Trial Outcomes & Findings for Efficacy and Safety Study of ABP 215 Compared With Bevacizumab in Patients With Advanced Non-Small Cell Lung Cancer (NCT NCT01966003)

NCT ID: NCT01966003

Last Updated: 2017-10-19

Results Overview

Tumor assessments were performed by central, independent, blinded radiologists according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 using computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest and abdomen. Objective response is defined as a best overall response of partial response (PR) or complete response (CR) as defined by RECIST v1.1. All participants who did not meet the criteria for CR or PR by the end of the study were considered non-responders. CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes must be reduced in short axis to \< 10 mm. PR: Disappearance of all target lesions with persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, and no new lesions, or, at least a 30% decrease in the sum of diameters of target lesions, with no progression of existing non-target lesions and no new lesions.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

642 participants

Primary outcome timeframe

Disease assessments were performed at weeks 1, 7, 13, 19, and approximately every 9 weeks thereafter. The mean actual follow-up time from randomization was 4.7 and 5.0 months for ABP 215 and bevacizumab, respectively.

Results posted on

2017-10-19

Participant Flow

This study was conducted at 101 sites (14 sites in the US, 11 in Russia, 10 in Australia, 9 in Germany, 8 in Poland, 7 in Hungary, 7 in Romania, 6 in Italy, 6 in Spain, 5 in Bulgaria, 5 in Greece, 3 in the Czech Republic, 3 in Mexico, 3 in Taiwan, 2 in the Netherlands, 1 in Canada, and 1 in Hong Kong).

Eligible participants were randomized in a 1:1 ratio to receive ABP 215 or bevacizumab. Participants were stratified by geographic region (Eastern Europe vs Western Europe vs Asia Pacific/Other vs North America), Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1), and sex.

Participant milestones

Participant milestones
Measure	ABP 215 Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Bevacizumab Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.
Overall Study STARTED	328	314
Overall Study Received Study Drug	324	309
Overall Study COMPLETED	58	44
Overall Study NOT COMPLETED	270	270

Reasons for withdrawal

Reasons for withdrawal
Measure	ABP 215 Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Bevacizumab Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.
Overall Study Death	43	36
Overall Study Protocol Violation	6	4
Overall Study Lost to Follow-up	4	3
Overall Study Physician Decision	12	13
Overall Study Withdrawal by Subject	29	19
Overall Study Plan to Receive Other Anticancer Therapy	131	127
Overall Study Plan to Receive Commercial Bevacizumab	44	67
Overall Study Other	1	1

Baseline Characteristics

Efficacy and Safety Study of ABP 215 Compared With Bevacizumab in Patients With Advanced Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ABP 215 n=328 Participants Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Bevacizumab n=314 Participants Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Total n=642 Participants Total of all reporting groups
Age, Continuous	61.6 years STANDARD_DEVIATION 9.09 • n=99 Participants	61.6 years STANDARD_DEVIATION 8.88 • n=107 Participants	61.6 years STANDARD_DEVIATION 8.98 • n=206 Participants
Age, Customized < 65 years	199 participants n=99 Participants	191 participants n=107 Participants	390 participants n=206 Participants
Age, Customized ≥ 65 years	129 participants n=99 Participants	123 participants n=107 Participants	252 participants n=206 Participants
Sex: Female, Male Female	132 Participants n=99 Participants	126 Participants n=107 Participants	258 Participants n=206 Participants
Sex: Female, Male Male	196 Participants n=99 Participants	188 Participants n=107 Participants	384 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=99 Participants	16 Participants n=107 Participants	30 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	314 Participants n=99 Participants	298 Participants n=107 Participants	612 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race/Ethnicity, Customized White	315 participants n=99 Participants	300 participants n=107 Participants	615 participants n=206 Participants
Race/Ethnicity, Customized Black or African American	2 participants n=99 Participants	5 participants n=107 Participants	7 participants n=206 Participants
Race/Ethnicity, Customized Asian	6 participants n=99 Participants	7 participants n=107 Participants	13 participants n=206 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 participants n=99 Participants	0 participants n=107 Participants	2 participants n=206 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants
Race/Ethnicity, Customized Other	4 participants n=99 Participants	2 participants n=107 Participants	6 participants n=206 Participants
Geographic Region Eastern Europe	189 participants n=99 Participants	186 participants n=107 Participants	375 participants n=206 Participants
Geographic Region Western Europe	78 participants n=99 Participants	76 participants n=107 Participants	154 participants n=206 Participants
Geographic Region North America	31 participants n=99 Participants	26 participants n=107 Participants	57 participants n=206 Participants
Geographic Region Asia Pacific/Other	30 participants n=99 Participants	26 participants n=107 Participants	56 participants n=206 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0	127 participants n=99 Participants	117 participants n=107 Participants	244 participants n=206 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 1	201 participants n=99 Participants	197 participants n=107 Participants	398 participants n=206 Participants

PRIMARY outcome

Timeframe: Disease assessments were performed at weeks 1, 7, 13, 19, and approximately every 9 weeks thereafter. The mean actual follow-up time from randomization was 4.7 and 5.0 months for ABP 215 and bevacizumab, respectively.

Population: Intent-to-treat population which consisted of all randomized participants.

Outcome measures

Outcome measures
Measure	ABP 215 n=328 Participants Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Bevacizumab n=314 Participants Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.
Percentage of Participants With an Objective Response	39.0 percentage of participants	41.7 percentage of participants

SECONDARY outcome

Population: Intent-to-treat population with an objective response

Duration of response (DOR) was calculated as the time from the first objective response (PR or CR) to disease progression per RECIST v1.1 based on the central, independent, blinded radiologists' review. DOR was only calculated for participants with an objective response. For responders not meeting the criterion for progression by the end of the study, DOR was censored at the date of the last evaluable tumor assessment. Progressive Disease was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm, or, unequivocal progression of existing non-target lesions, or any new lesions.

Outcome measures

Outcome measures
Measure	ABP 215 n=128 Participants Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Bevacizumab n=131 Participants Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.
Duration of Response	5.8 months Interval 4.9 to 7.7	5.6 months Interval 5.1 to 6.3

SECONDARY outcome

Timeframe: From randomization until the end of study; The mean actual follow-up time from randomization was 4.7 and 5.0 months for ABP 215 and bevacizumab, respectively.

Population: Intent-to-treat population

Progression-free survival (PFS) was defined as the time from the randomization date to the date of disease progression using RECIST v1.1 based on the central, independent, blinded radiologists' review, or death. Participants who were alive and did not meet the criteria for progression by the end of the study were censored at their last evaluable disease assessment date. Participants with no evaluable tumor assessments after randomization who did not die by the end of the study were censored on the randomization date. Progressive Disease was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm, or, unequivocal progression of existing non-target lesions, or any new lesions.

Outcome measures

Outcome measures
Measure	ABP 215 n=328 Participants Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Bevacizumab n=314 Participants Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.
Progression-free Survival	6.6 months Interval 6.3 to 7.9	7.9 months Interval 6.6 to 8.2

SECONDARY outcome

Timeframe: up to 19 weeks

Population: Safety analysis population consisted of all participants who received any amount of study drug.

Adverse events (AEs) were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4, and according to the following scale: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death due to AE. A serious adverse event (SAE) is defined as an AE that meets at least 1 of the following serious criteria: * fatal * life-threatening * required inpatient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event

Outcome measures

Outcome measures
Measure	ABP 215 n=324 Participants Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Bevacizumab n=309 Participants Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.
Number of Participants With Adverse Events Any adverse event	308 participants	289 participants
Number of Participants With Adverse Events Any fatal adverse event	13 participants	11 participants
Number of Participants With Adverse Events Any grade ≥ 3 adverse event	139 participants	137 participants
Number of Participants With Adverse Events Any serious adverse event	85 participants	71 participants
Number of Participants With Adverse Events Any AE leading to discontinuation of study drug	61 participants	53 participants
Number of Participants With Adverse Events Any AE leading to discontinuation of chemotherapy	74 participants	59 participants
Number of Participants With Adverse Events Any AE leading to dose delay of study drug	73 participants	69 participants
Number of Participants With Adverse Events Any AE leading to dose delay of any chemotherapy	86 participants	83 participants
Number of Participants With Adverse Events Any AE leading to dose reduction of chemotherapy	48 participants	49 participants

SECONDARY outcome

Timeframe: 44 weeks (6 months after end of treatment)

Population: Safety analysis population with available data

Two validated assays were used to detect the presence of anti-ABP 215 antibodies. Samples were first tested in an electrochemiluminescence (ECL)- based bridging immunoassay to detect antibodies capable of binding to ABP 215 (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a non-cell based target binding assay to determine neutralizing activity against ABP 215 (Neutralizing Antibody Assay). If a post-dose sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the sample was defined as positive for neutralizing antibodies.

Outcome measures

Outcome measures
Measure	ABP 215 n=294 Participants Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Bevacizumab n=284 Participants Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.
Number of Participants Who Developed Anti-drug Antibodies Binding antibody positive	4 participants	7 participants
Number of Participants Who Developed Anti-drug Antibodies Neutralizing antibody positive	0 participants	0 participants

SECONDARY outcome

Timeframe: From randomization until the end of study; The mean actual follow-up time from randomization was 4.7 and 5.0 months for ABP 215 and bevacizumab, respectively.

Population: Safety analysis population

Overall survival (OS) was defined as the time from the randomization date to date of death. Participants alive at the end of study were censored at the last date known to be alive, derived from dates collected within the study that implied a participant was alive. Participants were followed for survival status during the treatment phase and thereafter every 9 weeks until the end of the clinical study, consent was withdrawn, they were lost to follow-up, died, or had proscribed therapy (eg, commercial bevacizumab, non-study anti-cancer treatment).

Outcome measures

Outcome measures
Measure	ABP 215 n=324 Participants Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Bevacizumab n=309 Participants Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.
Overall Survival	NA months Could not be estimated due to the low number of deaths	NA months Interval 14.6 to Could not be estimated due to the low number of deaths

Adverse Events

ABP 215

Serious events: 85 serious events

Other events: 286 other events

Deaths: 0 deaths

Bevacizumab

Serious events: 71 serious events

Other events: 276 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	ABP 215 n=324 participants at risk Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.	Bevacizumab n=309 participants at risk Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles.
Blood and lymphatic system disorders Anaemia	20.1% 65/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	19.4% 60/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Leukopenia	7.1% 23/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.4% 23/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Neutropenia	17.0% 55/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	19.4% 60/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Thrombocytopenia	14.5% 47/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	13.9% 43/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Constipation	11.1% 36/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	11.7% 36/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Diarrhoea	12.0% 39/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	17.8% 55/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Gingival bleeding	2.8% 9/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.1% 19/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Nausea	25.3% 82/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	30.7% 95/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Stomatitis	4.6% 15/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.8% 18/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Vomiting	11.4% 37/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	13.3% 41/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Asthenia	15.1% 49/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	13.6% 42/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Fatigue	17.6% 57/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	19.1% 59/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Pyrexia	5.9% 19/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.5% 20/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Weight decreased	5.6% 18/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.2% 16/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Decreased appetite	16.7% 54/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	13.6% 42/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Arthralgia	7.1% 23/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	9.4% 29/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Back pain	4.3% 14/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.1% 19/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Bone pain	6.2% 20/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	8.1% 25/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Myalgia	12.0% 39/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	14.2% 44/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Pain in extremity	7.4% 24/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.5% 20/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Dizziness	4.0% 13/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	8.1% 25/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Headache	8.6% 28/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.8% 24/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Neuropathy peripheral	17.3% 56/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.3% 38/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Paraesthesia	8.6% 28/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.9% 40/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Peripheral sensory neuropathy	5.6% 18/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.2% 16/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Polyneuropathy	6.2% 20/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.1% 22/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Proteinuria	8.0% 26/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.1% 19/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Cough	8.0% 26/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.8% 21/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.4% 24/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.8% 24/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Epistaxis	13.6% 44/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.6% 39/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Alopecia	43.2% 140/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	41.1% 127/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypertension	15.7% 51/324 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	13.3% 41/309 • 19 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.