Trial Outcomes & Findings for Trial of Paclitaxel/Bevacizumab +/- Everolimus for Patients With HER2-Negative Metastatic Breast Cancer (NCT NCT00915603)

Last Updated: 2014-12-22

Results Overview

Progression-free survival will be measured from Day 1 of study drug administration to disease progression defined by Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

113 participants

Primary outcome timeframe

every 8 weeks until progressive disease, expected average of 18 months

Results posted on

2014-12-22

Participant Flow

Participant milestones

Participant milestones
Measure	Paclitaxel/Carboplatin/Placebo	Paclitaxel/Carboplatin/Everolimus
Overall Study STARTED	56	55
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	56	55

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Trial of Paclitaxel/Bevacizumab +/- Everolimus for Patients With HER2-Negative Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Paclitaxel/Carboplatin/Placebo n=57 Participants	Paclitaxel/Carboplatin/Everolimus n=56 Participants	Total n=113 Participants Total of all reporting groups
Age, Continuous	57 Years n=5 Participants	61 Years n=7 Participants	58 Years n=5 Participants
Sex: Female, Male Female	57 Participants n=5 Participants	56 Participants n=7 Participants	113 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	57 participants n=5 Participants	56 participants n=7 Participants	113 participants n=5 Participants

PRIMARY outcome

Timeframe: every 8 weeks until progressive disease, expected average of 18 months

Population: Includes all enrolled and randomized patients

Outcome measures

Outcome measures
Measure	Paclitaxel/Bevacizumab/Everolimus n=56 Participants Systemic Therapy	Paclitaxel/Bevacizumab/Placebo n=57 Participants Systemic Therapy
Progression-Free Survival (PFS)	9.1 months Interval 6.8 to 10.8	7.1 months Interval 5.6 to 10.8

SECONDARY outcome

Timeframe: every 4 weeks until intolerable toxicity occurs

Population: Includes patients who were enrolled, randomized and treated

Assessments will be made based on the analysis of reported incidence of treatment-emergent AEs

Outcome measures

Outcome measures
Measure	Paclitaxel/Bevacizumab/Everolimus n=55 Participants Systemic Therapy	Paclitaxel/Bevacizumab/Placebo n=56 Participants Systemic Therapy
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Neutropenia	27 participants	26 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Anorexia/weight loss	18 participants	13 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Proteinuria	17 participants	10 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Rash	25 participants	13 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Nausea/vomiting	26 participants	19 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Epistaxis	20 participants	15 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Febrile neutropenia	2 participants	2 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Anemia	23 participants	8 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Thrombocytopenia	12 participants	8 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Fatigue	38 participants	29 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Arthralgia/myalgia	19 participants	10 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Mucositis/stomatitis	35 participants	18 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Neuropathy	32 participants	31 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Diarrhea	30 participants	17 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Alopecia	19 participants	27 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Dysgeusia	11 participants	8 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Headache	11 participants	7 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Hypertension	10 participants	10 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Dyspnea	10 participants	9 participants
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability Hypercholesterolemia	9 participants	3 participants

SECONDARY outcome

Timeframe: every 8 weeks until treatment discontinuation, expected average of 18 months

Population: Includes patients who were enrolled and randomized

The number of patients with observed complete response \[CR\] or partial response \[PR\]. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Outcome measures

Outcome measures
Measure	Paclitaxel/Bevacizumab/Everolimus n=56 Participants Systemic Therapy	Paclitaxel/Bevacizumab/Placebo n=57 Participants Systemic Therapy
Overall Response Rate (ORR)	35 participants	32 participants

SECONDARY outcome

Timeframe: every 8 weeks until treatment discontinuation, expected average 6 months

Defined as time between date of objective response and date of response to disease progression or death, as defined by RECIST v1.1 criteria. Objective response is defined as either complete response \[CR\] or partial response \[PR\]. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Outcome measures

Outcome measures
Measure	Paclitaxel/Bevacizumab/Everolimus n=35 Participants Systemic Therapy	Paclitaxel/Bevacizumab/Placebo n=32 Participants Systemic Therapy
Duration of Response (DOR)	7.8 months Interval 5.8 to 9.2	6.0 months Interval 5.2 to 14.5

SECONDARY outcome

Timeframe: every 8 weeks until treatment discontinuation, expected average 6 months

Assessed from Day 1 of study drug administration to date of death due to any cause.

Outcome measures

Outcome measures
Measure	Paclitaxel/Bevacizumab/Everolimus n=56 Participants Systemic Therapy	Paclitaxel/Bevacizumab/Placebo n=57 Participants Systemic Therapy
Overall Survival (OS)	17.5 months Interval 14.9 to 23.9	19.6 months Interval 14.0 to 27.2

Adverse Events

Paclitaxel/Bevacizumab/Everolimus

Serious events: 16 serious events

Other events: 55 other events

Deaths: 0 deaths

Paclitaxel/Bevacizumab/Placebo

Serious events: 16 serious events

Other events: 56 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

John D. Hainsworth, MD

Sarah Cannon Research Institute

Phone: 1-877-691-7274

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can review/embargo results communications prior to public release for a period that is \>60 days but ≤180 days from the date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish results until 18 mos. after the trial has been completed at all sites.
Publication restrictions are in place

Restriction type: OTHER

Measure	Paclitaxel/Bevacizumab/Everolimus n=55 participants at risk	Paclitaxel/Bevacizumab/Placebo n=56 participants at risk
Blood and lymphatic system disorders NEUTROPENIA	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	3.6% 2/56 • Number of events 8 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Blood and lymphatic system disorders FEBRILE NEUTROPENIA	1.8% 1/55 • Number of events 3 Adverse Event analysis includes only patients who were enrolled, randomized and treated	3.6% 2/56 • Number of events 3 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Cardiac disorders LEFT VENTRICULAR DYSFUNCTION	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	0.00% 0/56 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Gastrointestinal disorders ABDOMINAL PAIN	0.00% 0/55 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Gastrointestinal disorders PANCREATITIS	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	0.00% 0/56 Adverse Event analysis includes only patients who were enrolled, randomized and treated
General disorders MUCOSAL INFLAMMATION	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	0.00% 0/56 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Hepatobiliary disorders JAUNDICE	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	0.00% 0/56 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Infections and infestations BRONCHITIS	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	0.00% 0/56 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Infections and infestations CLOSTRIDIUM DIFFICILE COLITIS	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	0.00% 0/56 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Infections and infestations DIVERTICULITIS	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	0.00% 0/56 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Infections and infestations INFECTION	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	0.00% 0/56 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Infections and infestations PELVIC INFLAMMATORY DISEASE	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	0.00% 0/56 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Infections and infestations PNEUMONIA	3.6% 2/55 • Number of events 2 Adverse Event analysis includes only patients who were enrolled, randomized and treated	0.00% 0/56 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Metabolism and nutrition disorders DEHYDRATION	5.5% 3/55 • Number of events 4 Adverse Event analysis includes only patients who were enrolled, randomized and treated	0.00% 0/56 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Metabolism and nutrition disorders HYPERGLYCAEMIA	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	0.00% 0/56 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Musculoskeletal and connective tissue disorders MUSCULAR WEAKNESS	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	0.00% 0/56 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Neoplasms benign, malignant and unspecified (incl cysts and polyps) LYMPHANGIOSIS CARCINOMATOSA	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	0.00% 0/56 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Nervous system disorders CONVULSION	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	0.00% 0/56 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Renal and urinary disorders RENAL FAILURE ACUTE	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Respiratory, thoracic and mediastinal disorders CHRONIC OBSTRUCTIVE PULMONARY DISEASE	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	0.00% 0/56 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Respiratory, thoracic and mediastinal disorders HYPOXIA	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	0.00% 0/56 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	3.6% 2/55 • Number of events 2 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Vascular disorders DEEP VEIN THROMBOSIS	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Blood and lymphatic system disorders PANCYTOPENIA	0.00% 0/55 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Cardiac disorders TACHYCARDIA	0.00% 0/55 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Gastrointestinal disorders HAEMATEMESIS	0.00% 0/55 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Gastrointestinal disorders INTESTINAL PERFORATION	0.00% 0/55 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Gastrointestinal disorders OESOPHAGEAL OBSTRUCTION	0.00% 0/55 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Infections and infestations CATHETER RELATED INFECTION	0.00% 0/55 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Infections and infestations CENTRAL LINE INFECTION	0.00% 0/55 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 2 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Neoplasms benign, malignant and unspecified (incl cysts and polyps) METASTASES TO CENTRAL NERVOUS SYSTEM	0.00% 0/55 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Nervous system disorders TRANSIENT ISCHAEMIC ATTACK	0.00% 0/55 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Psychiatric disorders CONFUSIONAL STATE	0.00% 0/55 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Renal and urinary disorders RENAL FAILURE	0.00% 0/55 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Respiratory, thoracic and mediastinal disorders BRONCHIAL OBSTRUCTION	0.00% 0/55 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Respiratory, thoracic and mediastinal disorders PNEUMONITIS	0.00% 0/55 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Respiratory, thoracic and mediastinal disorders RESPIRATORY FAILURE	0.00% 0/55 Adverse Event analysis includes only patients who were enrolled, randomized and treated	3.6% 2/56 • Number of events 2 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Vascular disorders THROMBOSIS	0.00% 0/55 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated

Measure	Paclitaxel/Bevacizumab/Everolimus n=55 participants at risk	Paclitaxel/Bevacizumab/Placebo n=56 participants at risk
Blood and lymphatic system disorders ANAEMIA	40.0% 22/55 • Number of events 67 Adverse Event analysis includes only patients who were enrolled, randomized and treated	14.3% 8/56 • Number of events 25 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Blood and lymphatic system disorders LEUKOPENIA	27.3% 15/55 • Number of events 43 Adverse Event analysis includes only patients who were enrolled, randomized and treated	17.9% 10/56 • Number of events 23 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Blood and lymphatic system disorders NEUTROPENIA	49.1% 27/55 • Number of events 71 Adverse Event analysis includes only patients who were enrolled, randomized and treated	42.9% 24/56 • Number of events 57 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Blood and lymphatic system disorders THROMBOCYTOPENIA	20.0% 11/55 • Number of events 29 Adverse Event analysis includes only patients who were enrolled, randomized and treated	12.5% 7/56 • Number of events 8 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Gastrointestinal disorders ABDOMINAL PAIN	16.4% 9/55 • Number of events 10 Adverse Event analysis includes only patients who were enrolled, randomized and treated	5.4% 3/56 • Number of events 4 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Gastrointestinal disorders ABDOMINAL PAIN UPPER	9.1% 5/55 • Number of events 5 Adverse Event analysis includes only patients who were enrolled, randomized and treated	5.4% 3/56 • Number of events 3 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Gastrointestinal disorders CONSTIPATION	30.9% 17/55 • Number of events 22 Adverse Event analysis includes only patients who were enrolled, randomized and treated	30.4% 17/56 • Number of events 26 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Gastrointestinal disorders DIARRHOEA	69.1% 38/55 • Number of events 68 Adverse Event analysis includes only patients who were enrolled, randomized and treated	42.9% 24/56 • Number of events 37 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Gastrointestinal disorders DRY MOUTH	7.3% 4/55 • Number of events 4 Adverse Event analysis includes only patients who were enrolled, randomized and treated	3.6% 2/56 • Number of events 2 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Gastrointestinal disorders DYSPEPSIA	9.1% 5/55 • Number of events 6 Adverse Event analysis includes only patients who were enrolled, randomized and treated	14.3% 8/56 • Number of events 8 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Gastrointestinal disorders GASTROOESOPHAGEAL REFLUX DISEASE	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	17.9% 10/56 • Number of events 10 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Gastrointestinal disorders HAEMORRHOIDS	9.1% 5/55 • Number of events 5 Adverse Event analysis includes only patients who were enrolled, randomized and treated	3.6% 2/56 • Number of events 2 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Gastrointestinal disorders NAUSEA	54.5% 30/55 • Number of events 54 Adverse Event analysis includes only patients who were enrolled, randomized and treated	44.6% 25/56 • Number of events 34 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Gastrointestinal disorders ORAL PAIN	12.7% 7/55 • Number of events 10 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 3 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Gastrointestinal disorders STOMATITIS	29.1% 16/55 • Number of events 39 Adverse Event analysis includes only patients who were enrolled, randomized and treated	7.1% 4/56 • Number of events 4 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Gastrointestinal disorders VOMITING	40.0% 22/55 • Number of events 29 Adverse Event analysis includes only patients who were enrolled, randomized and treated	23.2% 13/56 • Number of events 15 Adverse Event analysis includes only patients who were enrolled, randomized and treated
General disorders ASTHENIA	9.1% 5/55 • Number of events 6 Adverse Event analysis includes only patients who were enrolled, randomized and treated	12.5% 7/56 • Number of events 7 Adverse Event analysis includes only patients who were enrolled, randomized and treated
General disorders FATIGUE	76.4% 42/55 • Number of events 86 Adverse Event analysis includes only patients who were enrolled, randomized and treated	66.1% 37/56 • Number of events 76 Adverse Event analysis includes only patients who were enrolled, randomized and treated
General disorders MUCOSAL INFLAMMATION	38.2% 21/55 • Number of events 33 Adverse Event analysis includes only patients who were enrolled, randomized and treated	25.0% 14/56 • Number of events 21 Adverse Event analysis includes only patients who were enrolled, randomized and treated
General disorders OEDEMA PERIPHERAL	14.5% 8/55 • Number of events 14 Adverse Event analysis includes only patients who were enrolled, randomized and treated	21.4% 12/56 • Number of events 17 Adverse Event analysis includes only patients who were enrolled, randomized and treated
General disorders PAIN	5.5% 3/55 • Number of events 5 Adverse Event analysis includes only patients who were enrolled, randomized and treated	8.9% 5/56 • Number of events 6 Adverse Event analysis includes only patients who were enrolled, randomized and treated
General disorders PYREXIA	25.5% 14/55 • Number of events 21 Adverse Event analysis includes only patients who were enrolled, randomized and treated	12.5% 7/56 • Number of events 9 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Infections and infestations SINUSITIS	20.0% 11/55 • Number of events 19 Adverse Event analysis includes only patients who were enrolled, randomized and treated	10.7% 6/56 • Number of events 6 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	14.5% 8/55 • Number of events 9 Adverse Event analysis includes only patients who were enrolled, randomized and treated	16.1% 9/56 • Number of events 13 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Infections and infestations URINARY TRACT INFECTION	20.0% 11/55 • Number of events 16 Adverse Event analysis includes only patients who were enrolled, randomized and treated	21.4% 12/56 • Number of events 15 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	7.3% 4/55 • Number of events 7 Adverse Event analysis includes only patients who were enrolled, randomized and treated	3.6% 2/56 • Number of events 3 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Investigations WEIGHT DECREASED	29.1% 16/55 • Number of events 24 Adverse Event analysis includes only patients who were enrolled, randomized and treated	12.5% 7/56 • Number of events 7 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Metabolism and nutrition disorders ANOREXIA	23.6% 13/55 • Number of events 20 Adverse Event analysis includes only patients who were enrolled, randomized and treated	14.3% 8/56 • Number of events 9 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Metabolism and nutrition disorders DEHYDRATION	14.5% 8/55 • Number of events 8 Adverse Event analysis includes only patients who were enrolled, randomized and treated	8.9% 5/56 • Number of events 7 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Metabolism and nutrition disorders HYPERCHOLESTEROLAEMIA	12.7% 7/55 • Number of events 9 Adverse Event analysis includes only patients who were enrolled, randomized and treated	5.4% 3/56 • Number of events 3 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Metabolism and nutrition disorders HYPERGLYCAEMIA	9.1% 5/55 • Number of events 6 Adverse Event analysis includes only patients who were enrolled, randomized and treated	7.1% 4/56 • Number of events 5 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Metabolism and nutrition disorders HYPOKALAEMIA	9.1% 5/55 • Number of events 6 Adverse Event analysis includes only patients who were enrolled, randomized and treated	5.4% 3/56 • Number of events 3 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Musculoskeletal and connective tissue disorders ARTHRALGIA	23.6% 13/55 • Number of events 20 Adverse Event analysis includes only patients who were enrolled, randomized and treated	17.9% 10/56 • Number of events 19 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Musculoskeletal and connective tissue disorders BACK PAIN	14.5% 8/55 • Number of events 9 Adverse Event analysis includes only patients who were enrolled, randomized and treated	14.3% 8/56 • Number of events 11 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Musculoskeletal and connective tissue disorders BONE PAIN	12.7% 7/55 • Number of events 8 Adverse Event analysis includes only patients who were enrolled, randomized and treated	14.3% 8/56 • Number of events 12 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL CHEST PAIN	10.9% 6/55 • Number of events 6 Adverse Event analysis includes only patients who were enrolled, randomized and treated	5.4% 3/56 • Number of events 3 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	3.6% 2/55 • Number of events 2 Adverse Event analysis includes only patients who were enrolled, randomized and treated	7.1% 4/56 • Number of events 4 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Musculoskeletal and connective tissue disorders MYALGIA	18.2% 10/55 • Number of events 13 Adverse Event analysis includes only patients who were enrolled, randomized and treated	10.7% 6/56 • Number of events 8 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	10.9% 6/55 • Number of events 17 Adverse Event analysis includes only patients who were enrolled, randomized and treated	12.5% 7/56 • Number of events 8 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Nervous system disorders DIZZINESS	7.3% 4/55 • Number of events 4 Adverse Event analysis includes only patients who were enrolled, randomized and treated	14.3% 8/56 • Number of events 10 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Nervous system disorders DYSGEUSIA	20.0% 11/55 • Number of events 15 Adverse Event analysis includes only patients who were enrolled, randomized and treated	16.1% 9/56 • Number of events 11 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Nervous system disorders HEADACHE	34.5% 19/55 • Number of events 24 Adverse Event analysis includes only patients who were enrolled, randomized and treated	26.8% 15/56 • Number of events 26 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Nervous system disorders HYPOAESTHESIA	5.5% 3/55 • Number of events 3 Adverse Event analysis includes only patients who were enrolled, randomized and treated	7.1% 4/56 • Number of events 5 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Nervous system disorders NEUROPATHY PERIPHERAL	40.0% 22/55 • Number of events 52 Adverse Event analysis includes only patients who were enrolled, randomized and treated	48.2% 27/56 • Number of events 52 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Nervous system disorders PERIPHERAL SENSORY NEUROPATHY	23.6% 13/55 • Number of events 27 Adverse Event analysis includes only patients who were enrolled, randomized and treated	21.4% 12/56 • Number of events 21 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Psychiatric disorders ANXIETY	10.9% 6/55 • Number of events 9 Adverse Event analysis includes only patients who were enrolled, randomized and treated	10.7% 6/56 • Number of events 6 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Psychiatric disorders DEPRESSION	14.5% 8/55 • Number of events 10 Adverse Event analysis includes only patients who were enrolled, randomized and treated	10.7% 6/56 • Number of events 7 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Psychiatric disorders INSOMNIA	18.2% 10/55 • Number of events 10 Adverse Event analysis includes only patients who were enrolled, randomized and treated	14.3% 8/56 • Number of events 8 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Renal and urinary disorders DYSURIA	1.8% 1/55 • Number of events 2 Adverse Event analysis includes only patients who were enrolled, randomized and treated	12.5% 7/56 • Number of events 9 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Renal and urinary disorders PROTEINURIA	34.5% 19/55 • Number of events 46 Adverse Event analysis includes only patients who were enrolled, randomized and treated	21.4% 12/56 • Number of events 24 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Respiratory, thoracic and mediastinal disorders COUGH	30.9% 17/55 • Number of events 21 Adverse Event analysis includes only patients who were enrolled, randomized and treated	28.6% 16/56 • Number of events 20 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Respiratory, thoracic and mediastinal disorders DYSPHONIA	7.3% 4/55 • Number of events 4 Adverse Event analysis includes only patients who were enrolled, randomized and treated	5.4% 3/56 • Number of events 4 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Respiratory, thoracic and mediastinal disorders DYSPNOEA	30.9% 17/55 • Number of events 19 Adverse Event analysis includes only patients who were enrolled, randomized and treated	23.2% 13/56 • Number of events 18 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Respiratory, thoracic and mediastinal disorders EPISTAXIS	50.9% 28/55 • Number of events 40 Adverse Event analysis includes only patients who were enrolled, randomized and treated	33.9% 19/56 • Number of events 24 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Respiratory, thoracic and mediastinal disorders NASAL CONGESTION	7.3% 4/55 • Number of events 5 Adverse Event analysis includes only patients who were enrolled, randomized and treated	3.6% 2/56 • Number of events 2 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	16.4% 9/55 • Number of events 13 Adverse Event analysis includes only patients who were enrolled, randomized and treated	10.7% 6/56 • Number of events 7 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Respiratory, thoracic and mediastinal disorders PRODUCTIVE COUGH	10.9% 6/55 • Number of events 6 Adverse Event analysis includes only patients who were enrolled, randomized and treated	5.4% 3/56 • Number of events 5 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Respiratory, thoracic and mediastinal disorders RHINORRHOEA	5.5% 3/55 • Number of events 3 Adverse Event analysis includes only patients who were enrolled, randomized and treated	7.1% 4/56 • Number of events 5 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Skin and subcutaneous tissue disorders ALOPECIA	34.5% 19/55 • Number of events 23 Adverse Event analysis includes only patients who were enrolled, randomized and treated	53.6% 30/56 • Number of events 38 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Skin and subcutaneous tissue disorders DERMATITIS ACNEIFORM	9.1% 5/55 • Number of events 16 Adverse Event analysis includes only patients who were enrolled, randomized and treated	1.8% 1/56 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Skin and subcutaneous tissue disorders DRY SKIN	5.5% 3/55 • Number of events 3 Adverse Event analysis includes only patients who were enrolled, randomized and treated	8.9% 5/56 • Number of events 5 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Skin and subcutaneous tissue disorders NAIL DISORDER	10.9% 6/55 • Number of events 6 Adverse Event analysis includes only patients who were enrolled, randomized and treated	25.0% 14/56 • Number of events 20 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Skin and subcutaneous tissue disorders NIGHT SWEATS	1.8% 1/55 • Number of events 1 Adverse Event analysis includes only patients who were enrolled, randomized and treated	8.9% 5/56 • Number of events 6 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Skin and subcutaneous tissue disorders RASH	40.0% 22/55 • Number of events 36 Adverse Event analysis includes only patients who were enrolled, randomized and treated	26.8% 15/56 • Number of events 21 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Vascular disorders FLUSHING	3.6% 2/55 • Number of events 2 Adverse Event analysis includes only patients who were enrolled, randomized and treated	7.1% 4/56 • Number of events 4 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Vascular disorders HOT FLUSH	5.5% 3/55 • Number of events 3 Adverse Event analysis includes only patients who were enrolled, randomized and treated	14.3% 8/56 • Number of events 10 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Vascular disorders HYPERTENSION	21.8% 12/55 • Number of events 19 Adverse Event analysis includes only patients who were enrolled, randomized and treated	25.0% 14/56 • Number of events 30 Adverse Event analysis includes only patients who were enrolled, randomized and treated
Vascular disorders LYMPHOEDEMA	5.5% 3/55 • Number of events 3 Adverse Event analysis includes only patients who were enrolled, randomized and treated	7.1% 4/56 • Number of events 4 Adverse Event analysis includes only patients who were enrolled, randomized and treated