PR1 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 6 - SD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 10 - PD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 6 - PD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 7 - CR0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 7 - PR0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 11 - CR0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 7 - SD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitOff-treatment visit - PR1 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 7 - PD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 8 - CR0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 11 - PR0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1 - CR0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 8 - PR0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1 - PR3 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1 - SD9 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1 - PD6 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 8 - SD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 3 - SD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1.1 - PR1 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1.1 - SD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 8 - PD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 1.1 - PD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 11 - SD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2 - CR0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2 - PR6 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 9 - CR0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2 - SD2 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2 - PD2 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2.1 - CR0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 9 - PR0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2.1 - PR2 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2.1 - SD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 2.1 - PD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 9 - SD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 3 - CR0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 11 - PD0 Participants
Group 3Count of Patients With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Disease Progression (PD) at Each Assessment VisitAssessment 3 - PR4 Participants
Secondary

Median Time to Tumor Progression in Days (TTP)

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

Time frame: After 24 weeks

Population: Safety Population: all enrolled patients who took at least one dose of study drug, reparixin.

ArmMeasureValue (MEDIAN)
Group 1Median Time to Tumor Progression in Days (TTP)58 days
Group 2Median Time to Tumor Progression in Days (TTP)67 days
Group 3Median Time to Tumor Progression in Days (TTP)170 days

Source: ClinicalTrials.gov · Data processed: Feb 26, 2026