TASCO1: 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
Sponsor
Institut de Recherches Internationales Servier (Other)
Overall Status
Completed
CT.gov ID
NCT02743221
Collaborator
ADIR, a Servier Group company (Industry)
154
57
2
52.1
2.7
0.1
Study Details
Study Description
Brief Summary
The main purpose of this study is to evaluate the progression-free survival (PFS) in patients receiving S 95005 + bevacizumab (experimental arm) or capecitabine + bevacizumab (control arm) as first-line treatment for unresectable metastatic colorectal cancer in patients non-eligible for intensive therapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
154 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Randomised, Non-comparative Phase 2 Study Evaluating S 95005 (TAS-102) Plus Bevacizumab and Capecitabine Plus Bevacizumab in Patients With Previously Untreated Metastatic COlorectal Cancer Who Are Non-eligible for Intensive Therapy (TASCO1 Study).
Actual Study Start Date
:
Apr 29, 2016
Actual Primary Completion Date
:
Jan 15, 2018
Actual Study Completion Date
:
Sep 1, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Trifluridine/tipiracil + bevacizumab 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. |
Drug: Trifluridine/tipiracil + bevacizumab
Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.
|
| Active Comparator: Capecitabine + bevacizumab Capecitabine was administered at 1250 mg/m² orally BID (bis in die)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 |
Drug: Capecitabine + bevacizumab
Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival (PFS) [Baseline and every 8 weeks (maximum follow-up duration: 17.9 months)]
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.
Secondary Outcome Measures
- Overall Response Rate (ORR) [Baseline and every 8 weeks (maximum follow-up duration: 17.9 months)]
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.
- Duration of Response (DR) [Baseline and every 8 weeks (maximum follow-up duration: 16.6 months)]
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.
- Disease Control Rate (DCR) [Baseline and every 8 weeks (maximum follow-up duration: 17.9 months)]
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.
- Overall Survival (OS) [Baseline up to death or study cut-off (maximum follow-up duration: 19.9 months)]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Written informed consent obtained.
-
Has ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1 or 2 at the time of the randomisation.
-
Has definitive histologically or cytologically confirmed adenocarcinoma of the colon or rectum.
-
RAS status must have been determined (mutant or wild).
-
Has at least one measurable metastatic lesion.
-
No previous systemic anticancer therapy for unresectable metastatic colorectal cancer.
-
Previous adjuvant (or neoadjuvant for patients with rectal cancer) chemotherapy is allowed only if if it has been completed more than 6 months before start of study treatment.
-
Patient is not a candidate for combination chemotherapy with irinotecan or oxaliplatin, or for curative resection of metastatic lesions.
-
Is able to take medication orally (i.e., no feeding tube).
-
Has adequate organ function.
-
Coagulation parameters in normal limit (or in therapeutic limit for patients treated with anticoagulant drugs).
-
Women of childbearing potential must have been tested negative in a serum pregnancy test. Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use a highly effective method of birth control. Women and female partners using hormonal contraceptive must also use a barrier method.
Exclusion Criteria:
-
Is a pregnant or lactating female.
-
Has certain serious illness or serious medical condition(s) as described in the protocol.
-
Has had certain other recent treatment e.g. major surgery, field radiation, received investigational agent, within the specified time frames prior to randomisation.
-
Has previously received Trifluridine/tipiracil or history of allergic reactions attributed to compounds of similar composition to Trifluridine/tipiracil or any of its excipients.
-
Has rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
-
Has contra-indication to bevacizumab or capecitabine.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Chris O'Brien Lifehouse Oncology | Camperdown | Australia | NSW 2050 | |
| 2 | Austin Hospital Olivia Newton-John Cancer & Wellness Centre | Heidelberg | Australia | VIC 3084 | |
| 3 | Western Health, Sunshine Hospital | Saint Albans | Australia | VIC 3021 | |
| 4 | The Queen Elizabeth Hospital Haematology and Oncology Unit | Woodville | Australia | SA 5011 | |
| 5 | Grand Hôpital de Charleroi Oncologie-Hématologie | Charleroi | Belgium | 6000 | |
| 6 | UZ Leuven Campus Gasthuisberg Digestieve Oncologie | Leuven | Belgium | 3000 | |
| 7 | CHC Saint-Joseph Oncologie-Hématoimmunopathologie | Liège | Belgium | 4000 | |
| 8 | Hospital do Câncer de Barretos - Fundação Pio XII | Barretos | Brazil | 14784-400 | |
| 9 | Centro de Pesquisa Hospital de Caridade de Ijuí | Ijui | Brazil | 98700-000 | |
| 10 | Instituto Nacional do Câncer - INCA Unidade de Pesquisa ClínicaInstituto Nacional do Câncer - INCA Unidade de Pesquisa Clínica | Rio de Janeiro | Brazil | 20230-130 | |
| 11 | Hospital de Base, Centro Intergrado de Pesquisa | Sao Jose do Rio Preto | Brazil | 15090-000 | |
| 12 | Instituto do Câncer do Estado de São Paulo - ICESP, Núcleo de Pesquisa | Sao Paulo | Brazil | 01246-000 | |
| 13 | Rigshospitalet - Dpt of Oncology | Copenhagen | Denmark | 2100 | |
| 14 | Odense Universitetshospital - Department of Oncology | Odense | Denmark | 5000 | |
| 15 | CHU Jean Minjoz, Service d'oncologie médicale | Besançon | France | 25030 | |
| 16 | Hôpital Saint Antoine, oncology department | Paris | France | 75012 | |
| 17 | Centre René Gauducheau, Oncologie Médicale | Saint-Herblain | France | 44805 | |
| 18 | Onkologische Schwerpunktpraxis Kurfürstendamm | Berlin | Germany | 10707 | |
| 19 | Schwerpunktpraxis für Hämatologie und Onkologie | Magdeburg | Germany | 39104 | |
| 20 | Städtisches Krankenhaus München Neuperlach, Klinik für Onkologie und Hämatologie | Munich | Germany | 81737 | |
| 21 | Fondazione Poliambulanza Istituto Ospedaliero, Clinical Oncology | Brescia | Italy | 25124 | |
| 22 | A.O.U. SanMartino-IST, Unità Operativa Oncologia Medica 1 | Genova | Italy | 16132 | |
| 23 | A.O. Ospedale Niguarda Ca' Granda-Milano, Department of Onco-Haematology- Onoclogia Falck | Milan | Italy | 20162 | |
| 24 | Seconda Università degli Studi di Napoli, U.O.C. di Oncologia Medica ed Ematologia | Naples | Italy | 80131 | |
| 25 | .O.U. Pisana-Ospedale Santa Chiara, U.O. di Oncologia Medica 2 | Pisa | Italy | 56126 | |
| 26 | AMC Academisch Medisch Centrum Medische Oncologie | Amsterdam | Netherlands | 1105 AZ | |
| 27 | Amphia Ziekenhuis, Interne Geneeskunde/Oncologie, Langendijk 75 | Breda | Netherlands | 4819 EV | |
| 28 | Catharina Ziekenhuis, Interne Geneeskunde/Oncologie | Eindhoven | Netherlands | 5623 EJ | |
| 29 | Martini Ziekenhuizen, Interne Geneeskunde/Oncologie, Van Swietenplein 1 | Groningen | Netherlands | 9728 NT | |
| 30 | Tergooi Hilversum, Medische Oncologie, Van Riebeeckweg 212 | Hilversum | Netherlands | 1213 XZ | |
| 31 | Zuyderland Medisch Centrum Interne Geneeskunde | Sittard | Netherlands | 6162 BG | |
| 32 | Sint Antonius Ziekenhuis Interne Geneeskunde/Oncologie | Utrecht | Netherlands | 3543 CX | |
| 33 | VieCurie Medisch Centrum, Interne Geneeskunde, Tegelseweg 210 | Venlo | Netherlands | 5912 BL | |
| 34 | Isala Klinieken, Medische oncologie, Dokter Van Heeweg 2 | Zwolle | Netherlands | 8025 AB | |
| 35 | Szpitale Pomorskie Sp. z o.o. Oddzial Onkologii i Radioterapii | Gdynia | Poland | 81-519 | |
| 36 | SP ZOZ Szpital Uniwersytecki w Krakowie Oddzial Kliniczny Onkologii | Krakow | Poland | 31-531 | |
| 37 | Centralny Szpital Kliniczny MSW Klinika Onkologii i Hematologii | Warszawa | Poland | 02-507 | |
| 38 | NZOZ MAGODENT Oddzial Onkologii Klinicznej / Chemioterapii | Warszawa | Poland | 04-125 | |
| 39 | Russian Cancer Research Center n.a. NN Blokhin | Moscow | Russian Federation | 115478 | |
| 40 | Moscow City Oncology Hospital # 62, Chemotherapy | Moscow | Russian Federation | 143423 | |
| 41 | Russian Cancer Research Center n.a. NN Blokhin, Department of Research for New Antitumour Medicines | Moscow | Russian Federation | ||
| 42 | Scientific Centre for Specialized Medical Care (oncological) | St Petersburg | Russian Federation | 197758 | |
| 43 | Hospital Valle de Hebrón, Servicio de Oncología | Barcelona | Spain | 08035 | |
| 44 | Hospital Universitario Reina Sofia, Deparatmento Oncología Médica | Cordoba | Spain | 14004 | |
| 45 | Instituto Catalan De Oncología, Hospitalet de Llobregat | Hospitalet de Llobregat | Spain | 08908 | |
| 46 | Hospital Universitario Gregorio Maranon | Madrid | Spain | 28007 | |
| 47 | Hospital Ramón y Cajal, Oncología Médica | Madrid | Spain | 28034 | |
| 48 | H. Universitario La Paz Oncología Médica | Madrid | Spain | 28046 | |
| 49 | Hospital General Universitario, Oncología Médica | Malaga | Spain | 29010 | |
| 50 | Complejo Hospitalario de Navarra, Oncología Médica | Pamplona | Spain | 31008 | |
| 51 | The Beatson West of Scotland Cancer Centre GI cancers | Glasgow | United Kingdom | G12 0YN | |
| 52 | Leicester Royal Infirmary, The HOPE Clinical Trials Unit | Leicester | United Kingdom | LE1 5WW | |
| 53 | Hammersmith Hospital | London | United Kingdom | W12 0HS | |
| 54 | Imperial healthcare NHS Trust Charing Cross Hospital | London | United Kingdom | W6 8RF | |
| 55 | Christie Hospital NHS Foundation Trust, GI & Endocrine | Manchester | United Kingdom | M20 4BX | |
| 56 | Mount Vernon Hospital Department of Oncology | Northwood | United Kingdom | HA6 2RN | |
| 57 | Southampton General Hospital | Southampton | United Kingdom | SO16 6YD |
Sponsors and Collaborators
- Institut de Recherches Internationales Servier
- ADIR, a Servier Group company
Investigators
- Principal Investigator: Eric Van Custem, Prof, Leuven Cancer Institute, University Hospitals Leuven
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Institut de Recherches Internationales Servier
ClinicalTrials.gov Identifier:
NCT02743221
Other Study ID Numbers:
- CL2-95005-002
- 2015-004544-18
First Posted:
Apr 19, 2016
Last Update Posted:
Oct 5, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
Yes
Keywords provided by Institut de Recherches Internationales Servier
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 154 patients were randomized among whom one was deemed ineligible after randomization. |
| Arm/Group Title | Trifluridine/Tipiracil + Bevacizumab | Capecitabine + Bevacizumab |
|---|---|---|
| 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 | 21 | 17 |
| NOT COMPLETED | 56 | 60 |
Baseline Characteristics
| Arm/Group Title | Trifluridine/Tipiracil + Bevacizumab | Capecitabine + Bevacizumab | Total |
|---|---|---|---|
| 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 Participants | 77 | 77 | 154 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
20
26%
|
16
20.8%
|
36
23.4%
|
| >=65 years |
57
74%
|
61
79.2%
|
118
76.6%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
69.8
(10.2)
|
72.8
(11.0)
|
71.3
(10.7)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
37
48.1%
|
29
37.7%
|
66
42.9%
|
| Male |
40
51.9%
|
48
62.3%
|
88
57.1%
|
| Race/Ethnicity, Customized (Count of 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%
|
Outcome Measures
| Title | Progression Free Survival (PFS) |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 77 | 76 |
| Median (95% Confidence Interval) [months] |
9.2
|
7.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Trifluridine/Tipiracil + Bevacizumab, Capecitabine + Bevacizumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | This was a non-comparative study. | |
| Statistical Test of Hypothesis | p-Value | 0.09 |
| Comments | ||
| 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 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Response Rate (ORR) |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS |
| Arm/Group Title | Trifluridine/Tipiracil + Bevacizumab | Capecitabine + Bevacizumab |
|---|---|---|
| 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. |
| Measure Participants | 77 | 76 |
| Count of Participants [Participants] |
26
33.8%
|
23
29.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Trifluridine/Tipiracil + Bevacizumab, Capecitabine + Bevacizumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.73 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Duration of Response (DR) |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 74 | 73 |
| Median (80% Confidence Interval) [months] |
7.9
|
9.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Trifluridine/Tipiracil + Bevacizumab, Capecitabine + Bevacizumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.16 | |
| Confidence Interval |
(2-Sided) 95% 0.49 to 2.74 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Disease Control Rate (DCR) |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS |
| Arm/Group Title | Trifluridine/Tipiracil + Bevacizumab | Capecitabine + Bevacizumab |
|---|---|---|
| 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. |
| Measure Participants | 77 | 76 |
| Count of Participants [Participants] |
66
85.7%
|
59
76.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Trifluridine/Tipiracil + Bevacizumab, Capecitabine + Bevacizumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.22 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Overall Survival (OS) |
|---|---|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS |
| Arm/Group Title | Trifluridine/Tipiracil + Bevacizumab | Capecitabine + Bevacizumab |
|---|---|---|
| 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. |
| Measure Participants | 77 | 76 |
| Median (80% Confidence Interval) [months] |
18.0
|
16.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Trifluridine/Tipiracil + Bevacizumab, Capecitabine + Bevacizumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.04 |
| Comments | ||
| Method | Cox proportional hazard model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.56 | |
| Confidence Interval |
(2-Sided) 95% 0.32 to 0.98 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| 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 | ||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 22/77 (28.6%) | 33/76 (43.4%) | ||
Serious Adverse Events |
||||
| Trifluridine/Tipiracil + Bevacizumab | Capecitabine + Bevacizumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 42/77 (54.5%) | 44/76 (57.9%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 3/77 (3.9%) | 4 | 0/76 (0%) | 0 |
| Febrile neutropenia | 3/77 (3.9%) | 3 | 3/76 (3.9%) | 3 |
| Haemorrhagic anaemia | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Neutropenia | 4/77 (5.2%) | 5 | 0/76 (0%) | 0 |
| Cardiac disorders | ||||
| Acute coronary syndrome | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Atrial fibrillation | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Atrioventricular block complete | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Mitral valve incompetence | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Myocardial infarction | 2/77 (2.6%) | 2 | 0/76 (0%) | 0 |
| Supraventricular tachycardia | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Ventricular tachycardia | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Endocrine disorders | ||||
| Hypothyroidism | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Gastrointestinal disorders | ||||
| Ascites | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Diarrhoea | 2/77 (2.6%) | 2 | 5/76 (6.6%) | 5 |
| Enterocutaneous fistula | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Gastrointestinal angiodysplasia haemorrhagic | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Haematemesis | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Ileus paralytic | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Intestinal obstruction | 2/77 (2.6%) | 2 | 1/76 (1.3%) | 1 |
| Intestinal perforation | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Large intestinal obstruction | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Large intestine perforation | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Malignant bowel obstruction | 0/77 (0%) | 0 | 2/76 (2.6%) | 2 |
| Nausea | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Pancreatitis | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Proctalgia | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Small intestinal obstruction | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Umbilical hernia | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Vomiting | 2/77 (2.6%) | 4 | 1/76 (1.3%) | 1 |
| General disorders | ||||
| Death | 0/77 (0%) | 0 | 2/76 (2.6%) | 2 |
| General physical health deterioration | 0/77 (0%) | 0 | 2/76 (2.6%) | 2 |
| Mucosal dryness | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Multiple organ dysfunction syndrome | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Non-cardiac chest pain | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Hepatobiliary disorders | ||||
| Cholecystitis | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Cholecystitis acute | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Cholelithiasis | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Hepatic failure | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Hepatotoxicity | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Infections and infestations | ||||
| Abdominal abscess | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Arthritis bacterial | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Biliary sepsis | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Catheter site infection | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Clostridium difficile colitis | 2/77 (2.6%) | 2 | 0/76 (0%) | 0 |
| Device related sepsis | 2/77 (2.6%) | 2 | 0/76 (0%) | 0 |
| Escherichia urinary tract infection | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Neutropenic sepsis | 2/77 (2.6%) | 2 | 0/76 (0%) | 0 |
| Peritonitis | 2/77 (2.6%) | 2 | 0/76 (0%) | 0 |
| Pneumonia | 3/77 (3.9%) | 3 | 1/76 (1.3%) | 1 |
| Pneumonia toxoplasmal | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Septic shock | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Wound infection | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Fall | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Gastrointestinal stoma complication | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Postoperative wound complication | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Thoracic vertebral fracture | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Investigations | ||||
| Blood bilirubin increased | 0/77 (0%) | 0 | 2/76 (2.6%) | 2 |
| Blood calcium decreased | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Blood creatine phosphokinase increased | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Blood magnesium decreased | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Blood phosphorus decreased | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Blood potassium decreased | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Neutrophil count decreased | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Troponin T increased | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| White blood cell count decreased | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 3/77 (3.9%) | 3 | 5/76 (6.6%) | 5 |
| Fluid overload | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Hyperkalaemia | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Hyponatraemia | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Muscular weakness | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Cancer pain | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Malignant neoplasm progression | 8/77 (10.4%) | 8 | 16/76 (21.1%) | 16 |
| Metastases to peritoneum | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Metastases to spine | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Skin cancer | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Nervous system disorders | ||||
| Aphasia | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Cauda equina syndrome | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Ischaemic stroke | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Memory impairment | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Seizure | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Syncope | 1/77 (1.3%) | 3 | 2/76 (2.6%) | 2 |
| Psychiatric disorders | ||||
| Depressed mood | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Depression | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 2/77 (2.6%) | 3 | 2/76 (2.6%) | 2 |
| Renal failure | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Reproductive system and breast disorders | ||||
| Female genital tract fistula | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory distress syndrome | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Dyspnoea | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Dyspnoea exertional | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Hypoxia | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Pleural effusion | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Pneumonia aspiration | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Pulmonary congestion | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Pulmonary embolism | 3/77 (3.9%) | 3 | 3/76 (3.9%) | 4 |
| Pulmonary oedema | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Diabetic foot | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Palmar-plantar erythrodysaesthesia syndrome | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Rash erythematous | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Stevens-Johnson syndrome | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Vascular disorders | ||||
| Deep vein thrombosis | 0/77 (0%) | 0 | 4/76 (5.3%) | 4 |
| Hypertension | 3/77 (3.9%) | 3 | 0/76 (0%) | 0 |
| Hypotension | 1/77 (1.3%) | 2 | 2/76 (2.6%) | 2 |
| Thrombophlebitis superficial | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Trifluridine/Tipiracil + Bevacizumab | Capecitabine + Bevacizumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 75/77 (97.4%) | 69/76 (90.8%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 22/77 (28.6%) | 31 | 5/76 (6.6%) | 7 |
| Anaemia of chronic disease | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Anaemia of malignant disease | 5/77 (6.5%) | 5 | 1/76 (1.3%) | 2 |
| Febrile neutropenia | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Haemolytic anaemia | 2/77 (2.6%) | 2 | 0/76 (0%) | 0 |
| Leukopenia | 6/77 (7.8%) | 9 | 2/76 (2.6%) | 5 |
| Neutropenia | 40/77 (51.9%) | 181 | 5/76 (6.6%) | 5 |
| Spontaneous haematoma | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Thrombocytopenia | 11/77 (14.3%) | 22 | 4/76 (5.3%) | 5 |
| Thrombocytosis | 4/77 (5.2%) | 8 | 0/76 (0%) | 0 |
| Cardiac disorders | ||||
| Angina pectoris | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Aortic valve thickening | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Arrhythmia | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Atrial fibrillation | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Bundle branch block right | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Supraventricular extrasystoles | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Tachycardia | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Ear and labyrinth disorders | ||||
| Ear pain | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Vertigo | 2/77 (2.6%) | 2 | 0/76 (0%) | 0 |
| Eye disorders | ||||
| Dry eye | 1/77 (1.3%) | 2 | 0/76 (0%) | 0 |
| Eye pain | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Eye pruritus | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Lacrimation increased | 0/77 (0%) | 0 | 4/76 (5.3%) | 5 |
| Vision blurred | 1/77 (1.3%) | 1 | 2/76 (2.6%) | 2 |
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Abdominal pain | 9/77 (11.7%) | 18 | 6/76 (7.9%) | 7 |
| Abdominal pain lower | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Abdominal pain upper | 2/77 (2.6%) | 3 | 2/76 (2.6%) | 3 |
| Anal fissure | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Anal inflammation | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Aphthous ulcer | 2/77 (2.6%) | 2 | 1/76 (1.3%) | 1 |
| Chronic gastritis | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Constipation | 13/77 (16.9%) | 21 | 15/76 (19.7%) | 17 |
| Diarrhoea | 40/77 (51.9%) | 91 | 31/76 (40.8%) | 64 |
| Dry mouth | 2/77 (2.6%) | 2 | 6/76 (7.9%) | 7 |
| Dyschezia | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Dyspepsia | 6/77 (7.8%) | 7 | 2/76 (2.6%) | 2 |
| Dysphagia | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Eructation | 2/77 (2.6%) | 3 | 1/76 (1.3%) | 1 |
| Gastrointestinal motility disorder | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/77 (0%) | 0 | 2/76 (2.6%) | 2 |
| Gingival bleeding | 3/77 (3.9%) | 4 | 1/76 (1.3%) | 1 |
| Haemorrhoids | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Lip dry | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Lip pain | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Lip swelling | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Mesenteric vein thrombosis | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Mouth ulceration | 2/77 (2.6%) | 2 | 0/76 (0%) | 0 |
| Nausea | 36/77 (46.8%) | 84 | 13/76 (17.1%) | 23 |
| Oral mucosa erosion | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Oral pain | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Pancreatitis chronic | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Periodontal disease | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Proctalgia | 3/77 (3.9%) | 6 | 3/76 (3.9%) | 3 |
| Proctitis | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Rectal discharge | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Rectal haemorrhage | 0/77 (0%) | 0 | 2/76 (2.6%) | 2 |
| Stomatitis | 13/77 (16.9%) | 18 | 16/76 (21.1%) | 29 |
| Stomatitis haemorrhagic | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Toothache | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Vomiting | 22/77 (28.6%) | 44 | 8/76 (10.5%) | 8 |
| General disorders | ||||
| Asthenia | 14/77 (18.2%) | 19 | 17/76 (22.4%) | 22 |
| Chest discomfort | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Chills | 1/77 (1.3%) | 1 | 3/76 (3.9%) | 3 |
| Discomfort | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Early satiety | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Fatigue | 28/77 (36.4%) | 45 | 23/76 (30.3%) | 35 |
| Feeling hot | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Impaired healing | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Influenza like illness | 3/77 (3.9%) | 3 | 3/76 (3.9%) | 3 |
| Injection site haematoma | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Local swelling | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Malaise | 1/77 (1.3%) | 2 | 0/76 (0%) | 0 |
| Mucosal inflammation | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Non-cardiac chest pain | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Oedema peripheral | 3/77 (3.9%) | 4 | 3/76 (3.9%) | 3 |
| Pain | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Puncture site pain | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Pyrexia | 5/77 (6.5%) | 5 | 4/76 (5.3%) | 5 |
| Tenderness | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Xerosis | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Hepatobiliary disorders | ||||
| Cholecystitis chronic | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Hepatomegaly | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Hyperbilirubinaemia | 1/77 (1.3%) | 1 | 5/76 (6.6%) | 7 |
| Infections and infestations | ||||
| Bronchitis | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Conjunctivitis | 1/77 (1.3%) | 2 | 3/76 (3.9%) | 3 |
| Cystitis | 0/77 (0%) | 0 | 2/76 (2.6%) | 2 |
| Escherichia urinary tract infection | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Folliculitis | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Furuncle | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Gastroenteritis | 2/77 (2.6%) | 2 | 0/76 (0%) | 0 |
| Gastrointestinal viral infection | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Gingivitis | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Hepatic cyst infection | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Influenza | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Labyrinthitis | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Lower respiratory tract infection bacterial | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Lung infection | 1/77 (1.3%) | 2 | 1/76 (1.3%) | 1 |
| Oral candidiasis | 1/77 (1.3%) | 1 | 3/76 (3.9%) | 4 |
| Oral fungal infection | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Oral herpes | 1/77 (1.3%) | 1 | 4/76 (5.3%) | 4 |
| Oral infection | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Periumbilical abscess | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Pneumonia | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Pneumonia bacterial | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Rhinitis | 4/77 (5.2%) | 4 | 1/76 (1.3%) | 1 |
| Skin candida | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Tooth abscess | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Upper respiratory tract infection | 7/77 (9.1%) | 8 | 2/76 (2.6%) | 2 |
| Urinary tract infection | 7/77 (9.1%) | 8 | 5/76 (6.6%) | 6 |
| Urinary tract infection bacterial | 1/77 (1.3%) | 1 | 2/76 (2.6%) | 3 |
| Viral upper respiratory tract infection | 8/77 (10.4%) | 9 | 5/76 (6.6%) | 5 |
| Vulvovaginal candidiasis | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Abdominal wall wound | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Accidental overdose | 0/77 (0%) | 0 | 2/76 (2.6%) | 5 |
| Clavicle fracture | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Contusion | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Fall | 5/77 (6.5%) | 5 | 4/76 (5.3%) | 6 |
| Hand fracture | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Infusion related reaction | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Muscle strain | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Procedural pain | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Skin wound | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Stoma site haemorrhage | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Stoma site irritation | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Stoma site pain | 2/77 (2.6%) | 2 | 0/76 (0%) | 0 |
| Traumatic haematoma | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Wound | 0/77 (0%) | 0 | 2/76 (2.6%) | 2 |
| Wound complication | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Investigations | ||||
| Activated partial thromboplastin time prolonged | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Alanine aminotransferase increased | 9/77 (11.7%) | 11 | 2/76 (2.6%) | 2 |
| Aspartate aminotransferase increased | 7/77 (9.1%) | 8 | 2/76 (2.6%) | 2 |
| Bilirubin conjugated increased | 1/77 (1.3%) | 2 | 1/76 (1.3%) | 1 |
| Blood albumin decreased | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Blood alkaline phosphatase increased | 3/77 (3.9%) | 3 | 2/76 (2.6%) | 2 |
| Blood bilirubin increased | 6/77 (7.8%) | 18 | 8/76 (10.5%) | 13 |
| Blood bilirubin unconjugated increased | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Blood cholesterol increased | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Blood creatinine increased | 3/77 (3.9%) | 5 | 1/76 (1.3%) | 1 |
| Blood glucose increased | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Blood lactate dehydrogenase decreased | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Blood lactate dehydrogenase increased | 1/77 (1.3%) | 5 | 4/76 (5.3%) | 5 |
| Blood phosphorus increased | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Blood potassium decreased | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Blood potassium increased | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Blood pressure increased | 2/77 (2.6%) | 3 | 0/76 (0%) | 0 |
| Blood urea increased | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Blood urine present | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Carcinoembryonic antigen increased | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Creatinine renal clearance decreased | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Eosinophil count decreased | 2/77 (2.6%) | 2 | 0/76 (0%) | 0 |
| Gamma-glutamyltransferase increased | 6/77 (7.8%) | 6 | 2/76 (2.6%) | 3 |
| Glomerular filtration rate decreased | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Heart rate irregular | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| International normalised ratio increased | 1/77 (1.3%) | 1 | 2/76 (2.6%) | 2 |
| Lymphocyte count decreased | 4/77 (5.2%) | 7 | 1/76 (1.3%) | 2 |
| Monocyte count decreased | 2/77 (2.6%) | 2 | 0/76 (0%) | 0 |
| Neutrophil count decreased | 18/77 (23.4%) | 90 | 1/76 (1.3%) | 1 |
| Neutrophil count increased | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Platelet count decreased | 7/77 (9.1%) | 22 | 3/76 (3.9%) | 5 |
| Platelet count increased | 2/77 (2.6%) | 3 | 0/76 (0%) | 0 |
| Weight decreased | 9/77 (11.7%) | 12 | 6/76 (7.9%) | 7 |
| Weight increased | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| White blood cell count decreased | 15/77 (19.5%) | 37 | 1/76 (1.3%) | 1 |
| White blood cell count increased | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 29/77 (37.7%) | 46 | 15/76 (19.7%) | 23 |
| Gout | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Hypercalcaemia | 2/77 (2.6%) | 2 | 0/76 (0%) | 0 |
| Hyperglycaemia | 3/77 (3.9%) | 6 | 2/76 (2.6%) | 2 |
| Hyperkalaemia | 4/77 (5.2%) | 5 | 0/76 (0%) | 0 |
| Hyperphosphataemia | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Hypertriglyceridaemia | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Hypoalbuminaemia | 4/77 (5.2%) | 4 | 2/76 (2.6%) | 2 |
| Hypocalcaemia | 2/77 (2.6%) | 4 | 1/76 (1.3%) | 1 |
| Hypochloraemia | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Hypoglycaemia | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Hypokalaemia | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Hypomagnesaemia | 3/77 (3.9%) | 3 | 1/76 (1.3%) | 1 |
| Hyponatraemia | 3/77 (3.9%) | 3 | 0/76 (0%) | 0 |
| Hypophosphataemia | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Metabolic acidosis | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 6/77 (7.8%) | 8 | 3/76 (3.9%) | 3 |
| Back pain | 6/77 (7.8%) | 6 | 7/76 (9.2%) | 7 |
| Bursitis | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Coccydynia | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Intervertebral disc compression | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Joint swelling | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Mobility decreased | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Muscle spasms | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Muscular weakness | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Musculoskeletal chest pain | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Musculoskeletal pain | 2/77 (2.6%) | 2 | 1/76 (1.3%) | 1 |
| Myalgia | 1/77 (1.3%) | 2 | 4/76 (5.3%) | 5 |
| Neck pain | 2/77 (2.6%) | 2 | 1/76 (1.3%) | 1 |
| Osteoarthritis | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Pain in extremity | 4/77 (5.2%) | 4 | 1/76 (1.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Cancer pain | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Malignant neoplasm progression | 9/77 (11.7%) | 9 | 3/76 (3.9%) | 3 |
| Nervous system disorders | ||||
| Amnesia | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Aphonia | 0/77 (0%) | 0 | 2/76 (2.6%) | 2 |
| Balance disorder | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Dizziness | 5/77 (6.5%) | 7 | 8/76 (10.5%) | 10 |
| Dizziness exertional | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Dizziness postural | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Dysarthria | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Dysgeusia | 7/77 (9.1%) | 8 | 8/76 (10.5%) | 8 |
| Essential tremor | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Headache | 7/77 (9.1%) | 13 | 4/76 (5.3%) | 4 |
| Hyperaesthesia | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Hypoaesthesia | 0/77 (0%) | 0 | 1/76 (1.3%) | 2 |
| Memory impairment | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Neuralgia | 1/77 (1.3%) | 2 | 0/76 (0%) | 0 |
| Neuropathy peripheral | 0/77 (0%) | 0 | 3/76 (3.9%) | 3 |
| Neurotoxicity | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Orthostatic intolerance | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Paraesthesia | 1/77 (1.3%) | 1 | 2/76 (2.6%) | 2 |
| Peripheral sensory neuropathy | 2/77 (2.6%) | 2 | 1/76 (1.3%) | 1 |
| Presyncope | 1/77 (1.3%) | 1 | 2/76 (2.6%) | 3 |
| Restless legs syndrome | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Sciatica | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Somnolence | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Tremor | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Psychiatric disorders | ||||
| Anxiety | 0/77 (0%) | 0 | 2/76 (2.6%) | 2 |
| Confusional state | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 2 |
| Depression | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Disorientation | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Insomnia | 6/77 (7.8%) | 6 | 1/76 (1.3%) | 1 |
| Mood altered | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Restlessness | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Stress | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Renal and urinary disorders | ||||
| Anuria | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Dysuria | 0/77 (0%) | 0 | 3/76 (3.9%) | 3 |
| Glycosuria | 0/77 (0%) | 0 | 1/76 (1.3%) | 2 |
| Haematuria | 1/77 (1.3%) | 1 | 2/76 (2.6%) | 2 |
| Lower urinary tract symptoms | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Micturition urgency | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Nocturia | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Pollakiuria | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Proteinuria | 5/77 (6.5%) | 6 | 4/76 (5.3%) | 5 |
| Urinary incontinence | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Urinary retention | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Oedema genital | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Prostatitis | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Catarrh | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Chronic obstructive pulmonary disease | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Cough | 2/77 (2.6%) | 2 | 6/76 (7.9%) | 6 |
| Dysphonia | 4/77 (5.2%) | 5 | 1/76 (1.3%) | 1 |
| Dyspnoea | 5/77 (6.5%) | 5 | 8/76 (10.5%) | 11 |
| Dyspnoea exertional | 2/77 (2.6%) | 2 | 2/76 (2.6%) | 2 |
| Epistaxis | 4/77 (5.2%) | 6 | 4/76 (5.3%) | 6 |
| Hiccups | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Nasal congestion | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Nasal dryness | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Nasal inflammation | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Oropharyngeal pain | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Pneumonia aspiration | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Productive cough | 1/77 (1.3%) | 1 | 3/76 (3.9%) | 3 |
| Pulmonary mass | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Pulmonary pain | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Rhinalgia | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Rhinorrhoea | 0/77 (0%) | 0 | 3/76 (3.9%) | 3 |
| Sneezing | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 17/77 (22.1%) | 17 | 0/76 (0%) | 0 |
| Drug eruption | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Dry skin | 4/77 (5.2%) | 4 | 4/76 (5.3%) | 4 |
| Erythema | 0/77 (0%) | 0 | 2/76 (2.6%) | 2 |
| Hyperhidrosis | 0/77 (0%) | 0 | 2/76 (2.6%) | 2 |
| Nail discolouration | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Nail disorder | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Night sweats | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Onychalgia | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Onychomadesis | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Palmar-plantar erythrodysaesthesia syndrome | 3/77 (3.9%) | 4 | 39/76 (51.3%) | 49 |
| Pruritus | 2/77 (2.6%) | 3 | 1/76 (1.3%) | 1 |
| Rash | 1/77 (1.3%) | 1 | 1/76 (1.3%) | 1 |
| Rash erythematous | 0/77 (0%) | 0 | 2/76 (2.6%) | 2 |
| Skin discolouration | 0/77 (0%) | 0 | 1/76 (1.3%) | 2 |
| Skin fissures | 1/77 (1.3%) | 1 | 0/76 (0%) | 0 |
| Skin hyperpigmentation | 0/77 (0%) | 0 | 2/76 (2.6%) | 2 |
| Vascular disorders | ||||
| Deep vein thrombosis | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Hot flush | 0/77 (0%) | 0 | 1/76 (1.3%) | 1 |
| Hypertension | 9/77 (11.7%) | 10 | 10/76 (13.2%) | 12 |
| Hypotension | 4/77 (5.2%) | 5 | 1/76 (1.3%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
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
| Name/Title | Dr Patrick Therasse |
|---|---|
| Organization | Institut de Recherches Internationales Servier (I.R.I.S.) |
| Phone | +33 1 55 72 43 47 |
| patrick.therasse@servier.com |
Responsible Party:
Institut de Recherches Internationales Servier
ClinicalTrials.gov Identifier:
NCT02743221
Other Study ID Numbers:
- CL2-95005-002
- 2015-004544-18
First Posted:
Apr 19, 2016
Last Update Posted:
Oct 5, 2021
Last Verified:
Oct 1, 2021