Trial Outcomes & Findings for A Double-blind Study of Paclitaxel in Combination With Reparixin or Placebo for Metastatic Triple-Negative Breast Cancer (NCT NCT02370238)

NCT ID: NCT02370238

Last Updated: 2022-09-16

Results Overview

PFS was defined as the number of days between the date of randomization and the date of clinical disease progression, according to RECIST criteria version 1.1, as assessed by Independent Radiology Review, or to death due to any cause, whichever occurred first. Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 194 participants
• Primary outcome timeframe: Baseline up to every 8 weeks until disease progression or death, whichever occurs first, up to 721 days
• Results posted on: 2022-09-16

Participant Flow

Of the 194 enrolled patients, 123 were randomized and included in the ITT Population: 62 patients in Group 1 and 61 patients in Group 2.

Due to extreme enrollment difficulties during the first 6 months of 2018, enrollment to the study was terminated early (30 July 2018) and the final sample size is equal to 123 randomized patients.

Participant milestones

Measure	Paclitaxel+Reparixin (Group 1) paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy reparixin oral tablets + paclitaxel intravenous weekly three weeks on and one week off until disease progression according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.	Paclitaxel+Placebo (Group 2) paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.
Overall Study STARTED	62	61
Overall Study ITT Population	62	61
Overall Study Safety Population	61	60
Overall Study Responsable-evaluable Population	57	54
Overall Study COMPLETED	15	16
Overall Study NOT COMPLETED	47	45

Reasons for withdrawal

Measure	Paclitaxel+Reparixin (Group 1) paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy reparixin oral tablets + paclitaxel intravenous weekly three weeks on and one week off until disease progression according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.	Paclitaxel+Placebo (Group 2) paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.
Overall Study Death	42	35
Overall Study Lost to Follow-up	1	3
Overall Study Withdrawal by Subject	2	6
Overall Study Other	2	1

Baseline Characteristics

A Double-blind Study of Paclitaxel in Combination With Reparixin or Placebo for Metastatic Triple-Negative Breast Cancer

Baseline characteristics by cohort

Measure	Paclitaxel+Reparixin (Group 1) - Safety Population n=61 Participants paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy reparixin oral tablets + paclitaxel intravenous weekly three weeks on and one week off until disease progression according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.	Paclitaxel+Placebo (Group 2) - Safety Population n=60 Participants paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.	Total n=121 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	44 Participants n=5 Participants	44 Participants n=7 Participants	88 Participants n=5 Participants
Age, Categorical >=65 years	17 Participants n=5 Participants	16 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Female	61 Participants n=5 Participants	60 Participants n=7 Participants	121 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	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	48 Participants n=5 Participants	54 Participants n=7 Participants	102 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	10 Participants n=5 Participants	4 Participants n=7 Participants	14 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	0 Participants n=5 Participants	1 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	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) White	45 Participants n=5 Participants	49 Participants n=7 Participants	94 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	10 Participants n=5 Participants	4 Participants n=7 Participants	14 Participants n=5 Participants
Region of Enrollment Belgium	4 participants n=5 Participants	6 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants	19 participants n=7 Participants	34 participants n=5 Participants
Region of Enrollment Czechia	3 participants n=5 Participants	8 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment Poland	6 participants n=5 Participants	3 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Italy	16 participants n=5 Participants	12 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment France	10 participants n=5 Participants	4 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment Spain	7 participants n=5 Participants	8 participants n=7 Participants	15 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to every 8 weeks until disease progression or death, whichever occurs first, up to 721 days

Population: The Intent-to-Treat (ITT) Population consisted of all patients who are randomized and was based upon the randomized treatment, regardless of the treatment actually received. Patients were in the ITT analysis whether or not they received study drug. The primary and secondary efficacy analyses were presented primarily for the ITT Population.

PFS was defined as the number of days between the date of randomization and the date of clinical disease progression, according to RECIST criteria version 1.1, as assessed by Independent Radiology Review, or to death due to any cause, whichever occurred first.

Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.

Outcome measures

Measure	Paclitaxel+Reparixin (Group 1) - ITT Population n=62 Participants paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy reparixin oral tablets + paclitaxel intravenous weekly three weeks on and one week off until disease progression according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.	Paclitaxel+Placebo (Group 2) n=61 Participants paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.
Progression Free Survival (PFS)	166 Days Interval 62.0 to 292.0	171 Days Interval 105.0 to 393.0

SECONDARY outcome

Timeframe: Baseline until death due to any cause, up to 985 days

Population: The Intent-to-Treat (ITT) Population consisted of all patients who are randomized and was based upon the randomized treatment, regardless of the treatment actually received. Patients were in the ITT analysis whether or not they received study drug. The primary and secondary efficacy analyses were presented primarily for the ITT Population.

OS was defined as the time from randomization until death due to any cause. For patients who did not die, time of death was censored at the date of last contact.

Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.

Outcome measures

Measure	Paclitaxel+Reparixin (Group 1) - ITT Population n=62 Participants paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy reparixin oral tablets + paclitaxel intravenous weekly three weeks on and one week off until disease progression according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.	Paclitaxel+Placebo (Group 2) n=61 Participants paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.
Overall Survival (OS)	483 Days Interval 272.0 to 812.0	531 Days Interval 334.0 to 787.0

SECONDARY outcome

Timeframe: Baseline up to every 8 weeks until documented disease progression, up to 56 months

Population: Responsible-evaluable population: this population consisted of all patients who had completed at least one cycle of treatment and had a baseline assessment and have undergone at least one post-baseline disease assessment.

The ORR was defined as the percentage of patients achieving CR or PR in the Evaluable Population. The response rate was calculated from the independently reviewed assessment best response. In case of PR or CR, only confirmed cases were considered to be responses.

Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Patients with unknown or missing response, including response of "not all evaluated" or "unable to determine", were treated as non-responders; i.e., they were included in the denominator when calculating the percentages.

Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.

Outcome measures

Measure	Paclitaxel+Reparixin (Group 1) - ITT Population n=57 Participants paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy reparixin oral tablets + paclitaxel intravenous weekly three weeks on and one week off until disease progression according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.	Paclitaxel+Placebo (Group 2) n=54 Participants paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.
Objective Response Rate (ORR)	28.1 Percentage of patients Interval 17.0 to 41.5	25.9 Percentage of patients Interval 15.0 to 39.7

SECONDARY outcome

Timeframe: At screening and every 8 weeks, up to 721 days

Population: The Intent-to-Treat (ITT) Population consisted of all patients who are randomized and was based upon the randomized treatment, regardless of the treatment actually received. Patients were in the ITT analysis whether or not they received study drug. The primary and secondary efficacy analyses were presented primarily for the ITT Population.

PFS was defined as the time from randomization to first documentation of disease progression, according to RECIST criteria version 1.1, as assessed by Independent Radiology Review, or to death due to any cause, whichever occurred first. For each treatment group, the Kaplan-Meier estimates for the median PFS time, the first and third quartiles were presented, along with approximate 95% confidence intervals if there were a sufficient number of progressions or deaths.

Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.

Outcome measures

Measure	Paclitaxel+Reparixin (Group 1) - ITT Population n=62 Participants paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy reparixin oral tablets + paclitaxel intravenous weekly three weeks on and one week off until disease progression according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.	Paclitaxel+Placebo (Group 2) n=61 Participants paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.
Median Progression-free Survival (mPFS)	166 Days Interval 109.0 to 218.0	171 Days Interval 117.0 to 226.0

SECONDARY outcome

Timeframe: Baseline up to every 8 weeks until documented disease progression, up to 557 days

Population: The Response-Evaluable Population consisted of all patients who had completed at least one cycle of treatment and had a baseline assessment and have undergone at least one post-baseline disease assessment.

Duration of overall response (DOR) in days for the investigator assessments is measured from the time response criteria are first met for CR or PR (whichever is first recorded on the "Disease Response" page on the CRF) until either death or the first date that recurrent or PD is objectively documented (on the "Disease Response" p. on the CRF or the Follow-Up Disease Evaluation page indicates disease progression and there is supporting information in the Disease Status pages) per RECIST version 1.1. Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. If a patient is lost to follow-up with no documentation of PD, DOR was censored at the last evaluable tumor assessment. DOR was calculated only for responding patients (PR or CR) as recorded on the CRF page "Disease Response" based upon the RECIST version 1.1.

Duration of overall response wa

Outcome measures

Measure	Paclitaxel+Reparixin (Group 1) - ITT Population n=57 Participants paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy reparixin oral tablets + paclitaxel intravenous weekly three weeks on and one week off until disease progression according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.	Paclitaxel+Placebo (Group 2) n=54 Participants paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.
Duration of Overall Response (DOR)	293.0 Days Interval 119.0 to 505.0	172.0 Days Interval 115.0 to 443.0

SECONDARY outcome

Timeframe: From the start of treatment, every 8 weeks, up to 56 months

Population: The Response-Evaluable Population consisted of all patients who had completed at least one cycle of treatment and had a baseline assessment and have undergone at least one post-baseline disease assessment.

BOR is defined as the best response among all overall responses (in the order complete response [CR], partial response [PR], stable disease [SD], and progressive disease [PD]) recorded as an independent review response from the start of reparixin or placebo until disease progression/recurrence or end of treatment, or death, whichever comes first. The status of BOR of PR or CR needs to be confirmed by repeat tumor assessment within no less than 4 weeks according to RECIST version 1.1. Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. If the status of CR or PR cannot be confirmed by repeat tumor assessment, the best overall response of unconfirmed CR and PR will be PR and SD, respectively. Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.

Outcome measures

Measure	Paclitaxel+Reparixin (Group 1) - ITT Population n=57 Participants paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy reparixin oral tablets + paclitaxel intravenous weekly three weeks on and one week off until disease progression according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.	Paclitaxel+Placebo (Group 2) n=54 Participants paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.
Best Overall Response (BOR) CR	1 participants	0 participants
Best Overall Response (BOR) PR	15 participants	14 participants
Best Overall Response (BOR) SD	16 participants	23 participants
Best Overall Response (BOR) PD	22 participants	14 participants
Best Overall Response (BOR) NE	3 participants	3 participants
Best Overall Response (BOR) Unable to determine	0 participants	0 participants
Best Overall Response (BOR) Unknown/not done	0 participants	0 participants

SECONDARY outcome

Timeframe: Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days

Population: Safety population: this population consisted of all patients who had taken at least one dose of the study treatment and was based upon the treatment they actually received.

Treatment-emergent adverse events (TEAEs) are those which first occur or increase in severity or relationship to study drug after the first dose of study drug and before 30 days after the last dose of study treatment, reparixin/placebo. In the case of missing or partial dates, any AE that could have started on or after first dose date was assumed to be treatment-emergent. In the case of missing or partial dates, imputed dates (see section 10.1 AE date imputation) were used.

Outcome measures

Measure	Paclitaxel+Reparixin (Group 1) - ITT Population n=61 Participants paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy reparixin oral tablets + paclitaxel intravenous weekly three weeks on and one week off until disease progression according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.	Paclitaxel+Placebo (Group 2) n=60 Participants paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.
Number of Treatment-Emergent Adverse Events (TEAEs), Overall and by Grade Overall	865 number of events	730 number of events
Number of Treatment-Emergent Adverse Events (TEAEs), Overall and by Grade Grade 1 (mild)	563 number of events	478 number of events
Number of Treatment-Emergent Adverse Events (TEAEs), Overall and by Grade Grade 2 (moderate)	230 number of events	194 number of events
Number of Treatment-Emergent Adverse Events (TEAEs), Overall and by Grade Grade 3 (severe)	67 number of events	50 number of events
Number of Treatment-Emergent Adverse Events (TEAEs), Overall and by Grade Grade 4 (Life-threatening or disabling)	2 number of events	4 number of events
Number of Treatment-Emergent Adverse Events (TEAEs), Overall and by Grade Grade 5 (death)	3 number of events	4 number of events

SECONDARY outcome

Timeframe: Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days.

Population: Safety population: this population consisted of all patients who had taken at least one dose of the study treatment and was based upon the treatment they actually received.

A serious adverse event (SAE) in human drug trials is defined as any untoward medical occurrence that at any dose

1. - results in death, (fatal)

2. - is life-threatening

3. - requires inpatient hospitalization or causes prolongation of existing hospitalization

4. - results in persistent or significant disability/incapacity,

5. - may have caused a congenital anomaly/birth defect, or

6. - requires intervention to prevent permanent impairment or damage.

Outcome measures

Measure	Paclitaxel+Reparixin (Group 1) - ITT Population n=61 Participants paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy reparixin oral tablets + paclitaxel intravenous weekly three weeks on and one week off until disease progression according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.	Paclitaxel+Placebo (Group 2) n=60 Participants paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.
Serious AEs and Fatal AEs serious AE	31 number of events	25 number of events
Serious AEs and Fatal AEs Fatal AE	3 number of events	4 number of events

Adverse Events

Paclitaxel+Reparixin (Group 1) - Safety Population

Serious events: 13 serious events

Other events: 60 other events

Deaths: 42 deaths

Paclitaxel+Placebo (Group 2) - Safety Population

Serious events: 12 serious events

Other events: 57 other events

Deaths: 35 deaths

Serious adverse events

Measure	Paclitaxel+Reparixin (Group 1) - Safety Population n=61 participants at risk paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy reparixin oral tablets + paclitaxel intravenous weekly three weeks on and one week off until disease progression according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.	Paclitaxel+Placebo (Group 2) - Safety Population n=60 participants at risk paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.
Infections and infestations Erysipelas	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Infections and infestations Lung infection	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Infections and infestations Peritonitis	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Infections and infestations Pneumonia influenzal	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Infections and infestations Pneumonia	0.00% 0/61 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Infections and infestations Sepsis	0.00% 0/61 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
General disorders Non-cardiac chest pain	3.3% 2/61 • Number of events 2 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
General disorders Condition aggravated	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
General disorders General physical health deterioration	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
General disorders Pyrexia	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
General disorders Asthenia	0.00% 0/61 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
General disorders Disease progression	0.00% 0/61 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.3% 2/61 • Number of events 2 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Respiratory, thoracic and mediastinal disorders Haemothorax	0.00% 0/61 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/61 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/61 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	5.0% 3/60 • Number of events 3 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Gastrointestinal disorders Constipation	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Gastrointestinal disorders Intestinal perforation	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Gastrointestinal disorders Stomatitis	0.00% 0/61 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Vascular disorders Deep vein thrombosis	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Vascular disorders Embolism	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Vascular disorders Thrombosis	0.00% 0/61 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Blood and lymphatic system disorders Anaemia	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Blood and lymphatic system disorders Febrile neutropenia	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Investigations Alanine aminotransferase increased	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Investigations Aspartate aminotransferase increased	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Investigations Gamma-glutamyltransferase increased	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Metabolism and nutrition disorders Gout	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Metabolism and nutrition disorders Hyponatraemia	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/61 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Musculoskeletal and connective tissue disorders Back pain	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Nervous system disorders Myelopathy	1.6% 1/61 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	0.00% 0/60 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Nervous system disorders Headache	0.00% 0/61 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Metabolism and nutrition disorders Presyncope	0.00% 0/61 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Cardiac disorders Cardiac failure congestive	0.00% 0/61 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Cardiac disorders Pericardial effusion	0.00% 0/61 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/61 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Injury, poisoning and procedural complications Fall	0.00% 0/61 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.00% 0/61 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/61 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	1.7% 1/60 • Number of events 1 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.

Other adverse events

Measure	Paclitaxel+Reparixin (Group 1) - Safety Population n=61 participants at risk paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + reparixin oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy reparixin oral tablets + paclitaxel intravenous weekly three weeks on and one week off until disease progression according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.	Paclitaxel+Placebo (Group 2) - Safety Population n=60 participants at risk paclitaxel 80 mg/m2 i.v. (Days 1, 8, and 15) + placebo oral tablets 1200 mg t.i.d. continuing from D 1 to Day 21 of 28-day cycle. Duration of Treatment: 28-day cycles of combination therapy placebo oral tablets + paclitaxel intravenous weekly three weeks on and one week off until PD according to RECIST criteria version 1.1, withdrawal of consent or unacceptable toxicity, whichever occurred first.
General disorders Asthenia	26.2% 16/61 • Number of events 16 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	21.7% 13/60 • Number of events 13 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
General disorders Fatigue	18.0% 11/61 • Number of events 11 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	43.3% 26/60 • Number of events 26 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
General disorders Pyrexia	13.1% 8/61 • Number of events 8 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	13.3% 8/60 • Number of events 8 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
General disorders Oedema peripheral	11.5% 7/61 • Number of events 7 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	13.3% 8/60 • Number of events 8 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Gastrointestinal disorders Nausea	37.7% 23/61 • Number of events 23 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	36.7% 22/60 • Number of events 22 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Gastrointestinal disorders Diarrhoea	26.2% 16/61 • Number of events 16 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	25.0% 15/60 • Number of events 15 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Gastrointestinal disorders Constipation	23.0% 14/61 • Number of events 14 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	18.3% 11/60 • Number of events 11 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Gastrointestinal disorders Vomiting	14.8% 9/61 • Number of events 9 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	10.0% 6/60 • Number of events 6 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Gastrointestinal disorders Abdominal pain	11.5% 7/61 • Number of events 7 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	11.7% 7/60 • Number of events 7 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Gastrointestinal disorders Abdominal pain upper	8.2% 5/61 • Number of events 5 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	10.0% 6/60 • Number of events 6 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Gastrointestinal disorders Dyspepsia	6.6% 4/61 • Number of events 4 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	11.7% 7/60 • Number of events 7 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Gastrointestinal disorders Stomatitis	6.6% 4/61 • Number of events 4 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	8.3% 5/60 • Number of events 5 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Skin and subcutaneous tissue disorders Alopecia	34.4% 21/61 • Number of events 21 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	35.0% 21/60 • Number of events 21 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Skin and subcutaneous tissue disorders Rash	14.8% 9/61 • Number of events 9 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	8.3% 5/60 • Number of events 5 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Skin and subcutaneous tissue disorders Erythema	9.8% 6/61 • Number of events 6 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	3.3% 2/60 • Number of events 2 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Nervous system disorders Headache	21.3% 13/61 • Number of events 13 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	13.3% 8/60 • Number of events 8 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Nervous system disorders Neuropathy peripheral	19.7% 12/61 • Number of events 12 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	18.3% 11/60 • Number of events 11 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Nervous system disorders Dysgeusia	14.8% 9/61 • Number of events 9 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	8.3% 5/60 • Number of events 5 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Nervous system disorders Dizziness	11.5% 7/61 • Number of events 7 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	5.0% 3/60 • Number of events 3 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Nervous system disorders Paresthesia	11.5% 7/61 • Number of events 7 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	13.3% 8/60 • Number of events 8 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Musculoskeletal and connective tissue disorders Arthralgia	18.0% 11/61 • Number of events 11 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	11.7% 7/60 • Number of events 7 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Musculoskeletal and connective tissue disorders Back pain	18.0% 11/61 • Number of events 11 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	13.3% 8/60 • Number of events 8 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Musculoskeletal and connective tissue disorders Pain in extremity	16.4% 10/61 • Number of events 10 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	11.7% 7/60 • Number of events 7 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Musculoskeletal and connective tissue disorders Myalgia	11.5% 7/61 • Number of events 7 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	5.0% 3/60 • Number of events 3 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Infections and infestations Urinary tract infection	9.8% 6/61 • Number of events 6 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	8.3% 5/60 • Number of events 5 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Infections and infestations Upper respiratory tract infection	8.2% 5/61 • Number of events 5 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	6.7% 4/60 • Number of events 4 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Respiratory, thoracic and mediastinal disorders Cough	16.4% 10/61 • Number of events 10 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	18.3% 11/60 • Number of events 11 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Respiratory, thoracic and mediastinal disorders Dyspnoea	13.1% 8/61 • Number of events 8 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	11.7% 7/60 • Number of events 7 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Respiratory, thoracic and mediastinal disorders Epistaxis	4.9% 3/61 • Number of events 3 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	8.3% 5/60 • Number of events 5 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Blood and lymphatic system disorders Anaemia	29.5% 18/61 • Number of events 18 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	13.3% 8/60 • Number of events 8 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Blood and lymphatic system disorders Neutropenia	16.4% 10/61 • Number of events 10 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	11.7% 7/60 • Number of events 7 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Blood and lymphatic system disorders Leukopenia	8.2% 5/61 • Number of events 5 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	5.0% 3/60 • Number of events 3 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Investigations Alanine aminotransferase increased	13.1% 8/61 • Number of events 8 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	5.0% 3/60 • Number of events 3 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Investigations Aspartate aminotransferase increased	11.5% 7/61 • Number of events 7 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	5.0% 3/60 • Number of events 3 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Investigations White blood cell count decreased	4.9% 3/61 • Number of events 3 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	8.3% 5/60 • Number of events 5 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Metabolism and nutrition disorders Decreased appetite	8.2% 5/61 • Number of events 5 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	16.7% 10/60 • Number of events 10 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Vascular disorders Hot flush	9.8% 6/61 • Number of events 6 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	10.0% 6/60 • Number of events 6 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Psychiatric disorders insomnia	8.2% 5/61 • Number of events 5 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	6.7% 4/60 • Number of events 4 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.
Vascular disorders Hypertension	6.6% 4/61 • Number of events 4 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.	5.0% 3/60 • Number of events 3 • Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days. A Summary of the Most Frequent (i.e., 5 or More Patients Experiencing an Event by Preferred Term in Any Treatment Group) Treatment-Emergent Adverse Events by System Organ Class and Preferred Term is reported.

Additional Information

Dr Pier Adelchi Ruffini, MD

Dompé Farmaceutici SpA

Phone: +39 02 583831

Email: info@dompe.it

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place