Trial Outcomes & Findings for Pilot Study to Evaluate Safety & Biological Effects of Orally Administered Reparixin in Early Breast Cancer (NCT NCT01861054)
NCT ID: NCT01861054
Last Updated: 2021-05-14
Results Overview
CSCs were measured in tissue samples by the following techniques: ALDH-1 by ALDEFLUOR and by immunohistochemistry (IHC); CD44/CD24 by flow cytometry or examination of RNA transcripts by RT-PCR and by immunohistochemistry (IHC); epithelial mesenchymal markers (Snail, Twist, Notch) by immunohistochemistry (IHC).
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
20 participants
Primary outcome timeframe
At day 21
Results posted on
2021-05-14
Participant Flow
Patients recruitment: before initiating a study, the Investigator was required to have written and dated approval from the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) for the study protocol, written informed consent form (ICF), consent form updates, subject recruitment procedures (e.g., advertisements), and any other written information to be provided to subjects.
It was planned to enroll 2 sub-groups of patients into the study, Group A: ER+ and/or PR+/HER-2- and Group B: ER-/PR-/HER-2-, and the sample size of 20 patients per group was chosen. Twenty patients in total were enrolled, 18 in Group A and 2 in Group B. The study was closed prematurely due to slow enrollment in group B. All 20 patients were included in the Safety Population and 6 (30%) were included in the PK population. All 20 patients completed the study.
Participant milestones
| Measure |
ER+ and/or PR+/ HER-2 -
Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack.
|
ER-/PR-/HER-2-
Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack.
|
|---|---|---|
|
Overall Study
STARTED
|
18
|
2
|
|
Overall Study
Safety Population
|
18
|
2
|
|
Overall Study
PK Population
|
4
|
2
|
|
Overall Study
COMPLETED
|
18
|
2
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pilot Study to Evaluate Safety & Biological Effects of Orally Administered Reparixin in Early Breast Cancer
Baseline characteristics by cohort
| Measure |
ER+ and/or PR+/ HER-2 -
n=18 Participants
Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
ER-/PR-/HER-2-
n=2 Participants
Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
16 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Age, Continuous
|
54.0 years
STANDARD_DEVIATION 8.92 • n=5 Participants
|
56.5 years
STANDARD_DEVIATION 12.02 • n=7 Participants
|
54.3 years
STANDARD_DEVIATION 8.91 • n=5 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
18 participants
n=5 Participants
|
2 participants
n=7 Participants
|
20 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At day 21Population: The Safety Population included all enrolled patients who took at least one dose of study drug reparixin. This population was used for primary endpoints and safety analysis
CSCs were measured in tissue samples by the following techniques: ALDH-1 by ALDEFLUOR and by immunohistochemistry (IHC); CD44/CD24 by flow cytometry or examination of RNA transcripts by RT-PCR and by immunohistochemistry (IHC); epithelial mesenchymal markers (Snail, Twist, Notch) by immunohistochemistry (IHC).
Outcome measures
| Measure |
ER+ and/or PR+/ HER-2 -
n=18 Participants
Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
ER-/PR-/HER-2-
n=2 Participants
Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
|---|---|---|
|
Change From Baseline to Day 21 in Markers of Cancer Stem Cells (CSCs) in the Primary Tumor and the Tumoral Microenvironment (ALDH1,CD44/CD24)
ALDH+
|
1.34 percentage of cells
Standard Deviation 2.737
|
-0.40 percentage of cells
Standard Deviation 1.131
|
|
Change From Baseline to Day 21 in Markers of Cancer Stem Cells (CSCs) in the Primary Tumor and the Tumoral Microenvironment (ALDH1,CD44/CD24)
CD44+/CD24-
|
-0.57 percentage of cells
Standard Deviation 5.617
|
0.20 percentage of cells
Standard Deviation 1.273
|
PRIMARY outcome
Timeframe: Day 21 (or last day of treatment)Population: The Safety Population included all enrolled patients who took at least one dose of study drug reparixin. This population was used for primary endpoints and safety analysis.
Pathway markers (AKT, FAK, PTEN and CXCR1) were measured in tissue samples at the pre-study (Day -14 to 0) and Day 21 (or within 24 hours of last dose). For the evaluation of the stain extent, the following semi-quantitative score method (0 to 4) was used: 0, no positive cells; 1, 1-25%; 2, 26-50%; 3, 51-75%; and 4, 76-100%. Hence for this scale, the higher the values, the worse is the outcome. For the evaluation of the stain intensity, the following score method (0 to 3) was used: 0, negative; 1, weak; 2, moderate, 3; strong. Also for this scale, the higher the score, the worse the outcome. Serine-threonine protein kinase (AKT, also known as protein kinase B, PKB) Focal adhesion kinase (FAK) Chemokine receptor-1 (CXCR1)
Outcome measures
| Measure |
ER+ and/or PR+/ HER-2 -
n=18 Participants
Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
ER-/PR-/HER-2-
n=2 Participants
Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
|---|---|---|
|
Change From Baseline-1 to Day 21-1 in Pathway Markers by IHC
Stain Phospho-AKT Extent
|
0 score on a scale
Interval -1.0 to 2.0
|
0 score on a scale
Interval 0.0 to 0.0
|
|
Change From Baseline-1 to Day 21-1 in Pathway Markers by IHC
Stain Phospho-AKT Intensity
|
0 score on a scale
Interval -1.0 to 1.0
|
0 score on a scale
Interval 0.0 to 0.0
|
|
Change From Baseline-1 to Day 21-1 in Pathway Markers by IHC
Stain AKT Extent
|
0 score on a scale
Interval -4.0 to 1.0
|
1.0 score on a scale
Interval 1.0 to 1.0
|
|
Change From Baseline-1 to Day 21-1 in Pathway Markers by IHC
Stain AKT Intensity
|
-0.5 score on a scale
Interval -3.0 to 2.0
|
0 score on a scale
Interval 0.0 to 0.0
|
|
Change From Baseline-1 to Day 21-1 in Pathway Markers by IHC
Phospho-FAK Extent
|
0 score on a scale
Interval -1.0 to 2.0
|
0 score on a scale
Interval 0.0 to 0.0
|
|
Change From Baseline-1 to Day 21-1 in Pathway Markers by IHC
Phospho-FAK Intensity
|
0 score on a scale
Interval -1.0 to 2.0
|
-1.0 score on a scale
Interval -1.0 to -1.0
|
|
Change From Baseline-1 to Day 21-1 in Pathway Markers by IHC
Stain FAK Extent
|
0 score on a scale
Interval -2.0 to 1.0
|
1.0 score on a scale
Interval 1.0 to 1.0
|
|
Change From Baseline-1 to Day 21-1 in Pathway Markers by IHC
Stain FAK Intens
|
0 score on a scale
Interval -2.0 to 2.0
|
0 score on a scale
Interval 0.0 to 0.0
|
|
Change From Baseline-1 to Day 21-1 in Pathway Markers by IHC
Stain C-PTEN Extent
|
0 score on a scale
Interval -4.0 to 2.0
|
0 score on a scale
Interval 0.0 to 0.0
|
|
Change From Baseline-1 to Day 21-1 in Pathway Markers by IHC
Stain C-PTEN Intensity
|
0 score on a scale
Interval -2.0 to 1.0
|
0 score on a scale
Interval 0.0 to 0.0
|
|
Change From Baseline-1 to Day 21-1 in Pathway Markers by IHC
Stain D-PTEN Extent
|
0 score on a scale
Interval -4.0 to 2.0
|
0 score on a scale
Interval 0.0 to 0.0
|
|
Change From Baseline-1 to Day 21-1 in Pathway Markers by IHC
Stain D-PTEN Intensity
|
0 score on a scale
Interval -2.0 to 1.0
|
0 score on a scale
Interval 0.0 to 0.0
|
|
Change From Baseline-1 to Day 21-1 in Pathway Markers by IHC
Stain CXCR1 Extent
|
0 score on a scale
Interval -4.0 to 1.0
|
1.0 score on a scale
Interval 1.0 to 1.0
|
|
Change From Baseline-1 to Day 21-1 in Pathway Markers by IHC
Stain CXCR1 Intensity
|
-0.5 score on a scale
Interval -3.0 to 1.0
|
1.0 score on a scale
Interval 1.0 to 1.0
|
PRIMARY outcome
Timeframe: At Day 21Population: The Safety Population included all enrolled patients who took at least one dose of study drug reparixin. This population was used for primary endpoints and safety analysis.
Markers of inflammation (IL-1β, IL-6, IL-8, TNF-α, GM-CSF, VEGF, and b-FGF) were measured in plasma from peripheral blood. IL = interleukins TNF-α = tumor necrosis factor-alpha GM-CSF = macrophage colony stimulating factor VEGF = vascular endothelial growth factor b-FGF = basic fibroblast growth factor
Outcome measures
| Measure |
ER+ and/or PR+/ HER-2 -
n=18 Participants
Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
ER-/PR-/HER-2-
n=2 Participants
Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
|---|---|---|
|
Change From Baseline to Day 21 in Markers of Inflammation
Interleukin 1 Beta
|
7.019 pg/ML
Standard Deviation 30.3118
|
0 pg/ML
Standard Deviation 0.000
|
|
Change From Baseline to Day 21 in Markers of Inflammation
Interleukin 6
|
9.593 pg/ML
Standard Deviation 39.2733
|
0 pg/ML
Standard Deviation 0
|
|
Change From Baseline to Day 21 in Markers of Inflammation
Interleukin 8
|
-25.874 pg/ML
Standard Deviation 134.3213
|
29.320 pg/ML
Standard Deviation 41.6910
|
|
Change From Baseline to Day 21 in Markers of Inflammation
TNFα
|
2.669 pg/ML
Standard Deviation 8.0313
|
-0.890 pg/ML
Standard Deviation 3.5780
|
|
Change From Baseline to Day 21 in Markers of Inflammation
GM-CSF
|
-2.678 pg/ML
Standard Deviation 8.2154
|
8.705 pg/ML
Standard Deviation 12.3107
|
|
Change From Baseline to Day 21 in Markers of Inflammation
VEGF
|
253.584 pg/ML
Standard Deviation 1120.6125
|
27.635 pg/ML
Standard Deviation 39.0818
|
|
Change From Baseline to Day 21 in Markers of Inflammation
b-FGF
|
20.164 pg/ML
Standard Deviation 93.4614
|
-9.750 pg/ML
Standard Deviation 13.7886
|
PRIMARY outcome
Timeframe: At day 21Population: The Safety Population included all enrolled patients who took at least one dose of study drug reparixin. This population was used for primary endpoints and safety analysis.
CD31 staining by IHC. For the evaluation of the stain extent, the following semi-quantitative score method (0 to 4) was used: 0, no positive cells; 1, 1-25%; 2, 26-50%; 3, 51-75%; and 4, 76-100%. Hence for this scale, the higher the values, the worse is the outcome. For the evaluation of the stain intensity, the following score method (0 to 3) was used: 0, negative; 1, weak; 2, moderate, 3; strong. Also for this scale, the higher the score, the worse the outcome. CD31 is a transmembrane glycoprotein, 130-140 kDa, also know as platelet-endothelium cell adhesion molecule (PECAM-1). CD31 is ligand for CD38 and plays a role in thrombosis and angiogenesis. CD31 is strongly expressed in endothelial cells and weakly expressed in megakaryocytes, platelets, occasional plasma cells, lymphocytes (espc. marginal zone B-cells, peripheral T-cells) and neutrophils.
Outcome measures
| Measure |
ER+ and/or PR+/ HER-2 -
n=18 Participants
Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
ER-/PR-/HER-2-
n=2 Participants
Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
|---|---|---|
|
Change From Baseline-1 to Day 21-1 in Markers of Angiogenesis (CD31 Staining)
Stain CD31 Extent
|
0 score on a scale
Interval -2.0 to 1.0
|
1.0 score on a scale
Interval 1.0 to 1.0
|
|
Change From Baseline-1 to Day 21-1 in Markers of Angiogenesis (CD31 Staining)
Stain CD31 Intensity
|
0 score on a scale
Interval -1.0 to 1.0
|
1.0 score on a scale
Interval 1.0 to 1.0
|
PRIMARY outcome
Timeframe: At day 21Population: The Safety Population included all enrolled patients who took at least one dose of study drug reparixin. This population was used for primary endpoints and safety analysis.
Autophagy is a lysosomal degradation and recycling process implicated in cancer progression and therapy resistance. Labeling of p62 serves as a useful marker for the induction of autophagy, clearance of protein aggregates, and the inhibition of autophagy. Labeling of LC3B serves to track the binding of p62 and subsequent recruitment of autophagosomes. For the evaluation of the extent, the following semi-quantitative score method (0 to 4) was used: 0, no positive cells; 1, 1-25%; 2, 26-50%; 3, 51-75%; and 4, 76-100%. Hence for this scale, the higher the values, the worse is the outcome. For the evaluation of the intensity, the following score method (0 to 3) was used: 0, negative; 1, weak; 2, moderate, 3; strong. Also for this scale, the higher the score, the worse the outcome.
Outcome measures
| Measure |
ER+ and/or PR+/ HER-2 -
n=18 Participants
Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
ER-/PR-/HER-2-
n=2 Participants
Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
|---|---|---|
|
Change From Baseline-1 to Day 21-1 in Markers of Autophagy (P62 and LC3B by IHC)
Stain P62 Extent
|
-1.0 score on a scale
Interval -3.0 to 1.0
|
0 score on a scale
Interval 0.0 to 0.0
|
|
Change From Baseline-1 to Day 21-1 in Markers of Autophagy (P62 and LC3B by IHC)
Stain P62 Intensity
|
0 score on a scale
Interval -2.0 to 0.0
|
-1.0 score on a scale
Interval -1.0 to -1.0
|
SECONDARY outcome
Timeframe: At Days 1 (pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose) and 21(pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose)Population: The PK Population consisted of patients who received at least one dose of reparixin and had at least one valid, quantifiable PK parameter. This population was used for PK analyses.
Once absorbed, reparixin is highly protein bound. By comparing Cmax and AUC for unbound drug to that for total drug, only \< 0.1% to 0.2% of reparixin is available as unbound (free) drug. The intent of the PK outcomes was not to compare the results between the two cohorts; for this reason results for the PK outcomes are reported for the whole group of the treated patients. Cmax = Maximum plasma concentration obtained directly from the data without interpolation, expressed in concentration units
Outcome measures
| Measure |
ER+ and/or PR+/ HER-2 -
n=6 Participants
Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
ER-/PR-/HER-2-
Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
|---|---|---|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Cmax
Day1 - DF1681Y
|
62.925 micrograms/mL
Standard Deviation 31.5024
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Cmax
Day21 - DF1681Y
|
63.927 micrograms/mL
Standard Deviation 15.7616
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Cmax
Day1 - DF1681Y unbound
|
145.167 micrograms/mL
Standard Deviation 116.6114
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Cmax
Day21 - DF1681Y unbound
|
136.552 micrograms/mL
Standard Deviation 104.8681
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Cmax
Day 1 - DF2243Y
|
15.788 micrograms/mL
Standard Deviation 2.5240
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Cmax
Day 21 - DF2243Y
|
20.812 micrograms/mL
Standard Deviation 9.9776
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Cmax
Day 1 - DF2188Y
|
7.302 micrograms/mL
Standard Deviation 1.5129
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Cmax
Day 21 - DF2188Y
|
10.367 micrograms/mL
Standard Deviation 4.3439
|
—
|
SECONDARY outcome
Timeframe: At Days 1 (pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose) and 21(pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose)Population: The PK Population consisted of patients who received at least one dose of reparixin and had at least one valid, quantifiable PK parameter. This population was used for PK analyses.
Once absorbed, reparixin is highly protein-bound. By comparing Cmax and AUC for unbound drug to that for total drug, only \< 0.1% to 0.2% of reparixin is available as unbound (free) drug. The intent of the PK outcomes was not to compare the results between the two cohorts; for this reason results for the PK outcomes are reported for the whole group of the treated patients. tmax = Time to reach the maximum plasma concentration obtained directly from the data without interpolation t1/2 = Terminal elimination half-life calculated as ln(2)/ lambda z; calculated only if the coefficient of determination R2 in lambda z estimation is at least 0.8.
Outcome measures
| Measure |
ER+ and/or PR+/ HER-2 -
n=6 Participants
Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
ER-/PR-/HER-2-
Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
|---|---|---|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Tmax and T1/2
Day1 - DF1681Y tmax
|
2.667 hours
Standard Deviation 2.8752
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Tmax and T1/2
Day21 - DF1681Y tmax
|
0.997 hours
Standard Deviation 0.5508
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Tmax and T1/2
Day1 - DF1681Y unbound tmax
|
1.583 hours
Standard Deviation 1.2813
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Tmax and T1/2
Day21 - DF1681Y unbound tmax
|
1.092 hours
Standard Deviation 0.4903
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Tmax and T1/2
Day 1 - DF2243Y tmax
|
4.333 hours
Standard Deviation 2.3381
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Tmax and T1/2
Day 21 - DF2243Y tmax
|
2.331 hours
Standard Deviation 0.8179
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Tmax and T1/2
Day 1 - DF2188Y tmax
|
2.500 hours
Standard Deviation 1.2247
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Tmax and T1/2
Day 21 - DF2188Y tmax
|
1.508 hours
Standard Deviation 0.5389
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Tmax and T1/2
Day1 - DF1681Y t1/2
|
2.090 hours
Standard Deviation 0.9847
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Tmax and T1/2
Day21 - DF1681Y t1/2
|
1.626 hours
Standard Deviation 0.4068
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Tmax and T1/2
Day1 - DF1681Y unbound t1/2
|
1.403 hours
Standard Deviation 0.4592
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Tmax and T1/2
Day21 - DF1681Y unbound t1/2
|
0.989 hours
Standard Deviation 0.1683
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Tmax and T1/2
Day 1 - DF2243Y t1/2
|
1.913 hours
Standard Deviation 0.3268
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Tmax and T1/2
Day 21 - DF2243Y t1/2
|
2.575 hours
Standard Deviation 0.6442
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Tmax and T1/2
Day 1 - DF2188Y t1/2
|
2.035 hours
Standard Deviation 1.0618
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - Tmax and T1/2
Day 21 - DF2188Y t1/2
|
1.575 hours
Standard Deviation 0.1953
|
—
|
SECONDARY outcome
Timeframe: At Days 1 (pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose) and 21(pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose)Population: The PK Population consisted of patients who received at least one dose of reparixin and had at least one valid, quantifiable PK parameter. This population was used for PK analyses.
The intent of the PK outcomes was not to compare the results between the two cohorts; for this reason results for the PK outcomes are reported for the whole group of the treated patients. AUC0-8 = The area under the plasma concentration-time curve from time 0 to 8 hours post-dose; AUClast = The area under the concentration-time curve from time 0 to last quantifiable concentration AUCtau = The area under the plasma concentration-time curve for dosing interval (dosing interval \[tau\] = 8 hours); AUCinf = The total area under the plasma concentration-time curve from time zero to time infinity; AUC0-inf = AUClast + Clast/lambda zeta, where Clast is the last observed concentration ≥ lower limit of quantitation at time tlast. All these parameters were calculated by the linear trapezoidal rule.
Outcome measures
| Measure |
ER+ and/or PR+/ HER-2 -
n=6 Participants
Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
ER-/PR-/HER-2-
Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
|---|---|---|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF1681Y - AUC0-8 - Day 1
|
189.357 h*μg/mL
Standard Deviation 60.2362
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF1681Y - AUC0-8 - Day 21
|
174.303 h*μg/mL
Standard Deviation 29.8012
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF1681Y unbound- AUC0-8 - Day 1
|
222.602 h*μg/mL
Standard Deviation 128.0328
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF1681Y unbound- AUC0-8 - Day 21
|
233.382 h*μg/mL
Standard Deviation 166.0402
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF2243Y - AUC0-8 - Day 1
|
78.469 h*μg/mL
Standard Deviation 18.8116
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF2243Y - AUC0-8 - Day 21
|
105.001 h*μg/mL
Standard Deviation 58.2634
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF2188Y - AUC0-8 - Day 1
|
31.040 h*μg/mL
Standard Deviation 7.9369
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF2188Y - AUC0-8 - Day 21
|
33.395 h*μg/mL
Standard Deviation 13.2129
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF1681Y - AUCinf - Day 1
|
211.243 h*μg/mL
Standard Deviation 71.4823
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF1681Y - AUCinf - Day 21
|
182.479 h*μg/mL
Standard Deviation 36.1551
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF1681Y unbound - AUCinf - Day 1
|
235.152 h*μg/mL
Standard Deviation 180.1547
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF1681Y unbound - AUCinf - Day 21
|
234.547 h*μg/mL
Standard Deviation 166.3017
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF2243Y - AUCinf - Day 1
|
71.297 h*μg/mL
Standard Deviation 25.6857
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF2243Y - AUCinf - Day 21
|
129.275 h*μg/mL
Standard Deviation 74.5406
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF2188Y - AUCinf - Day 1
|
31.669 h*μg/mL
Standard Deviation 11.2792
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF2188Y - AUCinf - Day 21
|
35.092 h*μg/mL
Standard Deviation 13.9473
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF1681Y - AUClast - Day 1
|
189.319 h*μg/mL
Standard Deviation 60.2817
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF1681Y - AUClast - Day 21
|
172.296 h*μg/mL
Standard Deviation 28.1847
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF1681Y unbound - AUClast - Day 1
|
222.078 h*μg/mL
Standard Deviation 128.1305
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF1681Y unbound - AUClast - Day 21
|
231.235 h*μg/mL
Standard Deviation 167.0377
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF2243Y - AUClast - Day 1
|
76.821 h*μg/mL
Standard Deviation 17.3033
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF2243Y - AUClast - Day 21
|
97.360 h*μg/mL
Standard Deviation 46.6809
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF2188Y - AUClast - Day 1
|
31.028 h*μg/mL
Standard Deviation 7.9336
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF2188Y - AUClast - Day 21
|
35.433 h*μg/mL
Standard Deviation 12.8434
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF1681Y - AUCtau - Day 21
|
174.303 h*μg/mL
Standard Deviation 29.8012
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF1681Y unbound - AUCtau - Day 21
|
233.382 h*μg/mL
Standard Deviation 166.0402
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF2243Y - AUCtau - Day 21
|
105.001 h*μg/mL
Standard Deviation 58.2634
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - AUC0-8, AUCinf, AUClast, AUCtau at Day 21,
DF2188Y - AUCtau - Day 21
|
33.395 h*μg/mL
Standard Deviation 13.2129
|
—
|
SECONDARY outcome
Timeframe: At Days 1 (pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose) and 21(pre-first dose and 0.25, 0.5, 1, 2, 4, 6, 8h post dose)Population: The PK Population consisted of patients who received at least one dose of reparixin and had at least one valid, quantifiable PK parameter. This population was used for PK analyses.
The intent of the PK outcomes was not to compare the results between the two cohorts; for this reason results for the PK outcomes are reported for the whole group of the treated patients. CL/F = Apparent oral clearance - for DF1681Y only, calculated as dose/AUCinf.; calculated only when the coefficient of determination R2 in lambda zeta estimation is at least 0.8 and percent AUC extrapolation is less than or equal to 20%. CLss/F = Steady state apparent oral clearance - for DF1681Y only calculated as dose/AUCtau.
Outcome measures
| Measure |
ER+ and/or PR+/ HER-2 -
n=6 Participants
Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
ER-/PR-/HER-2-
Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
|---|---|---|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - CL/F (L/h) at Day 1, CLSS/F (L/h) Day 21)
DF1681Y - CL/F - Day 1
|
5.173 L/h
Standard Deviation 1.7466
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - CL/F (L/h) at Day 1, CLSS/F (L/h) Day 21)
DF1681Y - CLSS/F - Day 21
|
5.866 L/h
Standard Deviation 0.9086
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - CL/F (L/h) at Day 1, CLSS/F (L/h) Day 21)
DF1681Y unbound - CL/F - Day 1
|
7156.189 L/h
Standard Deviation 6334.8463
|
—
|
|
Pharmacokinetics of Reparixin (DF1681Y, DF1681Y Unbound, DF2243Y, DF2188Y) - CL/F (L/h) at Day 1, CLSS/F (L/h) Day 21)
DF1681Y unbound - CLSS/F - Day 21
|
5604.781 L/h
Standard Deviation 2335.8016
|
—
|
SECONDARY outcome
Timeframe: At Day 21Population: The Safety Population included all enrolled patients who took at least one dose of study drug reparixin. This population was used for primary endpoints and safety analysis
The Leukocytes subsets analyzed are the following: Lymphocyte in WBC, Total T cell in lymphocytes, B cells in lymphocytes, T-helper cell in lymphocytes, CTL in lymphocytes, NKT cell in lymphocytes, ADCC NK subsets in lymphocytes, Regulatory NK subsets in lymphocytes, Exhausted NK subsets in lymphocytes, CD56-CD16+ NK subsets in lymphocytes, CD11b in PMNs - IL-8, CD18 in PMNs - IL-8, MFI of CD11b - IL-8, MFI of CD66b - IL-8, MFI of CD18 - IL-8, CD11b in PMNs - US, CD18 in PMNs - US, MFI of CD11b - US, MFI of CD66b - US, MFI of CD18 - US, Percent Monocytes expressing IL6 - IL-8,Percent Monocytes expressing IL1b - IL-8, Percent Monocytes expressing IL8 - IL-8, Percent Monocytes expressing TNFa - IL-8, Percent Neutrophils expressing IL6 - IL-8, Percent Neutrophils expressing IL1b - IL-8, Percent Neutrophils expressing IL8 - IL-8, Percent Neutrophils expressing TNFa - IL-8,Percent Monocytes expressing IL6 - US,Percent Monocytes expressing IL1b - US, etc.
Outcome measures
| Measure |
ER+ and/or PR+/ HER-2 -
n=16 Participants
Patients of Group A (estrogen receptor positive (ER+) and/or progesterone receptor positive (PR+)/human epidermal growth factor receptor-2 negative (HER-2-)) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
ER-/PR-/HER-2-
n=1 Participants
Patients of Group B (estrogen receptor negative (ER-)/progesterone receptor negative (PR-)/HER-2-) were given Reparixin 1000 mg (two 500 mg tablets) for 21 consecutive days. Reparixin was administered orally, every six to eight hours t.i.d. preferably with food. However, if the patient was unable to eat, reparixin could still be administered. Reparixin was administered with about 250 mL water and a light meal or snack
|
|---|---|---|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Lymphocyte in WBC
|
-2.51 percent of total
Standard Deviation 9.099
|
-3.70 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Total T cell in lymphocytes
|
1.28 percent of total
Standard Deviation 4.602
|
-2.80 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
MFI of CD11b - IL-8
|
-1.63 percent of total
Standard Deviation 2.205
|
3.50 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
B cell in lymphocytes
|
2.678 percent of total
Standard Deviation 7.5565
|
43.190 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
T-helper cell in lymphocytes
|
-1.44 percent of total
Standard Deviation 5.158
|
-24.90 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
CTL in lymphocytes
|
-0.639 percent of total
Standard Deviation 5.5106
|
-24.100 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
NKT cell in lymphocytes
|
0.510 percent of total
Standard Deviation 1.5759
|
0.140 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
ADCC NK subsets in lymphocytes
|
0.727 percent of total
Standard Deviation 4.1787
|
1.430 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Regulatory NK subsets in lymphocytes
|
-1.358 percent of total
Standard Deviation 3.2465
|
0.370 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Exhausted NK subsets in lymphocytes
|
-0.177 percent of total
Standard Deviation 1.7006
|
-0.170 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
CD56-CD16+ NK subsets in lymphocytes
|
0.708 percent of total
Standard Deviation 1.6772
|
0.310 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
CD11b in PMNs - IL-8
|
-1.48 percent of total
Standard Deviation 4.877
|
-11.60 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
CD18 in PMNs - IL-8
|
-0.23 percent of total
Standard Deviation 4.104
|
2.10 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
MFI of CD66b - IL-8
|
-3.9 percent of total
Standard Deviation 507.79
|
-929.0 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
MFI of CD18 - IL-8
|
-13.0 percent of total
Standard Deviation 495.89
|
71.0 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
CD11b in PMNs - US
|
1.56 percent of total
Standard Deviation 9.515
|
-4.20 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
CD18 in PMNs - US
|
-5.758 percent of total
Standard Deviation 23.7696
|
-0.400 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
MFI of CD11b - US
|
-0.84 percent of total
Standard Deviation 1.571
|
-0.30 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
MFI of CD66b - US
|
35.1 percent of total
Standard Deviation 536.54
|
-757.0 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
MFI of CD18 - US
|
-105.64 percent of total
Standard Deviation 679.547
|
-47.00 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Monocytes expressing IL6 - IL-8
|
8.40590 percent of total
Standard Deviation 27.654326
|
0.52600 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Monocytes expressing IL1b - IL-8
|
8.27479 percent of total
Standard Deviation 24.364503
|
0.32600 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Monocytes expressing IL8 - IL-8
|
-0.35947 percent of total
Standard Deviation 3.983235
|
-0.04400 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Monocytes expressing TNFa - IL-8
|
0.40504 percent of total
Standard Deviation 1.906309
|
-0.39900 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Neutrophils expressing IL6 - IL-8
|
2.83019 percent of total
Standard Deviation 26.145843
|
0.36340 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Neutrophils expressing IL1b - IL-8
|
10.24530 percent of total
Standard Deviation 32.068081
|
0.33400 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Neutrophils expressing IL8 - IL-8
|
0.04596 percent of total
Standard Deviation 1.667000
|
0.05742 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Neutrophils expressing TNFa - IL-8
|
0.35635 percent of total
Standard Deviation 2.269023
|
0.03500 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Monocytes expressing IL6 - US
|
9.77675 percent of total
Standard Deviation 29.705447
|
0.26500 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Monocytes expressing IL1b - US
|
5.58031 percent of total
Standard Deviation 28.862940
|
1.03400 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Monocytes expressing IL8 - US
|
0.14087 percent of total
Standard Deviation 2.716051
|
-0.27600 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Monocytes expressing TNFa - US
|
-0.11532 percent of total
Standard Deviation 1.333406
|
0.28200 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Neutrophils expressing IL6 - US
|
5.50297 percent of total
Standard Deviation 21.932274
|
0.59260 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Neutrophils expressing IL1b - US
|
9.28329 percent of total
Standard Deviation 33.754437
|
1.36450 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Neutrophils expressing IL8 - US
|
0.45567 percent of total
Standard Deviation 2.053990
|
0.15020 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Neutrophils expressing TNFa - US
|
0.46929 percent of total
Standard Deviation 2.876200
|
0.54910 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Monocytes expressing IL6 - LPS
|
-0.23 percent of total
Standard Deviation 8.015
|
-9.60 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Monocytes expressing IL1b - LPS
|
-5.18 percent of total
Standard Deviation 18.237
|
27.80 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Monocytes expressing IL8 - LPS
|
-4.2057 percent of total
Standard Deviation 21.72201
|
-74.3700 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Monocytes expressing TNFa - LPS
|
-3.145 percent of total
Standard Deviation 8.8075
|
-56.400 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Neutrophils expressing IL6 - LPS
|
-2.0310 percent of total
Standard Deviation 4.60857
|
72.3690 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Neutrophils expressing IL1b - LPS
|
-1.68086 percent of total
Standard Deviation 5.470114
|
78.19200 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Neutrophils expressing IL8 - LPS
|
0.14986 percent of total
Standard Deviation 1.844687
|
1.18700 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Neutrophils expressing TNFa - LPS
|
0.1497 percent of total
Standard Deviation 1.97537
|
1.7720 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Monocytes expressing IL6 - LPS+IL-8
|
-3.42 percent of total
Standard Deviation 6.783
|
1.20 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Monocytes expressing IL1b - LPS+IL-8
|
-4.79 percent of total
Standard Deviation 14.168
|
25.90 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Monocytes expressing IL8 - LPS+IL-8
|
-7.738 percent of total
Standard Deviation 12.9421
|
-76.990 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Monocytes expressing TNFa - LPS+IL-8
|
-0.3018 percent of total
Standard Deviation 9.97119
|
-57.9100 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Neutrophils expressing IL6 - LPS+IL-8
|
1.2629 percent of total
Standard Deviation 20.77484
|
62.7900 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Neutrophils expressing IL1b - LPS+IL-8
|
0.1980 percent of total
Standard Deviation 27.96300
|
81.6290 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Neutrophils expressing IL8 - LPS+IL-8
|
0.0348 percent of total
Standard Deviation 1.81583
|
1.0010 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent Neutrophils expressing TNFa - LPS+IL-8
|
-0.0349 percent of total
Standard Deviation 1.75308
|
2.6490 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent FITC eColi Control
|
4.327 percent of total
Standard Deviation 7.7795
|
-8.500 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent FITC eColi Test
|
-1.056 percent of total
Standard Deviation 3.6456
|
-4.200 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent PMNs unstimulated
|
-5.025 percent of total
Standard Deviation 16.3554
|
28.690 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent PMNs fMLP
|
9.152 percent of total
Standard Deviation 18.2092
|
23.300 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent L-selectin unstimulated
|
4.341 percent of total
Standard Deviation 25.8071
|
-25.000 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
|
Change From Baseline to Day 21 in Leukocytes Subsets
Percent L-selectin fMLP
|
-0.2845 percent of total
Standard Deviation 0.95877
|
-0.2460 percent of total
Standard Deviation NA
Since the patient is only one, no SD can be calculated
|
Adverse Events
Total
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Total
n=20 participants at risk
This represents the total safety population of 20 patients
|
|---|---|
|
Infections and infestations
POSTOPERATIVE WOUND INFECTION
|
5.0%
1/20 • Number of events 1 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
Other adverse events
| Measure |
Total
n=20 participants at risk
This represents the total safety population of 20 patients
|
|---|---|
|
Gastrointestinal disorders
Nausea
|
25.0%
5/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Gastrointestinal disorders
Abdominal pain
|
10.0%
2/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Gastrointestinal disorders
Constipation
|
10.0%
2/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Gastrointestinal disorders
Flatulence
|
10.0%
2/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
2/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Gastrointestinal disorders
Abdominal discomfort
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Gastrointestinal disorders
Abdominal distension
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Gastrointestinal disorders
Diarrhoea
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Gastrointestinal disorders
Dry mouth
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Gastrointestinal disorders
Dyspepsia
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
General disorders
Fatigue
|
40.0%
8/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
General disorders
Pain
|
10.0%
2/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
General disorders
Oedema peripheral
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Injury, poisoning and procedural complications
Procedural pain
|
25.0%
5/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Injury, poisoning and procedural complications
Incision site haemorrhage
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Injury, poisoning and procedural complications
Incision site pain
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Injury, poisoning and procedural complications
Post procedural haematoma
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Nervous system disorders
Headache
|
15.0%
3/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Nervous system disorders
Dizziness
|
10.0%
2/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Nervous system disorders
Paraesthesia
|
10.0%
2/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Nervous system disorders
Pheripheral sensory neuropathy
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Skin and subcutaneous tissue disorders
Rash
|
10.0%
2/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Psychiatric disorders
Insomnia
|
15.0%
3/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Psychiatric disorders
Anxiety
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Psychiatric disorders
Mood swings
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Reproductive system and breast disorders
Breast mass
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Reproductive system and breast disorders
Breast pain
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Reproductive system and breast disorders
Pelvic pain
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Infections and infestations
Eye infection
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Infections and infestations
Infection
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Investigations
Aspartate aminotransferase increased
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Investigations
Blood alkaline phosphatase increased
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Respiratory, thoracic and mediastinal disorders
nasal congestion
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Blood and lymphatic system disorders
Anaemia
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Congenital, familial and genetic disorders
Epidermolysis
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Eye disorders
Vision blurred
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
|
Vascular disorders
Hot flush
|
5.0%
1/20 • throughout the study and at OTV (off treatment visit) up to the 30 days after the last dose of reparixin
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place