A Study of Trastuzumab Emtansine (T-DM1) Plus Pertuzumab/Pertuzumab Placebo Versus Trastuzumab [Herceptin] Plus a Taxane in Participants With Metastatic Breast Cancer (MARIANNE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT01120184

Recruitment Status : Completed

First Posted : May 10, 2010

Results First Posted : February 23, 2017

Last Update Posted : November 7, 2017

Sponsor:

Collaborator:

Genentech, Inc.

Information provided by (Responsible Party):

Hoffmann-La Roche

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Breast Cancer
Interventions:	Drug: docetaxel Drug: paclitaxel Drug: pertuzumab Drug: pertuzumab-placebo Drug: trastuzumab [Herceptin] Drug: trastuzumab emtansine

Participant Flow

Hide Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Trastuzumab + Taxane	Participants received trastuzumab plus either docetaxel or paclitaxel. The regimen was chosen at the investigator's discretion. Option 1: trastuzumab 8 mg/kg via IV infusion on Day 1 of Cycle 1, then 6 mg/kg IV on Day 1 of each subsequent 3-week cycle; plus a minimum of 6 cycles with docetaxel 75 or 100 mg/m^2 IV on Day 1 of each 3-week cycle. Option 2: trastuzumab 4 mg/kg IV on Day 1 of Cycle 1, then 2 mg/kg IV weekly beginning on Day 8 of Cycle 1; plus a minimum of 18 weeks with paclitaxel 80 mg/m^2 IV weekly. Treatment continued until disease progression, unacceptable toxicity, or study termination. If trastuzumab or docetaxel were discontinued for toxicity, the other agent could be continued as monotherapy.
Trastuzumab Emtansine + Placebo	Participants received trastuzumab emtansine plus pertuzumab-placebo. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the placebo IV infusion, on Day 1 of each 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.
Trastuzumab Emtansine + Pertuzumab	Participants received trastuzumab emtansine plus pertuzumab. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the pertuzumab IV infusion, on Day 1 of each 3-week cycle. Pertuzumab was given as 840 mg IV on Day 1 of Cycle 1, then 420 mg IV on Day 1 of each subsequent 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.

Participant Flow: Overall Study

	Trastuzumab + Taxane	Trastuzumab Emtansine + Placebo	Trastuzumab Emtansine + Pertuzumab
STARTED	365	367	363
Treated	355	365	360
COMPLETED	0	0	0
NOT COMPLETED	365	367	363
Adverse Event	0	1	0
Lost to Follow-up	13	13	11
Physician Decision	9	1	3
Reason not Specified	8	3	12
Sponsor Decision to Terminate Study	133	144	143
Subject/ Guardian Decision to Withdraw	32	29	25
Death	170	176	169

Baseline Characteristics

Hide Baseline Characteristics

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: All participants randomized in the study.

Reporting Groups

	Description
Trastuzumab + Taxane	Participants received trastuzumab plus either docetaxel or paclitaxel. The regimen was chosen at the investigator's discretion. Option 1: trastuzumab 8 mg/kg via IV infusion on Day 1 of Cycle 1, then 6 mg/kg IV on Day 1 of each subsequent 3-week cycle; plus a minimum of 6 cycles with docetaxel 75 or 100 mg/m^2 IV on Day 1 of each 3-week cycle. Option 2: trastuzumab 4 mg/kg IV on Day 1 of Cycle 1, then 2 mg/kg IV weekly beginning on Day 8 of Cycle 1; plus a minimum of 18 weeks with paclitaxel 80 mg/m^2 IV weekly. Treatment continued until disease progression, unacceptable toxicity, or study termination. If trastuzumab or docetaxel were discontinued for toxicity, the other agent could be continued as monotherapy.
Trastuzumab Emtansine + Placebo	Participants received trastuzumab emtansine plus pertuzumab-placebo. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the placebo IV infusion, on Day 1 of each 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.
Trastuzumab Emtansine + Pertuzumab	Participants received trastuzumab emtansine plus pertuzumab. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the pertuzumab IV infusion, on Day 1 of each 3-week cycle. Pertuzumab was given as 840 mg IV on Day 1 of Cycle 1, then 420 mg IV on Day 1 of each subsequent 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.
Total	Total of all reporting groups

Baseline Measures

	Trastuzumab + Taxane	Trastuzumab Emtansine + Placebo	Trastuzumab Emtansine + Pertuzumab	Total
Overall Participants Analyzed [Units: Participants]	365	367	363	1095

Age [Units: Years] Mean (Standard Deviation)	54.2 (11.3)	52.6 (11.4)	52.2 (12.0)	53.0 (11.6)

Sex: Female, Male [Units: Participants] Count of Participants
Female	362 99.2%	365 99.5%	361 99.4%	1088 99.4%
Male	3 0.8%	2 0.5%	2 0.6%	7 0.6%

Outcome Measures

Show All Outcome Measures

1. Primary:

Percentage of Participants With Death or Disease Progression According to Independent Review Facility (IRF) Assessment [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

Show Outcome Measure 1

2. Primary:

Progression-Free Survival (PFS) According to IRF Assessment [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

Show Outcome Measure 2

3. Secondary:

Percentage of Participants Who Died Prior to Clinical Cutoff [ Time Frame: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination) ]

Show Outcome Measure 3

4. Secondary:

Overall Survival (OS) at Clinical Cutoff [ Time Frame: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination) ]

Show Outcome Measure 4

5. Secondary:

Percentage of Participants With Death or Disease Progression According to Investigator Assessment [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

Show Outcome Measure 5

6. Secondary:

PFS According to Investigator Assessment [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

Show Outcome Measure 6

7. Secondary:

Percentage of Participants Experiencing Treatment Failure [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 ]

Show Outcome Measure 7

8. Secondary:

Time to Treatment Failure (TTF) [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 ]

Show Outcome Measure 8

9. Secondary:

One-Year Survival Rate [ Time Frame: From randomization until 1 year ]

Show Outcome Measure 9

10. Secondary:

Percentage of Participants With Grade ≥3 Adverse Events [ Time Frame: Up to 50 months from randomization until clinical cutoff of 16-Sept-2014 (continuously until 28 days after last dose ]

Show Outcome Measure 10

11. Secondary:

Percentage of Participants Who Died at 2 Years [ Time Frame: From randomization until 2 years ]

Show Outcome Measure 11

12. Secondary:

Overall Survival Truncated at 2 Years [ Time Frame: From randomization until 2 years ]

Show Outcome Measure 12

13. Secondary:

Percentage of Participants With Grade 5 Adverse Events [ Time Frame: Up to 50 months from randomization until clinical cutoff of 16-Sept-2014 (continuously until 28 days after last dose) ]

Show Outcome Measure 13

14. Secondary:

Percentage of Participants With Grade 3-4 Laboratory Parameters [ Time Frame: Day 1, 8, and 15 of Cycle 1–3 and on Day 1 of each subsequent cycle up to 50 months from randomization until clinical cutoff of 16-Sept-2014 ]

Show Outcome Measure 14

15. Secondary:

Percentage of Participants With Decline of ≥2 Points From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status [ Time Frame: Baseline, Day 1 of every Cycle up to Clinical Data Cut (up to 48 months) ]

Show Outcome Measure 15

16. Secondary:

Hospitalization Days [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 ]

Show Outcome Measure 16

17. Secondary:

Percentage of Participants With Hospitalization [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 ]

Show Outcome Measure 17

18. Secondary:

Percentage of Participants With Objective Response According to IRF Assessment [ Time Frame: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

Show Outcome Measure 18

19. Secondary:

Percentage of Participants With Objective Response According to Investigator Assessment [ Time Frame: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

Show Outcome Measure 19

20. Secondary:

Duration of Response According to IRF Assessment [ Time Frame: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

Show Outcome Measure 20

21. Secondary:

Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD) According to IRF Assessment [ Time Frame: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

Show Outcome Measure 21

22. Secondary:

Percentage of Participants Experiencing a Clinically Significant Increase in Taxane-Related Treatment Symptoms as Measured by Taxane Subscale of the Functional Assessment of Cancer Therapy (FACT) Taxane (FACT-TaxS) Score [ Time Frame: Up to 39 months from randomization until clinical cutoff of 16-Sept-2014 (at Baseline, on Day 1 of Cycles 2 to 8 and every even-numbered cycle thereafter and/or up to 42 days after last dose) ]

Show Outcome Measure 22

23. Secondary:

Percentage of Participants Reporting Nausea According to the Relevant Single Items of The FACT Colorectal Cancel (FACT-C) Module [ Time Frame: At Baseline, Day 8 of Cycle 1, and Days 1 and 8 of Cycle 2 ]

Show Outcome Measure 23

24. Secondary:

Percentage of Participants Reporting Diarrhea According to the Relevant Single Items of The FACT-C Module [ Time Frame: At Baseline, Day 8 of Cycle 1, and Days 1 and 8 of Cycle 2 ]

Show Outcome Measure 24

25. Secondary:

Percentage of Participants With a Clinically Significant Deterioration in Health Related Quality of Life (HRQoL) as Measured by FACT Breast (FACT-B) Trial Outcome Index-Physical Function Breast (TOI-PFB) Score [ Time Frame: Up to 39 months from randomization until clinical cutoff of 16-Sept-2014 (at Baseline, on Day 1 of Cycles 2 to 8 and every even-numbered cycle thereafter and/or up to 42 days after last dose) ]

Show Outcome Measure 25

26. Secondary:

Time to Deterioration in HRQoL as Assessed by FACT-B TOI-PFB Score [ Time Frame: Baseline up to 39 months from randomization until clinical cutoff of 16-Sept-2014 ]

Show Outcome Measure 26

27. Secondary:

Change From Baseline in Rotterdam Symptom Checklist (RSCL) Activity Level Scale Score [ Time Frame: Baseline, Cycle 7 (Week 18) ]

Show Outcome Measure 27

28. Secondary:

Change From Baseline in Work Productivity According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score [ Time Frame: Baseline, Cycle 7 (Week 18) ]

Show Outcome Measure 28

29. Secondary:

Change From Baseline in Activity Impairment According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score [ Time Frame: Baseline, Cycle 7 (Week 18) ]

Show Outcome Measure 29

30. Secondary:

Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With High Human Epidermal Growth Factor Receptor 2 (HER2) Messenger Ribonucleic Acid (mRNA) Levels [ Time Frame: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

Show Outcome Measure 30

31. Secondary:

Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With Low HER2 mRNA Levels [ Time Frame: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

Show Outcome Measure 31

32. Secondary:

Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With High HER2 mRNA Levels [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

Show Outcome Measure 32

33. Secondary:

PFS According to IRF Assessment Among Those With High HER2 mRNA Levels [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

Show Outcome Measure 33

34. Secondary:

Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With Low HER2 mRNA Levels [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

Show Outcome Measure 34

35. Secondary:

PFS According to IRF Assessment Among Those With Low HER2 mRNA Levels [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

Show Outcome Measure 35

36. Secondary:

Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With High HER2 mRNA Levels [ Time Frame: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination) ]

Show Outcome Measure 36

37. Secondary:

OS at Clinical Cutoff Among Those With High HER2 mRNA Levels [ Time Frame: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination) ]

Show Outcome Measure 37

38. Secondary:

Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With Low HER2 mRNA Levels [ Time Frame: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination) ]

Show Outcome Measure 38

39. Secondary:

OS at Clinical Cutoff Among Those With Low HER2 mRNA Levels [ Time Frame: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination) ]

Show Outcome Measure 39

Serious Adverse Events

Hide Serious Adverse Events

Time Frame	Up to 70 months from randomization until clinical cutoff of 16 September 2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination).
Additional Description	Safety Population: All randomized participants who received at least one dose of study treatment and the participants were analyzed based on the treatment they actually received (N=353 in Trastuzumab + Taxane arm, N=361 in Trastuzumab Emtansine, Pertuzumab-placebo arm, N=366 in Trastuzumab emtansine + pertuzumab arm).

Reporting Groups

	Description
Trastuzumab + Taxane	Participants received trastuzumab plus either docetaxel or paclitaxel. The regimen was chosen at the investigator's discretion. Option 1: trastuzumab 8 mg/kg via IV infusion on Day 1 of Cycle 1, then 6 mg/kg IV on Day 1 of each subsequent 3-week cycle; plus a minimum of 6 cycles with docetaxel 75 or 100 mg/m^2 IV on Day 1 of each 3-week cycle. Option 2: trastuzumab 4 mg/kg IV on Day 1 of Cycle 1, then 2 mg/kg IV weekly beginning on Day 8 of Cycle 1; plus a minimum of 18 weeks with paclitaxel 80 mg/m^2 IV weekly. Treatment continued until disease progression, unacceptable toxicity, or study termination. If trastuzumab or docetaxel were discontinued for toxicity, the other agent could be continued as monotherapy.
Trastuzumab Emtansine + Placebo	Participants received trastuzumab emtansine plus pertuzumab-placebo. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the placebo IV infusion, on Day 1 of each 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.
Trastuzumab Emtansine + Pertuzumab	Participants received trastuzumab emtansine plus pertuzumab. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the pertuzumab IV infusion, on Day 1 of each 3-week cycle. Pertuzumab was given as 840 mg IV on Day 1 of Cycle 1, then 420 mg IV on Day 1 of each subsequent 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.

Serious Adverse Events

	Trastuzumab + Taxane	Trastuzumab Emtansine + Placebo	Trastuzumab Emtansine + Pertuzumab
Total, Serious Adverse Events
# participants affected / at risk	81/353 (22.95%)	86/361 (23.82%)	93/366 (25.41%)
Blood and lymphatic system disorders
Febrile neutropenia ^* 1
# participants affected / at risk	13/353 (3.68%)	0/361 (0.00%)	0/366 (0.00%)
Anaemia ^* 2
# participants affected / at risk	1/353 (0.28%)	5/361 (1.39%)	6/366 (1.64%)
Neutropenia ^* 2
# participants affected / at risk	5/353 (1.42%)	0/361 (0.00%)	0/366 (0.00%)
Thrombocytopenia ^* 2
# participants affected / at risk	0/353 (0.00%)	2/361 (0.55%)	2/366 (0.55%)
Hypercoagulation ^* 2
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Leukopenia ^* 2
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Cardiac disorders
Atrial fibrillation ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	1/366 (0.27%)
Cardiac failure ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Cardiac failure congestive ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Myocardial infarction ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Pericardial effusion ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Supraventricular tachycardia ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Ventricular tachycardia ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Acute Myocardial Infarction ^* 2
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Ear and labyrinth disorders
Vertigo ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	2/366 (0.55%)
Eye disorders
Blindness transient ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Macular hole ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Ocular hypertension ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Gastrointestinal disorders
Diarrhoea ^* 1
# participants affected / at risk	4/353 (1.13%)	0/361 (0.00%)	0/366 (0.00%)
Vomiting ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	4/366 (1.09%)
Abdominal pain ^* 1
# participants affected / at risk	2/353 (0.57%)	1/361 (0.28%)	0/366 (0.00%)
Gastritis ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	2/366 (0.55%)
Rectal haemorrhage ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Anal fistula ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Colitis ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Diverticulum ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Gastric haemorrhage ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Gastric ulcer ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Gastritis erosive ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Large intestine perforation ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Lower gastrointestinal haemorrhage ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Mallory-Weiss syndrome ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Mouth haemorrhage ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Nausea ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Splenic artery aneurysm ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Umbilical hernia ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Upper gastrointestinal haemorrhage ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Abdominal Discomfort ^* 2
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Ascites ^* 2
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Gastrointestinal Haemorrhage ^* 2
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Haemorrhoidal Haemorrhage ^* 2
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
General disorders
Pyrexia ^* 1
# participants affected / at risk	2/353 (0.57%)	4/361 (1.11%)	5/366 (1.37%)
Fatigue ^* 1
# participants affected / at risk	3/353 (0.85%)	1/361 (0.28%)	1/366 (0.27%)
Non-cardiac chest pain ^* 1
# participants affected / at risk	0/353 (0.00%)	2/361 (0.55%)	1/366 (0.27%)
Death ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
General physical health deterioration ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	2/366 (0.55%)
Pain ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	2/366 (0.55%)
Asthenia ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Catheter site haematoma ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Malaise ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Oedema ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Peripheral swelling ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Adverse Drug Reaction ^* 2
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Sudden Death ^* 2
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Hepatobiliary disorders
Cholecystitis ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	1/366 (0.27%)
Hepatic Fibrosis ^* 2
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Hepatic Haematoma ^* 2
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Immune system disorders
Hypersensitivity ^* 1
# participants affected / at risk	0/353 (0.00%)	2/361 (0.55%)	2/366 (0.55%)
Anaphylactic reaction ^* 1
# participants affected / at risk	2/353 (0.57%)	0/361 (0.00%)	1/366 (0.27%)
Cytokine release syndrome ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Anaphylactic Shock ^* 2
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Anaphylactoid Reaction ^* 2
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Infections and infestations
Pneumonia ^* 1
# participants affected / at risk	4/353 (1.13%)	3/361 (0.83%)	5/366 (1.37%)
Cellulitis ^* 1
# participants affected / at risk	3/353 (0.85%)	3/361 (0.83%)	1/366 (0.27%)
Sepsis ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	4/366 (1.09%)
Device related infection ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	1/366 (0.27%)
Gastroenteritis ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	2/366 (0.55%)
Infection ^* 1
# participants affected / at risk	1/353 (0.28%)	1/361 (0.28%)	1/366 (0.27%)
Neutropenic sepsis ^* 1
# participants affected / at risk	3/353 (0.85%)	0/361 (0.00%)	0/366 (0.00%)
Septic shock ^* 1
# participants affected / at risk	2/353 (0.57%)	1/361 (0.28%)	1/366 (0.27%)
Bronchitis ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	3/366 (0.82%)
Herpes zoster ^* 1
# participants affected / at risk	2/353 (0.57%)	0/361 (0.00%)	0/366 (0.00%)
Upper respiratory tract infection ^* 1
# participants affected / at risk	1/353 (0.28%)	1/361 (0.28%)	0/366 (0.00%)
Urinary tract infection ^* 1
# participants affected / at risk	2/353 (0.57%)	0/361 (0.00%)	0/366 (0.00%)
Wound infection ^* 1
# participants affected / at risk	1/353 (0.28%)	1/361 (0.28%)	0/366 (0.00%)
Arthritis infective ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Atypical pneumonia ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Breast abscess ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Chorioretinitis ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Clostridium difficile colitis ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Clostridium difficile infection ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Cystitis ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Empyema ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Erysipelas ^* 1
# participants affected / at risk	1/353 (0.28%)	1/361 (0.28%)	0/366 (0.00%)
Escherichia sepsis ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Gastroenteritis viral ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Influenza ^* 1
# participants affected / at risk	1/353 (0.28%)	1/361 (0.28%)	0/366 (0.00%)
Klebsiella sepsis ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Localised infection ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Lower respiratory tract infection ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Lung infection ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Mastitis ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Nasopharyngitis ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Pneumonia pneumococcal ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Rectal abscess ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Respiratory tract infection ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Streptococcal sepsis ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Tooth infection ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Urosepsis ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Abscess Limb ^* 2
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Appendicitis Perforated ^* 2
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Catheter Site Infection ^* 2
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Skin Infection ^* 2
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Injury, poisoning and procedural complications
Infusion related reaction ^* 1
# participants affected / at risk	1/353 (0.28%)	7/361 (1.94%)	13/366 (3.55%)
Femur fracture ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	3/366 (0.82%)
Pubis fracture ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	1/366 (0.27%)
Arterial injury ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Contusion ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Fall ^* 1
# participants affected / at risk	0/353 (0.00%)	2/361 (0.55%)	0/366 (0.00%)
Femoral neck fracture ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Gastrointestinal stoma complication ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Hip fracture ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Radiation retinopathy ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Spinal compression fracture ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Subdural haematoma ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Wound secretion ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Abdominal Injury ^* 2
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Foot Fracture ^* 2
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Fracture ^* 2
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Stomal Hernia ^* 2
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Uncoded serious adverse event ^* 2 [4]
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Investigations
Alanine aminotransferase increased ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	2/366 (0.55%)
Aspartate aminotransferase increased ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	2/366 (0.55%)
Body temperature increased ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
International normalised ratio increased ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Oxygen saturation decreased ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Metabolism and nutrition disorders
Dehydration ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	1/366 (0.27%)
Hyperglycaemia ^* 1
# participants affected / at risk	0/353 (0.00%)	2/361 (0.55%)	0/366 (0.00%)
Decreased appetite ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Diabetic ketoacidosis ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Hypercalcaemia ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Hypokalaemia ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Hyponatraemia ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Diabetes Mellitus ^* 2
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Musculoskeletal and connective tissue disorders
Arthralgia ^* 1
# participants affected / at risk	1/353 (0.28%)	2/361 (0.55%)	1/366 (0.27%)
Back pain ^* 1
# participants affected / at risk	1/353 (0.28%)	1/361 (0.28%)	1/366 (0.27%)
Bone pain ^* 1
# participants affected / at risk	2/353 (0.57%)	1/361 (0.28%)	0/366 (0.00%)
Intervertebral disc protrusion ^* 1
# participants affected / at risk	1/353 (0.28%)	1/361 (0.28%)	0/366 (0.00%)
Exostosis ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Musculoskeletal chest pain ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Musculoskeletal pain ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Neck pain ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Pain in extremity ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Pathological fracture ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Rotator cuff syndrome ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Tenosynovitis ^* 2
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute leukaemia ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Breast neoplasm ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Chronic myeloid leukaemia ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Colon neoplasm ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Lung adenocarcinoma ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Myelodysplastic syndrome ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Squamous cell carcinoma of the cervix ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Tumour haemorrhage ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Uterine leiomyoma ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Basal Cell Carcinoma ^* 2
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Intracranial Tumour Haemorrhage ^* 2
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Nervous system disorders
Headache ^* 1
# participants affected / at risk	0/353 (0.00%)	2/361 (0.55%)	2/366 (0.55%)
Syncope ^* 1
# participants affected / at risk	0/353 (0.00%)	2/361 (0.55%)	1/366 (0.27%)
Haemorrhage intracranial ^* 1
# participants affected / at risk	1/353 (0.28%)	1/361 (0.28%)	0/366 (0.00%)
Cerebrovascular accident ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Cognitive disorder ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Depressed level of consciousness ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Guillain-Barre syndrome ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Lacunar infarction ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Paraparesis ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Peripheral sensory neuropathy ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Presyncope ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Somnolence ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Vascular dementia ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Cerebral Haemorrhage ^* 2
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Epilepsy ^* 2
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Neuropathy Peripheral ^* 2
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Sciatica ^* 2
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	1/366 (0.27%)
Seizure ^* 2
# participants affected / at risk	1/353 (0.28%)	1/361 (0.28%)	1/366 (0.27%)
Product Issues
Device Breakage ^* 2
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Psychiatric disorders
Confusional state ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	2/366 (0.55%)
Depression ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	2/366 (0.55%)
Anxiety ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Mental Status Changes ^* 2
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Suicide Attempt ^* 2
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Renal and urinary disorders
Calculus urinary ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Reproductive system and breast disorders
Menorrhagia ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	1/366 (0.27%)
Endometrial hypertrophy ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Vaginal haemorrhage ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion ^* 1
# participants affected / at risk	3/353 (0.85%)	1/361 (0.28%)	3/366 (0.82%)
Pulmonary embolism ^* 1
# participants affected / at risk	4/353 (1.13%)	2/361 (0.55%)	1/366 (0.27%)
Dyspnoea ^* 1
# participants affected / at risk	2/353 (0.57%)	1/361 (0.28%)	1/366 (0.27%)
Epistaxis ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	3/366 (0.82%)
Interstitial lung disease ^* 1
# participants affected / at risk	1/353 (0.28%)	1/361 (0.28%)	1/366 (0.27%)
Pneumothorax ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	2/366 (0.55%)
Acute respiratory failure ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Alveolitis allergic ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Chronic obstructive pulmonary disease ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Hypoxia ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Nasal turbinate hypertrophy ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Pneumonitis ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Pulmonary fibrosis ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Respiratory failure ^* 1
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Acute Pulmonary Oedema ^* 2
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)
Skin and subcutaneous tissue disorders
Rash ^* 1
# participants affected / at risk	0/353 (0.00%)	2/361 (0.55%)	0/366 (0.00%)
Dermatomyositis ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Peau d’orange ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Cutaneous Lupus Erythematosus ^* 2
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	1/366 (0.27%)
Vascular disorders
Hypertension ^* 1
# participants affected / at risk	1/353 (0.28%)	1/361 (0.28%)	0/366 (0.00%)
Haematoma ^* 1
# participants affected / at risk	0/353 (0.00%)	2/361 (0.55%)	0/366 (0.00%)
Haemorrhage ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Hypertensive crisis ^* 1
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Hypotension ^* 1
# participants affected / at risk	1/353 (0.28%)	0/361 (0.00%)	0/366 (0.00%)
Aneurysm ^* 2
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Hypovolaemic Shock ^* 2
# participants affected / at risk	0/353 (0.00%)	0/361 (0.00%)	1/366 (0.27%)
Orthostatic Hypotension ^* 2
# participants affected / at risk	0/353 (0.00%)	1/361 (0.28%)	0/366 (0.00%)

*	Events were collected by non-systematic assessment
1	Term from vocabulary, MedDRA (17.1)
2	Term from vocabulary, MedDRA (19.0)
[4]	Per investigator, this serious adverse event was, "gamma nail implant broke (status after femur fracture)."

Other Adverse Events

Show Other Adverse Events

Limitations and Caveats

Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

More Information

Hide 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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact:

Name/Title: Medical Communications
Organization: Hoffmann-La Roche
phone: 800-821-8590
e-mail: genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bighin C, Pronzato P, Del Mastro L. Trastuzumab emtansine in the treatment of HER-2-positive metastatic breast cancer patients. Future Oncol. 2013 Jul;9(7):955-7. doi: 10.2217/fon.13.74.

Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer. 2012 Mar 22;12(4):278-87. doi: 10.1038/nrc3236. Review.

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01120184 History of Changes
Other Study ID Numbers:	BO22589 2009-017905-13 ( EudraCT Number )
First Submitted:	April 28, 2010
First Posted:	May 10, 2010
Results First Submitted:	May 2, 2016
Results First Posted:	February 23, 2017
Last Update Posted:	November 7, 2017

To Top