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A Study Evaluating S 95005 Plus Bevacizumab and Capecitabine Plus Bevacizumab in Patients With Previously Untreated Colorectal Cancer Who Are Non-eligible for Intensive Therapy (TASCO1)

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ClinicalTrials.gov Identifier: NCT02743221
Recruitment Status : Active, not recruiting
First Posted : April 19, 2016
Results First Posted : April 16, 2019
Last Update Posted : October 1, 2019
Sponsor:
Collaborator:
ADIR, a Servier Group company
Information provided by (Responsible Party):
Servier ( Institut de Recherches Internationales Servier )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Colorectal Cancer
Interventions Drug: Trifluridine/tipiracil + bevacizumab
Drug: Capecitabine + bevacizumab
Enrollment 154
Recruitment Details  
Pre-assignment Details 154 patients were randomized among whom one was deemed ineligible after randomization.
Arm/Group Title Trifluridine/Tipiracil + Bevacizumab Capecitabine + Bevacizumab
Hide Arm/Group Description

Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride.

Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab.

Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks.

Trifluridine/tipiracil + bevacizumab: Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.

Capecitabine was administered at 1250 mg/m² orally BID on Days 1–14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks

Capecitabine + bevacizumab: Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.

Period Title: Overall Study
Started 77 77
Completed [1] 21 17
Not Completed 56 60
Reason Not Completed
Progressive disease             29             38
Adverse Event             17             14
non medical reason             8             2
Physician Decision             2             5
Patient not eligible, not treated             0             1
[1]
Of note, these patients were still under treatment at the primary completion date (cut-off date).
Arm/Group Title Trifluridine/Tipiracil + Bevacizumab Capecitabine + Bevacizumab Total
Hide Arm/Group Description

Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride.

Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab.

Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks.

Trifluridine/tipiracil + bevacizumab: Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.

Capecitabine was administered at 1250 mg/m² orally BID on Days 1–14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks

Capecitabine + bevacizumab: Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.

Total of all reporting groups
Overall Number of Baseline Participants 77 77 154
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 77 participants 154 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
20
  26.0%
16
  20.8%
36
  23.4%
>=65 years
57
  74.0%
61
  79.2%
118
  76.6%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 77 participants 77 participants 154 participants
69.8  (10.2) 72.8  (11.0) 71.3  (10.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 77 participants 154 participants
Female
37
  48.1%
29
  37.7%
66
  42.9%
Male
40
  51.9%
48
  62.3%
88
  57.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants 77 participants 154 participants
White
73
  94.8%
72
  93.5%
145
  94.2%
Asian
1
   1.3%
2
   2.6%
3
   1.9%
Other
1
   1.3%
1
   1.3%
2
   1.3%
Not collected
2
   2.6%
2
   2.6%
4
   2.6%
1.Primary Outcome
Title Progression Free Survival (PFS)
Hide Description The progression free survival (PFS), defined as the time from the date of randomisation until the date of the investigator-assessed radiological disease progression or death due to any cause according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progressive disease (PD) was defined at least a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) and an absolute increase of at least 5 mm in the sum of lesions or the appearance of new lesions.
Time Frame Baseline and every 8 weeks (maximum follow-up duration: 17.9 months)
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Hide Analysis Population Description
Full Analysis Set (FAS): all randomised patients who have taken at least one dose of study treatment.
Arm/Group Title Trifluridine/Tipiracil + Bevacizumab Capecitabine + Bevacizumab
Hide Arm/Group Description:

Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride.

Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab.

Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks.

Trifluridine/tipiracil + bevacizumab: Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.

Capecitabine was administered at 1250 mg/m² orally BID on Days 1–14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks

Capecitabine + bevacizumab: Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.

Overall Number of Participants Analyzed 77 76
Median (95% Confidence Interval)
Unit of Measure: months
9.2
(7.6 to 11.6)
7.8
(5.5 to 10.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trifluridine/Tipiracil + Bevacizumab, Capecitabine + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Other
Comments This was a non-comparative study.
Statistical Test of Hypothesis P-Value 0.09
Comments [Not Specified]
Method Cox proportional hazard model
Comments Cox proportional hazard model with adjustment for the stratification factors (RAS status, performance status ECOG)
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.48 to 1.06
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Response Rate (ORR)
Hide Description As per RECIST v1.1, Complete Response (CR) was disappearance of all target lesions; Partial Response (PR) was at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The ORR was the proportion of patients who presented CR or PR with confirmation at subsequent time point or at least 4 weeks later.
Time Frame Baseline and every 8 weeks (maximum follow-up duration: 17.9 months)
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Hide Analysis Population Description
FAS
Arm/Group Title Trifluridine/Tipiracil + Bevacizumab Capecitabine + Bevacizumab
Hide Arm/Group Description:

Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride.

Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab.

Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks.

Trifluridine/tipiracil + bevacizumab: Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.

Capecitabine was administered at 1250 mg/m² orally BID on Days 1–14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks

Capecitabine + bevacizumab: Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.

Overall Number of Participants Analyzed 77 76
Measure Type: Count of Participants
Unit of Measure: Participants
26
  33.8%
23
  30.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trifluridine/Tipiracil + Bevacizumab, Capecitabine + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.73
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Duration of Response (DR)
Hide Description The DR was calculated among patients with CR or PR as the time (months) from the first documentation of response to the first documentation of objective tumor progression or death due to any cause, whichever occurred first.
Time Frame Baseline and every 8 weeks (maximum follow-up duration: 16.6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Tumour Response population: patients with measurable disease at baseline and with at least one tumour evaluation while on treatment.
Arm/Group Title Trifluridine/Tipiracil + Bevacizumab Capecitabine + Bevacizumab
Hide Arm/Group Description:

Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride.

Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab.

Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks.

Trifluridine/tipiracil + bevacizumab: Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.

Capecitabine was administered at 1250 mg/m² orally BID on Days 1–14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks

Capecitabine + bevacizumab: Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.

Overall Number of Participants Analyzed 74 73
Median (80% Confidence Interval)
Unit of Measure: months
7.9
(6.01 to 14.75)
9.9
(8.41 to 10.02)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trifluridine/Tipiracil + Bevacizumab, Capecitabine + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.49 to 2.74
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description DCR was the proportion of patients with confirmed CR, PR or stable disease (SD) as best overall response. SD defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD.
Time Frame Baseline and every 8 weeks (maximum follow-up duration: 17.9 months)
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Hide Analysis Population Description
FAS
Arm/Group Title Trifluridine/Tipiracil + Bevacizumab Capecitabine + Bevacizumab
Hide Arm/Group Description:

Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride.

Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab.

Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks.

Trifluridine/tipiracil + bevacizumab: Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.

Capecitabine was administered at 1250 mg/m² orally BID on Days 1–14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks

Capecitabine + bevacizumab: Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.

Overall Number of Participants Analyzed 77 76
Measure Type: Count of Participants
Unit of Measure: Participants
66
  85.7%
59
  77.6%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trifluridine/Tipiracil + Bevacizumab, Capecitabine + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
5.Secondary Outcome
Title Overall Survival (OS)
Hide Description The OS was defined as the time from the date of randomisation to the date of death. If death was not confirmed, or patient was alive at study cut-off date, survival time was censored at the date of last follow-up or at the study cut-off date, whichever was earlier.
Time Frame Baseline up to death or study cut-off (maximum follow-up duration: 19.9 months)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Trifluridine/Tipiracil + Bevacizumab Capecitabine + Bevacizumab
Hide Arm/Group Description:

Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride.

Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab.

Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks.

Trifluridine/tipiracil + bevacizumab: Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.

Capecitabine was administered at 1250 mg/m² orally BID on Days 1–14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks

Capecitabine + bevacizumab: Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.

Overall Number of Participants Analyzed 77 76
Median (80% Confidence Interval)
Unit of Measure: months
18.0
(15.18 to 19.48)
16.2
(13.07 to 17.67)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trifluridine/Tipiracil + Bevacizumab, Capecitabine + Bevacizumab
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method Cox proportional hazard model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.56
Confidence Interval (2-Sided) 95%
0.32 to 0.98
Estimation Comments [Not Specified]
Time Frame All Adverse Events (AE) were collected from the informed consent signature up to the final visit regardless of seriousness or relationship to study drug (maximum exposure: 82 weeks).
Adverse Event Reporting Description

Reported AEs are Treatment-Emergent AEs (TEAE) that are AEs that developed/worsened during the treatment period i.e. between the first treatment intake date and the last treatment intake date + 35 days.

In the Capecitabine + bevacizumab group, the number of participants at Risk for TEAE (both serious and non-serious) was 76 which is different from Started patients in the Participant Flow module (=77). Indeed, 1 started patient in this group did not received any treatment dose

 
Arm/Group Title Trifluridine/Tipiracil + Bevacizumab Capecitabine + Bevacizumab
Hide Arm/Group Description

Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride.

Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab.

Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks.

Trifluridine/tipiracil + bevacizumab: Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.

Capecitabine was administered at 1250 mg/m² orally BID on Days 1–14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks

Capecitabine + bevacizumab: Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.

All-Cause Mortality
Trifluridine/Tipiracil + Bevacizumab Capecitabine + Bevacizumab
Affected / at Risk (%) Affected / at Risk (%)
Total   22/77 (28.57%)      33/76 (43.42%)    
Show Serious Adverse Events Hide Serious Adverse Events
Trifluridine/Tipiracil + Bevacizumab Capecitabine + Bevacizumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   42/77 (54.55%)      44/76 (57.89%)    
Blood and lymphatic system disorders     
Anaemia  1  3/77 (3.90%)  4 0/76 (0.00%)  0
Febrile neutropenia  1  3/77 (3.90%)  3 3/76 (3.95%)  3
Haemorrhagic anaemia  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Neutropenia  1  4/77 (5.19%)  5 0/76 (0.00%)  0
Cardiac disorders     
Acute coronary syndrome  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Atrial fibrillation  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Atrioventricular block complete  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Mitral valve incompetence  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Myocardial infarction  1  2/77 (2.60%)  2 0/76 (0.00%)  0
Supraventricular tachycardia  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Ventricular tachycardia  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Endocrine disorders     
Hypothyroidism  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Gastrointestinal disorders     
Ascites  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Diarrhoea  1  2/77 (2.60%)  2 5/76 (6.58%)  5
Enterocutaneous fistula  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Gastrointestinal angiodysplasia haemorrhagic  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Haematemesis  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Ileus paralytic  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Intestinal obstruction  1  2/77 (2.60%)  2 1/76 (1.32%)  1
Intestinal perforation  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Large intestinal obstruction  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Large intestine perforation  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Malignant bowel obstruction  1  0/77 (0.00%)  0 2/76 (2.63%)  2
Nausea  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Pancreatitis  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Proctalgia  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Small intestinal obstruction  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Umbilical hernia  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Vomiting  1  2/77 (2.60%)  4 1/76 (1.32%)  1
General disorders     
Death  1  0/77 (0.00%)  0 2/76 (2.63%)  2
General physical health deterioration  1  0/77 (0.00%)  0 2/76 (2.63%)  2
Mucosal dryness  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Multiple organ dysfunction syndrome  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Non-cardiac chest pain  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Hepatobiliary disorders     
Cholecystitis  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Cholecystitis acute  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Cholelithiasis  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Hepatic failure  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Hepatotoxicity  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Infections and infestations     
Abdominal abscess  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Arthritis bacterial  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Biliary sepsis  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Catheter site infection  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Clostridium difficile colitis  1  2/77 (2.60%)  2 0/76 (0.00%)  0
Device related sepsis  1  2/77 (2.60%)  2 0/76 (0.00%)  0
Escherichia urinary tract infection  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Neutropenic sepsis  1  2/77 (2.60%)  2 0/76 (0.00%)  0
Peritonitis  1  2/77 (2.60%)  2 0/76 (0.00%)  0
Pneumonia  1  3/77 (3.90%)  3 1/76 (1.32%)  1
Pneumonia toxoplasmal  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Septic shock  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Wound infection  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Injury, poisoning and procedural complications     
Fall  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Gastrointestinal stoma complication  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Postoperative wound complication  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Thoracic vertebral fracture  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Investigations     
Blood bilirubin increased  1  0/77 (0.00%)  0 2/76 (2.63%)  2
Blood calcium decreased  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Blood creatine phosphokinase increased  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Blood magnesium decreased  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Blood phosphorus decreased  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Blood potassium decreased  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Neutrophil count decreased  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Troponin T increased  1  0/77 (0.00%)  0 1/76 (1.32%)  1
White blood cell count decreased  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Metabolism and nutrition disorders     
Dehydration  1  3/77 (3.90%)  3 5/76 (6.58%)  5
Fluid overload  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Hyperkalaemia  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Hyponatraemia  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Musculoskeletal and connective tissue disorders     
Back pain  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Muscular weakness  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Malignant neoplasm progression  1  8/77 (10.39%)  8 16/76 (21.05%)  16
Metastases to peritoneum  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Metastases to spine  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Skin cancer  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Nervous system disorders     
Aphasia  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Cauda equina syndrome  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Ischaemic stroke  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Memory impairment  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Seizure  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Syncope  1  1/77 (1.30%)  3 2/76 (2.63%)  2
Psychiatric disorders     
Depressed mood  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Depression  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  2/77 (2.60%)  3 2/76 (2.63%)  2
Renal failure  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Reproductive system and breast disorders     
Female genital tract fistula  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Dyspnoea  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Dyspnoea exertional  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Hypoxia  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Pleural effusion  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Pneumonia aspiration  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Pulmonary congestion  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Pulmonary embolism  1  3/77 (3.90%)  3 3/76 (3.95%)  4
Pulmonary oedema  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Skin and subcutaneous tissue disorders     
Diabetic foot  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Palmar-plantar erythrodysaesthesia syndrome  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Rash erythematous  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Stevens-Johnson syndrome  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Vascular disorders     
Deep vein thrombosis  1  0/77 (0.00%)  0 4/76 (5.26%)  4
Hypertension  1  3/77 (3.90%)  3 0/76 (0.00%)  0
Hypotension  1  1/77 (1.30%)  2 2/76 (2.63%)  2
Thrombophlebitis superficial  1  0/77 (0.00%)  0 1/76 (1.32%)  1
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Trifluridine/Tipiracil + Bevacizumab Capecitabine + Bevacizumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   75/77 (97.40%)      69/76 (90.79%)    
Blood and lymphatic system disorders     
Anaemia  1  22/77 (28.57%)  31 5/76 (6.58%)  7
Anaemia of chronic disease  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Anaemia of malignant disease  1  5/77 (6.49%)  5 1/76 (1.32%)  2
Febrile neutropenia  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Haemolytic anaemia  1  2/77 (2.60%)  2 0/76 (0.00%)  0
Leukopenia  1  6/77 (7.79%)  9 2/76 (2.63%)  5
Neutropenia  1  40/77 (51.95%)  181 5/76 (6.58%)  5
Spontaneous haematoma  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Thrombocytopenia  1  11/77 (14.29%)  22 4/76 (5.26%)  5
Thrombocytosis  1  4/77 (5.19%)  8 0/76 (0.00%)  0
Cardiac disorders     
Angina pectoris  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Aortic valve thickening  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Arrhythmia  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Atrial fibrillation  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Bundle branch block right  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Supraventricular extrasystoles  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Tachycardia  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Ear and labyrinth disorders     
Ear pain  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Vertigo  1  2/77 (2.60%)  2 0/76 (0.00%)  0
Eye disorders     
Dry eye  1  1/77 (1.30%)  2 0/76 (0.00%)  0
Eye pain  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Eye pruritus  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Lacrimation increased  1  0/77 (0.00%)  0 4/76 (5.26%)  5
Vision blurred  1  1/77 (1.30%)  1 2/76 (2.63%)  2
Gastrointestinal disorders     
Abdominal discomfort  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Abdominal pain  1  9/77 (11.69%)  18 6/76 (7.89%)  7
Abdominal pain lower  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Abdominal pain upper  1  2/77 (2.60%)  3 2/76 (2.63%)  3
Anal fissure  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Anal inflammation  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Aphthous ulcer  1  2/77 (2.60%)  2 1/76 (1.32%)  1
Chronic gastritis  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Constipation  1  13/77 (16.88%)  21 15/76 (19.74%)  17
Diarrhoea  1  40/77 (51.95%)  91 31/76 (40.79%)  64
Dry mouth  1  2/77 (2.60%)  2 6/76 (7.89%)  7
Dyschezia  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Dyspepsia  1  6/77 (7.79%)  7 2/76 (2.63%)  2
Dysphagia  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Eructation  1  2/77 (2.60%)  3 1/76 (1.32%)  1
Gastrointestinal motility disorder  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Gastrooesophageal reflux disease  1  0/77 (0.00%)  0 2/76 (2.63%)  2
Gingival bleeding  1  3/77 (3.90%)  4 1/76 (1.32%)  1
Haemorrhoids  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Lip dry  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Lip pain  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Lip swelling  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Mesenteric vein thrombosis  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Mouth ulceration  1  2/77 (2.60%)  2 0/76 (0.00%)  0
Nausea  1  36/77 (46.75%)  84 13/76 (17.11%)  23
Oral mucosa erosion  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Oral pain  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Pancreatitis chronic  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Periodontal disease  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Proctalgia  1  3/77 (3.90%)  6 3/76 (3.95%)  3
Proctitis  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Rectal discharge  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Rectal haemorrhage  1  0/77 (0.00%)  0 2/76 (2.63%)  2
Stomatitis  1  13/77 (16.88%)  18 16/76 (21.05%)  29
Stomatitis haemorrhagic  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Toothache  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Vomiting  1  22/77 (28.57%)  44 8/76 (10.53%)  8
General disorders     
Asthenia  1  14/77 (18.18%)  19 17/76 (22.37%)  22
Chest discomfort  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Chills  1  1/77 (1.30%)  1 3/76 (3.95%)  3
Discomfort  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Early satiety  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Fatigue  1  28/77 (36.36%)  45 23/76 (30.26%)  35
Feeling hot  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Impaired healing  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Influenza like illness  1  3/77 (3.90%)  3 3/76 (3.95%)  3
Injection site haematoma  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Local swelling  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Malaise  1  1/77 (1.30%)  2 0/76 (0.00%)  0
Mucosal inflammation  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Non-cardiac chest pain  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Oedema peripheral  1  3/77 (3.90%)  4 3/76 (3.95%)  3
Pain  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Puncture site pain  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Pyrexia  1  5/77 (6.49%)  5 4/76 (5.26%)  5
Tenderness  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Xerosis  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Hepatobiliary disorders     
Cholecystitis chronic  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Hepatomegaly  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Hyperbilirubinaemia  1  1/77 (1.30%)  1 5/76 (6.58%)  7
Infections and infestations     
Bronchitis  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Conjunctivitis  1  1/77 (1.30%)  2 3/76 (3.95%)  3
Cystitis  1  0/77 (0.00%)  0 2/76 (2.63%)  2
Escherichia urinary tract infection  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Folliculitis  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Furuncle  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Gastroenteritis  1  2/77 (2.60%)  2 0/76 (0.00%)  0
Gastrointestinal viral infection  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Gingivitis  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Hepatic cyst infection  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Influenza  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Labyrinthitis  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Lower respiratory tract infection bacterial  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Lung infection  1  1/77 (1.30%)  2 1/76 (1.32%)  1
Oral candidiasis  1  1/77 (1.30%)  1 3/76 (3.95%)  4
Oral fungal infection  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Oral herpes  1  1/77 (1.30%)  1 4/76 (5.26%)  4
Oral infection  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Periumbilical abscess  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Pneumonia  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Pneumonia bacterial  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Rhinitis  1  4/77 (5.19%)  4 1/76 (1.32%)  1
Skin candida  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Tooth abscess  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Upper respiratory tract infection  1  7/77 (9.09%)  8 2/76 (2.63%)  2
Urinary tract infection  1  7/77 (9.09%)  8 5/76 (6.58%)  6
Urinary tract infection bacterial  1  1/77 (1.30%)  1 2/76 (2.63%)  3
Viral upper respiratory tract infection  1  8/77 (10.39%)  9 5/76 (6.58%)  5
Vulvovaginal candidiasis  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Injury, poisoning and procedural complications     
Abdominal wall wound  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Accidental overdose  1  0/77 (0.00%)  0 2/76 (2.63%)  5
Clavicle fracture  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Contusion  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Fall  1  5/77 (6.49%)  5 4/76 (5.26%)  6
Hand fracture  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Infusion related reaction  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Muscle strain  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Procedural pain  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Skin wound  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Stoma site haemorrhage  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Stoma site irritation  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Stoma site pain  1  2/77 (2.60%)  2 0/76 (0.00%)  0
Traumatic haematoma  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Wound  1  0/77 (0.00%)  0 2/76 (2.63%)  2
Wound complication  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Investigations     
Activated partial thromboplastin time prolonged  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Alanine aminotransferase increased  1  9/77 (11.69%)  11 2/76 (2.63%)  2
Aspartate aminotransferase increased  1  7/77 (9.09%)  8 2/76 (2.63%)  2
Bilirubin conjugated increased  1  1/77 (1.30%)  2 1/76 (1.32%)  1
Blood albumin decreased  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Blood alkaline phosphatase increased  1  3/77 (3.90%)  3 2/76 (2.63%)  2
Blood bilirubin increased  1  6/77 (7.79%)  18 8/76 (10.53%)  13
Blood bilirubin unconjugated increased  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Blood cholesterol increased  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Blood creatinine increased  1  3/77 (3.90%)  5 1/76 (1.32%)  1
Blood glucose increased  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Blood lactate dehydrogenase decreased  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Blood lactate dehydrogenase increased  1  1/77 (1.30%)  5 4/76 (5.26%)  5
Blood phosphorus increased  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Blood potassium decreased  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Blood potassium increased  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Blood pressure increased  1  2/77 (2.60%)  3 0/76 (0.00%)  0
Blood urea increased  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Blood urine present  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Carcinoembryonic antigen increased  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Creatinine renal clearance decreased  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Eosinophil count decreased  1  2/77 (2.60%)  2 0/76 (0.00%)  0
Gamma-glutamyltransferase increased  1  6/77 (7.79%)  6 2/76 (2.63%)  3
Glomerular filtration rate decreased  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Heart rate irregular  1  0/77 (0.00%)  0 1/76 (1.32%)  1
International normalised ratio increased  1  1/77 (1.30%)  1 2/76 (2.63%)  2
Lymphocyte count decreased  1  4/77 (5.19%)  7 1/76 (1.32%)  2
Monocyte count decreased  1  2/77 (2.60%)  2 0/76 (0.00%)  0
Neutrophil count decreased  1  18/77 (23.38%)  90 1/76 (1.32%)  1
Neutrophil count increased  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Platelet count decreased  1  7/77 (9.09%)  22 3/76 (3.95%)  5
Platelet count increased  1  2/77 (2.60%)  3 0/76 (0.00%)  0
Weight decreased  1  9/77 (11.69%)  12 6/76 (7.89%)  7
Weight increased  1  0/77 (0.00%)  0 1/76 (1.32%)  1
White blood cell count decreased  1  15/77 (19.48%)  37 1/76 (1.32%)  1
White blood cell count increased  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite  1  29/77 (37.66%)  46 15/76 (19.74%)  23
Gout  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Hypercalcaemia  1  2/77 (2.60%)  2 0/76 (0.00%)  0
Hyperglycaemia  1  3/77 (3.90%)  6 2/76 (2.63%)  2
Hyperkalaemia  1  4/77 (5.19%)  5 0/76 (0.00%)  0
Hyperphosphataemia  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Hypertriglyceridaemia  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Hypoalbuminaemia  1  4/77 (5.19%)  4 2/76 (2.63%)  2
Hypocalcaemia  1  2/77 (2.60%)  4 1/76 (1.32%)  1
Hypochloraemia  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Hypoglycaemia  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Hypokalaemia  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Hypomagnesaemia  1  3/77 (3.90%)  3 1/76 (1.32%)  1
Hyponatraemia  1  3/77 (3.90%)  3 0/76 (0.00%)  0
Hypophosphataemia  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Metabolic acidosis  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia  1  6/77 (7.79%)  8 3/76 (3.95%)  3
Back pain  1  6/77 (7.79%)  6 7/76 (9.21%)  7
Bursitis  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Coccydynia  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Intervertebral disc compression  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Joint swelling  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Mobility decreased  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Muscle spasms  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Muscular weakness  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Musculoskeletal chest pain  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Musculoskeletal pain  1  2/77 (2.60%)  2 1/76 (1.32%)  1
Myalgia  1  1/77 (1.30%)  2 4/76 (5.26%)  5
Neck pain  1  2/77 (2.60%)  2 1/76 (1.32%)  1
Osteoarthritis  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Pain in extremity  1  4/77 (5.19%)  4 1/76 (1.32%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Malignant neoplasm progression  1  9/77 (11.69%)  9 3/76 (3.95%)  3
Nervous system disorders     
Amnesia  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Aphonia  1  0/77 (0.00%)  0 2/76 (2.63%)  2
Balance disorder  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Dizziness  1  5/77 (6.49%)  7 8/76 (10.53%)  10
Dizziness exertional  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Dizziness postural  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Dysarthria  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Dysgeusia  1  7/77 (9.09%)  8 8/76 (10.53%)  8
Essential tremor  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Headache  1  7/77 (9.09%)  13 4/76 (5.26%)  4
Hyperaesthesia  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Hypoaesthesia  1  0/77 (0.00%)  0 1/76 (1.32%)  2
Memory impairment  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Neuralgia  1  1/77 (1.30%)  2 0/76 (0.00%)  0
Neuropathy peripheral  1  0/77 (0.00%)  0 3/76 (3.95%)  3
Neurotoxicity  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Orthostatic intolerance  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Paraesthesia  1  1/77 (1.30%)  1 2/76 (2.63%)  2
Peripheral sensory neuropathy  1  2/77 (2.60%)  2 1/76 (1.32%)  1
Presyncope  1  1/77 (1.30%)  1 2/76 (2.63%)  3
Restless legs syndrome  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Sciatica  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Somnolence  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Tremor  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Psychiatric disorders     
Anxiety  1  0/77 (0.00%)  0 2/76 (2.63%)  2
Confusional state  1  1/77 (1.30%)  1 1/76 (1.32%)  2
Depression  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Disorientation  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Insomnia  1  6/77 (7.79%)  6 1/76 (1.32%)  1
Mood altered  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Restlessness  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Stress  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Renal and urinary disorders     
Anuria  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Dysuria  1  0/77 (0.00%)  0 3/76 (3.95%)  3
Glycosuria  1  0/77 (0.00%)  0 1/76 (1.32%)  2
Haematuria  1  1/77 (1.30%)  1 2/76 (2.63%)  2
Lower urinary tract symptoms  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Micturition urgency  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Nocturia  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Pollakiuria  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Proteinuria  1  5/77 (6.49%)  6 4/76 (5.26%)  5
Urinary incontinence  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Urinary retention  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Oedema genital  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Prostatitis  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Respiratory, thoracic and mediastinal disorders     
Catarrh  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Chronic obstructive pulmonary disease  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Cough  1  2/77 (2.60%)  2 6/76 (7.89%)  6
Dysphonia  1  4/77 (5.19%)  5 1/76 (1.32%)  1
Dyspnoea  1  5/77 (6.49%)  5 8/76 (10.53%)  11
Dyspnoea exertional  1  2/77 (2.60%)  2 2/76 (2.63%)  2
Epistaxis  1  4/77 (5.19%)  6 4/76 (5.26%)  6
Hiccups  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Nasal congestion  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Nasal dryness  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Nasal inflammation  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Oropharyngeal pain  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Pneumonia aspiration  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Productive cough  1  1/77 (1.30%)  1 3/76 (3.95%)  3
Pulmonary mass  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Pulmonary pain  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Rhinalgia  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Rhinorrhoea  1  0/77 (0.00%)  0 3/76 (3.95%)  3
Sneezing  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Skin and subcutaneous tissue disorders     
Alopecia  1  17/77 (22.08%)  17 0/76 (0.00%)  0
Drug eruption  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Dry skin  1  4/77 (5.19%)  4 4/76 (5.26%)  4
Erythema  1  0/77 (0.00%)  0 2/76 (2.63%)  2
Hyperhidrosis  1  0/77 (0.00%)  0 2/76 (2.63%)  2
Nail discolouration  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Nail disorder  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Night sweats  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Onychalgia  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Onychomadesis  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Palmar-plantar erythrodysaesthesia syndrome  1  3/77 (3.90%)  4 39/76 (51.32%)  49
Pruritus  1  2/77 (2.60%)  3 1/76 (1.32%)  1
Rash  1  1/77 (1.30%)  1 1/76 (1.32%)  1
Rash erythematous  1  0/77 (0.00%)  0 2/76 (2.63%)  2
Skin discolouration  1  0/77 (0.00%)  0 1/76 (1.32%)  2
Skin fissures  1  1/77 (1.30%)  1 0/76 (0.00%)  0
Skin hyperpigmentation  1  0/77 (0.00%)  0 2/76 (2.63%)  2
Vascular disorders     
Deep vein thrombosis  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Hot flush  1  0/77 (0.00%)  0 1/76 (1.32%)  1
Hypertension  1  9/77 (11.69%)  10 10/76 (13.16%)  12
Hypotension  1  4/77 (5.19%)  5 1/76 (1.32%)  1
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr Patrick Therasse
Organization: Institut de Recherches Internationales Servier (I.R.I.S.)
Phone: +33 1 55 72 43 47
EMail: patrick.therasse@servier.com
Layout table for additonal information
Responsible Party: Servier ( Institut de Recherches Internationales Servier )
ClinicalTrials.gov Identifier: NCT02743221     History of Changes
Other Study ID Numbers: CL2-95005-002
2015-004544-18 ( EudraCT Number )
First Submitted: February 24, 2016
First Posted: April 19, 2016
Results First Submitted: January 15, 2019
Results First Posted: April 16, 2019
Last Update Posted: October 1, 2019