PALLAS: PALbociclib CoLlaborative Adjuvant Study

Sponsor

Alliance Foundation Trials, LLC. (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02513394

Collaborator

Austrian Breast & Colorectal Cancer Study Group (Other), NSABP Foundation Inc (Other), PrECOG, LLC. (Other), Breast International Group (Other), Pfizer (Industry)

5,796

Enrollment

438

Locations

Arms

121

Duration (Months)

13.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a prospective, two arm, international, multicenter, randomized, open-label Phase III study evaluating the addition of 2 years of palbociclib to standard adjuvant endocrine therapy for patients with HR+ / HER2- early breast cancer (EBC).

The purpose of the PALLAS study is to determine whether the addition of palbociclib to adjuvant endocrine therapy will improve outcomes over endocrine therapy alone for HR+/HER2- early breast cancer. Assessment of a variety of correlative analysis, including evaluation of the effect of palbociclib in genomically defined tumor subgroups, is planned.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Palbociclib Drug: Standard Adjuvant Endocrine Therapy	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

5796 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

PALbociclib CoLlaborative Adjuvant Study: A Randomized Phase III Trial of Palbociclib With Standard Adjuvant Endocrine Therapy Versus Standard Adjuvant Endocrine Therapy Alone for Hormone Receptor Positive (HR+) / Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Early Breast Cancer

Study Start Date :

Aug 1, 2015

Actual Primary Completion Date :

Nov 1, 2020

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Drug: Palbociclib Drug: Standard Adjuvant Endocrine Therapy
Other: Arm B Standard adjuvant endocrine therapy for a duration of at least 5 years.	Drug: Standard Adjuvant Endocrine Therapy

Arm

Intervention/Treatment

Experimental: Arm A

Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.

Drug: Palbociclib

Drug: Standard Adjuvant Endocrine Therapy

Other: Arm B

Standard adjuvant endocrine therapy for a duration of at least 5 years.

Drug: Standard Adjuvant Endocrine Therapy

Outcome Measures

Primary Outcome Measures

Invasive Disease Free Survival (iDFS) [4 years]
Invasive disease-free survival (iDFS) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC) at 4 years. iDFS is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, second primary invasive cancer of non-breast origin or death from any cause. Direct comparison between arms used time to iDFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered iDFS at 4 years is reported.

Secondary Outcome Measures

Invasive Disease Free Survival (iDFS) Excluding Second Primary Invasive Cancers of Non-breast Origin. [4 years]
Invasive disease-free survival (iDFS, excluding second primary invasive cancers of non-breast origin) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC) at 4 years. iDFS excluding second primary invasive cancers of non-breast origin is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause. Second primary invasive cancers of non-breast origin will not be considered as events for this endpoint. Direct comparison between arms used time to iDFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered iDFS at 4 years is reported.
Distant Recurrence-free Survival (DRFS) [4 years]
Compare time to distant recurrence-free survival (DRFS). Distant recurrence is defined according to STEEP criteria as the time from randomization to the date of the first event: distant recurrence or death from any cause. Patients with a locoregional recurrence will continue to be followed for DRFS. Surviving patients who are event-free will be censored at: the date of last disease assessment, or withdrawal of consent to be followed, or death whichever came first. Direct comparison between arms used time to DRFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered DRFS at 4 years is reported.
Overall Survival (OS) [4 years]
Compare overall survival (OS). Overall survival is defined as the time period between randomization and death. Surviving patients classified as lost-to-follow up or having withdrawn consent to be followed will be censored at their date of last contact or withdrawal of consent to be followed, whichever occurs first.
Locoregional Recurrences-free Survival (LRRFS) [4 years]
Compare locoregional recurrence-free survival (LRRFS). LRRFS is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, or death from any cause. Patients with second primary invasive cancers of non-breast origin or distant recurrence will be censored at the date of diagnosis. Surviving patients who are event-free will be censored at: the date of last disease assessment, or withdrawal of consent to be followed, whichever occurs first.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed informed consent prior to study specific procedures.
Age ≥18 years (or per national guidelines).
Pre- and postmenopausal women or men with Stage II (Stage IIA limited to max. 1000 patients) or Stage III early invasive breast cancer
Patients with multicentric and/or multifocal and/or bilateral early invasive breast cancer are eligible if all histopathologically examined tumors meet pathologic criteria for ER+ and/or PR+ and HER2-.
Patients must have histologically confirmed ER+ and/or PR+, HER2-, early invasive breast cancer.
Patients must have undergone adequate (definitive) breast surgery for the current malignancy.

FFPE tumor tissue block must be confirmed to be received at the central sample repository prior to randomization.

ECOG performance status 0-1.
Patients must be able and willing to swallow and retain oral medication.
Serum or urine pregnancy test must be negative in premenopausal women within 14 days of randomization, or in women with amenorrhea of less than 12 months at time of randomization.
Patients who received neo/adjuvant therapy must be after last dose of chemotherapy and/or biologic therapy and must have sufficient resolution of side effects.
Patients who received breast/axilla/post-mastectomy chest wall radiotherapy must be after last dose of radiotherapy and must have sufficient resolution of side effects.
Patients must have sufficient resolution of any surgical side effects (no active wound healing complications).

-Patients must either be initiating or have already started adjuvant hormonal treatment. -

Patients who already received neo/adjuvant endocrine therapy are eligible as long as they are enrolled within 12 months of initial histological diagnosis and after completing no more than 6 months of adjuvant endocrine therapy.
Absolute neutrophil count ≥ 1,500/µL
Platelets ≥ 100,000/ mm3
Hemoglobin ≥ 10g/dL
Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in patients with documented Gilbert's Syndrome.
Aspartate amino transferase (AST or SGOT) and alanine amino transferase (ALT or SGPT) ≤ 1.5 × institutional ULN.
Serum creatinine below the upper limit of the institutional normal range (ULN) or creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with serum creatinine levels above institutional ULN.

Exclusion Criteria:

Concurrent therapy with other Investigational Products.
Prior therapy with any CDK inhibitor.
Patients with Stage I or IV breast cancer are not eligible.
History of allergic reactions attributed to compounds of chemical or biologic composition similar to palbociclib.
Patients receiving any medications or substances that are potent inhibitors or inducers of
CYP3A isoenzymes within 7 days of randomization.
Uncontrolled intercurrent illness that would limit compliance with study requirements.
Pregnant women, or women of childbearing potential without a negative pregnancy test within 14 days prior to randomization.
Patients with a history of any malignancy are ineligible
Patients who previously received endocrine therapy within 5 years prior to diagnosis of the current malignancy.
Patients on antiretroviral therapy.
Patients with clinically significant history of any chronic liver disease.
Patients receiving concurrent exogenous hormone therapy (topical vaginal estrogen therapy is allowable).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama	United States	36604
2	Southern Cancer Center PC - Providence	Mobile	Alabama	United States	36608
3	Katmai Oncology Group	Anchorage	Alaska	United States	99508
4	Providence Alaska Cancer Center	Anchorage	Alaska	United States	99508
5	Mayo Clinic in Arizona	Phoenix	Arizona	United States	85054
6	Kaiser Permanente Anaheim Medical Center	Anaheim	California	United States	92806
7	Kaiser Permanente Baldwin Park Medical Center	Baldwin Park	California	United States	91706
8	Kaiser Permanente Bellflower Medical Center	Bellflower	California	United States	90706
9	Kaiser Permanente Fontana Medical Center	Fontana	California	United States	92335
10	Marin Cancer Care	Greenbrae	California	United States	94904
11	Marin Cancer Center	Greenbrae	California	United States	94904
12	Kaiser Permanente Harbor City Medical Center	Harbor City	California	United States	90710
13	Kaiser Permanente Irvine Medical Center	Irvine	California	United States	92618
14	UCSD Moores Cancer Center	La Jolla	California	United States	92093
15	Long Beach Memorial Medical Center - Todd Cancer Institute	Long Beach	California	United States	90806
16	Kaiser Permanente Sunset Medical Center	Los Angeles	California	United States	90027
17	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
18	Kaiser Permanente Oakland Medical Center	Oakland	California	United States	94611
19	Palo Alto Medical Foundation Health Care	Palo Alto	California	United States	94301
20	Kaiser Permanente Panorama City Medical Center	Panorama City	California	United States	91402
21	Kaiser Permanente Riverside Medical Center	Riverside	California	United States	92505
22	Kaiser Permanente Roseville Medical Center	Roseville	California	United States	95661
23	Kaiser Permanente Sacramento Medical Center	Sacramento	California	United States	95825
24	University of California	San Diego	California	United States	92093
25	Kaiser Permanente San Diego Medical Center	San Diego	California	United States	92120
26	Sharp Memorial Hospital	San Diego	California	United States	92123
27	Kaiser Permanente San Francisco Medical Center	San Francisco	California	United States	94115
28	UCSF Helen Diller Comprehensive Cancer Center	San Francisco	California	United States	94115
29	Kaiser Permanente San Jose Medical Center	San Jose	California	United States	95119
30	Kaiser Permanente San Leandro Medical Center	San Leandro	California	United States	94577
31	Kaiser Permanente San Marcos Medical Center	San Marcos	California	United States	92078
32	Kaiser Permanente Santa Clara Medical Center	Santa Clara	California	United States	95051
33	Kaiser Permanente South San Francisco Medical Center	South San Francisco	California	United States	94080
34	Stanford Women's Cancer Center	Stanford	California	United States	94305
35	Kaiser Permanente Vallejo Medical Center	Vallejo	California	United States	94589
36	Kaiser Permanente Walnut Creek Medical Center	Walnut Creek	California	United States	94596
37	Kaiser Permanente Cadillac Medical Center	West Los Angeles	California	United States	90034
38	Kaiser Permanente Woodland Hills Medical Center	Woodland Hills	California	United States	91367
39	Western States Cancer Research NCORP	Denver	Colorado	United States	80222
40	Hartford Hospital	Hartford	Connecticut	United States	06102
41	Memorial Sloan Cancer Center - Hartford Healthcare Center Institute at HOCC	New Britain	Connecticut	United States	06053
42	Christiana Health System - Christiana Hospital	Newark	Delaware	United States	19718
43	Georgetown University Medical Center	Washington	District of Columbia	United States	20007
44	George Washington University Medical Faculty Associates	Washington	District of Columbia	United States	20037
45	Morton Plant Hospital	Clearwater	Florida	United States	33756
46	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224
47	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida	United States	33140
48	University of Miami Miller School of Medicine Sylvester Cancer Center	Miami	Florida	United States	33136
49	Advent Health Orlando	Orlando	Florida	United States	32804
50	Orlando Health Cancer Institute	Orlando	Florida	United States	32806
51	Phoebe Putney Memorial Hospital	Albany	Georgia	United States	31701
52	Emory University Hospital	Atlanta	Georgia	United States	30322
53	Memorial Health University Medical Center	Savannah	Georgia	United States	317404
54	Rush University Medical Center	Chicago	Illinois	United States	60612
55	University of Illinois	Chicago	Illinois	United States	60612
56	University of Chicago Cancer Center LAPS	Chicago	Illinois	United States	60637
57	Cancer Care Specialist of Central Illinois	Decatur	Illinois	United States	62526
58	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
59	NorthShore University Health System - Evanston Hospital	Evanston	Illinois	United States	60201
60	Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
61	Joliet Oncology Hematology Associates Limited	Joliet	Illinois	United States	60435
62	Advocate Lutheran General Hospital	Park Ridge	Illinois	United States	60068
63	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
64	OSF Saint Anthony Medical Center	Rockford	Illinois	United States	61108
65	Orchard Healthcare Research Inc.	Skokie	Illinois	United States	60017
66	NorthShore Hematology Oncology-Libertyville	Skokie	Illinois	United States	60077
67	Carle Cancer Center	Urbana	Illinois	United States	61801
68	Indiana University - Melvin and Bren Simon Cancer Center LAPS	Indianapolis	Indiana	United States	46202
69	IU Health Ball Memorial Hospital	Muncie	Indiana	United States	47303
70	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa	United States	50010
71	McFarland Clinic, P.C.	Ames	Iowa	United States	50010
72	Physicians' Clinic of Iowa PC	Cedar Rapids	Iowa	United States	52403
73	Iowa Oncology Research Assoc	Des Moines	Iowa	United States	50309
74	Medical Oncology and Hematology Associates - Des Moines	Des Moines	Iowa	United States	50309
75	University of Iowa Hospitals & Clinics	Iowa City	Iowa	United States	52242
76	Covenant Medical Center	Waterloo	Iowa	United States	50702
77	University of Kentucky-Markey Cancer Center	Lexington	Kentucky	United States	40536
78	Norton Cancer Institute - Brownsboro	Louisville	Kentucky	United States	20202
79	Ochsner Medical Center	New Orleans	Louisiana	United States	70121
80	Eastern Maine Medical Center d/b/a Northern Light Cancer Institute	Bangor	Maine	United States	04401
81	New England Cancer Specialists - Scarborough	Scarborough	Maine	United States	04074
82	Anne Arundel Medical Center	Annapolis	Maryland	United States	21401
83	Mercy Medical Center	Baltimore	Maryland	United States	21202
84	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
85	MedStar Good Samaritan Hospital	Baltimore	Maryland	United States	21218
86	MedStar Franklin Square Medical Center Winberg Cancer Institute	Baltimore	Maryland	United States	21237
87	Medstar Union Memorial Hospital	Baltimore	Maryland	United States	21237
88	JHU Sidney Kimmel Comprehensive Cancer Center LAPS	Baltimore	Maryland	United States	21287
89	Frederick Regional Health System James M Stockman Cancer Institute	Baltimore	Maryland	United States	21701
90	Maryland Oncology Hematology PA	Bethesda	Maryland	United States	20817
91	Tidal Health Peninsula Regional	Salisbury	Maryland	United States	21801
92	Holy Cross Hospital	Silver Spring	Maryland	United States	20910
93	Tufts Medical Center	Boston	Massachusetts	United States	02111
94	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
95	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
96	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
97	Lowell General Hospital	Lowell	Massachusetts	United States	01852
98	Beth Israel Deaconess Hospital - Plymouth Jordan Club Cancer Center	Plymouth	Massachusetts	United States	02360
99	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
100	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan	United States	49503
101	Spectrum Health Butterworth Research Pharmacy	Grand Rapids	Michigan	United States	49503
102	Trinity Health Michigan	Livonia	Michigan	United States	48152
103	Essentia Health NCORP	Duluth	Minnesota	United States	55805
104	Mayo Clinic-Rochester	Rochester	Minnesota	United States	55902
105	Mayo Clinic	Rochester	Minnesota	United States	55905
106	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota	United States	56303
107	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
108	Metro Minnesota Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
109	St. Luke's Hospital	Kansas City	Missouri	United States	64111
110	Phelps Country Regional Medical Center	Rolla	Missouri	United States	65401
111	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
112	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
113	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
114	Cancer Research for the Ozarks NCORP	Springfield	Missouri	United States	65807
115	Nebraska Hematology and Oncology	Lincoln	Nebraska	United States	68506
116	Southeast Nebraska Cancer Center	Lincoln	Nebraska	United States	68510
117	Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
118	New Hampshire Oncology-Hematology PA, Concord	Concord	New Hampshire	United States	03301
119	New Hampshire Oncology-Hematology PA	Hooksett	New Hampshire	United States	03106
120	Solinsky Center for Cancer Care	Hooksett	New Hampshire	United States	03106
121	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
122	Norris Cotton Cancer Center - Nashua	Lebanon	New Hampshire	United States	03766
123	Englewood Hospital and Medical Center	Englewood	New Jersey	United States	07631
124	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
125	Rutgers Cancer Center Institute of New Jersey	New Brunswick	New Jersey	United States	08903
126	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey	United States	08876
127	University of New Mexico Comprehensive Cancer Center	Albuquerque	New Mexico	United States	87131
128	University of New Mexico	Albuquerque	New Mexico	United States	87131
129	Montefiore Medical Center - Einstein Campus	Bronx	New York	United States	10461
130	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
131	Mary Imogene Bassett Hospital	Cooperstown	New York	United States	11326
132	Hematology Oncology Associates of Central New York - East Syracuse	East Syracuse	New York	United States	13057
133	Queens Hospital Center	Jamaica	New York	United States	11432
134	Northwell Health NCORP	New Hyde Park	New York	United States	11042
135	Beth Israel Medical Center - New York	New York	New York	United States	10011
136	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
137	Memorial Sloan Kettering Cancer Center - LAPS	New York	New York	United States	10065
138	Oneonta FoxCare Center	Oneonta	New York	United States	13820
139	SUNY Upstate Medical University	Syracuse	New York	United States	13210
140	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28204
141	The Charlotte-Mecklenburg Hospital Authority	Charlotte	North Carolina	United States	28204
142	Duke University Medical Center	Durham	North Carolina	United States	27710
143	Cone Health Cancer Center	Greensboro	North Carolina	United States	27403
144	Kinston Medical Specialists, PA	Kinston	North Carolina	United States	28504
145	First Health of the Carolinas - Moore Regional Hospital	Pinehurst	North Carolina	United States	28374
146	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
147	Cleveland Clinic	Cleveland	Ohio	United States	44195
148	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
149	Cleveland Clinic Cancer Center/Hillcrest Hospital	Mayfield Heights	Ohio	United States	44124
150	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma	United States	73505
151	Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
152	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
153	Providence Portland Medical Center	Portland	Oregon	United States	97213
154	Hematology & Oncology Associates of Northeastern PA	Dunmore	Pennsylvania	United States	18512
155	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States	17033
156	Lancaster General Hospital	Lancaster	Pennsylvania	United States	17604
157	Hospital of the University of Pennsylvania Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania	United States	19104
158	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
159	Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19106
160	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
161	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
162	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
163	UPMC MaGee Women's Hospital	Pittsburgh	Pennsylvania	United States	15213
164	University of Pittsburgh Cancer Institute- Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
165	Reading Hospital/McGlinn Cancer Institute	Wyomissing	Pennsylvania	United States	19610
166	WellSpan Health York Cancer Center	York	Pennsylvania	United States	17403
167	Rhode Island Hospital	Providence	Rhode Island	United States	02903
168	Women & Infants Hospital of Rhode Island	Providence	Rhode Island	United States	02905
169	Lexington Medical Center/Lexington Oncology Associates	Columbia	South Carolina	United States	29169
170	Avera Cancer Institute-Aberdeen	Aberdeen	South Dakota	United States	57401
171	Monument Health Rapid City Hospital	Rapid City	South Dakota	United States	57701
172	Rapid City Regional Hospital/Regional Cancer Care Institute	Rapid City	South Dakota	United States	57701
173	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
174	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37204
175	Nashville General Hospital at Meharry	Nashville	Tennessee	United States	37208
176	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas	United States	77030
177	Houston Methodist Hospital Cancer Center	Houston	Texas	United States	77030
178	MD Anderson Cancer Center	Houston	Texas	United States	77030
179	Doctors Hospital of Laredo	Laredo	Texas	United States	78045
180	Huntsman Cancer Institute - University of Utah	Salt Lake City	Utah	United States	84112
181	Inova Schar Cancer Institute	Fairfax	Virginia	United States	22031
182	VCU Massey Cancer Center	Richmond	Virginia	United States	23298
183	CAMC Cancer Center	Charleston	West Virginia	United States	25304
184	ThedaCare Regional Cancer Center	Appleton	Wisconsin	United States	54913
185	HSHS Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301
186	Gunderson Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
187	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
188	Wheaton Franciscan Healthcare - St. Joseph	Milwaukee	Wisconsin	United States	53210
189	Columbia St. Mary's Water Tower Medical Commons	Milwaukee	Wisconsin	United States	53711
190	Wheaton Franciscan Healthcare-All Saints	Racine	Wisconsin	United States	53405
191	Orchard Healthcare Research Inc.	Waukesha	Wisconsin	United States	53188
192	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin	United States	53188
193	Wheaton Franciscan Healthcare - Wauwatosa	Wauwatosa	Wisconsin	United States	53226
194	Southern Highlands Cancer Centre	Bowral	New South Wales	Australia	2576
195	Coffs Harbour Health Campus - MNCCI	Coffs Harbour	New South Wales	Australia	2450
196	The Breast & Endocrine Centre	Gateshead	New South Wales	Australia	2290
197	Gosford Hospital	Gosford	New South Wales	Australia	2500
198	Macquarie University Hospital	Macquarie Park	New South Wales	Australia	2109
199	Orange Health Service	Orange	New South Wales	Australia	2800
200	Wollongong Hospital	Wollongong	New South Wales	Australia	2500
201	Royal Brisbane & Women's Hospital	Brisbane	Queensland	Australia	4029
202	Flinders Drive	Bedford Park	South Australia	Australia	5042
203	Royal Hobart Hospital	Hobart	Tasmania	Australia	7000
204	The Northern Hospital	Epping	Victoria	Australia	3076
205	St Vincent's Hospital	Fitzroy	Victoria	Australia	3065
206	Peninsula Health - Frankston Hospital	Frankston	Victoria	Australia	3199
207	University Hospital, Geelong	Geelong	Victoria	Australia	3220
208	Peter MacCallum Cancer Centre	Melbourne	Victoria	Australia	3000
209	Peninsula Health - Frankston Hospital	Melbourne	Victoria	Australia
210	Western Health, Sunshine Hospital	St. Albans	Victoria	Australia	3021
211	South West Healthcare, Warrnambool	Warrnambool	Victoria	Australia	3280
212	St John of God Bunbury Hospital	Bunbury	Western Australia	Australia	6231
213	Fiona Stanley Hospital	Murdoch	Western Australia	Australia
214	Breast Cancer Research Centre - WA	Nedlands	Western Australia	Australia	6009
215	LKH Feldkirch, Department of Internal Medicine	Feldkirch		Austria	6807
216	LKH Univ Klinikum Graz, Dept of Internal Med. and Oncology	Graz		Austria	8036
217	Medical University of Graz, Gyn. Dept.	Graz		Austria	8036
218	University Hospital Innsbruck, Department of Obstetrics and Gynaecology	Innsbruck		Austria	6020
219	BKH Kufstein, Innere Medizin	Kufstein		Austria	6330
220	LKH Hochsteiermark Leoben	Leoben		Austria	8700
221	Hospital of the Sisters of Charity Linz, Surg. Dept., Breast Health Center	Linz		Austria	4010
222	Kepler Universitätsklinikum Med. Campus III	Linz		Austria	4020
223	Weinviertelklinikum Mistelbach, Department of Surgery	Mistelbach		Austria	2130
224	BHS Ried, Abt. f. Gynäkologie	Ried		Austria	4910
225	LKH Salzburg, Univ. Klinik f. Innere Med. III	Salzburg		Austria	5020
226	Universitätsklinikum St. Pölten, Innere Medizin	St. Pölten		Austria	3100
227	Breast Centre Dr. Wette Viktor	St. Veit an der Glan		Austria	9300
228	Phyrn-Eisenwurzen Klinikum Steyr	Steyr		Austria	4400
229	Medical University of Vienna Department of Obstetrics and Gynaecology	Vienna		Austria	1090
230	Medical University Vienna - Coop Group Surgery/Oncology	Vienna		Austria	1090
231	Hospital Hietzing, Gynecology	Vienna		Austria	1130
232	St. Josef Krankenhaus, Department of Internal I	Vienna		Austria	1130
233	Klinik Ottakring	Vienna		Austria	1160
234	Salzkammergut-Klinikum Vöcklabruck	Voecklabruck		Austria	4840
235	Brustordination Dr. Thiel	Weiz		Austria	8160
236	Klinikum Wels - Grieskirchen GmbH, Department of Internal Medicine IV	Wels		Austria	4600
237	LKH Wolfsberg, Department of Surgery	Wolfsberg		Austria	9400
238	Landesklinikum Wr. Neustadt, Department of Surgery	Wr. Neustadt		Austria	2700
239	OLV ziekenhuis Aalst/Radiotherapy-Oncology	Aalst		Belgium	9300
240	CHU Saint Pierre/Medical Oncology	Brussels		Belgium	1000
241	Institut Jules Bordet/Medical Oncology Department	Brussels		Belgium	1000
242	Cliniques Universitaires Saint-Luc, Oncologisch centrum	Bruxelles		Belgium	1200
243	Grand Hopital de Charleroi - Oncologie-hématologie	Charleroi		Belgium	6000
244	University Hospital Antwerp (UZA)	Edegem		Belgium	2650
245	UZ Leuven/ Gynaecologie-Oncologie	Leuven		Belgium	3000
246	CHC - Saint-Joseph/Oncology-Hematology	Liège		Belgium	4000
247	CHU Sart Tilman Liège (Medical Oncology)	Liège		Belgium	4000
248	Clinique et Maternite Sainte-Elisabeth - Oncology Department	Namur		Belgium	5000
249	CHR - Centre Hospitalier Peltzer La Tourelle/ Oncology Department	Verviers		Belgium	4800
250	GZA Ziekenhuizen (Campus Sint-Augustinus) / Oncologische Centrum	Wilrijk		Belgium	2610
251	Tom Baker Cancer Centre - Dept. of Oncology	Calgary	Alberta	Canada	T2N4N2
252	BC Cancer Agency- Abbotsford Centre	Abbotsford	British Columbia	Canada	V2S0C2
253	BC Cancer Agency - Sindi Ahluwalia Hawkins Centre for the Southern Interior	Kelowna	British Columbia	Canada	V1Y5L3
254	BC Cancer Agency - Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z4E6
255	CancerCare Manitoba - St. Boniface Hospital	Winnipeg	Manitoba	Canada	R2H2A6
256	The Vitalite Health Network - Dr. Leon Richard	Moncton	New Brunswick	Canada	E1C8X3
257	Horizon Health Network - Saint John Regional Hospital	Saint John	New Brunswick	Canada	E2L4L4
258	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H2Y9
259	Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V5C2
260	Kingston General Hospital, Cancer Centre of Southeastern Ontario/Oncology	Kingston	Ontario	Canada	K7L5P9
261	Grand River Regional Cancer Center	Kitchener	Ontario	Canada	N2G1G3
262	Niagara Health System	St. Catharines	Ontario	Canada	L2S0A9
263	Sunnybrook	Toronto	Ontario	Canada	M4N3M
264	University Health Network Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G1X5
265	The Jewish General Hospital	Montréal	Quebec	Canada	H2L4M1
266	CHUM Hôtel Dieu	Montréal	Quebec	Canada	H2W1T8
267	CHU de Québec - Hôpital du St Sacrement	Québec	Quebec	Canada	G1S4L8
268	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T7TI
269	Saskatoon Cancer Center, University of Saskatchewan	Saskatoon	Saskatchewan	Canada	S7N4H4
270	University Hospital Aachen	Aachen		Germany	52074
271	Praxisklinik Krebsheilkunde für Frauen	Berlin		Germany	10367
272	Helios Klinikum Berlin-Buch	Berlin		Germany	13125
273	Studienzentrum City	Berlin		Germany	14169
274	Marienhospital Bottrop, Klinik für Gynäkologie und Geburtshilfe	Bottrop		Germany	46236
275	Studien GbR Braunschweig, Lorenz&HeckerWesche	Braunschweig		Germany	38100
276	Praxis und Tagesklinik für gynäkologische Onkologie,	Ebersberg		Germany	85560
277	MVZ Eggenfelden	Eggenfelden		Germany	84307
278	Frauenklinik/University Hospital Erlangen	Erlangen		Germany	91054
279	Centrum für Hämatologie und Onkologie Bethanien	Frankfurt		Germany	60389
280	Agaplesion Markus Krankenhaus	Frankfurt		Germany	60431
281	Klinikum Frankfurt Höchst	Frankfurt		Germany	65929
282	Onkol. GP Dres. med. Wilke/Wagner/Petzoldt	Fürth		Germany	90766
283	Universitätsfrauenklinik Halle (Saale)	Halle (Saale)		Germany	'06120
284	University Medical Center Hamburg-Eppendorf, Department of Gynecology	Hamburg		Germany	20246
285	Albertinen Krankenhaus	Hamburg		Germany	22457
286	Städtisches Klinikum Karlsruhe	Karlsruhe		Germany	76133
287	Elisabeth Krankenhaus Kassel Brustzentrum	Kassel		Germany	34125
288	St. Elisabeth Krankenhaus Leipzig	Leipzig		Germany	04277
289	St. Vincenz KH Limburg Frauenklinik	Limburg		Germany	65549
290	UKSH Campus Lübeck, Klinik für Frauenheilkunde und Geburtshilfe	Lübeck		Germany	23538
291	Universitätsmedizin Mainz	Mainz		Germany	55131
292	Praxis Gynäkologie Arabella	München		Germany	81925
293	University Clinic Oldenburg	Oldenburg		Germany	26133
294	Oncologianova GmbH	Recklinghausen		Germany	45657
295	HELIOS Klinik Rottweil - Gynäkologie	Rottweil		Germany	78628
296	St. Josefs-Hospital	Wiesbaden		Germany	65189
297	Országos Onkológiai Intézet - "B" Belgyógyászati Onkológiai és Klinikai Farmakológiai Osztály	Budapest		Hungary	1122
298	Uzsoki Utcai Kórház - Onkoradiológia, Sugárterápia, Fővárosi Onkoradiológiai Központ	Budapest		Hungary	1145
299	University of Debrecen Medical Center, Clinic of Oncology	Debrecen		Hungary	4032
300	Petz Aladár Megyei Oktatókórház - Onkoradiológiai Osztály	Győr		Hungary	9023
301	Szegedi Tudomanyegyetem Általános Orvostudományi Kar Szent-Györgyi Albert Klinikai Központ, Onkoterápiás Klinika	Szeged		Hungary	6720
302	Bon Secours Hospital, Cork	Cork		Ireland
303	Cork University Hospital, Oncology Clinical Trials Unit	Cork		Ireland
304	Beaumont Hospital - Cancer Clinical Trials Unit	Dublin		Ireland
305	Mater Misericordiae University Hospital	Dublin		Ireland
306	St James's Hospital, Cancer Clinical Trials Office, Old Admin Building,	Dublin		Ireland
307	St Vincent Hospital - Medical Oncology Research Department	Dublin		Ireland
308	University Hospital Limerick, Midwestern Cancer Centre	Limerick		Ireland
309	Sligo University Hospital	Sligo		Ireland
310	University Hospital Waterford, Cancer Research Department	Waterford		Ireland
311	Rabin Medical Center (RMC)	Petah Tikva	Central	Israel	49100
312	Sheba Medical Center Tel Hashomer	Ramat Gan	Tel Aviv	Israel	52621
313	Sourasky Medical Center	Tel-Aviv		Israel	64239
314	Azienda Ospedaliero-Universitaria di Ferrara	Ferrara		Italy	44124
315	Azienda Ospedaliero-Universitaria Careggi/Florence University/Radiation Oncology Unit	Florence		Italy	50134
316	Department of Internal Medicine (DIMI) - IRCCS San Martino University Hospital	Genoa		Italy	16132
317	P.O. Misericordia AUSL Toscana Sud Est	Grosseto		Italy	58100
318	Ospedale "Mater Salutis" di Legnago, Dept. of Medical Oncology	Legnago		Italy	37045
319	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) IRCCS	Meldola		Italy	47014
320	Ospedale San Raffaele	Milano		Italy	20132
321	Istituto Europeo di Oncologia	Milano		Italy	20141
322	Policlinico di Monza - Istituto di Oncologia del Policlinico di Monza	Monza		Italy	20900
323	Medical Oncology Unit; University Hospital of Parma (Azienda Ospedaliero-Universitaria di Parma)	Parma		Italy	43100
324	Nuovo Ospedale di Prato (NOP) - Azienda USL4 Prato	Prato		Italy	59100
325	ASST Bergamo Ovest	Treviglio		Italy	24047
326	S. Anna Hospital (Ospedale Sant'Anna)- Turin	Turin		Italy	10126
327	Nagoya City University Hospital/Dept. of Breast & Endocrine Surgery	Nagoya	Aichi	Japan	467-8601
328	Department of Breast Surgery National Hospital Organization Hokkaido Cancer Center	Sapporo	Hokkaido	Japan	003-0804
329	Chiba Cancer Center	Chiba		Japan	260-8717
330	Kyoto University Hospital/Breast Surgery	Kyoto		Japan	606-8507
331	National Hospital Organization Osaka National Hospital	Osaka		Japan	540-0006
332	Osaka International Cancer Institute	Osaka		Japan	541-8567
333	Seoul National University Hospital, Hematology-Medical Oncology	Seoul		Korea, Republic of	03080
334	Severance Hospital Medical Doctor at Department of Medical Oncology	Seoul		Korea, Republic of	03722
335	Samsung Medical Centre, Breast Cancer Center, Department of Medicine, Division of Hematology/Oncology	Seoul		Korea, Republic of	06351
336	Centro Médico Zambrano Hellion	Monterrey	Nuevo León	Mexico	66278
337	Centro Oncológico Estatal ISSEMYM	Toluca de Lerdo	Toluca	Mexico	50180
338	National Cancer Institute Mexico, Breast Cancer Department	Mexico City		Mexico	14080
339	Hagaziekenhuis	Den Haag		Netherlands	2545 AA
340	Máxima Medisch Centrum	Eindhoven		Netherlands	5631 BM
341	Zuyderland Ziekenhuis, Oncology	Geleen		Netherlands	6162 BG
342	St Antonius Hospital	Nieuwegein		Netherlands	3435 CM
343	Zaans Medical Center	Zaandam		Netherlands	1502 DV
344	Isala, Dept of Medical Oncology	Zwolle		Netherlands	8025 AB
345	Uniwersyteckie Centrum Kliniczne (UCK), Klinika Onkologii I Radioterapii	Gdansk		Poland	80-952
346	Opolskie Centrum Onkologii, Oddzial Onkologii Klinicznej	Opole		Poland	45-001
347	Klinika Nowotworów Piersi i Chirurgii Rekonstrukcyjnej, Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie	Warsaw		Poland	02-781
348	Instytut MSF Spółka z ograniczoną odpowiedzialnością	Łódź		Poland
349	Instituto Português de Oncologia (IPO) de Lisboa Francisco Gentil	Lisboa		Portugal	1099-023
350	Hospital da Luz	Lisboa		Portugal	1500-650
351	CUF Descobertas Hospital, Hemato-Oncologia	Lisboa		Portugal	1998-018
352	Centro Clinico Champalimaud	Lisbon		Portugal	1400-038
353	Instituto Português de Oncologia (IPO) Francisco Gentil do Porto	Porto		Portugal	4200
354	Complejo Hospitalario Universitario A Coruña (CHUAC)	A Coruña		Spain	15006
355	Centro Oncologico de Galicia	A Coruña		Spain	15009
356	Hospital General Universitario Alicante	Alicante		Spain	03010
357	ICO Badalona	Badalona		Spain	08916
358	Hospital del Mar	Barcelona		Spain	08003
359	Hospital Universitari Quirón Dexeus	Barcelona		Spain	08028
360	Hospital Clinic Barcelona	Barcelona		Spain	08036
361	Hospital General de Granollers	Barcelona		Spain	08402
362	Instituto Catalán de Oncología (ICO) de L'Hospitalet de Llobregat	Barcelona		Spain	08908
363	Hospital Vall d´Hebron	Barcelona		Spain	8035
364	Hospital Universitario de Burgos	Burgos		Spain	09006
365	Consorcio Hospitalario Provincial de Castellon	Castellón De La Plana		Spain	12002
366	San Pedro de Alcántara	Cáceres		Spain	10003
367	Hospital Reina Sofía	Córdoba		Spain	14004
368	Hospital General Universitario de Elche	Elche		Spain	03203
369	ICO/ H. Josep Trueta	Girona		Spain	17007
370	Complejo asistencial universitario de Leon	León		Spain	24001
371	Hospital Universitario Gregorio Marañón	Madrid		Spain	28007
372	MD Anderson Cancer Center	Madrid		Spain	28033
373	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
374	Fundación Jiménez Díaz	Madrid		Spain	28040
375	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
376	Hospital La Paz, Servicio de Oncologia Médica	Madrid		Spain	28046
377	CIOCC - Centro Integral Oncológico Clara Campal / Hospital HM Universitario Sanchinarro	Madrid		Spain	28050
378	Hospital Puerta de Hierro Majadahonda, Oncologia Médica	Madrid		Spain	28222
379	Hospital Universitario Fundacion Alcorcón	Madrid		Spain	28922
380	Hospital General Universitario José Mª Morales Meseguer	Murcia		Spain	30008
381	Hospital Clínico Universitario Virgen de la Arrixaca	Murcia		Spain	30120
382	Hospital Clínico Universitario Virgen de la Victoria	Málaga		Spain	29010
383	Hospital Universitario Central de Asturias	Oviedo		Spain	33011
384	Hospitali Universitari son Espases	Palma		Spain	07120
385	Hospital Son Llatzer	Palma		Spain	07198
386	Complejo Hospitalario de Navarra	Pamplona		Spain	31008
387	Hospital Universitari Sant Joan de Reus	Reus		Spain	43204
388	Hospital Universitario Donostia	San Sebastián		Spain	20014
389	Hospital de Sant Juan Despi Moisés Broggi	Sant Joan Despì		Spain	08970
390	Hospital Clinico Universitario de Santiago	Santiago		Spain	15706
391	Hospital Unversitario Virgen Macarena	Sevilla		Spain	41009
392	Hospital Quirón Sagrado Corazón	Sevilla		Spain	41013
393	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
394	Consorci Sanitari de Terrassa	Terrassa		Spain	08227
395	Hospital Virgen de la Salud	Toledo		Spain	45004
396	Hospital Clínico Universitario de Valencia	Valencia		Spain	46010
397	Hosital Arnau de Vilanova Valencia	Valencia		Spain	46015
398	Hospital Clinico Universitario Lozano Blesa	Zaragoza		Spain	50009
399	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009
400	Gävle Hospital, Dept. of Oncology	Gävle		Sweden	801 87
401	Sahlgrenska University Hospital, Dept. Oncology	Göteborg		Sweden	413 45
402	Karolinska Universitetssjukhuset, Bröstcentrum A2:00	Stockholm		Sweden	171 76
403	Akademiska Sjukhuset Uppsala (University Hospital), Onkologkliniken	Uppsala		Sweden	751 85
404	Universitetssjukhuset Örebro (University Hospital) Örebro, Onkologkliniken	Örebro		Sweden	701 85
405	Kantonspital Baden	Baden	Aargau	Switzerland	5404
406	Spital STS AG, Onkologiezentrum Thun-Berner Oberland	Thun	Bern	Switzerland	3600
407	Hôpitaux Universitaires de Genève	Genève	Geneva	Switzerland	1211
408	Kantonsspital Graubünden	Chur	Graubünden	Switzerland	7000
409	IOSI-Breast Cancer Unit-Ospedale San Giovanni-Bellinzona	Bellinzona	Tessin	Switzerland	6500
410	Fondazione Oncologia Lago Maggiore, Locarno	Locarno	Tessin	Switzerland	6600
411	Dep. Oncology, University Hospital	Basel		Switzerland	4031
412	HFR Fribourg, Oncology Department	Fribourg		Switzerland	1708
413	Luzerner Kantonsspital, Dept. of Medical Oncology	Luzern		Switzerland	6000
414	Onkologisches Forschungszentrum Klinik St. Anna, Hirslanden	Luzern		Switzerland	6006
415	Kantonsspital St.Gallen, Onkologie/Hämatologie	St.Gallen		Switzerland	9007
416	Brust-Zentrum Zürich	Zurich		Switzerland	8008
417	Universitätsspital Zürich, Klinik für Onkologie	Zurich		Switzerland	8091
418	Changhua Christian Hospital/General Surgery	Changhua	Changhua County	Taiwan	500
419	Kaohsiung Medical University Hospital	Kaohsiung		Taiwan	807
420	National Cheng Kung University Hospital, Division of Hemato-Oncology, Dept. Internal Medicine	Tainan		Taiwan	704
421	National Taiwan University Hospital/Department of Surgery	Taipei		Taiwan	100
422	Taipei Veterans General Hospital/General Surgery	Taipei		Taiwan	112
423	City Hospital Birmingham	Birmingham		United Kingdom	B18 7QH
424	University Hospitals Bristol NHS Foundation Trust	Bristol		United Kingdom	BS2 8ED
425	Velindre Cancer Centre	Cardiff		United Kingdom	CF14 2TL
426	Royal Marsden Hospital Chelsea	Chelsea		United Kingdom	SW3 6JJ
427	The Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 0YN
428	University Hospitals of Leicester	Leicester		United Kingdom	LE1 5WW
429	Royal Liverpool University Hospital	Liverpool		United Kingdom	L7 8XP
430	Guy's and St Thomas' NHS Foundation Trust	London		United Kingdom	SE1 7EH
431	The Royal Marsden Sutton	London		United Kingdom	SW3 6JJ
432	Charing Cross Hospital	London		United Kingdom	W6 8RF UK
433	Maidstone Hospital, Kent Oncology Centre	Maidstone		United Kingdom	ME16 9QQ
434	The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX
435	Northern Centre for Cancer Care	Newcastle upon Tyne		United Kingdom	NE7 7DN
436	Nottingham University Hospitals NHS TRUST UK	Nottingham		United Kingdom	NG5 1PB
437	Weston Park Hospital, Sheffield Teaching Hospitals	Sheffield		United Kingdom	S10 2SJ
438	Royal Cornwall Hospitals NHS Trust, Oncology Trials, Sunrise Centre	Truro		United Kingdom	TR1 3LQ

Sponsors and Collaborators

Alliance Foundation Trials, LLC.
Austrian Breast & Colorectal Cancer Study Group
NSABP Foundation Inc
PrECOG, LLC.
Breast International Group
Pfizer

Investigators

Principal Investigator: Monica Bertagnolli, MD, Alliance Foundation Trials, LLC.
Principal Investigator: Erica Mayer, MD, Dana-Farber Cancer Institute
Principal Investigator: Angela DeMichele, MD, University of Pennsylvania
Principal Investigator: Michael Gnant, MD, ABCSG, Medical University Vienna

Study Documents (Full-Text)

Study Protocol and Statistical Analysis Plan - Dec 23, 2020

More Information

Publications

None provided.

Responsible Party:

Alliance Foundation Trials, LLC.

ClinicalTrials.gov Identifier:

NCT02513394

Other Study ID Numbers:

AFT-05
ABCSG 42
BIG 14-03
2014-005181-30

First Posted:

Jul 31, 2015

Last Update Posted:

Apr 13, 2022

Last Verified:

Mar 1, 2022

Keywords provided by Alliance Foundation Trials, LLC.

HR+/HER2- breast cancer

Palbociclib

Additional relevant MeSH terms:

Breast Neoplasms

Palbociclib

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail

Arm/Group Title	Palbociclib Plus Endocrine Therapy (Arm A)	Endocrine Therapy Alone (Arm B)
Arm/Group Description	Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Standard adjuvant endocrine therapy for a duration of at least 5 years.
Period Title: Overall Study
STARTED	2896	2900
COMPLETED	2884	2877
NOT COMPLETED	12	23

Baseline Characteristics

Arm/Group Title	Palbociclib Plus Endocrine Therapy (Arm A)	Endocrine Therapy Alone (Arm B)	Total
Arm/Group Description	Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Standard adjuvant endocrine therapy for a duration of at least 5 years.	Total of all reporting groups
Overall Participants	2884	2877	5761
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	52	52	52
Sex: Female, Male (Count of Participants)
Female	2867 99.4%	2858 99.3%	5725 99.4%
Male	17 0.6%	19 0.7%	36 0.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	138 4.8%	127 4.4%	265 4.6%
Not Hispanic or Latino	2504 86.8%	2532 88%	5036 87.4%
Unknown or Not Reported	242 8.4%	218 7.6%	460 8%
Race/Ethnicity, Customized (Count of Participants)
Asain	138 4.8%	141 4.9%	279 4.8%
Black or African American/African Heritage	74 2.6%	75 2.6%	149 2.6%
White	2521 87.4%	2498 86.8%	5019 87.1%
Native Hawaiian or other Pacific Islander	4 0.1%	8 0.3%	12 0.2%
American Indian or Alaska Native	14 0.5%	22 0.8%	36 0.6%
Other	37 1.3%	36 1.3%	73 1.3%
Unknown	96 3.3%	97 3.4%	193 3.4%

Outcome Measures

1. Primary Outcome

Title	Invasive Disease Free Survival (iDFS)
Description	Invasive disease-free survival (iDFS) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC) at 4 years. iDFS is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, second primary invasive cancer of non-breast origin or death from any cause. Direct comparison between arms used time to iDFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered iDFS at 4 years is reported.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Palbociclib Plus Endocrine Therapy (Arm A)	Endocrine Therapy Alone (Arm B)
Arm/Group Description	Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Standard adjuvant endocrine therapy for a duration of at least 5 years.
Measure Participants	2884	2877
Number [percentage of participants]	84.2 2.9%	84.5 2.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Palbociclib Plus Endocrine Therapy (Arm A), Endocrine Therapy Alone (Arm B)
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.65
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95% 0.81 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	This two sided p value was stratified by (neo)adjuvant chemotherapy (yes vs no) and age (<=50 vs >50).

2. Secondary Outcome

Title	Invasive Disease Free Survival (iDFS) Excluding Second Primary Invasive Cancers of Non-breast Origin.
Description	Invasive disease-free survival (iDFS, excluding second primary invasive cancers of non-breast origin) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC) at 4 years. iDFS excluding second primary invasive cancers of non-breast origin is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause. Second primary invasive cancers of non-breast origin will not be considered as events for this endpoint. Direct comparison between arms used time to iDFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered iDFS at 4 years is reported.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Palbociclib Plus Endocrine Therapy (Arm A)	Endocrine Therapy Alone (Arm B)
Arm/Group Description	Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Standard adjuvant endocrine therapy for a duration of at least 5 years.
Measure Participants	2884	2877
Number [percentage of patients]	85.4	86.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Palbociclib Plus Endocrine Therapy (Arm A), Endocrine Therapy Alone (Arm B)
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95% 0.82 to 1.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Distant Recurrence-free Survival (DRFS)
Description	Compare time to distant recurrence-free survival (DRFS). Distant recurrence is defined according to STEEP criteria as the time from randomization to the date of the first event: distant recurrence or death from any cause. Patients with a locoregional recurrence will continue to be followed for DRFS. Surviving patients who are event-free will be censored at: the date of last disease assessment, or withdrawal of consent to be followed, or death whichever came first. Direct comparison between arms used time to DRFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered DRFS at 4 years is reported.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Palbociclib Plus Endocrine Therapy (Arm A)	Endocrine Therapy Alone (Arm B)
Arm/Group Description	Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Standard adjuvant endocrine therapy for a duration of at least 5 years.
Measure Participants	2884	2877
Number [percentage of patients]	86.2	87.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Palbociclib Plus Endocrine Therapy (Arm A), Endocrine Therapy Alone (Arm B)
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95% 0.87 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Overall Survival (OS)
Description	Compare overall survival (OS). Overall survival is defined as the time period between randomization and death. Surviving patients classified as lost-to-follow up or having withdrawn consent to be followed will be censored at their date of last contact or withdrawal of consent to be followed, whichever occurs first.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Palbociclib Plus Endocrine Therapy (Arm A)	Endocrine Therapy Alone (Arm B)
Arm/Group Description	Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Standard adjuvant endocrine therapy for a duration of at least 5 years.
Measure Participants	2884	2877
Number [percentage of patients]	93.8	95.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Palbociclib Plus Endocrine Therapy (Arm A), Endocrine Therapy Alone (Arm B)
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95% 0.98 to 1.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Locoregional Recurrences-free Survival (LRRFS)
Description	Compare locoregional recurrence-free survival (LRRFS). LRRFS is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, or death from any cause. Patients with second primary invasive cancers of non-breast origin or distant recurrence will be censored at the date of diagnosis. Surviving patients who are event-free will be censored at: the date of last disease assessment, or withdrawal of consent to be followed, whichever occurs first.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title	Palbociclib Plus Endocrine Therapy (Arm A)	Endocrine Therapy Alone (Arm B)
Arm/Group Description	Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Standard adjuvant endocrine therapy for a duration of at least 5 years.
Measure Participants	2884	2877
Number [percentage of patients]	96.8	95.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Palbociclib Plus Endocrine Therapy (Arm A), Endocrine Therapy Alone (Arm B)
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95% 0.57 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

	Palbociclib Plus Endocrine Therapy (Arm A)		Endocrine Therapy Alone (Arm B)
Time Frame	4 years
Adverse Event Reporting Description	The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).

Arm/Group Title	Palbociclib Plus Endocrine Therapy (Arm A)		Endocrine Therapy Alone (Arm B)
Arm/Group Description	Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.		Standard adjuvant endocrine therapy for a duration of at least 5 years.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	99/2841 (3.5%)		76/2902 (2.6%)
Serious Adverse Events
	Palbociclib Plus Endocrine Therapy (Arm A)		Endocrine Therapy Alone (Arm B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	369/2841 (13%)		229/2902 (7.9%)
Blood and lymphatic system disorders
Anaemia	3/2841 (0.1%)	3	0/2902 (0%)	0
Anaemia macrocytic	1/2841 (0%)	1	0/2902 (0%)	0
Febrile neutropenia	13/2841 (0.5%)	13	0/2902 (0%)	0
Leukocytosis	2/2841 (0.1%)	2	0/2902 (0%)	0
Lymphadenitis	0/2841 (0%)	0	1/2902 (0%)	1
Neutropenia	4/2841 (0.1%)	5	0/2902 (0%)	0
Pancytopenia	1/2841 (0%)	1	0/2902 (0%)	0
Splenic infarction	0/2841 (0%)	0	1/2902 (0%)	1
Cardiac disorders
Acute coronary syndrome	0/2841 (0%)	0	2/2902 (0.1%)	2
Acute myocardial infarction	1/2841 (0%)	1	0/2902 (0%)	0
Angina pectoris	0/2841 (0%)	0	1/2902 (0%)	1
Arteriospasm coronary	1/2841 (0%)	1	0/2902 (0%)	0
Atrial fibrillation	2/2841 (0.1%)	2	4/2902 (0.1%)	4
Atrioventricular block	0/2841 (0%)	0	1/2902 (0%)	1
Atrioventricular block complete	0/2841 (0%)	0	1/2902 (0%)	1
Cardiac arrest	1/2841 (0%)	1	0/2902 (0%)	0
Cardiac failure	2/2841 (0.1%)	2	1/2902 (0%)	1
Cardiac failure acute	1/2841 (0%)	1	0/2902 (0%)	0
Cardiac failure congestive	2/2841 (0.1%)	2	1/2902 (0%)	1
Cardiac ventricular thrombosis	0/2841 (0%)	0	1/2902 (0%)	1
Cardiomyopathy	0/2841 (0%)	0	1/2902 (0%)	1
Coronary artery disease	0/2841 (0%)	0	2/2902 (0.1%)	2
Extrasystoles	1/2841 (0%)	1	0/2902 (0%)	0
Left ventricular failure	1/2841 (0%)	1	0/2902 (0%)	0
Myocardial ischaemia	0/2841 (0%)	0	1/2902 (0%)	1
Palpitations	1/2841 (0%)	1	0/2902 (0%)	0
Sinus bradycardia	1/2841 (0%)	1	1/2902 (0%)	1
Stress cardiomyopathy	0/2841 (0%)	0	1/2902 (0%)	1
Supraventricular tachycardia	1/2841 (0%)	1	0/2902 (0%)	0
Congenital, familial and genetic disorders
Atrial septal defect	0/2841 (0%)	0	1/2902 (0%)	1
Gene mutation	0/2841 (0%)	0	1/2902 (0%)	1
Ear and labyrinth disorders
Deafness unilateral	1/2841 (0%)	1	0/2902 (0%)	0
Vertigo	2/2841 (0.1%)	2	0/2902 (0%)	0
Vertigo positional	1/2841 (0%)	1	0/2902 (0%)	0
Endocrine disorders
Goitre	3/2841 (0.1%)	3	0/2902 (0%)	0
Hyperparathyroidism	0/2841 (0%)	0	1/2902 (0%)	1
Hypothyroidism	1/2841 (0%)	1	0/2902 (0%)	0
Eye disorders
Cataract	2/2841 (0.1%)	2	0/2902 (0%)	0
Diplopia	0/2841 (0%)	0	1/2902 (0%)	1
Eyelid function disorder	1/2841 (0%)	1	0/2902 (0%)	0
Maculopathy	1/2841 (0%)	1	0/2902 (0%)	0
Gastrointestinal disorders
Abdominal hernia	1/2841 (0%)	1	0/2902 (0%)	0
Abdominal pain	2/2841 (0.1%)	2	0/2902 (0%)	0
Abdominal pain upper	1/2841 (0%)	1	0/2902 (0%)	0
Colitis	2/2841 (0.1%)	2	0/2902 (0%)	0
Colitis ischaemic	1/2841 (0%)	1	0/2902 (0%)	0
Diarrhoea	2/2841 (0.1%)	2	1/2902 (0%)	1
Duodenal ulcer	1/2841 (0%)	1	0/2902 (0%)	0
Duodenitis	0/2841 (0%)	0	1/2902 (0%)	1
Enteritis	1/2841 (0%)	1	0/2902 (0%)	0
Gastrooesophageal reflux disease	1/2841 (0%)	1	1/2902 (0%)	1
Ileus	1/2841 (0%)	1	1/2902 (0%)	1
Intestinal obstruction	0/2841 (0%)	0	2/2902 (0.1%)	2
Intestinal perforation	1/2841 (0%)	1	0/2902 (0%)	0
Intussusception	0/2841 (0%)	0	1/2902 (0%)	1
Large intestine perforation	1/2841 (0%)	1	0/2902 (0%)	0
Large intestine polyp	0/2841 (0%)	0	1/2902 (0%)	1
Nausea	1/2841 (0%)	1	1/2902 (0%)	1
Neutropenic colitis	1/2841 (0%)	1	0/2902 (0%)	0
Oedematous pancreatitis	1/2841 (0%)	1	0/2902 (0%)	0
Oesophagitis	1/2841 (0%)	1	0/2902 (0%)	0
Pancreatitis	2/2841 (0.1%)	2	0/2902 (0%)	0
Peritoneal perforation	1/2841 (0%)	1	0/2902 (0%)	0
Small intestinal obstruction	2/2841 (0.1%)	2	1/2902 (0%)	1
Volvulus of small bowel	1/2841 (0%)	1	0/2902 (0%)	0
Vomiting	2/2841 (0.1%)	2	2/2902 (0.1%)	2
General disorders
Capsular contracture associated with breast implant	0/2841 (0%)	0	1/2902 (0%)	1
Chest discomfort	1/2841 (0%)	1	0/2902 (0%)	0
Chest pain	3/2841 (0.1%)	5	1/2902 (0%)	1
Death	2/2841 (0.1%)	2	0/2902 (0%)	0
Disease progression	1/2841 (0%)	1	2/2902 (0.1%)	4
Disease recurrence	1/2841 (0%)	2	1/2902 (0%)	1
Dysplasia	0/2841 (0%)	0	1/2902 (0%)	1
Fatigue	2/2841 (0.1%)	3	0/2902 (0%)	0
Hypothermia	1/2841 (0%)	1	0/2902 (0%)	0
Impaired healing	1/2841 (0%)	1	1/2902 (0%)	1
Implant site fibrosis	1/2841 (0%)	1	0/2902 (0%)	0
Influenza like illness	1/2841 (0%)	1	0/2902 (0%)	0
Infusion site extravasation	1/2841 (0%)	1	0/2902 (0%)	0
Non-cardiac chest pain	4/2841 (0.1%)	4	0/2902 (0%)	0
Pyrexia	3/2841 (0.1%)	4	1/2902 (0%)	1
Hepatobiliary disorders
Acute hepatic failure	0/2841 (0%)	0	1/2902 (0%)	1
Bile duct stone	1/2841 (0%)	1	0/2902 (0%)	0
Cholangitis	1/2841 (0%)	1	0/2902 (0%)	0
Cholecystitis	3/2841 (0.1%)	3	1/2902 (0%)	1
Cholecystitis acute	0/2841 (0%)	0	1/2902 (0%)	1
Cholelithiasis	4/2841 (0.1%)	4	2/2902 (0.1%)	2
Drug-induced liver injury	1/2841 (0%)	1	0/2902 (0%)	0
Hepatic failure	0/2841 (0%)	0	1/2902 (0%)	1
Hepatitis acute	1/2841 (0%)	1	0/2902 (0%)	0
Immune system disorders
Anaphylactic reaction	0/2841 (0%)	0	1/2902 (0%)	1
Infections and infestations
Anal abscess	1/2841 (0%)	1	0/2902 (0%)	0
Anorectal infection	1/2841 (0%)	1	0/2902 (0%)	0
Appendiceal abscess	1/2841 (0%)	1	0/2902 (0%)	0
Appendicitis	3/2841 (0.1%)	3	5/2902 (0.2%)	5
Appendicitis perforated	1/2841 (0%)	1	0/2902 (0%)	0
Bacterial infection	0/2841 (0%)	0	1/2902 (0%)	1
Breast abscess	2/2841 (0.1%)	2	1/2902 (0%)	1
Breast cellulitis	16/2841 (0.6%)	17	10/2902 (0.3%)	10
Bronchitis	1/2841 (0%)	1	0/2902 (0%)	0
COVID-19 pneumonia	1/2841 (0%)	1	1/2902 (0%)	2
Campylobacter infection	1/2841 (0%)	1	0/2902 (0%)	0
Cellulitis	24/2841 (0.8%)	26	9/2902 (0.3%)	10
Cystitis	1/2841 (0%)	1	0/2902 (0%)	0
Device related infection	2/2841 (0.1%)	2	4/2902 (0.1%)	4
Disseminated varicella zoster virus infection	0/2841 (0%)	0	1/2902 (0%)	1
Diverticulitis	0/2841 (0%)	0	3/2902 (0.1%)	3
Erysipelas	5/2841 (0.2%)	5	0/2902 (0%)	0
Erysipelothrix sepsis	0/2841 (0%)	0	1/2902 (0%)	1
Escherichia pyelonephritis	1/2841 (0%)	1	0/2902 (0%)	0
Escherichia sepsis	1/2841 (0%)	1	0/2902 (0%)	0
Gastroenteritis	4/2841 (0.1%)	4	3/2902 (0.1%)	3
Gastroenteritis norovirus	0/2841 (0%)	0	1/2902 (0%)	1
Gastroenteritis viral	4/2841 (0.1%)	4	0/2902 (0%)	0
Herpes zoster	1/2841 (0%)	1	0/2902 (0%)	0
Infected seroma	1/2841 (0%)	1	0/2902 (0%)	0
Infection	2/2841 (0.1%)	2	3/2902 (0.1%)	4
Influenza	16/2841 (0.6%)	16	2/2902 (0.1%)	2
Laryngitis	1/2841 (0%)	1	0/2902 (0%)	0
Listeria sepsis	1/2841 (0%)	2	0/2902 (0%)	0
Localised infection	1/2841 (0%)	1	0/2902 (0%)	0
Lower respiratory tract infection	2/2841 (0.1%)	2	1/2902 (0%)	1
Mastitis	13/2841 (0.5%)	14	10/2902 (0.3%)	11
Paronychia	1/2841 (0%)	1	0/2902 (0%)	0
Pelvic inflammatory disease	1/2841 (0%)	1	0/2902 (0%)	0
Peritonitis	1/2841 (0%)	1	0/2902 (0%)	0
Pneumonia	16/2841 (0.6%)	18	7/2902 (0.2%)	8
Postoperative wound infection	1/2841 (0%)	1	2/2902 (0.1%)	2
Pyelonephritis	2/2841 (0.1%)	2	0/2902 (0%)	0
Pyelonephritis acute	0/2841 (0%)	0	1/2902 (0%)	1
Respiratory tract infection	1/2841 (0%)	1	1/2902 (0%)	1
Sepsis	8/2841 (0.3%)	9	3/2902 (0.1%)	3
Septic shock	1/2841 (0%)	1	1/2902 (0%)	1
Sinusitis	2/2841 (0.1%)	2	0/2902 (0%)	0
Skin infection	8/2841 (0.3%)	8	0/2902 (0%)	0
Soft tissue infection	1/2841 (0%)	1	0/2902 (0%)	0
Staphylococcal bacteraemia	0/2841 (0%)	0	1/2902 (0%)	1
Staphylococcal infection	0/2841 (0%)	0	2/2902 (0.1%)	2
Upper respiratory tract infection	2/2841 (0.1%)	2	1/2902 (0%)	3
Urinary tract infection	8/2841 (0.3%)	8	3/2902 (0.1%)	3
Urosepsis	1/2841 (0%)	1	0/2902 (0%)	0
Vascular device infection	1/2841 (0%)	1	0/2902 (0%)	0
Vestibular neuronitis	0/2841 (0%)	0	1/2902 (0%)	2
Viral infection	4/2841 (0.1%)	4	0/2902 (0%)	0
Viral labyrinthitis	1/2841 (0%)	1	0/2902 (0%)	0
Viral pericarditis	1/2841 (0%)	1	0/2902 (0%)	0
Vulvovaginal candidiasis	1/2841 (0%)	1	0/2902 (0%)	0
Wound abscess	2/2841 (0.1%)	2	0/2902 (0%)	0
Wound infection	3/2841 (0.1%)	4	4/2902 (0.1%)	4
Injury, poisoning and procedural complications
Abdominal wound dehiscence	2/2841 (0.1%)	2	0/2902 (0%)	0
Alcohol poisoning	1/2841 (0%)	1	0/2902 (0%)	0
Animal bite	1/2841 (0%)	1	0/2902 (0%)	0
Ankle fracture	3/2841 (0.1%)	3	2/2902 (0.1%)	2
Brain contusion	1/2841 (0%)	1	0/2902 (0%)	0
Breast procedural complication	0/2841 (0%)	0	1/2902 (0%)	1
Clavicle fracture	0/2841 (0%)	0	2/2902 (0.1%)	2
Concussion	1/2841 (0%)	1	0/2902 (0%)	0
Craniocerebral injury	1/2841 (0%)	1	0/2902 (0%)	0
Fall	3/2841 (0.1%)	3	3/2902 (0.1%)	4
Head injury	0/2841 (0%)	0	1/2902 (0%)	1
Hip fracture	1/2841 (0%)	1	0/2902 (0%)	0
Humerus fracture	0/2841 (0%)	0	1/2902 (0%)	1
Limb injury	0/2841 (0%)	0	1/2902 (0%)	1
Lower limb fracture	0/2841 (0%)	0	1/2902 (0%)	1
Meniscus injury	0/2841 (0%)	0	2/2902 (0.1%)	2
Open fracture	0/2841 (0%)	0	1/2902 (0%)	1
Post procedural haematoma	1/2841 (0%)	1	1/2902 (0%)	1
Postoperative wound complication	1/2841 (0%)	1	1/2902 (0%)	1
Procedural complication	2/2841 (0.1%)	2	0/2902 (0%)	0
Radiation pneumonitis	1/2841 (0%)	1	1/2902 (0%)	1
Radius fracture	1/2841 (0%)	1	0/2902 (0%)	0
Rib fracture	1/2841 (0%)	1	0/2902 (0%)	0
Seroma	3/2841 (0.1%)	4	4/2902 (0.1%)	4
Skin flap necrosis	1/2841 (0%)	3	0/2902 (0%)	0
Spinal fracture	0/2841 (0%)	0	1/2902 (0%)	3
Sternal fracture	1/2841 (0%)	1	0/2902 (0%)	0
Subdural haematoma	1/2841 (0%)	1	1/2902 (0%)	1
Thermal burn	1/2841 (0%)	1	0/2902 (0%)	0
Thoracic vertebral fracture	0/2841 (0%)	0	1/2902 (0%)	1
Upper limb fracture	1/2841 (0%)	1	0/2902 (0%)	0
Vaginal cuff dehiscence	0/2841 (0%)	0	1/2902 (0%)	1
Vascular access site thrombosis	1/2841 (0%)	1	0/2902 (0%)	0
Wound complication	1/2841 (0%)	1	0/2902 (0%)	0
Wound dehiscence	9/2841 (0.3%)	9	5/2902 (0.2%)	5
Wrist fracture	3/2841 (0.1%)	3	2/2902 (0.1%)	2
Investigations
Alanine aminotransferase increased	1/2841 (0%)	1	0/2902 (0%)	0
Blood bilirubin increased	1/2841 (0%)	1	0/2902 (0%)	0
Liver function test increased	1/2841 (0%)	1	0/2902 (0%)	0
Neutrophil count decreased	1/2841 (0%)	1	0/2902 (0%)	0
Troponin increased	1/2841 (0%)	1	0/2902 (0%)	0
White blood cell count decreased	1/2841 (0%)	1	0/2902 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/2841 (0%)	1	0/2902 (0%)	0
Hypercalcaemia	1/2841 (0%)	2	1/2902 (0%)	1
Hypoglycaemia	1/2841 (0%)	1	0/2902 (0%)	0
Hypokalaemia	0/2841 (0%)	0	1/2902 (0%)	1
Hyponatraemia	0/2841 (0%)	0	2/2902 (0.1%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	1/2841 (0%)	1	4/2902 (0.1%)	5
Arthritis	0/2841 (0%)	0	2/2902 (0.1%)	2
Back pain	2/2841 (0.1%)	2	0/2902 (0%)	0
Flank pain	0/2841 (0%)	0	1/2902 (0%)	1
Foot deformity	0/2841 (0%)	0	2/2902 (0.1%)	3
Haemarthrosis	1/2841 (0%)	1	0/2902 (0%)	0
Intervertebral disc protrusion	1/2841 (0%)	1	1/2902 (0%)	1
Joint range of motion decreased	0/2841 (0%)	0	1/2902 (0%)	2
Osteoarthritis	1/2841 (0%)	1	3/2902 (0.1%)	4
Pain in extremity	1/2841 (0%)	1	1/2902 (0%)	1
Rotator cuff syndrome	0/2841 (0%)	0	1/2902 (0%)	1
Soft tissue necrosis	1/2841 (0%)	1	0/2902 (0%)	0
Spinal synovial cyst	0/2841 (0%)	0	1/2902 (0%)	1
Tendonitis	1/2841 (0%)	1	0/2902 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	0/2841 (0%)	0	1/2902 (0%)	1
Acute promyelocytic leukaemia	0/2841 (0%)	0	1/2902 (0%)	1
Adenocarcinoma pancreas	1/2841 (0%)	1	0/2902 (0%)	0
B-cell small lymphocytic lymphoma	1/2841 (0%)	1	0/2902 (0%)	0
Basal cell carcinoma	0/2841 (0%)	0	1/2902 (0%)	1
Benign breast neoplasm	0/2841 (0%)	0	1/2902 (0%)	1
Bladder neoplasm	1/2841 (0%)	1	0/2902 (0%)	0
Breast cancer metastatic	2/2841 (0.1%)	3	1/2902 (0%)	1
Breast cancer recurrent	1/2841 (0%)	1	0/2902 (0%)	0
Cervix carcinoma	0/2841 (0%)	0	1/2902 (0%)	1
Cervix carcinoma stage 0	0/2841 (0%)	0	1/2902 (0%)	1
Colon cancer	0/2841 (0%)	0	1/2902 (0%)	1
Endometrial adenocarcinoma	0/2841 (0%)	0	1/2902 (0%)	1
Intraductal papillary-mucinous carcinoma of pancreas	0/2841 (0%)	0	1/2902 (0%)	1
Lung neoplasm malignant	1/2841 (0%)	1	1/2902 (0%)	1
Lymphoma	0/2841 (0%)	0	1/2902 (0%)	1
Lymphoplasmacytoid lymphoma/immunocytoma	1/2841 (0%)	1	0/2902 (0%)	0
Malignant melanoma	1/2841 (0%)	1	0/2902 (0%)	0
Malignant melanoma in situ	0/2841 (0%)	0	2/2902 (0.1%)	2
Metastatic malignant melanoma	1/2841 (0%)	1	0/2902 (0%)	0
Ovarian adenoma	1/2841 (0%)	1	0/2902 (0%)	0
Renal cell carcinoma	1/2841 (0%)	1	1/2902 (0%)	1
Salivary gland adenoma	0/2841 (0%)	0	1/2902 (0%)	2
Second primary malignancy	1/2841 (0%)	2	0/2902 (0%)	0
Small cell carcinoma	1/2841 (0%)	1	0/2902 (0%)	0
Squamous cell carcinoma	0/2841 (0%)	0	1/2902 (0%)	1
Squamous cell carcinoma of the tongue	1/2841 (0%)	1	0/2902 (0%)	0
Thyroid adenoma	0/2841 (0%)	0	2/2902 (0.1%)	2
Uterine leiomyoma	1/2841 (0%)	1	1/2902 (0%)	1
Uterine leiomyosarcoma	0/2841 (0%)	0	1/2902 (0%)	1
Uveal melanoma	1/2841 (0%)	1	0/2902 (0%)	0
Nervous system disorders
Ageusia	1/2841 (0%)	1	0/2902 (0%)	0
Aphasia	0/2841 (0%)	0	2/2902 (0.1%)	2
Carotid artery stenosis	0/2841 (0%)	0	1/2902 (0%)	1
Carpal tunnel syndrome	1/2841 (0%)	1	0/2902 (0%)	0
Cerebral infarction	1/2841 (0%)	1	0/2902 (0%)	0
Cerebral ischaemia	0/2841 (0%)	0	1/2902 (0%)	1
Cerebrovascular accident	2/2841 (0.1%)	2	0/2902 (0%)	0
Dizziness	2/2841 (0.1%)	2	2/2902 (0.1%)	2
Encephalopathy	1/2841 (0%)	1	0/2902 (0%)	0
Epilepsy	2/2841 (0.1%)	2	0/2902 (0%)	0
Facial paralysis	1/2841 (0%)	1	0/2902 (0%)	0
Haemorrhage intracranial	1/2841 (0%)	1	1/2902 (0%)	1
Headache	3/2841 (0.1%)	3	1/2902 (0%)	1
IIIrd nerve disorder	1/2841 (0%)	1	0/2902 (0%)	0
Intercostal neuralgia	1/2841 (0%)	1	0/2902 (0%)	0
Ischaemic stroke	2/2841 (0.1%)	2	0/2902 (0%)	0
Myasthenia gravis	0/2841 (0%)	0	1/2902 (0%)	1
Paraesthesia	1/2841 (0%)	1	0/2902 (0%)	0
Presyncope	3/2841 (0.1%)	3	0/2902 (0%)	0
Ruptured cerebral aneurysm	1/2841 (0%)	2	0/2902 (0%)	0
Subarachnoid haemorrhage	0/2841 (0%)	0	1/2902 (0%)	1
Syncope	2/2841 (0.1%)	2	4/2902 (0.1%)	4
Transient ischaemic attack	2/2841 (0.1%)	2	3/2902 (0.1%)	3
VIth nerve paralysis	0/2841 (0%)	0	1/2902 (0%)	1
Vertigo CNS origin	1/2841 (0%)	1	0/2902 (0%)	0
Product Issues
Device breakage	1/2841 (0%)	1	0/2902 (0%)	0
Device dislocation	1/2841 (0%)	1	1/2902 (0%)	3
Device leakage	0/2841 (0%)	0	1/2902 (0%)	1
Psychiatric disorders
Alcohol abuse	2/2841 (0.1%)	2	0/2902 (0%)	0
Alcohol use disorder	0/2841 (0%)	0	1/2902 (0%)	1
Alcohol withdrawal syndrome	0/2841 (0%)	0	1/2902 (0%)	1
Anxiety	2/2841 (0.1%)	2	0/2902 (0%)	0
Confusional state	3/2841 (0.1%)	3	1/2902 (0%)	1
Delusion	0/2841 (0%)	0	1/2902 (0%)	1
Depression	3/2841 (0.1%)	3	1/2902 (0%)	1
Drug abuse	0/2841 (0%)	0	1/2902 (0%)	1
Mania	1/2841 (0%)	1	0/2902 (0%)	0
Mental disorder	0/2841 (0%)	0	1/2902 (0%)	1
Mental status changes	2/2841 (0.1%)	2	0/2902 (0%)	0
Panic attack	1/2841 (0%)	1	0/2902 (0%)	0
Paranoia	0/2841 (0%)	0	1/2902 (0%)	1
Psychotic disorder	0/2841 (0%)	0	1/2902 (0%)	1
Suicidal ideation	1/2841 (0%)	1	0/2902 (0%)	0
Suicide attempt	0/2841 (0%)	0	3/2902 (0.1%)	4
Renal and urinary disorders
Acute kidney injury	4/2841 (0.1%)	5	1/2902 (0%)	1
Chronic kidney disease	0/2841 (0%)	0	1/2902 (0%)	1
Nephrolithiasis	1/2841 (0%)	1	4/2902 (0.1%)	4
Renal colic	1/2841 (0%)	1	1/2902 (0%)	1
Subcapsular renal haematoma	1/2841 (0%)	1	0/2902 (0%)	0
Ureteric obstruction	0/2841 (0%)	0	1/2902 (0%)	1
Ureteric stenosis	1/2841 (0%)	4	0/2902 (0%)	0
Ureterolithiasis	1/2841 (0%)	1	0/2902 (0%)	0
Reproductive system and breast disorders
Adnexa uteri cyst	1/2841 (0%)	1	0/2902 (0%)	0
Breast calcifications	0/2841 (0%)	0	1/2902 (0%)	1
Breast cyst	1/2841 (0%)	1	0/2902 (0%)	0
Breast haematoma	1/2841 (0%)	1	0/2902 (0%)	0
Breast necrosis	1/2841 (0%)	1	2/2902 (0.1%)	2
Breast swelling	1/2841 (0%)	1	0/2902 (0%)	0
Cervical cyst	0/2841 (0%)	0	1/2902 (0%)	1
Endometrial disorder	0/2841 (0%)	0	1/2902 (0%)	1
Endometrial hyperplasia	1/2841 (0%)	1	2/2902 (0.1%)	2
Endometrial hypertrophy	1/2841 (0%)	1	1/2902 (0%)	1
Endometrial thickening	0/2841 (0%)	0	1/2902 (0%)	1
Endometriosis	0/2841 (0%)	0	1/2902 (0%)	1
Ovarian cyst	1/2841 (0%)	1	0/2902 (0%)	0
Uterine polyp	1/2841 (0%)	1	0/2902 (0%)	0
Uterine prolapse	2/2841 (0.1%)	2	0/2902 (0%)	0
Vaginal haematoma	0/2841 (0%)	0	1/2902 (0%)	1
Vaginal prolapse	0/2841 (0%)	0	1/2902 (0%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/2841 (0%)	1	0/2902 (0%)	0
Acute respiratory failure	1/2841 (0%)	1	0/2902 (0%)	0
Asthma	0/2841 (0%)	0	1/2902 (0%)	1
Asthma-chronic obstructive pulmonary disease overlap syndrome	0/2841 (0%)	0	1/2902 (0%)	1
Bronchospasm	1/2841 (0%)	1	1/2902 (0%)	1
Chronic obstructive pulmonary disease	1/2841 (0%)	1	0/2902 (0%)	0
Dyspnoea	2/2841 (0.1%)	2	2/2902 (0.1%)	2
Hypoxia	1/2841 (0%)	1	0/2902 (0%)	0
Laryngeal stenosis	1/2841 (0%)	1	0/2902 (0%)	0
Pleural effusion	2/2841 (0.1%)	2	1/2902 (0%)	1
Pleurisy	1/2841 (0%)	1	1/2902 (0%)	1
Pneumonitis	4/2841 (0.1%)	4	0/2902 (0%)	0
Pulmonary embolism	13/2841 (0.5%)	13	5/2902 (0.2%)	5
Pulmonary fibrosis	1/2841 (0%)	1	0/2902 (0%)	0
Pulmonary haemorrhage	1/2841 (0%)	1	0/2902 (0%)	0
Pulmonary oedema	1/2841 (0%)	1	0/2902 (0%)	0
Pulmonary sarcoidosis	1/2841 (0%)	1	0/2902 (0%)	0
Respiratory disorder	1/2841 (0%)	1	0/2902 (0%)	0
Respiratory failure	1/2841 (0%)	2	1/2902 (0%)	2
Vocal cord dysfunction	0/2841 (0%)	0	1/2902 (0%)	1
Vocal cord polyp	0/2841 (0%)	0	1/2902 (0%)	1
Skin and subcutaneous tissue disorders
Keloid scar	0/2841 (0%)	0	1/2902 (0%)	1
Skin necrosis	0/2841 (0%)	0	1/2902 (0%)	1
Urticaria	1/2841 (0%)	1	0/2902 (0%)	0
Vascular disorders
Axillary vein thrombosis	1/2841 (0%)	1	0/2902 (0%)	0
Deep vein thrombosis	2/2841 (0.1%)	2	0/2902 (0%)	0
Embolism	4/2841 (0.1%)	4	2/2902 (0.1%)	2
Hypertensive crisis	0/2841 (0%)	0	2/2902 (0.1%)	2
Hypotension	2/2841 (0.1%)	2	0/2902 (0%)	0
Lymphoedema	1/2841 (0%)	1	0/2902 (0%)	0
Peripheral ischaemia	1/2841 (0%)	1	0/2902 (0%)	0
Other (Not Including Serious) Adverse Events
	Palbociclib Plus Endocrine Therapy (Arm A)		Endocrine Therapy Alone (Arm B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2824/2841 (99.4%)		2600/2902 (89.6%)
Blood and lymphatic system disorders
Agranulocytosis	3/2841 (0.1%)	3	0/2902 (0%)	0
Anaemia	634/2841 (22.3%)	1161	147/2902 (5.1%)	211
Anaemia macrocytic	4/2841 (0.1%)	6	0/2902 (0%)	0
Anaemia vitamin B12 deficiency	0/2841 (0%)	0	1/2902 (0%)	1
Blood disorder	1/2841 (0%)	1	0/2902 (0%)	0
Bone marrow oedema	0/2841 (0%)	0	1/2902 (0%)	2
Eosinophilia	0/2841 (0%)	0	2/2902 (0.1%)	2
Febrile neutropenia	16/2841 (0.6%)	16	0/2902 (0%)	0
Haematotoxicity	1/2841 (0%)	1	0/2902 (0%)	0
Haemorrhagic diathesis	3/2841 (0.1%)	3	0/2902 (0%)	0
Increased tendency to bruise	3/2841 (0.1%)	3	1/2902 (0%)	1
Iron deficiency anaemia	2/2841 (0.1%)	2	0/2902 (0%)	0
Leukocytosis	2/2841 (0.1%)	6	1/2902 (0%)	1
Leukopenia	397/2841 (14%)	1798	64/2902 (2.2%)	98
Lymph node pain	3/2841 (0.1%)	3	1/2902 (0%)	1
Lymphadenitis	0/2841 (0%)	0	1/2902 (0%)	1
Lymphadenopathy	6/2841 (0.2%)	6	10/2902 (0.3%)	12
Lymphadenopathy mediastinal	0/2841 (0%)	0	1/2902 (0%)	1
Lymphatic disorder	1/2841 (0%)	1	1/2902 (0%)	1
Lymphopenia	58/2841 (2%)	184	24/2902 (0.8%)	40
Macrocytosis	7/2841 (0.2%)	7	0/2902 (0%)	0
Microcytosis	1/2841 (0%)	1	0/2902 (0%)	0
Monocytopenia	1/2841 (0%)	1	0/2902 (0%)	0
Myelosuppression	1/2841 (0%)	1	0/2902 (0%)	0
Neutropenia	1125/2841 (39.6%)	5381	76/2902 (2.6%)	112
Pancytopenia	2/2841 (0.1%)	2	0/2902 (0%)	0
Polycythaemia	1/2841 (0%)	1	0/2902 (0%)	0
Thrombocytopenia	195/2841 (6.9%)	403	15/2902 (0.5%)	18
Thrombocytosis	4/2841 (0.1%)	4	0/2902 (0%)	0
White blood cell disorder	2/2841 (0.1%)	4	0/2902 (0%)	0
Cardiac disorders
Acute left ventricular failure	1/2841 (0%)	1	0/2902 (0%)	0
Angina pectoris	4/2841 (0.1%)	4	0/2902 (0%)	0
Arrhythmia	2/2841 (0.1%)	4	2/2902 (0.1%)	2
Atrial fibrillation	0/2841 (0%)	0	2/2902 (0.1%)	2
Atrial thrombosis	1/2841 (0%)	1	0/2902 (0%)	0
Bradycardia	2/2841 (0.1%)	2	5/2902 (0.2%)	5
Bundle branch block right	1/2841 (0%)	1	1/2902 (0%)	1
Cardiac failure	3/2841 (0.1%)	3	3/2902 (0.1%)	3
Cardiac failure chronic	0/2841 (0%)	0	1/2902 (0%)	1
Cardiac failure congestive	1/2841 (0%)	1	1/2902 (0%)	1
Cardiac flutter	0/2841 (0%)	0	1/2902 (0%)	1
Cardiac ventricular thrombosis	1/2841 (0%)	1	0/2902 (0%)	0
Cardiomyopathy	1/2841 (0%)	1	2/2902 (0.1%)	2
Cardiovascular disorder	1/2841 (0%)	1	2/2902 (0.1%)	2
Chronic left ventricular failure	0/2841 (0%)	0	1/2902 (0%)	1
Coronary artery disease	1/2841 (0%)	1	0/2902 (0%)	0
Extrasystoles	1/2841 (0%)	1	0/2902 (0%)	0
Left ventricular dysfunction	0/2841 (0%)	0	3/2902 (0.1%)	3
Left ventricular failure	1/2841 (0%)	1	0/2902 (0%)	0
Mitral valve disease	0/2841 (0%)	0	1/2902 (0%)	1
Palpitations	46/2841 (1.6%)	52	38/2902 (1.3%)	39
Pericarditis	0/2841 (0%)	0	1/2902 (0%)	1
Sinus arrhythmia	0/2841 (0%)	0	1/2902 (0%)	1
Sinus bradycardia	4/2841 (0.1%)	4	4/2902 (0.1%)	5
Sinus tachycardia	13/2841 (0.5%)	14	12/2902 (0.4%)	17
Supraventricular tachycardia	5/2841 (0.2%)	5	1/2902 (0%)	1
Systolic dysfunction	1/2841 (0%)	1	0/2902 (0%)	0
Tachyarrhythmia	0/2841 (0%)	0	1/2902 (0%)	1
Tachycardia	17/2841 (0.6%)	19	29/2902 (1%)	31
Tachycardia induced cardiomyopathy	0/2841 (0%)	0	1/2902 (0%)	1
Ventricular arrhythmia	1/2841 (0%)	1	2/2902 (0.1%)	2
Ventricular extrasystoles	1/2841 (0%)	1	1/2902 (0%)	1
Congenital, familial and genetic disorders
Developmental hip dysplasia	0/2841 (0%)	0	1/2902 (0%)	1
Gilbert's syndrome	0/2841 (0%)	0	1/2902 (0%)	1
Hereditary haemochromatosis	1/2841 (0%)	1	0/2902 (0%)	0
Hyper IgM syndrome	0/2841 (0%)	0	1/2902 (0%)	1
Ear and labyrinth disorders
Veritgo	1/2841 (0%)	1	0/2902 (0%)	0
Cerumen impaction	2/2841 (0.1%)	2	2/2902 (0.1%)	2
Deafness	4/2841 (0.1%)	4	7/2902 (0.2%)	8
Deafness unilateral	2/2841 (0.1%)	3	2/2902 (0.1%)	2
Ear congestion	1/2841 (0%)	1	0/2902 (0%)	0
Ear discomfort	5/2841 (0.2%)	5	4/2902 (0.1%)	4
Ear disorder	0/2841 (0%)	0	2/2902 (0.1%)	2
Ear pain	40/2841 (1.4%)	43	11/2902 (0.4%)	11
Ear pruritus	1/2841 (0%)	1	0/2902 (0%)	0
Eustachian tube patulous	0/2841 (0%)	0	1/2902 (0%)	1
Excessive cerumen production	1/2841 (0%)	1	0/2902 (0%)	0
External ear inflammation	3/2841 (0.1%)	3	2/2902 (0.1%)	2
External ear pain	1/2841 (0%)	1	0/2902 (0%)	0
Hyperacusis	1/2841 (0%)	1	1/2902 (0%)	1
Hypoacusis	9/2841 (0.3%)	10	1/2902 (0%)	1
Middle ear inflammation	1/2841 (0%)	1	0/2902 (0%)	0
Motion sickness	1/2841 (0%)	2	2/2902 (0.1%)	2
Otorrhoea	2/2841 (0.1%)	2	0/2902 (0%)	0
Tinnitus	23/2841 (0.8%)	24	20/2902 (0.7%)	20
Tympanic membrane perforation	0/2841 (0%)	0	1/2902 (0%)	1
Vertigo	74/2841 (2.6%)	84	38/2902 (1.3%)	40
Vertigo positional	0/2841 (0%)	0	2/2902 (0.1%)	2
Vestibular disorder	1/2841 (0%)	1	0/2902 (0%)	0
Endocrine disorders
Autoimmune thyroiditis	2/2841 (0.1%)	2	4/2902 (0.1%)	5
Goitre	3/2841 (0.1%)	3	1/2902 (0%)	1
Hyperparathyroidism	0/2841 (0%)	0	3/2902 (0.1%)	3
Hyperthyroidism	5/2841 (0.2%)	5	3/2902 (0.1%)	3
Hypothyroidism	21/2841 (0.7%)	22	41/2902 (1.4%)	44
Thyroid mass	4/2841 (0.1%)	4	7/2902 (0.2%)	7
Thyroid pain	0/2841 (0%)	0	1/2902 (0%)	1
Eye disorders
Asthenopia	1/2841 (0%)	1	1/2902 (0%)	1
Blepharitis	5/2841 (0.2%)	5	2/2902 (0.1%)	2
Blepharospasm	3/2841 (0.1%)	3	1/2902 (0%)	1
Blindness	1/2841 (0%)	1	1/2902 (0%)	1
Blindness transient	1/2841 (0%)	1	1/2902 (0%)	1
Cataract	16/2841 (0.6%)	20	19/2902 (0.7%)	22
Cataract nuclear	0/2841 (0%)	0	1/2902 (0%)	1
Chalazion	1/2841 (0%)	1	1/2902 (0%)	1
Choroidal effusion	1/2841 (0%)	1	0/2902 (0%)	0
Conjunctival disorder	0/2841 (0%)	0	1/2902 (0%)	1
Conjunctival haemorrhage	6/2841 (0.2%)	6	4/2902 (0.1%)	4
Conjunctivitis allergic	1/2841 (0%)	1	0/2902 (0%)	0
Corneal thickening	0/2841 (0%)	0	1/2902 (0%)	1
Dacryostenosis acquired	3/2841 (0.1%)	3	0/2902 (0%)	0
Diplopia	3/2841 (0.1%)	3	2/2902 (0.1%)	2
Dry eye	68/2841 (2.4%)	75	42/2902 (1.4%)	48
Eye disorder	1/2841 (0%)	1	2/2902 (0.1%)	2
Eye haemorrhage	1/2841 (0%)	1	0/2902 (0%)	0
Eye inflammation	1/2841 (0%)	1	1/2902 (0%)	1
Eye irritation	5/2841 (0.2%)	5	2/2902 (0.1%)	2
Eye oedema	1/2841 (0%)	1	1/2902 (0%)	1
Eye pain	1/2841 (0%)	1	2/2902 (0.1%)	2
Eye pruritus	10/2841 (0.4%)	11	5/2902 (0.2%)	6
Eye swelling	2/2841 (0.1%)	2	1/2902 (0%)	1
Eyelid cyst	1/2841 (0%)	1	0/2902 (0%)	0
Eyelid disorder	1/2841 (0%)	1	1/2902 (0%)	1
Eyelid function disorder	1/2841 (0%)	1	1/2902 (0%)	1
Eyelid oedema	2/2841 (0.1%)	2	1/2902 (0%)	1
Eyelid ptosis	1/2841 (0%)	1	1/2902 (0%)	1
Eyelids pruritus	1/2841 (0%)	1	0/2902 (0%)	0
Glaucoma	3/2841 (0.1%)	3	3/2902 (0.1%)	3
Iritis	2/2841 (0.1%)	2	1/2902 (0%)	1
Keratitis	4/2841 (0.1%)	8	0/2902 (0%)	0
Keratopathy	1/2841 (0%)	2	0/2902 (0%)	0
Lacrimal cyst	1/2841 (0%)	1	0/2902 (0%)	0
Lacrimation increased	96/2841 (3.4%)	105	6/2902 (0.2%)	6
Macular degeneration	3/2841 (0.1%)	4	3/2902 (0.1%)	3
Macular fibrosis	1/2841 (0%)	1	0/2902 (0%)	0
Mydriasis	1/2841 (0%)	1	0/2902 (0%)	0
Neovascular age-related macular degeneration	1/2841 (0%)	1	0/2902 (0%)	0
Ocular hyperaemia	1/2841 (0%)	1	2/2902 (0.1%)	2
Orbital haemorrhage	1/2841 (0%)	1	0/2902 (0%)	0
Orbital oedema	1/2841 (0%)	1	0/2902 (0%)	0
Pars plana cyst	1/2841 (0%)	1	0/2902 (0%)	0
Periorbital oedema	2/2841 (0.1%)	4	0/2902 (0%)	0
Periorbital swelling	1/2841 (0%)	1	0/2902 (0%)	0
Photophobia	4/2841 (0.1%)	4	3/2902 (0.1%)	3
Photopsia	2/2841 (0.1%)	2	2/2902 (0.1%)	2
Presbyopia	0/2841 (0%)	0	1/2902 (0%)	1
Punctate keratitis	1/2841 (0%)	1	0/2902 (0%)	0
Retinal detachment	2/2841 (0.1%)	2	1/2902 (0%)	1
Retinal dystrophy	1/2841 (0%)	1	0/2902 (0%)	0
Retinal haemorrhage	1/2841 (0%)	1	0/2902 (0%)	0
Retinal tear	1/2841 (0%)	1	2/2902 (0.1%)	3
Retinoschisis	1/2841 (0%)	1	0/2902 (0%)	0
Scleral cyst	1/2841 (0%)	1	0/2902 (0%)	0
Swelling of eyelid	3/2841 (0.1%)	3	0/2902 (0%)	0
Ulcerative keratitis	1/2841 (0%)	1	1/2902 (0%)	1
Uveitis	3/2841 (0.1%)	3	1/2902 (0%)	2
Vision blurred	69/2841 (2.4%)	75	36/2902 (1.2%)	40
Visual acuity reduced	6/2841 (0.2%)	6	4/2902 (0.1%)	4
Visual impairment	19/2841 (0.7%)	19	11/2902 (0.4%)	11
Visual snow syndrome	1/2841 (0%)	1	0/2902 (0%)	0
Vitreous detachment	1/2841 (0%)	1	1/2902 (0%)	1
Vitreous floaters	6/2841 (0.2%)	6	10/2902 (0.3%)	10
Xerophthalmia	3/2841 (0.1%)	3	1/2902 (0%)	2
Gastrointestinal disorders
Abdominal discomfort	22/2841 (0.8%)	27	16/2902 (0.6%)	16
Abdominal distension	30/2841 (1.1%)	36	33/2902 (1.1%)	35
Abdominal mass	1/2841 (0%)	1	1/2902 (0%)	1
Abdominal pain	153/2841 (5.4%)	190	110/2902 (3.8%)	134
Abdominal pain lower	14/2841 (0.5%)	14	16/2902 (0.6%)	17
Abdominal pain upper	84/2841 (3%)	103	53/2902 (1.8%)	61
Abdominal rigidity	1/2841 (0%)	1	0/2902 (0%)	0
Abdominal tenderness	2/2841 (0.1%)	2	2/2902 (0.1%)	2
Abdominal wall haematoma	0/2841 (0%)	0	1/2902 (0%)	1
Anal fissure	12/2841 (0.4%)	16	3/2902 (0.1%)	3
Anal fistula	3/2841 (0.1%)	3	0/2902 (0%)	0
Anal haemorrhage	11/2841 (0.4%)	12	1/2902 (0%)	1
Anal incontinence	2/2841 (0.1%)	2	1/2902 (0%)	1
Anal inflammation	1/2841 (0%)	2	0/2902 (0%)	0
Anal pruritus	1/2841 (0%)	1	2/2902 (0.1%)	2
Anal skin tags	0/2841 (0%)	0	1/2902 (0%)	1
Angular cheilitis	4/2841 (0.1%)	6	2/2902 (0.1%)	2
Aphthous ulcer	16/2841 (0.6%)	17	3/2902 (0.1%)	3
Apical granuloma	2/2841 (0.1%)	2	0/2902 (0%)	0
Ascites	0/2841 (0%)	0	1/2902 (0%)	1
Barrett's oesophagus	1/2841 (0%)	1	1/2902 (0%)	1
Bowel movement irregularity	1/2841 (0%)	1	0/2902 (0%)	0
Change of bowel habit	3/2841 (0.1%)	3	0/2902 (0%)	0
Cheilitis	4/2841 (0.1%)	4	1/2902 (0%)	1
Chronic gastritis	2/2841 (0.1%)	3	2/2902 (0.1%)	2
Colitis	5/2841 (0.2%)	5	3/2902 (0.1%)	3
Colitis ischaemic	1/2841 (0%)	1	0/2902 (0%)	0
Colitis ulcerative	0/2841 (0%)	0	1/2902 (0%)	1
Constipation	395/2841 (13.9%)	485	172/2902 (5.9%)	190
Crohn's disease	1/2841 (0%)	1	0/2902 (0%)	0
Dental caries	16/2841 (0.6%)	17	5/2902 (0.2%)	7
Diarrhoea	475/2841 (16.7%)	682	150/2902 (5.2%)	194
Diarrhoea haemorrhagic	1/2841 (0%)	1	0/2902 (0%)	0
Diverticulum	5/2841 (0.2%)	5	1/2902 (0%)	1
Diverticulum intestinal	2/2841 (0.1%)	2	4/2902 (0.1%)	4
Dry mouth	81/2841 (2.9%)	92	46/2902 (1.6%)	49
Duodenitis	1/2841 (0%)	1	0/2902 (0%)	0
Dyschezia	1/2841 (0%)	1	0/2902 (0%)	0
Dyspepsia	137/2841 (4.8%)	162	64/2902 (2.2%)	67
Dysphagia	28/2841 (1%)	34	15/2902 (0.5%)	16
Enteritis	3/2841 (0.1%)	4	0/2902 (0%)	0
Enterocolitis	3/2841 (0.1%)	3	2/2902 (0.1%)	3
Epigastric discomfort	4/2841 (0.1%)	4	1/2902 (0%)	1
Epiploic appendagitis	1/2841 (0%)	1	0/2902 (0%)	0
Erosive oesophagitis	0/2841 (0%)	0	1/2902 (0%)	1
Eructation	0/2841 (0%)	0	1/2902 (0%)	1
Faeces discoloured	4/2841 (0.1%)	4	0/2902 (0%)	0
Faeces hard	1/2841 (0%)	1	0/2902 (0%)	0
Faeces soft	2/2841 (0.1%)	2	0/2902 (0%)	0
Flatulence	27/2841 (1%)	31	14/2902 (0.5%)	15
Food poisoning	3/2841 (0.1%)	4	1/2902 (0%)	1
Frequent bowel movements	1/2841 (0%)	1	0/2902 (0%)	0
Gastric disorder	2/2841 (0.1%)	2	0/2902 (0%)	0
Gastric polyps	0/2841 (0%)	0	2/2902 (0.1%)	2
Gastric ulcer	0/2841 (0%)	0	2/2902 (0.1%)	2
Gastritis	29/2841 (1%)	32	9/2902 (0.3%)	9
Gastritis erosive	0/2841 (0%)	0	1/2902 (0%)	1
Gastrointestinal disorder	6/2841 (0.2%)	7	3/2902 (0.1%)	3
Gastrointestinal haemorrhage	1/2841 (0%)	1	0/2902 (0%)	0
Gastrointestinal inflammation	1/2841 (0%)	1	0/2902 (0%)	0
Gastrointestinal pain	6/2841 (0.2%)	7	3/2902 (0.1%)	3
Gastrointestinal sounds abnormal	1/2841 (0%)	1	0/2902 (0%)	0
Gastrointestinal wall thickening	1/2841 (0%)	1	0/2902 (0%)	0
Gastrooesophageal reflux disease	90/2841 (3.2%)	106	55/2902 (1.9%)	59
Gingival bleeding	10/2841 (0.4%)	12	1/2902 (0%)	1
Gingival discomfort	0/2841 (0%)	0	1/2902 (0%)	1
Gingival oedema	1/2841 (0%)	1	0/2902 (0%)	0
Gingival pain	11/2841 (0.4%)	15	3/2902 (0.1%)	3
Gingival recession	1/2841 (0%)	1	1/2902 (0%)	1
Gingival swelling	2/2841 (0.1%)	2	2/2902 (0.1%)	2
Glossitis	3/2841 (0.1%)	4	2/2902 (0.1%)	2
Glossodynia	6/2841 (0.2%)	6	1/2902 (0%)	1
Haematemesis	1/2841 (0%)	1	0/2902 (0%)	0
Haematochezia	10/2841 (0.4%)	11	3/2902 (0.1%)	3
Haemorrhoidal haemorrhage	7/2841 (0.2%)	9	7/2902 (0.2%)	12
Haemorrhoids	43/2841 (1.5%)	44	25/2902 (0.9%)	26
Hiatus hernia	4/2841 (0.1%)	4	2/2902 (0.1%)	2
Hyperaesthesia teeth	2/2841 (0.1%)	2	0/2902 (0%)	0
Hypertrophic anal papilla	0/2841 (0%)	0	1/2902 (0%)	1
Hypoaesthesia oral	3/2841 (0.1%)	4	1/2902 (0%)	1
Ileus	0/2841 (0%)	0	1/2902 (0%)	1
Impaired gastric emptying	1/2841 (0%)	1	1/2902 (0%)	1
Inguinal hernia	2/2841 (0.1%)	2	0/2902 (0%)	0
Intestinal obstruction	1/2841 (0%)	1	1/2902 (0%)	1
Intestinal polyp	1/2841 (0%)	1	0/2902 (0%)	0
Intra-abdominal haematoma	0/2841 (0%)	0	1/2902 (0%)	2
Intussusception	0/2841 (0%)	0	1/2902 (0%)	1
Irritable bowel syndrome	2/2841 (0.1%)	2	4/2902 (0.1%)	4
Large intestinal ulcer	1/2841 (0%)	1	0/2902 (0%)	0
Large intestine polyp	4/2841 (0.1%)	4	4/2902 (0.1%)	5
Lip blister	1/2841 (0%)	1	0/2902 (0%)	0
Lip discolouration	0/2841 (0%)	0	1/2902 (0%)	1
Lip disorder	0/2841 (0%)	0	1/2902 (0%)	1
Lip dry	4/2841 (0.1%)	4	1/2902 (0%)	1
Lip erythema	1/2841 (0%)	1	0/2902 (0%)	0
Lip pain	3/2841 (0.1%)	3	0/2902 (0%)	0
Lip pruritus	1/2841 (0%)	1	0/2902 (0%)	0
Lip swelling	1/2841 (0%)	1	2/2902 (0.1%)	2
Lip ulceration	2/2841 (0.1%)	2	0/2902 (0%)	0
Loose tooth	1/2841 (0%)	1	0/2902 (0%)	0
Lower gastrointestinal haemorrhage	1/2841 (0%)	1	0/2902 (0%)	0
Melaena	1/2841 (0%)	1	0/2902 (0%)	0
Mouth haemorrhage	1/2841 (0%)	1	0/2902 (0%)	0
Mouth ulceration	51/2841 (1.8%)	67	6/2902 (0.2%)	6
Nausea	552/2841 (19.4%)	735	241/2902 (8.3%)	294
Noninfective gingivitis	1/2841 (0%)	1	0/2902 (0%)	0
Noninfective sialoadenitis	1/2841 (0%)	1	0/2902 (0%)	0
Odynophagia	13/2841 (0.5%)	14	4/2902 (0.1%)	5
Oedematous pancreatitis	1/2841 (0%)	1	0/2902 (0%)	0
Oesophageal achalasia	0/2841 (0%)	0	1/2902 (0%)	2
Oesophageal discomfort	1/2841 (0%)	1	0/2902 (0%)	0
Oesophageal disorder	1/2841 (0%)	1	0/2902 (0%)	0
Oesophageal pain	1/2841 (0%)	1	0/2902 (0%)	0
Oesophageal spasm	1/2841 (0%)	1	0/2902 (0%)	0
Oesophageal ulcer	1/2841 (0%)	1	0/2902 (0%)	0
Oesophagitis	6/2841 (0.2%)	8	3/2902 (0.1%)	3
Oral discomfort	1/2841 (0%)	1	0/2902 (0%)	0
Oral disorder	1/2841 (0%)	1	0/2902 (0%)	0
Oral dysaesthesia	5/2841 (0.2%)	5	0/2902 (0%)	0
Oral mucosal blistering	1/2841 (0%)	3	0/2902 (0%)	0
Oral pain	49/2841 (1.7%)	61	6/2902 (0.2%)	6
Pancreatitis	1/2841 (0%)	1	2/2902 (0.1%)	2
Paraesthesia oral	4/2841 (0.1%)	5	0/2902 (0%)	0
Peptic ulcer	0/2841 (0%)	0	1/2902 (0%)	1
Periodontal disease	3/2841 (0.1%)	3	2/2902 (0.1%)	2
Proctalgia	6/2841 (0.2%)	6	1/2902 (0%)	1
Proctitis	1/2841 (0%)	1	0/2902 (0%)	0
Ranula	1/2841 (0%)	1	0/2902 (0%)	0
Rectal haemorrhage	20/2841 (0.7%)	21	12/2902 (0.4%)	13
Rectal lesion	1/2841 (0%)	1	0/2902 (0%)	0
Rectal polyp	0/2841 (0%)	0	1/2902 (0%)	1
Rectal tenesmus	1/2841 (0%)	2	2/2902 (0.1%)	2
Rectal ulcer	1/2841 (0%)	1	0/2902 (0%)	0
Reflux gastritis	1/2841 (0%)	2	0/2902 (0%)	0
Salivary duct inflammation	2/2841 (0.1%)	2	0/2902 (0%)	0
Salivary gland calculus	1/2841 (0%)	1	0/2902 (0%)	0
Salivary hypersecretion	1/2841 (0%)	1	1/2902 (0%)	1
Small intestinal obstruction	0/2841 (0%)	0	1/2902 (0%)	1
Stomatitis	280/2841 (9.9%)	428	21/2902 (0.7%)	23
Swollen tongue	1/2841 (0%)	1	2/2902 (0.1%)	2
Teeth brittle	1/2841 (0%)	1	1/2902 (0%)	1
Tongue coated	2/2841 (0.1%)	2	0/2902 (0%)	0
Tongue geographic	1/2841 (0%)	2	0/2902 (0%)	0
Tongue ulceration	7/2841 (0.2%)	7	0/2902 (0%)	0
Tooth disorder	2/2841 (0.1%)	2	0/2902 (0%)	0
Tooth loss	1/2841 (0%)	1	1/2902 (0%)	1
Toothache	35/2841 (1.2%)	39	17/2902 (0.6%)	18
Umbilical hernia	2/2841 (0.1%)	2	2/2902 (0.1%)	2
Volvulus	1/2841 (0%)	1	0/2902 (0%)	0
Vomiting	219/2841 (7.7%)	278	91/2902 (3.1%)	120
General disorders
Acute phase reaction	0/2841 (0%)	0	1/2902 (0%)	1
Adverse drug reaction	1/2841 (0%)	1	2/2902 (0.1%)	2
Application site coldness	0/2841 (0%)	0	1/2902 (0%)	1
Asthenia	274/2841 (9.6%)	468	153/2902 (5.3%)	193
Axillary pain	43/2841 (1.5%)	44	48/2902 (1.7%)	55
Capsular contracture associated with breast implant	2/2841 (0.1%)	2	2/2902 (0.1%)	2
Capsular contracture associated with implant	0/2841 (0%)	0	1/2902 (0%)	1
Catheter site inflammation	1/2841 (0%)	1	0/2902 (0%)	0
Catheter site pain	0/2841 (0%)	0	6/2902 (0.2%)	7
Catheter site pruritus	0/2841 (0%)	0	1/2902 (0%)	1
Catheter site scab	1/2841 (0%)	1	0/2902 (0%)	0
Catheter site thrombosis	1/2841 (0%)	1	0/2902 (0%)	0
Chest discomfort	37/2841 (1.3%)	42	22/2902 (0.8%)	24
Chest pain	56/2841 (2%)	64	51/2902 (1.8%)	54
Chills	70/2841 (2.5%)	78	17/2902 (0.6%)	17
Complication associated with device	1/2841 (0%)	1	0/2902 (0%)	0
Cyst	7/2841 (0.2%)	7	7/2902 (0.2%)	7
Decreased activity	1/2841 (0%)	1	0/2902 (0%)	0
Discomfort	7/2841 (0.2%)	7	7/2902 (0.2%)	7
Early satiety	1/2841 (0%)	1	0/2902 (0%)	0
Exercise tolerance decreased	1/2841 (0%)	1	2/2902 (0.1%)	2
Face oedema	5/2841 (0.2%)	5	4/2902 (0.1%)	4
Facial pain	4/2841 (0.1%)	4	4/2902 (0.1%)	4
Fat necrosis	2/2841 (0.1%)	2	0/2902 (0%)	0
Fatigue	1163/2841 (40.9%)	1869	560/2902 (19.3%)	714
Feeling abnormal	3/2841 (0.1%)	3	3/2902 (0.1%)	3
Feeling cold	3/2841 (0.1%)	3	2/2902 (0.1%)	2
Feeling hot	1/2841 (0%)	1	0/2902 (0%)	0
Feeling jittery	1/2841 (0%)	1	0/2902 (0%)	0
Fibrosis	1/2841 (0%)	1	3/2902 (0.1%)	3
Gait disturbance	6/2841 (0.2%)	6	6/2902 (0.2%)	6
General physical health deterioration	6/2841 (0.2%)	7	2/2902 (0.1%)	2
Granuloma	2/2841 (0.1%)	2	1/2902 (0%)	1
Hernia pain	0/2841 (0%)	0	2/2902 (0.1%)	2
Hyperthermia	1/2841 (0%)	1	0/2902 (0%)	0
Hypertrophy	1/2841 (0%)	1	1/2902 (0%)	1
Hypothermia	2/2841 (0.1%)	2	0/2902 (0%)	0
Illness	4/2841 (0.1%)	5	2/2902 (0.1%)	2
Impaired healing	14/2841 (0.5%)	14	5/2902 (0.2%)	6
Implant site pain	1/2841 (0%)	2	3/2902 (0.1%)	3
Induration	0/2841 (0%)	0	1/2902 (0%)	1
Inflammation	3/2841 (0.1%)	3	2/2902 (0.1%)	2
Influenza like illness	166/2841 (5.8%)	205	90/2902 (3.1%)	108
Injection site pain	0/2841 (0%)	0	1/2902 (0%)	1
Injection site phlebitis	0/2841 (0%)	0	1/2902 (0%)	1
Injection site reaction	1/2841 (0%)	1	1/2902 (0%)	1
Localised oedema	16/2841 (0.6%)	16	10/2902 (0.3%)	11
Malaise	32/2841 (1.1%)	34	11/2902 (0.4%)	16
Mass	5/2841 (0.2%)	5	3/2902 (0.1%)	3
Mucosal disorder	1/2841 (0%)	1	0/2902 (0%)	0
Mucosal dryness	11/2841 (0.4%)	12	14/2902 (0.5%)	15
Mucosal haemorrhage	1/2841 (0%)	1	0/2902 (0%)	0
Mucosal inflammation	206/2841 (7.3%)	362	10/2902 (0.3%)	10
Mucosal pain	1/2841 (0%)	1	0/2902 (0%)	0
Mucosal toxicity	1/2841 (0%)	1	0/2902 (0%)	0
Necrosis	1/2841 (0%)	1	1/2902 (0%)	1
Nodule	4/2841 (0.1%)	6	5/2902 (0.2%)	6
Non-cardiac chest pain	24/2841 (0.8%)	29	29/2902 (1%)	33
Oedema	27/2841 (1%)	35	25/2902 (0.9%)	29
Oedema peripheral	178/2841 (6.3%)	218	121/2902 (4.2%)	137
Pain	107/2841 (3.8%)	122	94/2902 (3.2%)	102
Pelvic mass	1/2841 (0%)	1	0/2902 (0%)	0
Peripheral swelling	55/2841 (1.9%)	61	33/2902 (1.1%)	36
Polyp	2/2841 (0.1%)	2	1/2902 (0%)	2
Pyrexia	205/2841 (7.2%)	251	83/2902 (2.9%)	92
Sensitivity to weather change	1/2841 (0%)	1	1/2902 (0%)	1
Suprapubic pain	0/2841 (0%)	0	1/2902 (0%)	1
Swelling	13/2841 (0.5%)	17	9/2902 (0.3%)	10
Swelling face	3/2841 (0.1%)	3	2/2902 (0.1%)	2
Temperature intolerance	6/2841 (0.2%)	6	1/2902 (0%)	1
Temperature regulation disorder	2/2841 (0.1%)	2	0/2902 (0%)	0
Tenderness	10/2841 (0.4%)	10	3/2902 (0.1%)	3
Thirst	1/2841 (0%)	1	3/2902 (0.1%)	3
Unevaluable event	9/2841 (0.3%)	9	4/2902 (0.1%)	4
Vessel puncture site pain	1/2841 (0%)	1	0/2902 (0%)	0
Xerosis	6/2841 (0.2%)	7	2/2902 (0.1%)	2
Hepatobiliary disorders
Biliary colic	2/2841 (0.1%)	2	1/2902 (0%)	1
Cholecystitis	8/2841 (0.3%)	8	4/2902 (0.1%)	4
Cholecystitis chronic	0/2841 (0%)	0	1/2902 (0%)	1
Cholelithiasis	7/2841 (0.2%)	7	8/2902 (0.3%)	9
Gallbladder polyp	1/2841 (0%)	1	1/2902 (0%)	1
Hepatic cyst	1/2841 (0%)	1	2/2902 (0.1%)	2
Hepatic lesion	0/2841 (0%)	0	1/2902 (0%)	1
Hepatic pain	2/2841 (0.1%)	2	0/2902 (0%)	0
Hepatic steatosis	9/2841 (0.3%)	9	9/2902 (0.3%)	9
Hepatitis toxic	1/2841 (0%)	1	0/2902 (0%)	0
Hepatocellular injury	0/2841 (0%)	0	1/2902 (0%)	1
Hepatomegaly	0/2841 (0%)	0	1/2902 (0%)	1
Hepatotoxicity	1/2841 (0%)	1	0/2902 (0%)	0
Hyperbilirubinaemia	2/2841 (0.1%)	3	5/2902 (0.2%)	12
Hypertransaminasaemia	2/2841 (0.1%)	3	0/2902 (0%)	0
Jaundice	1/2841 (0%)	1	0/2902 (0%)	0
Liver disorder	0/2841 (0%)	0	1/2902 (0%)	1
Liver tenderness	1/2841 (0%)	1	0/2902 (0%)	0
Porcelain gallbladder	1/2841 (0%)	1	1/2902 (0%)	1
Steatohepatitis	0/2841 (0%)	0	1/2902 (0%)	1
Immune system disorders
Allergy to arthropod bite	1/2841 (0%)	1	1/2902 (0%)	1
Allergy to vaccine	1/2841 (0%)	1	0/2902 (0%)	0
Anaphylactic reaction	1/2841 (0%)	1	0/2902 (0%)	0
Anaphylactic shock	0/2841 (0%)	0	1/2902 (0%)	1
Drug hypersensitivity	5/2841 (0.2%)	6	2/2902 (0.1%)	2
Food allergy	1/2841 (0%)	1	0/2902 (0%)	0
Hypersensitivity	16/2841 (0.6%)	18	4/2902 (0.1%)	4
Immune system disorder	0/2841 (0%)	0	2/2902 (0.1%)	3
Mite allergy	0/2841 (0%)	0	1/2902 (0%)	1
Multiple allergies	2/2841 (0.1%)	2	3/2902 (0.1%)	3
Perfume sensitivity	0/2841 (0%)	0	1/2902 (0%)	1
Sarcoidosis	2/2841 (0.1%)	2	0/2902 (0%)	0
Seasonal allergy	19/2841 (0.7%)	20	10/2902 (0.3%)	11
Infections and infestations
Abdominal infection	1/2841 (0%)	1	1/2902 (0%)	1
Abscess	3/2841 (0.1%)	4	2/2902 (0.1%)	2
Abscess limb	0/2841 (0%)	0	1/2902 (0%)	1
Abscess neck	1/2841 (0%)	1	0/2902 (0%)	0
Abscess oral	4/2841 (0.1%)	4	1/2902 (0%)	1
Acarodermatitis	2/2841 (0.1%)	2	0/2902 (0%)	0
Acute sinusitis	2/2841 (0.1%)	2	3/2902 (0.1%)	4
Anal abscess	2/2841 (0.1%)	2	0/2902 (0%)	0
Appendicitis	0/2841 (0%)	0	2/2902 (0.1%)	2
Arthritis infective	1/2841 (0%)	1	0/2902 (0%)	0
Babesiosis	1/2841 (0%)	1	0/2902 (0%)	0
Bacterial infection	0/2841 (0%)	0	1/2902 (0%)	1
Bacterial vaginosis	2/2841 (0.1%)	2	4/2902 (0.1%)	4
Bacterial vulvovaginitis	0/2841 (0%)	0	1/2902 (0%)	1
Bacteriuria	0/2841 (0%)	0	1/2902 (0%)	1
Bartholin's abscess	0/2841 (0%)	0	1/2902 (0%)	1
Beta haemolytic streptococcal infection	1/2841 (0%)	1	0/2902 (0%)	0
Blastocystis infection	0/2841 (0%)	0	1/2902 (0%)	1
Blister infected	1/2841 (0%)	1	0/2902 (0%)	0
Breast abscess	2/2841 (0.1%)	2	0/2902 (0%)	0
Breast cellulitis	17/2841 (0.6%)	22	15/2902 (0.5%)	15
Bronchitis	68/2841 (2.4%)	85	56/2902 (1.9%)	60
Bronchitis bacterial	1/2841 (0%)	1	0/2902 (0%)	0
Bronchitis viral	2/2841 (0.1%)	2	0/2902 (0%)	0
COVID-19	3/2841 (0.1%)	3	2/2902 (0.1%)	2
Candida infection	15/2841 (0.5%)	18	6/2902 (0.2%)	6
Catheter site pustule	1/2841 (0%)	1	0/2902 (0%)	0
Cellulitis	53/2841 (1.9%)	66	31/2902 (1.1%)	38
Cervicitis	1/2841 (0%)	1	0/2902 (0%)	0
Cervicitis human papilloma virus	1/2841 (0%)	1	0/2902 (0%)	0
Chest wall abscess	0/2841 (0%)	0	1/2902 (0%)	1
Chronic hepatitis C	1/2841 (0%)	1	0/2902 (0%)	0
Chronic sinusitis	2/2841 (0.1%)	2	1/2902 (0%)	1
Clostridium difficile colitis	1/2841 (0%)	1	0/2902 (0%)	0
Clostridium difficile infection	1/2841 (0%)	1	0/2902 (0%)	0
Conjunctivitis	36/2841 (1.3%)	37	27/2902 (0.9%)	28
Conjunctivitis bacterial	1/2841 (0%)	1	1/2902 (0%)	1
Conjunctivitis viral	1/2841 (0%)	1	0/2902 (0%)	0
Cystitis	30/2841 (1.1%)	34	29/2902 (1%)	33
Dacryocystitis	1/2841 (0%)	1	0/2902 (0%)	0
Demodicidosis	1/2841 (0%)	1	0/2902 (0%)	0
Dengue fever	0/2841 (0%)	0	1/2902 (0%)	1
Dermatophytosis	1/2841 (0%)	1	0/2902 (0%)	0
Device related infection	1/2841 (0%)	1	3/2902 (0.1%)	4
Diverticulitis	7/2841 (0.2%)	8	2/2902 (0.1%)	2
Ear infection	20/2841 (0.7%)	23	10/2902 (0.3%)	11
Ear infection fungal	0/2841 (0%)	0	1/2902 (0%)	1
Endometritis	1/2841 (0%)	2	0/2902 (0%)	0
Enteritis infectious	0/2841 (0%)	0	1/2902 (0%)	1
Enterocolitis infectious	2/2841 (0.1%)	2	1/2902 (0%)	1
Epstein-Barr virus infection	0/2841 (0%)	0	1/2902 (0%)	1
Erysipelas	9/2841 (0.3%)	11	3/2902 (0.1%)	3
Erythema migrans	0/2841 (0%)	0	1/2902 (0%)	1
Eye infection	17/2841 (0.6%)	20	7/2902 (0.2%)	8
Eyelid infection	1/2841 (0%)	1	0/2902 (0%)	0
Febrile infection	1/2841 (0%)	1	1/2902 (0%)	1
Folliculitis	10/2841 (0.4%)	12	9/2902 (0.3%)	9
Fungal infection	16/2841 (0.6%)	18	9/2902 (0.3%)	9
Fungal skin infection	6/2841 (0.2%)	6	6/2902 (0.2%)	7
Furuncle	3/2841 (0.1%)	5	0/2902 (0%)	0
Gastroenteritis	46/2841 (1.6%)	51	20/2902 (0.7%)	21
Gastroenteritis norovirus	0/2841 (0%)	0	1/2902 (0%)	1
Gastroenteritis salmonella	1/2841 (0%)	2	0/2902 (0%)	0
Gastroenteritis viral	18/2841 (0.6%)	19	10/2902 (0.3%)	10
Gastrointestinal bacterial overgrowth	1/2841 (0%)	1	1/2902 (0%)	1
Gastrointestinal infection	5/2841 (0.2%)	5	4/2902 (0.1%)	4
Gastrointestinal viral infection	4/2841 (0.1%)	4	0/2902 (0%)	0
Genital herpes	3/2841 (0.1%)	4	3/2902 (0.1%)	3
Genital herpes simplex	1/2841 (0%)	1	0/2902 (0%)	0
Gingival abscess	0/2841 (0%)	0	1/2902 (0%)	1
Gingivitis	6/2841 (0.2%)	7	9/2902 (0.3%)	9
Haemophilus infection	0/2841 (0%)	0	1/2902 (0%)	1
Haemorrhoid infection	1/2841 (0%)	1	0/2902 (0%)	0
Hand-foot-and-mouth disease	0/2841 (0%)	0	1/2902 (0%)	1
Helicobacter gastritis	1/2841 (0%)	1	1/2902 (0%)	1
Helicobacter infection	6/2841 (0.2%)	6	4/2902 (0.1%)	4
Herpes ophthalmic	0/2841 (0%)	0	2/2902 (0.1%)	2
Herpes simplex	12/2841 (0.4%)	13	4/2902 (0.1%)	4
Herpes simplex reactivation	1/2841 (0%)	1	0/2902 (0%)	0
Herpes virus infection	9/2841 (0.3%)	10	3/2902 (0.1%)	6
Herpes zoster	52/2841 (1.8%)	57	50/2902 (1.7%)	53
Hordeolum	6/2841 (0.2%)	6	8/2902 (0.3%)	8
Incision site cellulitis	1/2841 (0%)	1	0/2902 (0%)	0
Infected bite	4/2841 (0.1%)	4	1/2902 (0%)	1
Infected cyst	0/2841 (0%)	0	1/2902 (0%)	1
Infected dermal cyst	1/2841 (0%)	1	2/2902 (0.1%)	2
Infected seroma	1/2841 (0%)	1	2/2902 (0.1%)	4
Infected skin ulcer	1/2841 (0%)	1	0/2902 (0%)	0
Infection	17/2841 (0.6%)	18	10/2902 (0.3%)	11
Infection parasitic	1/2841 (0%)	1	0/2902 (0%)	0
Infective tenosynovitis	0/2841 (0%)	0	1/2902 (0%)	1
Influenza	102/2841 (3.6%)	109	45/2902 (1.6%)	48
Kidney infection	1/2841 (0%)	1	1/2902 (0%)	1
Labyrinthitis	0/2841 (0%)	0	1/2902 (0%)	1
Laryngitis	21/2841 (0.7%)	22	5/2902 (0.2%)	5
Laryngitis viral	1/2841 (0%)	1	0/2902 (0%)	0
Lip infection	8/2841 (0.3%)	8	3/2902 (0.1%)	3
Localised infection	7/2841 (0.2%)	8	4/2902 (0.1%)	4
Lower respiratory tract infection	36/2841 (1.3%)	49	20/2902 (0.7%)	21
Lower respiratory tract infection viral	0/2841 (0%)	0	1/2902 (0%)	1
Lyme disease	4/2841 (0.1%)	4	2/2902 (0.1%)	2
Lymph gland infection	0/2841 (0%)	0	2/2902 (0.1%)	2
Lymphangitis	4/2841 (0.1%)	4	2/2902 (0.1%)	3
Mastitis	29/2841 (1%)	43	43/2902 (1.5%)	47
Mucosal infection	6/2841 (0.2%)	8	3/2902 (0.1%)	3
Nail infection	5/2841 (0.2%)	5	5/2902 (0.2%)	7
Nasal abscess	3/2841 (0.1%)	4	0/2902 (0%)	0
Nasal herpes	1/2841 (0%)	1	1/2902 (0%)	1
Nasopharyngitis	210/2841 (7.4%)	275	127/2902 (4.4%)	157
Nipple infection	1/2841 (0%)	1	1/2902 (0%)	1
Oesophageal candidiasis	1/2841 (0%)	1	0/2902 (0%)	0
Oesophageal infection	1/2841 (0%)	1	0/2902 (0%)	0
Onychomycosis	8/2841 (0.3%)	9	7/2902 (0.2%)	7
Oral candidiasis	12/2841 (0.4%)	13	4/2902 (0.1%)	4
Oral fungal infection	1/2841 (0%)	1	0/2902 (0%)	0
Oral herpes	65/2841 (2.3%)	88	16/2902 (0.6%)	17
Oral infection	4/2841 (0.1%)	4	2/2902 (0.1%)	2
Otitis externa	6/2841 (0.2%)	6	3/2902 (0.1%)	3
Otitis media	19/2841 (0.7%)	22	5/2902 (0.2%)	5
Papilloma viral infection	1/2841 (0%)	1	1/2902 (0%)	1
Parainfluenzae virus infection	0/2841 (0%)	0	1/2902 (0%)	1
Parasitic gastroenteritis	1/2841 (0%)	1	1/2902 (0%)	1
Paronychia	9/2841 (0.3%)	9	8/2902 (0.3%)	8
Parotitis	1/2841 (0%)	1	0/2902 (0%)	0
Pelvic inflammatory disease	1/2841 (0%)	1	0/2902 (0%)	0
Pericoronitis	1/2841 (0%)	1	0/2902 (0%)	0
Perineal abscess	1/2841 (0%)	1	1/2902 (0%)	1
Periodontitis	3/2841 (0.1%)	4	1/2902 (0%)	1
Periorbital cellulitis	1/2841 (0%)	1	0/2902 (0%)	0
Periorbital infection	1/2841 (0%)	1	0/2902 (0%)	0
Peripheral nerve infection	1/2841 (0%)	1	0/2902 (0%)	0
Periumbilical abscess	1/2841 (0%)	1	0/2902 (0%)	0
Pertussis	1/2841 (0%)	1	0/2902 (0%)	0
Pharyngitis	50/2841 (1.8%)	63	19/2902 (0.7%)	20
Pharyngitis streptococcal	1/2841 (0%)	1	1/2902 (0%)	1
Pilonidal cyst	0/2841 (0%)	0	1/2902 (0%)	1
Pneumonia	38/2841 (1.3%)	42	35/2902 (1.2%)	37
Pneumonia influenzal	0/2841 (0%)	0	1/2902 (0%)	1
Post procedural cellulitis	0/2841 (0%)	0	1/2902 (0%)	1
Post procedural infection	1/2841 (0%)	1	0/2902 (0%)	0
Postoperative wound infection	8/2841 (0.3%)	8	3/2902 (0.1%)	3
Psoas abscess	1/2841 (0%)	1	0/2902 (0%)	0
Pulpitis dental	2/2841 (0.1%)	3	2/2902 (0.1%)	2
Pustule	3/2841 (0.1%)	3	0/2902 (0%)	0
Pyelonephritis	1/2841 (0%)	1	3/2902 (0.1%)	3
Rash pustular	12/2841 (0.4%)	13	4/2902 (0.1%)	5
Respiratory tract infection	52/2841 (1.8%)	73	31/2902 (1.1%)	35
Respiratory tract infection viral	3/2841 (0.1%)	4	3/2902 (0.1%)	3
Rhinitis	36/2841 (1.3%)	46	12/2902 (0.4%)	13
Sialoadenitis	1/2841 (0%)	1	0/2902 (0%)	0
Sinobronchitis	0/2841 (0%)	0	1/2902 (0%)	1
Sinusitis	105/2841 (3.7%)	132	61/2902 (2.1%)	74
Skin candida	2/2841 (0.1%)	2	3/2902 (0.1%)	3
Skin infection	63/2841 (2.2%)	85	29/2902 (1%)	31
Soft tissue infection	2/2841 (0.1%)	2	3/2902 (0.1%)	3
Sputum purulent	1/2841 (0%)	1	0/2902 (0%)	0
Staphylococcal infection	1/2841 (0%)	1	2/2902 (0.1%)	3
Streptococcal infection	1/2841 (0%)	3	0/2902 (0%)	0
Subcutaneous abscess	1/2841 (0%)	1	0/2902 (0%)	0
Suspected COVID-19	1/2841 (0%)	1	1/2902 (0%)	1
Tinea infection	0/2841 (0%)	0	1/2902 (0%)	1
Tinea pedis	4/2841 (0.1%)	4	1/2902 (0%)	1
Tinea versicolour	0/2841 (0%)	0	1/2902 (0%)	1
Tonsillitis	9/2841 (0.3%)	10	10/2902 (0.3%)	10
Tooth abscess	14/2841 (0.5%)	16	7/2902 (0.2%)	8
Tooth infection	26/2841 (0.9%)	30	21/2902 (0.7%)	21
Toxoplasmosis	0/2841 (0%)	0	1/2902 (0%)	1
Tracheitis	7/2841 (0.2%)	8	0/2902 (0%)	0
Tuberculosis	1/2841 (0%)	1	0/2902 (0%)	0
Upper respiratory tract infection	304/2841 (10.7%)	390	185/2902 (6.4%)	229
Urethritis	1/2841 (0%)	2	1/2902 (0%)	2
Urinary tract infection	234/2841 (8.2%)	320	145/2902 (5%)	204
Urinary tract infection viral	1/2841 (0%)	1	1/2902 (0%)	1
Vaginal infection	27/2841 (1%)	28	18/2902 (0.6%)	21
Varicella	0/2841 (0%)	0	1/2902 (0%)	1
Vascular device infection	1/2841 (0%)	1	1/2902 (0%)	1
Vestibulitis	0/2841 (0%)	0	1/2902 (0%)	1
Viral infection	28/2841 (1%)	30	18/2902 (0.6%)	18
Viral skin infection	1/2841 (0%)	1	0/2902 (0%)	0
Viral upper respiratory tract infection	7/2841 (0.2%)	7	5/2902 (0.2%)	6
Vulval cellulitis	0/2841 (0%)	0	1/2902 (0%)	1
Vulvitis	2/2841 (0.1%)	2	1/2902 (0%)	1
Vulvovaginal candidiasis	15/2841 (0.5%)	17	3/2902 (0.1%)	3
Vulvovaginal human papilloma virus infection	1/2841 (0%)	1	0/2902 (0%)	0
Vulvovaginal mycotic infection	8/2841 (0.3%)	8	12/2902 (0.4%)	13
Wound infection	14/2841 (0.5%)	16	7/2902 (0.2%)	8
Injury, poisoning and procedural complications
Abdominal wound dehiscence	1/2841 (0%)	1	0/2902 (0%)	0
Animal bite	4/2841 (0.1%)	4	3/2902 (0.1%)	3
Ankle fracture	10/2841 (0.4%)	11	13/2902 (0.4%)	13
Arthropod bite	22/2841 (0.8%)	24	11/2902 (0.4%)	11
Arthropod sting	0/2841 (0%)	0	1/2902 (0%)	1
Axillary web syndrome	14/2841 (0.5%)	15	5/2902 (0.2%)	5
Back injury	1/2841 (0%)	1	0/2902 (0%)	0
Bite	1/2841 (0%)	1	0/2902 (0%)	0
Bone contusion	0/2841 (0%)	0	2/2902 (0.1%)	2
Breast injury	0/2841 (0%)	0	1/2902 (0%)	1
Breast procedural complication	0/2841 (0%)	0	1/2902 (0%)	1
Chest injury	1/2841 (0%)	1	0/2902 (0%)	0
Chillblains	1/2841 (0%)	1	0/2902 (0%)	0
Clavicle fracture	0/2841 (0%)	0	4/2902 (0.1%)	6
Compression fracture	0/2841 (0%)	0	1/2902 (0%)	1
Concussion	0/2841 (0%)	0	3/2902 (0.1%)	3
Contusion	95/2841 (3.3%)	108	37/2902 (1.3%)	43
Corneal abrasion	2/2841 (0.1%)	2	0/2902 (0%)	0
Craniocerebral injury	0/2841 (0%)	0	1/2902 (0%)	1
Epicondylitis	5/2841 (0.2%)	6	3/2902 (0.1%)	3
Exposure to toxic agent	0/2841 (0%)	0	3/2902 (0.1%)	3
Eye contusion	0/2841 (0%)	0	2/2902 (0.1%)	2
Eye injury	0/2841 (0%)	0	1/2902 (0%)	1
Face injury	1/2841 (0%)	1	0/2902 (0%)	0
Fall	57/2841 (2%)	68	40/2902 (1.4%)	49
Fibula fracture	2/2841 (0.1%)	2	1/2902 (0%)	1
Foot fracture	10/2841 (0.4%)	10	16/2902 (0.6%)	17
Forearm fracture	1/2841 (0%)	1	0/2902 (0%)	0
Fracture	3/2841 (0.1%)	3	3/2902 (0.1%)	3
Fractured coccyx	1/2841 (0%)	1	0/2902 (0%)	0
Fractured sacrum	0/2841 (0%)	0	1/2902 (0%)	1
Gastroparesis postoperative	0/2841 (0%)	0	1/2902 (0%)	1
Hair injury	1/2841 (0%)	1	0/2902 (0%)	0
Hand fracture	1/2841 (0%)	2	4/2902 (0.1%)	4
Head injury	1/2841 (0%)	1	1/2902 (0%)	1
Heat stroke	1/2841 (0%)	1	0/2902 (0%)	0
Humerus fracture	3/2841 (0.1%)	3	5/2902 (0.2%)	5
Iliotibial band syndrome	1/2841 (0%)	1	1/2902 (0%)	1
Incision site complication	1/2841 (0%)	1	1/2902 (0%)	1
Incision site erythema	1/2841 (0%)	1	2/2902 (0.1%)	2
Incision site fibrosis	0/2841 (0%)	0	1/2902 (0%)	2
Incision site pain	18/2841 (0.6%)	21	17/2902 (0.6%)	19
Incision site pruritus	1/2841 (0%)	1	1/2902 (0%)	1
Infusion related reaction	1/2841 (0%)	1	2/2902 (0.1%)	2
Injury	2/2841 (0.1%)	2	1/2902 (0%)	1
Joint dislocation	2/2841 (0.1%)	3	2/2902 (0.1%)	2
Joint injury	3/2841 (0.1%)	3	3/2902 (0.1%)	3
Ligament injury	0/2841 (0%)	0	1/2902 (0%)	1
Ligament rupture	2/2841 (0.1%)	2	5/2902 (0.2%)	6
Ligament sprain	12/2841 (0.4%)	12	10/2902 (0.3%)	10
Limb injury	8/2841 (0.3%)	8	4/2902 (0.1%)	4
Lip injury	0/2841 (0%)	0	1/2902 (0%)	1
Lower limb fracture	3/2841 (0.1%)	3	1/2902 (0%)	1
Lumbar vertebral fracture	1/2841 (0%)	1	1/2902 (0%)	1
Median nerve injury	1/2841 (0%)	1	0/2902 (0%)	0
Meniscus injury	5/2841 (0.2%)	6	7/2902 (0.2%)	7
Mouth injury	1/2841 (0%)	1	0/2902 (0%)	0
Mucosal excoriation	1/2841 (0%)	1	0/2902 (0%)	0
Muscle injury	0/2841 (0%)	0	1/2902 (0%)	1
Muscle rupture	1/2841 (0%)	2	3/2902 (0.1%)	3
Muscle strain	6/2841 (0.2%)	6	4/2902 (0.1%)	4
Musculoskeletal injury	0/2841 (0%)	0	1/2902 (0%)	1
Musculoskeletal procedural complication	0/2841 (0%)	0	1/2902 (0%)	1
Nail injury	1/2841 (0%)	1	0/2902 (0%)	0
Nerve injury	0/2841 (0%)	0	1/2902 (0%)	1
Patella fracture	1/2841 (0%)	1	1/2902 (0%)	1
Post procedural complication	2/2841 (0.1%)	2	3/2902 (0.1%)	3
Post procedural constipation	1/2841 (0%)	1	0/2902 (0%)	0
Post procedural contusion	1/2841 (0%)	1	0/2902 (0%)	0
Post procedural discomfort	0/2841 (0%)	0	2/2902 (0.1%)	2
Post procedural haematoma	0/2841 (0%)	0	1/2902 (0%)	1
Post procedural haemorrhage	2/2841 (0.1%)	2	0/2902 (0%)	0
Post procedural inflammation	1/2841 (0%)	1	1/2902 (0%)	1
Post procedural oedema	1/2841 (0%)	1	0/2902 (0%)	0
Post procedural swelling	1/2841 (0%)	1	0/2902 (0%)	0
Post-traumatic neck syndrome	1/2841 (0%)	1	1/2902 (0%)	1
Post-traumatic pain	0/2841 (0%)	0	2/2902 (0.1%)	4
Postpericardiotomy syndrome	0/2841 (0%)	0	1/2902 (0%)	1
Procedural complication	4/2841 (0.1%)	4	1/2902 (0%)	1
Procedural nausea	1/2841 (0%)	1	1/2902 (0%)	1
Procedural pain	48/2841 (1.7%)	58	45/2902 (1.6%)	55
Procedural site reaction	0/2841 (0%)	0	1/2902 (0%)	1
Procedural vomiting	1/2841 (0%)	1	0/2902 (0%)	0
Pulmonary radiation injury	1/2841 (0%)	1	1/2902 (0%)	1
Radiation associated pain	0/2841 (0%)	0	1/2902 (0%)	1
Radiation fibrosis	3/2841 (0.1%)	3	0/2902 (0%)	0
Radiation fibrosis - lung	1/2841 (0%)	1	0/2902 (0%)	0
Radiation injury	1/2841 (0%)	1	1/2902 (0%)	1
Radiation neuropathy	0/2841 (0%)	0	1/2902 (0%)	2
Radiation pneumonitis	6/2841 (0.2%)	6	6/2902 (0.2%)	7
Radiation skin injury	12/2841 (0.4%)	15	20/2902 (0.7%)	20
Radius fracture	7/2841 (0.2%)	7	6/2902 (0.2%)	6
Rectal injury	0/2841 (0%)	0	1/2902 (0%)	1
Rib fracture	10/2841 (0.4%)	10	12/2902 (0.4%)	13
Road traffic accident	2/2841 (0.1%)	2	0/2902 (0%)	0
Scar	1/2841 (0%)	1	0/2902 (0%)	0
Seroma	24/2841 (0.8%)	28	36/2902 (1.2%)	46
Skin abrasion	2/2841 (0.1%)	2	4/2902 (0.1%)	4
Skin flap necrosis	1/2841 (0%)	3	1/2902 (0%)	1
Skin laceration	4/2841 (0.1%)	4	4/2902 (0.1%)	4
Spinal compression fracture	1/2841 (0%)	1	3/2902 (0.1%)	3
Spinal fracture	0/2841 (0%)	0	5/2902 (0.2%)	8
Sternal fracture	0/2841 (0%)	0	1/2902 (0%)	1
Stress fracture	2/2841 (0.1%)	2	2/2902 (0.1%)	2
Subdural haematoma	0/2841 (0%)	0	1/2902 (0%)	1
Sunburn	1/2841 (0%)	1	1/2902 (0%)	1
Suture related complication	1/2841 (0%)	1	0/2902 (0%)	0
Synovial rupture	0/2841 (0%)	0	1/2902 (0%)	1
Tendon injury	1/2841 (0%)	1	1/2902 (0%)	1
Tendon rupture	0/2841 (0%)	0	5/2902 (0.2%)	5
Thermal burn	6/2841 (0.2%)	6	8/2902 (0.3%)	10
Thoracic vertebral fracture	0/2841 (0%)	0	1/2902 (0%)	1
Tibia fracture	0/2841 (0%)	0	3/2902 (0.1%)	3
Tooth fracture	9/2841 (0.3%)	9	3/2902 (0.1%)	4
Traumatic fracture	0/2841 (0%)	0	1/2902 (0%)	1
Ulna fracture	1/2841 (0%)	1	1/2902 (0%)	1
Upper limb fracture	7/2841 (0.2%)	7	5/2902 (0.2%)	7
Vascular access site thrombosis	1/2841 (0%)	1	0/2902 (0%)	0
Wound	12/2841 (0.4%)	12	4/2902 (0.1%)	5
Wound complication	19/2841 (0.7%)	21	3/2902 (0.1%)	3
Wound decomposition	1/2841 (0%)	1	0/2902 (0%)	0
Wound dehiscence	16/2841 (0.6%)	19	7/2902 (0.2%)	7
Wound secretion	1/2841 (0%)	1	0/2902 (0%)	0
Wrist fracture	9/2841 (0.3%)	9	10/2902 (0.3%)	10
Investigations
AST/ALT ratio abnormal	1/2841 (0%)	1	0/2902 (0%)	0
Activated partial thromboplastin time prolonged	1/2841 (0%)	1	0/2902 (0%)	0
Alanine aminotransferase	0/2841 (0%)	0	1/2902 (0%)	1
Alanine aminotransferase decreased	5/2841 (0.2%)	6	4/2902 (0.1%)	4
Alanine aminotransferase increased	212/2841 (7.5%)	345	138/2902 (4.8%)	175
Albumin globulin ratio decreased	1/2841 (0%)	1	0/2902 (0%)	0
Amylase increased	0/2841 (0%)	0	2/2902 (0.1%)	2
Anion gap decreased	1/2841 (0%)	1	0/2902 (0%)	0
Anion gap increased	5/2841 (0.2%)	6	1/2902 (0%)	1
Antimitochondrial antibody positive	1/2841 (0%)	1	0/2902 (0%)	0
Antinuclear antibody increased	1/2841 (0%)	1	0/2902 (0%)	0
Aspartate aminotransferase	2/2841 (0.1%)	2	1/2902 (0%)	1
Aspartate aminotransferase decreased	6/2841 (0.2%)	6	2/2902 (0.1%)	2
Aspartate aminotransferase increased	210/2841 (7.4%)	288	114/2902 (3.9%)	151
Bacterial test	0/2841 (0%)	0	2/2902 (0.1%)	2
Basophil count increased	5/2841 (0.2%)	7	0/2902 (0%)	0
Bilirubin conjugated decreased	0/2841 (0%)	0	3/2902 (0.1%)	5
Biopsy skin	0/2841 (0%)	0	1/2902 (0%)	1
Blood 1,25-dihydroxycholecalciferol decreased	0/2841 (0%)	0	1/2902 (0%)	1
Blood albumin decreased	5/2841 (0.2%)	6	8/2902 (0.3%)	9
Blood albumin increased	2/2841 (0.1%)	2	1/2902 (0%)	1
Blood alkaline phosphatase	5/2841 (0.2%)	7	2/2902 (0.1%)	2
Blood alkaline phosphatase decreased	6/2841 (0.2%)	8	4/2902 (0.1%)	4
Blood alkaline phosphatase increased	75/2841 (2.6%)	91	98/2902 (3.4%)	127
Blood bicarbonate increased	0/2841 (0%)	0	1/2902 (0%)	1
Blood bilirubin	1/2841 (0%)	1	1/2902 (0%)	1
Blood bilirubin abnormal	0/2841 (0%)	0	2/2902 (0.1%)	2
Blood bilirubin decreased	0/2841 (0%)	0	2/2902 (0.1%)	2
Blood bilirubin increased	29/2841 (1%)	47	28/2902 (1%)	41
Blood calcium decreased	6/2841 (0.2%)	8	2/2902 (0.1%)	3
Blood calcium increased	1/2841 (0%)	1	3/2902 (0.1%)	4
Blood chloride decreased	0/2841 (0%)	0	3/2902 (0.1%)	5
Blood chloride increased	4/2841 (0.1%)	4	2/2902 (0.1%)	2
Blood cholesterol increased	21/2841 (0.7%)	22	47/2902 (1.6%)	51
Blood creatine increased	1/2841 (0%)	1	1/2902 (0%)	1
Blood creatine phosphokinase increased	4/2841 (0.1%)	4	0/2902 (0%)	0
Blood creatinine decreased	5/2841 (0.2%)	5	3/2902 (0.1%)	4
Blood creatinine increased	91/2841 (3.2%)	133	50/2902 (1.7%)	80
Blood culture positive	1/2841 (0%)	1	0/2902 (0%)	0
Blood folate decreased	2/2841 (0.1%)	2	0/2902 (0%)	0
Blood glucose decreased	2/2841 (0.1%)	4	2/2902 (0.1%)	2
Blood glucose increased	17/2841 (0.6%)	24	25/2902 (0.9%)	30
Blood iron decreased	1/2841 (0%)	1	1/2902 (0%)	1
Blood ketone body	1/2841 (0%)	1	0/2902 (0%)	0
Blood lactate dehydrogenase increased	8/2841 (0.3%)	8	0/2902 (0%)	0
Blood magnesium decreased	3/2841 (0.1%)	3	4/2902 (0.1%)	4
Blood phosphorus decreased	0/2841 (0%)	0	2/2902 (0.1%)	2
Blood phosphorus increased	1/2841 (0%)	1	0/2902 (0%)	0
Blood potassium decreased	8/2841 (0.3%)	9	1/2902 (0%)	1
Blood potassium increased	2/2841 (0.1%)	4	2/2902 (0.1%)	2
Blood pressure diastolic increased	0/2841 (0%)	0	1/2902 (0%)	1
Blood pressure increased	3/2841 (0.1%)	3	5/2902 (0.2%)	8
Blood pressure systolic increased	1/2841 (0%)	1	1/2902 (0%)	1
Blood sodium decreased	1/2841 (0%)	1	3/2902 (0.1%)	4
Blood sodium increased	0/2841 (0%)	0	3/2902 (0.1%)	3
Blood testosterone decreased	0/2841 (0%)	0	1/2902 (0%)	1
Blood thyroid stimulating hormone decreased	1/2841 (0%)	1	0/2902 (0%)	0
Blood thyroid stimulating hormone increased	2/2841 (0.1%)	2	2/2902 (0.1%)	2
Blood triglycerides increased	6/2841 (0.2%)	6	7/2902 (0.2%)	10
Blood urea decreased	2/2841 (0.1%)	3	2/2902 (0.1%)	3
Blood urea increased	11/2841 (0.4%)	15	8/2902 (0.3%)	11
Blood urea nitrogen/creatinine ratio	2/2841 (0.1%)	4	0/2902 (0%)	0
Blood uric acid increased	0/2841 (0%)	0	6/2902 (0.2%)	6
Blood urine present	2/2841 (0.1%)	2	0/2902 (0%)	0
Body temperature increased	2/2841 (0.1%)	2	2/2902 (0.1%)	2
Bone density decreased	1/2841 (0%)	1	0/2902 (0%)	0
Brain natriuretic peptide increased	0/2841 (0%)	0	1/2902 (0%)	1
C-reactive protein increased	4/2841 (0.1%)	4	0/2902 (0%)	0
Carbon dioxide abnormal	3/2841 (0.1%)	3	1/2902 (0%)	1
Carbon dioxide decreased	3/2841 (0.1%)	3	2/2902 (0.1%)	2
Carbon dioxide increased	2/2841 (0.1%)	2	3/2902 (0.1%)	3
Cardiac murmur	4/2841 (0.1%)	4	2/2902 (0.1%)	2
Carotid bruit	1/2841 (0%)	1	0/2902 (0%)	0
Coagulation time prolonged	1/2841 (0%)	1	0/2902 (0%)	0
Colonoscopy abnormal	0/2841 (0%)	0	1/2902 (0%)	1
Ejection fraction decreased	4/2841 (0.1%)	5	3/2902 (0.1%)	3
Electrocardiogram QT prolonged	2/2841 (0.1%)	2	0/2902 (0%)	0
Eosinophil count increased	2/2841 (0.1%)	2	2/2902 (0.1%)	3
Eosinophil percentage decreased	0/2841 (0%)	0	1/2902 (0%)	1
Eosinophil percentage increased	0/2841 (0%)	0	2/2902 (0.1%)	2
Fibrin D dimer increased	0/2841 (0%)	0	1/2902 (0%)	1
Gamma-glutamyltransferase	1/2841 (0%)	1	0/2902 (0%)	0
Gamma-glutamyltransferase increased	18/2841 (0.6%)	35	21/2902 (0.7%)	35
Glomerular filtration rate decreased	6/2841 (0.2%)	11	1/2902 (0%)	1
Glomerular filtration rate increased	1/2841 (0%)	2	0/2902 (0%)	0
Glycosylated haemoglobin decreased	1/2841 (0%)	1	0/2902 (0%)	0
Glycosylated haemoglobin increased	15/2841 (0.5%)	18	20/2902 (0.7%)	22
Granulocyte count decreased	1/2841 (0%)	2	0/2902 (0%)	0
Granulocyte count increased	1/2841 (0%)	1	0/2902 (0%)	0
Haematocrit decreased	28/2841 (1%)	41	6/2902 (0.2%)	7
Haemoglobin decreased	42/2841 (1.5%)	79	12/2902 (0.4%)	15
Haemoglobin increased	0/2841 (0%)	0	2/2902 (0.1%)	2
Heart rate decreased	1/2841 (0%)	1	0/2902 (0%)	0
Heart rate increased	4/2841 (0.1%)	6	2/2902 (0.1%)	3
Heart rate irregular	1/2841 (0%)	1	0/2902 (0%)	0
Hepatic enzyme increased	7/2841 (0.2%)	9	5/2902 (0.2%)	5
High density lipoprotein decreased	3/2841 (0.1%)	3	0/2902 (0%)	0
Influenza A virus test positive	1/2841 (0%)	1	0/2902 (0%)	0
International normalised ratio increased	1/2841 (0%)	2	2/2902 (0.1%)	5
Intestinal transit time abnormal	1/2841 (0%)	1	0/2902 (0%)	0
Intraocular pressure increased	1/2841 (0%)	1	2/2902 (0.1%)	2
Liver function test abnormal	1/2841 (0%)	1	1/2902 (0%)	1
Liver function test increased	4/2841 (0.1%)	4	8/2902 (0.3%)	8
Low density lipoprotein increased	1/2841 (0%)	1	0/2902 (0%)	0
Lymph node palpable	0/2841 (0%)	0	1/2902 (0%)	1
Lymphocyte count	1/2841 (0%)	2	1/2902 (0%)	1
Lymphocyte count decreased	317/2841 (11.2%)	926	100/2902 (3.4%)	161
Lymphocyte count increased	7/2841 (0.2%)	7	1/2902 (0%)	2
Lymphocyte percentage increased	1/2841 (0%)	2	0/2902 (0%)	0
Mean cell haemoglobin concentration	0/2841 (0%)	0	1/2902 (0%)	1
Mean cell haemoglobin concentration abnormal	0/2841 (0%)	0	1/2902 (0%)	1
Mean cell haemoglobin concentration decreased	1/2841 (0%)	1	0/2902 (0%)	0
Mean cell haemoglobin concentration increased	3/2841 (0.1%)	3	0/2902 (0%)	0
Mean cell haemoglobin decreased	0/2841 (0%)	0	1/2902 (0%)	1
Mean cell haemoglobin increased	11/2841 (0.4%)	14	1/2902 (0%)	1
Mean cell volume	1/2841 (0%)	1	0/2902 (0%)	0
Mean cell volume abnormal	8/2841 (0.3%)	8	0/2902 (0%)	0
Mean cell volume decreased	2/2841 (0.1%)	2	0/2902 (0%)	0
Mean cell volume increased	14/2841 (0.5%)	17	1/2902 (0%)	1
Mean platelet volume decreased	5/2841 (0.2%)	6	2/2902 (0.1%)	3
Mean platelet volume increased	1/2841 (0%)	2	0/2902 (0%)	0
Monocyte count decreased	13/2841 (0.5%)	24	1/2902 (0%)	1
Monocyte count increased	8/2841 (0.3%)	9	1/2902 (0%)	1
Monocyte percentage decreased	0/2841 (0%)	0	1/2902 (0%)	1
Neutrophil count	9/2841 (0.3%)	13	0/2902 (0%)	0
Neutrophil count abnormal	1/2841 (0%)	1	0/2902 (0%)	0
Neutrophil count decreased	1344/2841 (47.3%)	6144	67/2902 (2.3%)	109
Neutrophil count increased	4/2841 (0.1%)	5	6/2902 (0.2%)	6
Neutrophil percentage decreased	0/2841 (0%)	0	1/2902 (0%)	2
Non-high-density lipoprotein cholesterol increased	1/2841 (0%)	1	1/2902 (0%)	1
Occult blood positive	0/2841 (0%)	0	1/2902 (0%)	1
Pancreatic enzymes decreased	1/2841 (0%)	1	0/2902 (0%)	0
Physical examination abnormal	0/2841 (0%)	0	1/2902 (0%)	1
Platelet count decreased	436/2841 (15.3%)	850	35/2902 (1.2%)	50
Platelet count increased	7/2841 (0.2%)	7	2/2902 (0.1%)	2
Prostatic specific antigen increased	1/2841 (0%)	1	0/2902 (0%)	0
Protein total abnormal	1/2841 (0%)	1	0/2902 (0%)	0
Protein total decreased	5/2841 (0.2%)	5	8/2902 (0.3%)	10
Protein total increased	0/2841 (0%)	0	1/2902 (0%)	1
Red blood cell count decreased	35/2841 (1.2%)	49	7/2902 (0.2%)	7
Red blood cell count increased	1/2841 (0%)	1	0/2902 (0%)	0
Red blood cell sedimentation rate increased	1/2841 (0%)	1	1/2902 (0%)	1
Red cell distribution width decreased	1/2841 (0%)	1	0/2902 (0%)	0
Red cell distribution width increased	13/2841 (0.5%)	14	1/2902 (0%)	1
Rheumatoid factor increased	1/2841 (0%)	1	0/2902 (0%)	0
Smear cervix abnormal	0/2841 (0%)	0	1/2902 (0%)	1
Specific gravity urine increased	1/2841 (0%)	1	0/2902 (0%)	0
Transaminases increased	7/2841 (0.2%)	8	7/2902 (0.2%)	7
Troponin I increased	1/2841 (0%)	1	1/2902 (0%)	1
Urine analysis abnormal	1/2841 (0%)	1	0/2902 (0%)	0
Urine leukocyte esterase	0/2841 (0%)	0	1/2902 (0%)	1
Vitamin B12 decreased	4/2841 (0.1%)	4	1/2902 (0%)	1
Vitamin D decreased	9/2841 (0.3%)	9	13/2902 (0.4%)	13
Weight decreased	44/2841 (1.5%)	48	29/2902 (1%)	40
Weight increased	116/2841 (4.1%)	155	136/2902 (4.7%)	162
White blood cell count	3/2841 (0.1%)	3	0/2902 (0%)	0
White blood cell count decreased	1187/2841 (41.8%)	5122	155/2902 (5.3%)	242
White blood cell count increased	1/2841 (0%)	1	4/2902 (0.1%)	4
White blood cells urine	1/2841 (0%)	1	0/2902 (0%)	0
Metabolism and nutrition disorders
Abnormal loss of weight	1/2841 (0%)	1	0/2902 (0%)	0
Appetite disorder	1/2841 (0%)	1	0/2902 (0%)	0
Decreased appetite	151/2841 (5.3%)	176	73/2902 (2.5%)	87
Dehydration	17/2841 (0.6%)	18	5/2902 (0.2%)	5
Diabetes mellitus	3/2841 (0.1%)	3	6/2902 (0.2%)	6
Diabetes mellitus inadequate control	0/2841 (0%)	0	1/2902 (0%)	1
Dyslipidaemia	2/2841 (0.1%)	2	8/2902 (0.3%)	9
Fluid retention	5/2841 (0.2%)	5	10/2902 (0.3%)	11
Folate deficiency	4/2841 (0.1%)	4	1/2902 (0%)	1
Food craving	1/2841 (0%)	1	0/2902 (0%)	0
Glucose tolerance impaired	3/2841 (0.1%)	3	6/2902 (0.2%)	7
Gout	5/2841 (0.2%)	6	4/2902 (0.1%)	4
Hyperalbuminaemia	0/2841 (0%)	0	2/2902 (0.1%)	2
Hypercalcaemia	45/2841 (1.6%)	59	44/2902 (1.5%)	61
Hyperchloraemia	1/2841 (0%)	1	0/2902 (0%)	0
Hypercholesterolaemia	8/2841 (0.3%)	8	23/2902 (0.8%)	30
Hyperglycaemia	119/2841 (4.2%)	185	95/2902 (3.3%)	141
Hyperkalaemia	29/2841 (1%)	36	35/2902 (1.2%)	35
Hyperlipidaemia	6/2841 (0.2%)	6	9/2902 (0.3%)	9
Hypermagnesaemia	1/2841 (0%)	1	0/2902 (0%)	0
Hypernatraemia	29/2841 (1%)	32	35/2902 (1.2%)	39
Hyperphagia	1/2841 (0%)	1	1/2902 (0%)	1
Hyperphosphataemia	0/2841 (0%)	0	1/2902 (0%)	1
Hypertriglyceridaemia	13/2841 (0.5%)	15	14/2902 (0.5%)	17
Hyperuricaemia	5/2841 (0.2%)	6	10/2902 (0.3%)	14
Hypoalbuminaemia	43/2841 (1.5%)	63	28/2902 (1%)	40
Hypocalcaemia	47/2841 (1.7%)	69	30/2902 (1%)	35
Hypochloraemia	2/2841 (0.1%)	2	1/2902 (0%)	1
Hypoglycaemia	24/2841 (0.8%)	24	17/2902 (0.6%)	18
Hypokalaemia	93/2841 (3.3%)	140	53/2902 (1.8%)	69
Hypomagnesaemia	22/2841 (0.8%)	23	8/2902 (0.3%)	10
Hyponatraemia	50/2841 (1.8%)	57	36/2902 (1.2%)	46
Hypophosphataemia	15/2841 (0.5%)	20	7/2902 (0.2%)	9
Hypoproteinaemia	1/2841 (0%)	1	0/2902 (0%)	0
Hypovitaminosis	0/2841 (0%)	0	1/2902 (0%)	1
Increased appetite	3/2841 (0.1%)	3	6/2902 (0.2%)	6
Iron deficiency	1/2841 (0%)	2	3/2902 (0.1%)	3
Lipoedema	0/2841 (0%)	0	1/2902 (0%)	1
Metabolic alkalosis	0/2841 (0%)	0	1/2902 (0%)	1
Obesity	3/2841 (0.1%)	7	0/2902 (0%)	0
Polydipsia	3/2841 (0.1%)	3	0/2902 (0%)	0
Tetany	0/2841 (0%)	0	1/2902 (0%)	1
Type 1 diabetes mellitus	1/2841 (0%)	4	0/2902 (0%)	0
Type 2 diabetes mellitus	2/2841 (0.1%)	2	2/2902 (0.1%)	2
Vitamin B complex deficiency	1/2841 (0%)	1	0/2902 (0%)	0
Vitamin B12 deficiency	6/2841 (0.2%)	6	2/2902 (0.1%)	2
Vitamin D deficiency	29/2841 (1%)	29	25/2902 (0.9%)	26
Weight loss poor	2/2841 (0.1%)	2	0/2902 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1087/2841 (38.3%)	1650	1305/2902 (45%)	2034
Arthritis	25/2841 (0.9%)	28	33/2902 (1.1%)	41
Arthropathy	1/2841 (0%)	2	1/2902 (0%)	2
Axillary mass	6/2841 (0.2%)	6	4/2902 (0.1%)	4
Back pain	311/2841 (10.9%)	369	287/2902 (9.9%)	346
Bone disorder	1/2841 (0%)	1	0/2902 (0%)	0
Bone loss	1/2841 (0%)	1	1/2902 (0%)	1
Bone pain	80/2841 (2.8%)	93	87/2902 (3%)	97
Bursitis	13/2841 (0.5%)	13	14/2902 (0.5%)	16
Cervical spinal stenosis	1/2841 (0%)	1	0/2902 (0%)	0
Chest wall haematoma	1/2841 (0%)	1	0/2902 (0%)	0
Chest wall mass	2/2841 (0.1%)	2	1/2902 (0%)	1
Chest wall necrosis	1/2841 (0%)	1	0/2902 (0%)	0
Chondrocalcinosis pyrophosphate	0/2841 (0%)	0	1/2902 (0%)	1
Chondromalacia	1/2841 (0%)	1	0/2902 (0%)	0
Coccydynia	7/2841 (0.2%)	8	9/2902 (0.3%)	9
Costochondritis	1/2841 (0%)	2	2/2902 (0.1%)	2
Enthesopathy	1/2841 (0%)	1	1/2902 (0%)	1
Exostosis	2/2841 (0.1%)	3	1/2902 (0%)	1
Fasciitis	0/2841 (0%)	0	1/2902 (0%)	1
Fibromyalgia	5/2841 (0.2%)	6	1/2902 (0%)	1
Fistula	1/2841 (0%)	1	0/2902 (0%)	0
Flank pain	23/2841 (0.8%)	25	12/2902 (0.4%)	14
Foot deformity	2/2841 (0.1%)	2	3/2902 (0.1%)	3
Groin pain	5/2841 (0.2%)	5	8/2902 (0.3%)	8
Hand deformity	0/2841 (0%)	0	1/2902 (0%)	1
Interspinous osteoarthritis	1/2841 (0%)	1	0/2902 (0%)	0
Intervertebral disc degeneration	1/2841 (0%)	1	0/2902 (0%)	0
Intervertebral disc disorder	1/2841 (0%)	1	0/2902 (0%)	0
Intervertebral disc protrusion	7/2841 (0.2%)	7	8/2902 (0.3%)	8
Jaw cyst	0/2841 (0%)	0	1/2902 (0%)	1
Joint ankylosis	0/2841 (0%)	0	3/2902 (0.1%)	4
Joint contracture	0/2841 (0%)	0	2/2902 (0.1%)	2
Joint effusion	7/2841 (0.2%)	8	1/2902 (0%)	1
Joint instability	0/2841 (0%)	0	1/2902 (0%)	1
Joint noise	3/2841 (0.1%)	3	4/2902 (0.1%)	4
Joint range of motion decreased	33/2841 (1.2%)	36	29/2902 (1%)	34
Joint stiffness	58/2841 (2%)	63	49/2902 (1.7%)	52
Joint swelling	20/2841 (0.7%)	23	15/2902 (0.5%)	20
Limb discomfort	8/2841 (0.3%)	10	12/2902 (0.4%)	13
Limb mass	3/2841 (0.1%)	4	0/2902 (0%)	0
Lupus-like syndrome	1/2841 (0%)	1	0/2902 (0%)	0
Mandibular mass	1/2841 (0%)	1	0/2902 (0%)	0
Medial tibial stress syndrome	0/2841 (0%)	0	1/2902 (0%)	1
Mobility decreased	1/2841 (0%)	1	3/2902 (0.1%)	3
Muscle contracture	6/2841 (0.2%)	7	5/2902 (0.2%)	6
Muscle discomfort	1/2841 (0%)	1	1/2902 (0%)	1
Muscle disorder	1/2841 (0%)	1	0/2902 (0%)	0
Muscle fatigue	1/2841 (0%)	1	0/2902 (0%)	0
Muscle rigidity	3/2841 (0.1%)	3	2/2902 (0.1%)	3
Muscle spasms	193/2841 (6.8%)	229	124/2902 (4.3%)	131
Muscle tightness	3/2841 (0.1%)	4	12/2902 (0.4%)	12
Muscle twitching	2/2841 (0.1%)	2	3/2902 (0.1%)	4
Muscular weakness	45/2841 (1.6%)	51	29/2902 (1%)	32
Musculoskeletal chest pain	99/2841 (3.5%)	117	85/2902 (2.9%)	92
Musculoskeletal discomfort	16/2841 (0.6%)	23	20/2902 (0.7%)	25
Musculoskeletal disorder	3/2841 (0.1%)	3	6/2902 (0.2%)	6
Musculoskeletal pain	65/2841 (2.3%)	93	81/2902 (2.8%)	107
Musculoskeletal stiffness	40/2841 (1.4%)	47	64/2902 (2.2%)	71
Myalgia	250/2841 (8.8%)	315	235/2902 (8.1%)	276
Myofascial pain syndrome	1/2841 (0%)	1	1/2902 (0%)	1
Myositis	1/2841 (0%)	1	0/2902 (0%)	0
Neck mass	1/2841 (0%)	1	1/2902 (0%)	1
Neck pain	69/2841 (2.4%)	73	72/2902 (2.5%)	78
Nodal osteoarthritis	0/2841 (0%)	0	1/2902 (0%)	1
Osteitis	1/2841 (0%)	1	1/2902 (0%)	1
Osteoarthritis	18/2841 (0.6%)	19	27/2902 (0.9%)	30
Osteochondrosis	0/2841 (0%)	0	2/2902 (0.1%)	2
Osteopenia	60/2841 (2.1%)	60	70/2902 (2.4%)	70
Osteoporosis	75/2841 (2.6%)	75	90/2902 (3.1%)	91
Pain in extremity	265/2841 (9.3%)	347	280/2902 (9.6%)	349
Pain in jaw	21/2841 (0.7%)	22	12/2902 (0.4%)	14
Periarthritis	7/2841 (0.2%)	7	10/2902 (0.3%)	11
Periostitis	1/2841 (0%)	1	0/2902 (0%)	0
Plantar fascial fibromatosis	0/2841 (0%)	0	1/2902 (0%)	1
Plantar fasciitis	16/2841 (0.6%)	17	16/2902 (0.6%)	17
Polyarthritis	1/2841 (0%)	1	3/2902 (0.1%)	3
Polymyalgia rheumatica	0/2841 (0%)	0	1/2902 (0%)	1
Pubic pain	1/2841 (0%)	1	0/2902 (0%)	0
Rheumatic disorder	1/2841 (0%)	1	0/2902 (0%)	0
Rheumatoid arthritis	0/2841 (0%)	0	2/2902 (0.1%)	2
Rotator cuff syndrome	3/2841 (0.1%)	3	12/2902 (0.4%)	12
Scoliosis	1/2841 (0%)	1	0/2902 (0%)	0
Soft tissue disorder	1/2841 (0%)	1	0/2902 (0%)	0
Soft tissue mass	2/2841 (0.1%)	2	0/2902 (0%)	0
Soft tissue swelling	0/2841 (0%)	0	1/2902 (0%)	1
Spinal osteoarthritis	3/2841 (0.1%)	3	6/2902 (0.2%)	6
Spinal pain	8/2841 (0.3%)	10	10/2902 (0.3%)	11
Spinal stenosis	1/2841 (0%)	1	1/2902 (0%)	1
Spinal synovial cyst	0/2841 (0%)	0	1/2902 (0%)	1
Synovial cyst	3/2841 (0.1%)	3	10/2902 (0.3%)	11
Synovitis	0/2841 (0%)	0	1/2902 (0%)	1
Systemic scleroderma	0/2841 (0%)	0	1/2902 (0%)	1
Temporomandibular joint syndrome	2/2841 (0.1%)	2	3/2902 (0.1%)	3
Tendon calcification	1/2841 (0%)	1	0/2902 (0%)	0
Tendon discomfort	0/2841 (0%)	0	2/2902 (0.1%)	2
Tendon disorder	4/2841 (0.1%)	4	5/2902 (0.2%)	5
Tendon pain	5/2841 (0.2%)	7	2/2902 (0.1%)	2
Tendon sheath disorder	1/2841 (0%)	1	0/2902 (0%)	0
Tendonitis	28/2841 (1%)	32	28/2902 (1%)	35
Tenosynovitis	1/2841 (0%)	1	6/2902 (0.2%)	6
Tenosynovitis stenosans	9/2841 (0.3%)	13	9/2902 (0.3%)	10
Torticollis	3/2841 (0.1%)	3	0/2902 (0%)	0
Trigger finger	28/2841 (1%)	35	28/2902 (1%)	29
Trismus	0/2841 (0%)	0	1/2902 (0%)	1
Wrist deformity	0/2841 (0%)	0	1/2902 (0%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acrochordon	2/2841 (0.1%)	2	1/2902 (0%)	1
Adenocarcinoma of colon	0/2841 (0%)	0	1/2902 (0%)	1
Adenoma benign	0/2841 (0%)	0	1/2902 (0%)	1
Basal cell carcinoma	6/2841 (0.2%)	6	14/2902 (0.5%)	15
Benign breast neoplasm	0/2841 (0%)	0	2/2902 (0.1%)	2
Benign neoplasm	3/2841 (0.1%)	3	4/2902 (0.1%)	4
Benign neoplasm of skin	1/2841 (0%)	1	0/2902 (0%)	0
Benign neoplasm of thyroid gland	0/2841 (0%)	0	3/2902 (0.1%)	3
Borderline serous tumour of ovary	0/2841 (0%)	0	1/2902 (0%)	1
Bowen's disease	1/2841 (0%)	1	1/2902 (0%)	1
Cervix carcinoma	0/2841 (0%)	0	1/2902 (0%)	2
Clear cell renal cell carcinoma	1/2841 (0%)	1	0/2902 (0%)	0
Colon adenoma	0/2841 (0%)	0	4/2902 (0.1%)	4
Colon cancer	0/2841 (0%)	0	1/2902 (0%)	1
Colorectal adenocarcinoma	0/2841 (0%)	0	1/2902 (0%)	1
Dysplastic naevus	1/2841 (0%)	1	0/2902 (0%)	0
Fibroadenoma of breast	0/2841 (0%)	0	1/2902 (0%)	1
Fibroma	0/2841 (0%)	0	1/2902 (0%)	1
Fibrous histiocytoma	1/2841 (0%)	1	2/2902 (0.1%)	2
Haemangioma	1/2841 (0%)	1	2/2902 (0.1%)	2
Haemangioma of liver	1/2841 (0%)	1	0/2902 (0%)	0
Haemangioma of skin	0/2841 (0%)	0	2/2902 (0.1%)	2
Hair follicle tumour benign	0/2841 (0%)	0	1/2902 (0%)	1
Hypergammaglobulinaemia benign monoclonal	0/2841 (0%)	0	1/2902 (0%)	1
Intraductal papillary-mucinous carcinoma of pancreas	0/2841 (0%)	0	1/2902 (0%)	1
Keratinising squamous cell carcinoma of nasopharynx	0/2841 (0%)	0	1/2902 (0%)	1
Leiomyoma	0/2841 (0%)	0	1/2902 (0%)	1
Lentigo maligna	1/2841 (0%)	1	0/2902 (0%)	0
Leukaemia	0/2841 (0%)	0	1/2902 (0%)	1
Lipoma	6/2841 (0.2%)	6	6/2902 (0.2%)	8
Lipoma of breast	1/2841 (0%)	1	0/2902 (0%)	0
Lymphoma	0/2841 (0%)	0	1/2902 (0%)	1
Malignant melanoma	1/2841 (0%)	1	0/2902 (0%)	0
Malignant melanoma in situ	0/2841 (0%)	0	2/2902 (0.1%)	2
Melanocytic naevus	8/2841 (0.3%)	9	6/2902 (0.2%)	6
Meningioma	1/2841 (0%)	1	0/2902 (0%)	0
Metastases to bone	1/2841 (0%)	1	0/2902 (0%)	0
Mucinous adenocarcinoma of appendix	0/2841 (0%)	0	1/2902 (0%)	1
Neoplasm	0/2841 (0%)	0	1/2902 (0%)	1
Neoplasm malignant	0/2841 (0%)	0	1/2902 (0%)	1
Neoplasm skin	0/2841 (0%)	0	1/2902 (0%)	1
Neuroendocrine tumour	1/2841 (0%)	1	0/2902 (0%)	0
Oral fibroma	0/2841 (0%)	0	1/2902 (0%)	1
Oral neoplasm	1/2841 (0%)	1	0/2902 (0%)	0
Ovarian cancer	1/2841 (0%)	1	0/2902 (0%)	0
Ovarian neoplasm	1/2841 (0%)	1	0/2902 (0%)	0
Papilloma	0/2841 (0%)	0	1/2902 (0%)	1
Parathyroid tumour benign	1/2841 (0%)	1	0/2902 (0%)	0
Pituitary tumour benign	0/2841 (0%)	0	1/2902 (0%)	1
Prostate cancer	0/2841 (0%)	0	1/2902 (0%)	1
Renal hamartoma	1/2841 (0%)	1	0/2902 (0%)	0
Salivary gland adenoma	0/2841 (0%)	0	1/2902 (0%)	2
Sarcomatoid mesothelioma	0/2841 (0%)	0	1/2902 (0%)	1
Seborrhoeic keratosis	3/2841 (0.1%)	3	2/2902 (0.1%)	2
Serous cystadenocarcinoma ovary	0/2841 (0%)	0	1/2902 (0%)	1
Skin papilloma	5/2841 (0.2%)	6	3/2902 (0.1%)	3
Squamous cell carcinoma	1/2841 (0%)	1	0/2902 (0%)	0
Squamous cell carcinoma of skin	0/2841 (0%)	0	1/2902 (0%)	1
Squamous cell carcinoma of the tongue	1/2841 (0%)	1	0/2902 (0%)	0
Tendon neoplasm	0/2841 (0%)	0	1/2902 (0%)	1
Thyroid adenoma	1/2841 (0%)	1	0/2902 (0%)	0
Tumour pain	1/2841 (0%)	1	0/2902 (0%)	0
Uterine leiomyoma	4/2841 (0.1%)	4	8/2902 (0.3%)	8
Vulval neoplasm	0/2841 (0%)	0	1/2902 (0%)	1
Vulvovaginal warts	1/2841 (0%)	1	0/2902 (0%)	0
Nervous system disorders
Ageusia	5/2841 (0.2%)	5	0/2902 (0%)	0
Akathisia	1/2841 (0%)	1	1/2902 (0%)	1
Allodynia	1/2841 (0%)	1	0/2902 (0%)	0
Amnesia	24/2841 (0.8%)	24	21/2902 (0.7%)	23
Anosmia	1/2841 (0%)	1	0/2902 (0%)	0
Aphasia	2/2841 (0.1%)	2	3/2902 (0.1%)	4
Ataxia	0/2841 (0%)	0	1/2902 (0%)	1
Auditory nerve disorder	1/2841 (0%)	1	0/2902 (0%)	0
Aura	1/2841 (0%)	1	0/2902 (0%)	0
Autonomic nervous system imbalance	1/2841 (0%)	1	0/2902 (0%)	0
Balance disorder	5/2841 (0.2%)	5	4/2902 (0.1%)	4
Brachial plexopathy	0/2841 (0%)	0	2/2902 (0.1%)	2
Brain oedema	1/2841 (0%)	1	0/2902 (0%)	0
Burning sensation	4/2841 (0.1%)	4	1/2902 (0%)	1
Carpal tunnel syndrome	21/2841 (0.7%)	25	31/2902 (1.1%)	35
Cerebral haemorrhage	0/2841 (0%)	0	1/2902 (0%)	1
Cerebrovascular accident	2/2841 (0.1%)	2	1/2902 (0%)	1
Cerebrovascular disorder	1/2841 (0%)	1	0/2902 (0%)	0
Cervicobrachial syndrome	2/2841 (0.1%)	2	0/2902 (0%)	0
Cognitive disorder	34/2841 (1.2%)	41	20/2902 (0.7%)	22
Complex regional pain syndrome	0/2841 (0%)	0	1/2902 (0%)	1
Dementia	1/2841 (0%)	1	0/2902 (0%)	0
Demyelination	1/2841 (0%)	1	0/2902 (0%)	0
Depressed level of consciousness	1/2841 (0%)	1	1/2902 (0%)	1
Disturbance in attention	33/2841 (1.2%)	38	22/2902 (0.8%)	22
Dizziness	248/2841 (8.7%)	306	169/2902 (5.8%)	190
Dizziness postural	4/2841 (0.1%)	4	2/2902 (0.1%)	2
Drooling	0/2841 (0%)	0	1/2902 (0%)	1
Dysaesthesia	14/2841 (0.5%)	15	7/2902 (0.2%)	8
Dysarthria	1/2841 (0%)	2	1/2902 (0%)	1
Dysgeusia	72/2841 (2.5%)	81	14/2902 (0.5%)	14
Dysgraphia	1/2841 (0%)	1	0/2902 (0%)	0
Dyskinesia	2/2841 (0.1%)	2	4/2902 (0.1%)	4
Encephalopathy	0/2841 (0%)	0	1/2902 (0%)	1
Extrapyramidal disorder	0/2841 (0%)	0	1/2902 (0%)	1
Facial nerve disorder	0/2841 (0%)	0	1/2902 (0%)	1
Facial neuralgia	1/2841 (0%)	1	0/2902 (0%)	0
Facial paralysis	1/2841 (0%)	1	2/2902 (0.1%)	2
Head discomfort	2/2841 (0.1%)	2	1/2902 (0%)	1
Headache	445/2841 (15.7%)	590	338/2902 (11.6%)	405
Hydrocephalus	1/2841 (0%)	1	0/2902 (0%)	0
Hyperaesthesia	8/2841 (0.3%)	8	3/2902 (0.1%)	3
Hypersomnia	4/2841 (0.1%)	4	1/2902 (0%)	1
Hypertonia	1/2841 (0%)	1	3/2902 (0.1%)	3
Hypoaesthesia	30/2841 (1.1%)	38	31/2902 (1.1%)	35
Hypokinesia	1/2841 (0%)	1	0/2902 (0%)	0
Hyposmia	2/2841 (0.1%)	2	1/2902 (0%)	1
Intercostal neuralgia	3/2841 (0.1%)	3	1/2902 (0%)	1
Intracranial aneurysm	0/2841 (0%)	0	1/2902 (0%)	1
Lethargy	14/2841 (0.5%)	16	7/2902 (0.2%)	7
Memory impairment	46/2841 (1.6%)	50	59/2902 (2%)	64
Mental impairment	1/2841 (0%)	1	1/2902 (0%)	1
Migraine	27/2841 (1%)	32	21/2902 (0.7%)	23
Migraine with aura	2/2841 (0.1%)	2	0/2902 (0%)	0
Morton's neuralgia	0/2841 (0%)	0	1/2902 (0%)	1
Muscle contractions involuntary	2/2841 (0.1%)	3	0/2902 (0%)	0
Muscle spasticity	2/2841 (0.1%)	2	1/2902 (0%)	1
Myoclonus	0/2841 (0%)	0	1/2902 (0%)	1
Nerve compression	0/2841 (0%)	0	3/2902 (0.1%)	4
Nervous system disorder	1/2841 (0%)	1	1/2902 (0%)	2
Neuralgia	21/2841 (0.7%)	21	15/2902 (0.5%)	15
Neuritis	1/2841 (0%)	1	0/2902 (0%)	0
Neuropathy peripheral	148/2841 (5.2%)	186	102/2902 (3.5%)	121
Neurotoxicity	10/2841 (0.4%)	10	11/2902 (0.4%)	11
Occipital neuralgia	1/2841 (0%)	1	0/2902 (0%)	0
Paraesthesia	115/2841 (4%)	129	82/2902 (2.8%)	89
Paresis	1/2841 (0%)	1	0/2902 (0%)	0
Parkinson's disease	1/2841 (0%)	1	2/2902 (0.1%)	2
Parosmia	1/2841 (0%)	1	0/2902 (0%)	0
Partial seizures	1/2841 (0%)	1	0/2902 (0%)	0
Peripheral motor neuropathy	8/2841 (0.3%)	11	7/2902 (0.2%)	7
Peripheral nerve lesion	1/2841 (0%)	1	0/2902 (0%)	0
Peripheral sensory neuropathy	65/2841 (2.3%)	78	49/2902 (1.7%)	53
Petit mal epilepsy	1/2841 (0%)	1	1/2902 (0%)	1
Phantom limb syndrome	2/2841 (0.1%)	2	0/2902 (0%)	0
Polyneuropathy	12/2841 (0.4%)	14	12/2902 (0.4%)	14
Poor quality sleep	2/2841 (0.1%)	2	0/2902 (0%)	0
Post herpetic neuralgia	2/2841 (0.1%)	3	1/2902 (0%)	1
Presyncope	9/2841 (0.3%)	9	3/2902 (0.1%)	3
Radicular pain	1/2841 (0%)	1	0/2902 (0%)	0
Resting tremor	1/2841 (0%)	1	0/2902 (0%)	0
Restless legs syndrome	7/2841 (0.2%)	7	9/2902 (0.3%)	9
Sciatica	19/2841 (0.7%)	20	19/2902 (0.7%)	22
Seizure	1/2841 (0%)	1	0/2902 (0%)	0
Sensorimotor disorder	1/2841 (0%)	1	0/2902 (0%)	0
Sensory disturbance	2/2841 (0.1%)	2	0/2902 (0%)	0
Sinus headache	6/2841 (0.2%)	7	4/2902 (0.1%)	4
Somnolence	7/2841 (0.2%)	7	7/2902 (0.2%)	7
Speech disorder	0/2841 (0%)	0	1/2902 (0%)	1
Spinal cord herniation	0/2841 (0%)	0	1/2902 (0%)	1
Syncope	23/2841 (0.8%)	23	17/2902 (0.6%)	19
Taste disorder	27/2841 (1%)	29	4/2902 (0.1%)	4
Tension headache	4/2841 (0.1%)	4	3/2902 (0.1%)	3
Thoracic outlet syndrome	0/2841 (0%)	0	1/2902 (0%)	1
Transient ischaemic attack	1/2841 (0%)	1	0/2902 (0%)	0
Tremor	14/2841 (0.5%)	14	12/2902 (0.4%)	13
Trigeminal neuralgia	1/2841 (0%)	1	0/2902 (0%)	0
Visual field defect	1/2841 (0%)	1	0/2902 (0%)	0
Product Issues
Device failure	1/2841 (0%)	1	0/2902 (0%)	0
Device leakage	0/2841 (0%)	0	1/2902 (0%)	1
Psychiatric disorders
Agitation Mood Disturbance	0/2841 (0%)	0	1/2902 (0%)	1
Abnormal dreams	0/2841 (0%)	0	2/2902 (0.1%)	2
Adjustment disorder with depressed mood	2/2841 (0.1%)	2	1/2902 (0%)	1
Adjustment disorder with mixed disturbance of emotion and conduct	0/2841 (0%)	0	1/2902 (0%)	1
Affect lability	9/2841 (0.3%)	10	17/2902 (0.6%)	20
Affective disorder	0/2841 (0%)	0	3/2902 (0.1%)	3
Aggression	1/2841 (0%)	1	0/2902 (0%)	0
Agitated depression	1/2841 (0%)	1	1/2902 (0%)	1
Agitation	22/2841 (0.8%)	22	12/2902 (0.4%)	12
Agoraphobia	1/2841 (0%)	1	0/2902 (0%)	0
Alcohol abuse	2/2841 (0.1%)	3	0/2902 (0%)	0
Anger	0/2841 (0%)	0	1/2902 (0%)	1
Anhedonia	0/2841 (0%)	0	2/2902 (0.1%)	2
Anxiety	157/2841 (5.5%)	184	143/2902 (4.9%)	168
Anxiety disorder	1/2841 (0%)	1	0/2902 (0%)	0
Apathy	1/2841 (0%)	1	0/2902 (0%)	0
Attention deficit hyperactivity disorder	1/2841 (0%)	1	3/2902 (0.1%)	3
Bradyphrenia	1/2841 (0%)	1	4/2902 (0.1%)	4
Bruxism	0/2841 (0%)	0	1/2902 (0%)	1
Confusional state	7/2841 (0.2%)	7	5/2902 (0.2%)	6
Conversion disorder	0/2841 (0%)	0	1/2902 (0%)	1
Daydreaming	1/2841 (0%)	1	1/2902 (0%)	1
Delirium	0/2841 (0%)	0	1/2902 (0%)	1
Depressed mood	38/2841 (1.3%)	44	33/2902 (1.1%)	39
Depression	156/2841 (5.5%)	191	150/2902 (5.2%)	175
Depressive symptom	0/2841 (0%)	0	2/2902 (0.1%)	2
Disorientation	0/2841 (0%)	0	1/2902 (0%)	1
Eating disorder	0/2841 (0%)	0	1/2902 (0%)	1
Emotional disorder	0/2841 (0%)	0	2/2902 (0.1%)	2
Emotional distress	1/2841 (0%)	1	3/2902 (0.1%)	3
Female orgasmic disorder	0/2841 (0%)	0	1/2902 (0%)	2
Flashback	0/2841 (0%)	0	1/2902 (0%)	1
Genito-pelvic pain/penetration disorder	2/2841 (0.1%)	2	0/2902 (0%)	0
Hallucination, auditory	0/2841 (0%)	0	1/2902 (0%)	1
Initial insomnia	2/2841 (0.1%)	3	2/2902 (0.1%)	2
Insomnia	383/2841 (13.5%)	468	357/2902 (12.3%)	418
Irritability	30/2841 (1.1%)	34	25/2902 (0.9%)	28
Libido decreased	31/2841 (1.1%)	33	34/2902 (1.2%)	38
Libido disorder	1/2841 (0%)	1	0/2902 (0%)	0
Loss of libido	1/2841 (0%)	1	2/2902 (0.1%)	2
Mania	1/2841 (0%)	1	0/2902 (0%)	0
Mental disorder	3/2841 (0.1%)	3	0/2902 (0%)	0
Middle insomnia	2/2841 (0.1%)	2	0/2902 (0%)	0
Mixed anxiety and depressive disorder	2/2841 (0.1%)	2	5/2902 (0.2%)	5
Mood altered	20/2841 (0.7%)	23	26/2902 (0.9%)	28
Mood swings	20/2841 (0.7%)	24	28/2902 (1%)	30
Negative thoughts	1/2841 (0%)	1	0/2902 (0%)	0
Nervousness	3/2841 (0.1%)	3	3/2902 (0.1%)	3
Nightmare	2/2841 (0.1%)	3	1/2902 (0%)	1
Orgasm abnormal	0/2841 (0%)	0	1/2902 (0%)	1
Panic attack	5/2841 (0.2%)	5	3/2902 (0.1%)	3
Paranoia	0/2841 (0%)	0	1/2902 (0%)	1
Perinatal depression	0/2841 (0%)	0	1/2902 (0%)	1
Persistent depressive disorder	4/2841 (0.1%)	5	1/2902 (0%)	2
Personality change	2/2841 (0.1%)	2	0/2902 (0%)	0
Phonophobia	0/2841 (0%)	0	1/2902 (0%)	1
Post-traumatic stress disorder	0/2841 (0%)	0	1/2902 (0%)	1
Restlessness	0/2841 (0%)	0	3/2902 (0.1%)	3
Seasonal affective disorder	0/2841 (0%)	0	2/2902 (0.1%)	2
Sleep disorder	24/2841 (0.8%)	31	26/2902 (0.9%)	33
Stress	1/2841 (0%)	1	7/2902 (0.2%)	7
Suicidal ideation	2/2841 (0.1%)	2	4/2902 (0.1%)	4
Suicide attempt	0/2841 (0%)	0	1/2902 (0%)	1
Tearfulness	2/2841 (0.1%)	3	1/2902 (0%)	1
Terminal insomnia	0/2841 (0%)	0	1/2902 (0%)	1
Thinking abnormal	2/2841 (0.1%)	2	0/2902 (0%)	0
Renal and urinary disorders
Acute kidney injury	3/2841 (0.1%)	3	4/2902 (0.1%)	5
Bladder discomfort	1/2841 (0%)	1	1/2902 (0%)	1
Bladder dysfunction	0/2841 (0%)	0	1/2902 (0%)	1
Bladder prolapse	0/2841 (0%)	0	1/2902 (0%)	1
Bladder spasm	2/2841 (0.1%)	2	0/2902 (0%)	0
Calculus urinary	0/2841 (0%)	0	1/2902 (0%)	1
Chromaturia	2/2841 (0.1%)	2	1/2902 (0%)	1
Chronic kidney disease	4/2841 (0.1%)	7	9/2902 (0.3%)	10
Cystitis noninfective	3/2841 (0.1%)	3	1/2902 (0%)	1
Dysuria	36/2841 (1.3%)	43	18/2902 (0.6%)	21
Haematuria	13/2841 (0.5%)	13	12/2902 (0.4%)	13
Hydronephrosis	2/2841 (0.1%)	2	0/2902 (0%)	0
Hypercalciuria	0/2841 (0%)	0	1/2902 (0%)	1
Hypertonic bladder	1/2841 (0%)	1	2/2902 (0.1%)	2
Incontinence	2/2841 (0.1%)	2	2/2902 (0.1%)	2
Leukocyturia	1/2841 (0%)	1	0/2902 (0%)	0
Micturition urgency	7/2841 (0.2%)	7	8/2902 (0.3%)	10
Nephrolithiasis	6/2841 (0.2%)	6	9/2902 (0.3%)	10
Nocturia	6/2841 (0.2%)	6	3/2902 (0.1%)	3
Pollakiuria	30/2841 (1.1%)	33	21/2902 (0.7%)	23
Polyuria	0/2841 (0%)	0	1/2902 (0%)	1
Proteinuria	1/2841 (0%)	1	1/2902 (0%)	1
Renal colic	1/2841 (0%)	1	4/2902 (0.1%)	4
Renal cyst	1/2841 (0%)	1	0/2902 (0%)	0
Renal failure	3/2841 (0.1%)	3	0/2902 (0%)	0
Renal injury	1/2841 (0%)	1	0/2902 (0%)	0
Renal mass	1/2841 (0%)	1	0/2902 (0%)	0
Renal pain	2/2841 (0.1%)	2	2/2902 (0.1%)	2
Strangury	0/2841 (0%)	0	1/2902 (0%)	1
Stress urinary incontinence	3/2841 (0.1%)	3	2/2902 (0.1%)	2
Ureteric obstruction	0/2841 (0%)	0	1/2902 (0%)	1
Ureteric stenosis	1/2841 (0%)	4	0/2902 (0%)	0
Urge incontinence	1/2841 (0%)	1	0/2902 (0%)	0
Urinary bladder polyp	1/2841 (0%)	1	1/2902 (0%)	1
Urinary hesitation	1/2841 (0%)	1	1/2902 (0%)	1
Urinary incontinence	19/2841 (0.7%)	22	22/2902 (0.8%)	27
Urinary retention	1/2841 (0%)	1	2/2902 (0.1%)	2
Urinary tract disorder	1/2841 (0%)	1	2/2902 (0.1%)	2
Urinary tract inflammation	0/2841 (0%)	0	1/2902 (0%)	1
Urinary tract obstruction	0/2841 (0%)	0	2/2902 (0.1%)	2
Urinary tract pain	9/2841 (0.3%)	9	7/2902 (0.2%)	9
Urine flow decreased	1/2841 (0%)	1	0/2902 (0%)	0
Urine odour abnormal	3/2841 (0.1%)	3	0/2902 (0%)	0
Reproductive system and breast disorders
Adnexa uteri pain	1/2841 (0%)	1	1/2902 (0%)	1
Amenorrhoea	2/2841 (0.1%)	2	3/2902 (0.1%)	3
Anisomastia	1/2841 (0%)	1	0/2902 (0%)	0
Atrophic vulvovaginitis	6/2841 (0.2%)	9	11/2902 (0.4%)	11
Bartholin's cyst	2/2841 (0.1%)	2	0/2902 (0%)	0
Breast calcifications	1/2841 (0%)	1	1/2902 (0%)	1
Breast cyst	3/2841 (0.1%)	3	3/2902 (0.1%)	3
Breast discharge	3/2841 (0.1%)	4	1/2902 (0%)	1
Breast discomfort	15/2841 (0.5%)	16	9/2902 (0.3%)	9
Breast disorder	1/2841 (0%)	1	2/2902 (0.1%)	2
Breast fibrosis	5/2841 (0.2%)	5	10/2902 (0.3%)	10
Breast haematoma	5/2841 (0.2%)	5	3/2902 (0.1%)	3
Breast hyperplasia	0/2841 (0%)	0	1/2902 (0%)	1
Breast induration	2/2841 (0.1%)	2	0/2902 (0%)	0
Breast inflammation	2/2841 (0.1%)	2	3/2902 (0.1%)	3
Breast mass	12/2841 (0.4%)	13	10/2902 (0.3%)	10
Breast necrosis	4/2841 (0.1%)	4	1/2902 (0%)	1
Breast oedema	20/2841 (0.7%)	21	18/2902 (0.6%)	18
Breast pain	145/2841 (5.1%)	163	158/2902 (5.4%)	186
Breast swelling	7/2841 (0.2%)	7	13/2902 (0.4%)	14
Breast tenderness	2/2841 (0.1%)	2	17/2902 (0.6%)	17
Breast ulceration	1/2841 (0%)	1	2/2902 (0.1%)	2
Cervical dysplasia	1/2841 (0%)	1	1/2902 (0%)	1
Cervical polyp	3/2841 (0.1%)	3	1/2902 (0%)	1
Coital bleeding	0/2841 (0%)	0	1/2902 (0%)	1
Dysmenorrhoea	3/2841 (0.1%)	3	4/2902 (0.1%)	4
Dyspareunia	37/2841 (1.3%)	43	35/2902 (1.2%)	38
Endometrial atrophy	2/2841 (0.1%)	2	0/2902 (0%)	0
Endometrial disorder	0/2841 (0%)	0	2/2902 (0.1%)	2
Endometrial hyperplasia	8/2841 (0.3%)	8	9/2902 (0.3%)	9
Endometrial hypertrophy	0/2841 (0%)	0	1/2902 (0%)	1
Endometrial thickening	2/2841 (0.1%)	3	0/2902 (0%)	0
Endometriosis	0/2841 (0%)	0	2/2902 (0.1%)	2
Fibrocystic breast disease	1/2841 (0%)	1	0/2902 (0%)	0
Genital haemorrhage	1/2841 (0%)	1	0/2902 (0%)	0
Genital lesion	1/2841 (0%)	1	0/2902 (0%)	0
Gynaecomastia	1/2841 (0%)	1	0/2902 (0%)	0
Menopausal disorder	0/2841 (0%)	0	1/2902 (0%)	1
Menopausal symptoms	6/2841 (0.2%)	7	2/2902 (0.1%)	2
Menorrhagia	7/2841 (0.2%)	7	12/2902 (0.4%)	15
Menstrual disorder	1/2841 (0%)	1	0/2902 (0%)	0
Menstruation irregular	7/2841 (0.2%)	7	9/2902 (0.3%)	10
Metrorrhagia	3/2841 (0.1%)	3	5/2902 (0.2%)	5
Nipple disorder	1/2841 (0%)	1	1/2902 (0%)	1
Nipple exudate bloody	0/2841 (0%)	0	1/2902 (0%)	1
Nipple pain	0/2841 (0%)	0	4/2902 (0.1%)	4
Ovarian cyst	7/2841 (0.2%)	7	12/2902 (0.4%)	13
Ovarian disorder	0/2841 (0%)	0	1/2902 (0%)	1
Ovarian mass	0/2841 (0%)	0	1/2902 (0%)	1
Pelvic adhesions	0/2841 (0%)	0	1/2902 (0%)	1
Pelvic floor muscle weakness	1/2841 (0%)	1	4/2902 (0.1%)	4
Pelvic pain	16/2841 (0.6%)	18	21/2902 (0.7%)	23
Perineal pain	1/2841 (0%)	1	1/2902 (0%)	1
Postmenopausal haemorrhage	1/2841 (0%)	1	1/2902 (0%)	1
Premature menopause	1/2841 (0%)	1	3/2902 (0.1%)	3
Prostatitis	1/2841 (0%)	1	1/2902 (0%)	1
Reproductive tract disorder	1/2841 (0%)	1	0/2902 (0%)	0
Retracted nipple	2/2841 (0.1%)	2	1/2902 (0%)	1
Uterine haemorrhage	1/2841 (0%)	1	1/2902 (0%)	2
Uterine polyp	5/2841 (0.2%)	5	7/2902 (0.2%)	8
Uterine prolapse	1/2841 (0%)	1	0/2902 (0%)	0
Uterine spasm	1/2841 (0%)	1	0/2902 (0%)	0
Vaginal discharge	31/2841 (1.1%)	32	42/2902 (1.4%)	49
Vaginal haemorrhage	43/2841 (1.5%)	46	68/2902 (2.3%)	79
Vaginal lesion	0/2841 (0%)	0	1/2902 (0%)	1
Vaginal prolapse	1/2841 (0%)	1	1/2902 (0%)	1
Vulvovaginal burning sensation	1/2841 (0%)	1	0/2902 (0%)	0
Vulvovaginal discomfort	3/2841 (0.1%)	3	1/2902 (0%)	1
Vulvovaginal dryness	182/2841 (6.4%)	211	213/2902 (7.3%)	254
Vulvovaginal inflammation	1/2841 (0%)	1	3/2902 (0.1%)	3
Vulvovaginal pain	3/2841 (0.1%)	3	4/2902 (0.1%)	5
Vulvovaginal pruritus	12/2841 (0.4%)	15	11/2902 (0.4%)	14
Respiratory, thoracic and mediastinal disorders
Allergic bronchitis	1/2841 (0%)	1	0/2902 (0%)	0
Allergic cough	1/2841 (0%)	1	0/2902 (0%)	0
Allergic respiratory symptom	1/2841 (0%)	2	0/2902 (0%)	0
Allergic sinusitis	1/2841 (0%)	2	1/2902 (0%)	1
Aphonia	1/2841 (0%)	1	3/2902 (0.1%)	3
Apnoea	0/2841 (0%)	0	1/2902 (0%)	1
Asphyxia	2/2841 (0.1%)	2	0/2902 (0%)	0
Aspiration	1/2841 (0%)	1	0/2902 (0%)	0
Asthma	8/2841 (0.3%)	8	4/2902 (0.1%)	4
Asthma exercise induced	0/2841 (0%)	0	1/2902 (0%)	1
Atelectasis	1/2841 (0%)	1	3/2902 (0.1%)	3
Bronchial disorder	0/2841 (0%)	0	1/2902 (0%)	1
Bronchial hyperreactivity	0/2841 (0%)	0	1/2902 (0%)	1
Bronchial obstruction	1/2841 (0%)	1	0/2902 (0%)	0
Bronchiectasis	0/2841 (0%)	0	1/2902 (0%)	1
Bronchitis chronic	0/2841 (0%)	0	2/2902 (0.1%)	2
Bronchospasm	2/2841 (0.1%)	2	1/2902 (0%)	3
Catarrh	8/2841 (0.3%)	10	5/2902 (0.2%)	6
Chronic obstructive pulmonary disease	4/2841 (0.1%)	6	3/2902 (0.1%)	3
Cough	416/2841 (14.6%)	543	222/2902 (7.6%)	256
Cough variant asthma	1/2841 (0%)	5	0/2902 (0%)	0
Dry throat	4/2841 (0.1%)	4	2/2902 (0.1%)	2
Dysphonia	29/2841 (1%)	31	9/2902 (0.3%)	9
Dyspnoea	197/2841 (6.9%)	247	130/2902 (4.5%)	144
Dyspnoea exertional	31/2841 (1.1%)	31	12/2902 (0.4%)	12
Dyspnoea paroxysmal nocturnal	0/2841 (0%)	0	1/2902 (0%)	1
Emphysema	1/2841 (0%)	1	1/2902 (0%)	1
Epistaxis	108/2841 (3.8%)	131	16/2902 (0.6%)	16
Haemoptysis	1/2841 (0%)	1	2/2902 (0.1%)	2
Hiccups	8/2841 (0.3%)	8	0/2902 (0%)	0
Hyperventilation	0/2841 (0%)	0	1/2902 (0%)	1
Hypoxia	2/2841 (0.1%)	4	2/2902 (0.1%)	2
Increased bronchial secretion	1/2841 (0%)	1	0/2902 (0%)	0
Interstitial lung disease	1/2841 (0%)	1	0/2902 (0%)	0
Laryngeal inflammation	5/2841 (0.2%)	5	3/2902 (0.1%)	3
Laryngeal oedema	1/2841 (0%)	1	0/2902 (0%)	0
Laryngeal pain	0/2841 (0%)	0	2/2902 (0.1%)	2
Lung disorder	0/2841 (0%)	0	2/2902 (0.1%)	2
Lymphangioleiomyomatosis	1/2841 (0%)	1	0/2902 (0%)	0
Nasal congestion	98/2841 (3.4%)	118	26/2902 (0.9%)	29
Nasal discomfort	7/2841 (0.2%)	9	0/2902 (0%)	0
Nasal disorder	3/2841 (0.1%)	3	0/2902 (0%)	0
Nasal dryness	18/2841 (0.6%)	19	1/2902 (0%)	1
Nasal inflammation	0/2841 (0%)	0	1/2902 (0%)	1
Nasal polyps	0/2841 (0%)	0	1/2902 (0%)	1
Nasal pruritus	0/2841 (0%)	0	1/2902 (0%)	1
Nasal septum deviation	0/2841 (0%)	0	1/2902 (0%)	1
Nasal turbinate hypertrophy	0/2841 (0%)	0	1/2902 (0%)	1
Nasal ulcer	1/2841 (0%)	1	0/2902 (0%)	0
Oropharyngeal discomfort	0/2841 (0%)	0	1/2902 (0%)	1
Oropharyngeal pain	155/2841 (5.5%)	169	60/2902 (2.1%)	65
Orthopnoea	1/2841 (0%)	1	0/2902 (0%)	0
Painful respiration	1/2841 (0%)	1	1/2902 (0%)	1
Paranasal sinus discomfort	3/2841 (0.1%)	3	0/2902 (0%)	0
Pharyngeal erythema	1/2841 (0%)	1	0/2902 (0%)	0
Pharyngeal inflammation	1/2841 (0%)	1	0/2902 (0%)	0
Pharyngeal paraesthesia	1/2841 (0%)	1	0/2902 (0%)	0
Pharyngeal swelling	2/2841 (0.1%)	2	0/2902 (0%)	0
Pleural effusion	8/2841 (0.3%)	8	3/2902 (0.1%)	3
Pleurisy	3/2841 (0.1%)	3	1/2902 (0%)	1
Pleuritic pain	3/2841 (0.1%)	5	2/2902 (0.1%)	2
Pneumonitis	9/2841 (0.3%)	11	5/2902 (0.2%)	5
Productive cough	41/2841 (1.4%)	45	21/2902 (0.7%)	24
Pulmonary congestion	6/2841 (0.2%)	7	1/2902 (0%)	1
Pulmonary embolism	9/2841 (0.3%)	9	4/2902 (0.1%)	4
Pulmonary fibrosis	2/2841 (0.1%)	2	1/2902 (0%)	1
Pulmonary hypertension	1/2841 (0%)	1	1/2902 (0%)	1
Pulmonary infarction	0/2841 (0%)	0	1/2902 (0%)	1
Pulmonary mass	2/2841 (0.1%)	2	3/2902 (0.1%)	3
Pulmonary sarcoidosis	1/2841 (0%)	2	0/2902 (0%)	0
Respiratory disorder	3/2841 (0.1%)	3	1/2902 (0%)	1
Respiratory distress	1/2841 (0%)	1	0/2902 (0%)	0
Respiratory symptom	2/2841 (0.1%)	2	2/2902 (0.1%)	2
Respiratory tract irritation	1/2841 (0%)	1	0/2902 (0%)	0
Rhinalgia	0/2841 (0%)	0	1/2902 (0%)	1
Rhinitis allergic	42/2841 (1.5%)	48	24/2902 (0.8%)	25
Rhinitis atrophic	1/2841 (0%)	1	0/2902 (0%)	0
Rhinorrhoea	52/2841 (1.8%)	56	16/2902 (0.6%)	16
Sinus congestion	15/2841 (0.5%)	15	4/2902 (0.1%)	4
Sinus disorder	2/2841 (0.1%)	2	1/2902 (0%)	1
Sinus pain	9/2841 (0.3%)	11	4/2902 (0.1%)	4
Sleep apnoea syndrome	5/2841 (0.2%)	9	9/2902 (0.3%)	9
Sneezing	5/2841 (0.2%)	5	1/2902 (0%)	1
Snoring	0/2841 (0%)	0	2/2902 (0.1%)	2
Sputum increased	2/2841 (0.1%)	2	0/2902 (0%)	0
Throat irritation	3/2841 (0.1%)	4	1/2902 (0%)	1
Throat lesion	1/2841 (0%)	1	0/2902 (0%)	0
Throat tightness	1/2841 (0%)	1	4/2902 (0.1%)	5
Tonsillar hypertrophy	0/2841 (0%)	0	1/2902 (0%)	1
Tonsillar ulcer	1/2841 (0%)	1	0/2902 (0%)	0
Tonsillolith	1/2841 (0%)	1	0/2902 (0%)	0
Upper respiratory tract congestion	1/2841 (0%)	1	1/2902 (0%)	1
Upper respiratory tract irritation	1/2841 (0%)	1	0/2902 (0%)	0
Upper-airway cough syndrome	32/2841 (1.1%)	36	19/2902 (0.7%)	20
Vocal cord atrophy	0/2841 (0%)	0	1/2902 (0%)	1
Vocal cord dysfunction	0/2841 (0%)	0	1/2902 (0%)	2
Wheezing	7/2841 (0.2%)	10	10/2902 (0.3%)	15
Skin and subcutaneous tissue disorders
Acne	11/2841 (0.4%)	12	4/2902 (0.1%)	5
Actinic keratosis	0/2841 (0%)	0	3/2902 (0.1%)	3
Alopecia	510/2841 (18%)	558	149/2902 (5.1%)	163
Alopecia totalis	1/2841 (0%)	2	0/2902 (0%)	0
Blister	11/2841 (0.4%)	13	2/2902 (0.1%)	2
Blood blister	1/2841 (0%)	1	0/2902 (0%)	0
Capillaritis	1/2841 (0%)	1	0/2902 (0%)	0
Chloasma	1/2841 (0%)	1	1/2902 (0%)	1
Chronic pigmented purpura	0/2841 (0%)	0	1/2902 (0%)	1
Cold sweat	1/2841 (0%)	1	0/2902 (0%)	0
Cutaneous lupus erythematosus	0/2841 (0%)	0	1/2902 (0%)	2
Cutaneous symptom	1/2841 (0%)	1	1/2902 (0%)	1
Dermal cyst	4/2841 (0.1%)	4	7/2902 (0.2%)	7
Dermatitis	11/2841 (0.4%)	11	12/2902 (0.4%)	12
Dermatitis acneiform	32/2841 (1.1%)	39	13/2902 (0.4%)	15
Dermatitis allergic	1/2841 (0%)	1	2/2902 (0.1%)	2
Dermatitis bullous	0/2841 (0%)	0	1/2902 (0%)	1
Dermatitis contact	2/2841 (0.1%)	2	3/2902 (0.1%)	3
Dermatomyositis	1/2841 (0%)	1	0/2902 (0%)	0
Drug eruption	1/2841 (0%)	5	1/2902 (0%)	1
Dry skin	153/2841 (5.4%)	178	56/2902 (1.9%)	67
Dyshidrotic eczema	0/2841 (0%)	0	1/2902 (0%)	1
Ecchymosis	3/2841 (0.1%)	4	1/2902 (0%)	1
Eczema	22/2841 (0.8%)	24	13/2902 (0.4%)	14
Eczema nummular	0/2841 (0%)	0	1/2902 (0%)	1
Erythema	54/2841 (1.9%)	56	42/2902 (1.4%)	45
Erythema multiforme	3/2841 (0.1%)	5	1/2902 (0%)	1
Hair growth abnormal	2/2841 (0.1%)	2	0/2902 (0%)	0
Hair texture abnormal	2/2841 (0.1%)	2	0/2902 (0%)	0
Hand dermatitis	0/2841 (0%)	0	1/2902 (0%)	1
Hidradenitis	1/2841 (0%)	1	1/2902 (0%)	1
Hirsutism	2/2841 (0.1%)	2	3/2902 (0.1%)	3
Hyperhidrosis	38/2841 (1.3%)	40	31/2902 (1.1%)	36
Hyperkeratosis	1/2841 (0%)	1	0/2902 (0%)	0
Hypertrichosis	4/2841 (0.1%)	4	2/2902 (0.1%)	2
Hypertrophic scar	1/2841 (0%)	1	1/2902 (0%)	1
Idiopathic urticaria	0/2841 (0%)	0	1/2902 (0%)	1
Ingrowing nail	2/2841 (0.1%)	2	2/2902 (0.1%)	3
Intertrigo	0/2841 (0%)	0	3/2902 (0.1%)	3
Itching scar	1/2841 (0%)	1	0/2902 (0%)	0
Keloid scar	0/2841 (0%)	0	2/2902 (0.1%)	2
Lichen planus	1/2841 (0%)	1	2/2902 (0.1%)	3
Lichen sclerosus	1/2841 (0%)	1	1/2902 (0%)	1
Lichenoid keratosis	1/2841 (0%)	1	0/2902 (0%)	0
Madarosis	22/2841 (0.8%)	25	4/2902 (0.1%)	4
Milia	0/2841 (0%)	0	1/2902 (0%)	1
Miliaria	2/2841 (0.1%)	2	1/2902 (0%)	1
Myxoid cyst	1/2841 (0%)	1	1/2902 (0%)	1
Nail bed disorder	3/2841 (0.1%)	3	0/2902 (0%)	0
Nail bed inflammation	0/2841 (0%)	0	1/2902 (0%)	1
Nail discolouration	9/2841 (0.3%)	9	3/2902 (0.1%)	3
Nail disorder	31/2841 (1.1%)	35	11/2902 (0.4%)	13
Nail dystrophy	4/2841 (0.1%)	4	1/2902 (0%)	1
Nail ridging	10/2841 (0.4%)	10	3/2902 (0.1%)	3
Nail toxicity	4/2841 (0.1%)	4	1/2902 (0%)	1
Neurodermatitis	1/2841 (0%)	1	1/2902 (0%)	2
Night sweats	42/2841 (1.5%)	50	50/2902 (1.7%)	53
Onychalgia	1/2841 (0%)	1	1/2902 (0%)	1
Onychoclasis	29/2841 (1%)	29	3/2902 (0.1%)	3
Onycholysis	4/2841 (0.1%)	4	3/2902 (0.1%)	3
Onychomadesis	16/2841 (0.6%)	16	9/2902 (0.3%)	9
Pain of skin	14/2841 (0.5%)	15	1/2902 (0%)	1
Palmar-plantar erythrodysaesthesia syndrome	10/2841 (0.4%)	11	1/2902 (0%)	1
Panniculitis	0/2841 (0%)	0	1/2902 (0%)	2
Papule	2/2841 (0.1%)	2	2/2902 (0.1%)	2
Papulopustular rosacea	1/2841 (0%)	1	0/2902 (0%)	0
Peau d'orange	2/2841 (0.1%)	2	0/2902 (0%)	0
Perioral dermatitis	1/2841 (0%)	1	0/2902 (0%)	0
Petechiae	4/2841 (0.1%)	5	1/2902 (0%)	1
Photodermatosis	1/2841 (0%)	1	0/2902 (0%)	0
Photosensitivity reaction	7/2841 (0.2%)	7	2/2902 (0.1%)	2
Pigmentation disorder	2/2841 (0.1%)	2	1/2902 (0%)	1
Pityriasis rosea	1/2841 (0%)	1	0/2902 (0%)	0
Plantar erythema	1/2841 (0%)	2	0/2902 (0%)	0
Prurigo	1/2841 (0%)	2	0/2902 (0%)	0
Pruritus	183/2841 (6.4%)	222	95/2902 (3.3%)	105
Psoriasis	7/2841 (0.2%)	10	7/2902 (0.2%)	7
Purpura	1/2841 (0%)	1	1/2902 (0%)	1
Rash	229/2841 (8.1%)	288	90/2902 (3.1%)	102
Rash erythematous	2/2841 (0.1%)	2	5/2902 (0.2%)	5
Rash follicular	1/2841 (0%)	1	0/2902 (0%)	0
Rash macular	6/2841 (0.2%)	6	3/2902 (0.1%)	4
Rash maculo-papular	65/2841 (2.3%)	108	25/2902 (0.9%)	32
Rash papular	4/2841 (0.1%)	4	1/2902 (0%)	1
Rash pruritic	12/2841 (0.4%)	12	9/2902 (0.3%)	11
Rosacea	10/2841 (0.4%)	10	4/2902 (0.1%)	4
Scab	1/2841 (0%)	1	0/2902 (0%)	0
Scar pain	15/2841 (0.5%)	16	23/2902 (0.8%)	26
Sebaceous hyperplasia	0/2841 (0%)	0	1/2902 (0%)	1
Seborrhoeic dermatitis	2/2841 (0.1%)	2	1/2902 (0%)	1
Sensitive skin	1/2841 (0%)	1	0/2902 (0%)	0
Skin atrophy	3/2841 (0.1%)	3	1/2902 (0%)	1
Skin burning sensation	3/2841 (0.1%)	3	1/2902 (0%)	1
Skin discolouration	2/2841 (0.1%)	2	3/2902 (0.1%)	4
Skin discomfort	2/2841 (0.1%)	2	0/2902 (0%)	0
Skin disorder	4/2841 (0.1%)	5	9/2902 (0.3%)	10
Skin exfoliation	10/2841 (0.4%)	10	4/2902 (0.1%)	4
Skin fissures	7/2841 (0.2%)	8	0/2902 (0%)	0
Skin hyperpigmentation	11/2841 (0.4%)	13	17/2902 (0.6%)	18
Skin hypertrophy	1/2841 (0%)	1	0/2902 (0%)	0
Skin hypopigmentation	2/2841 (0.1%)	2	1/2902 (0%)	1
Skin induration	2/2841 (0.1%)	2	3/2902 (0.1%)	3
Skin irritation	7/2841 (0.2%)	7	1/2902 (0%)	1
Skin lesion	17/2841 (0.6%)	18	9/2902 (0.3%)	11
Skin mass	2/2841 (0.1%)	2	1/2902 (0%)	1
Skin oedema	0/2841 (0%)	0	1/2902 (0%)	1
Skin plaque	1/2841 (0%)	1	0/2902 (0%)	0
Skin reaction	1/2841 (0%)	1	0/2902 (0%)	0
Skin striae	0/2841 (0%)	0	1/2902 (0%)	1
Skin tightness	1/2841 (0%)	1	2/2902 (0.1%)	2
Skin toxicity	1/2841 (0%)	1	0/2902 (0%)	0
Skin ulcer	7/2841 (0.2%)	9	2/2902 (0.1%)	2
Skin warm	0/2841 (0%)	0	1/2902 (0%)	1
Skin weeping	1/2841 (0%)	1	0/2902 (0%)	0
Solar lentigo	0/2841 (0%)	0	1/2902 (0%)	1
Stevens-Johnson syndrome	0/2841 (0%)	0	1/2902 (0%)	1
Telangiectasia	1/2841 (0%)	1	1/2902 (0%)	1
Toxic skin eruption	1/2841 (0%)	1	0/2902 (0%)	0
Trichorrhexis	3/2841 (0.1%)	3	1/2902 (0%)	1
Urticaria	24/2841 (0.8%)	29	11/2902 (0.4%)	12
Vitiligo	0/2841 (0%)	0	1/2902 (0%)	2
Xeroderma	2/2841 (0.1%)	5	2/2902 (0.1%)	2
Social circumstances
Postmenopause	1/2841 (0%)	1	0/2902 (0%)	0
Sight disability	2/2841 (0.1%)	2	0/2902 (0%)	0
Surgical and medical procedures
Breast operation	3/2841 (0.1%)	3	1/2902 (0%)	1
Breast prosthesis removal	1/2841 (0%)	1	1/2902 (0%)	1
Breast reconstruction	9/2841 (0.3%)	11	7/2902 (0.2%)	9
Cataract operation	1/2841 (0%)	1	2/2902 (0.1%)	2
Central venous catheter removal	1/2841 (0%)	1	2/2902 (0.1%)	2
Cholecystectomy	1/2841 (0%)	1	0/2902 (0%)	0
Dental care	1/2841 (0%)	2	0/2902 (0%)	0
Dental operation	0/2841 (0%)	0	1/2902 (0%)	1
Drain removal	1/2841 (0%)	1	0/2902 (0%)	0
Endodontic procedure	0/2841 (0%)	0	1/2902 (0%)	1
Hernia repair	1/2841 (0%)	1	0/2902 (0%)	0
Hip arthroplasty	0/2841 (0%)	0	1/2902 (0%)	1
Hysterosalpingo-oophorectomy	1/2841 (0%)	1	1/2902 (0%)	1
Incisional drainage	2/2841 (0.1%)	2	1/2902 (0%)	1
Infection prophylaxis	1/2841 (0%)	1	0/2902 (0%)	0
Joint dislocation reduction	0/2841 (0%)	0	1/2902 (0%)	1
Lipoma excision	1/2841 (0%)	1	0/2902 (0%)	0
Mammoplasty	2/2841 (0.1%)	2	0/2902 (0%)	0
Medical device removal	0/2841 (0%)	0	1/2902 (0%)	1
Medical procedure	1/2841 (0%)	1	0/2902 (0%)	0
Meniscus operation	0/2841 (0%)	0	1/2902 (0%)	1
Metabolic surgery	0/2841 (0%)	0	1/2902 (0%)	1
Micrographic skin surgery	1/2841 (0%)	2	0/2902 (0%)	0
Mole excision	2/2841 (0.1%)	2	1/2902 (0%)	1
Nail operation	0/2841 (0%)	0	1/2902 (0%)	1
Oophorectomy	2/2841 (0.1%)	2	0/2902 (0%)	0
Post procedural drainage	1/2841 (0%)	1	1/2902 (0%)	2
Salpingo-oophorectomy bilateral	1/2841 (0%)	1	2/2902 (0.1%)	2
Sinus operation	5/2841 (0.2%)	5	0/2902 (0%)	0
Skin lesion removal	1/2841 (0%)	1	0/2902 (0%)	0
Skin neoplasm excision	1/2841 (0%)	1	0/2902 (0%)	0
Spinal operation	1/2841 (0%)	1	0/2902 (0%)	0
Surgery	4/2841 (0.1%)	5	1/2902 (0%)	1
Tendon sheath incision	0/2841 (0%)	0	1/2902 (0%)	1
Thyroid operation	0/2841 (0%)	0	1/2902 (0%)	1
Tooth extraction	2/2841 (0.1%)	3	0/2902 (0%)	0
Weight loss diet	3/2841 (0.1%)	3	1/2902 (0%)	1
Wound drainage	3/2841 (0.1%)	3	0/2902 (0%)	0
Vascular disorders
Angiopathy	2/2841 (0.1%)	2	3/2902 (0.1%)	3
Aortic aneurysm	1/2841 (0%)	1	0/2902 (0%)	0
Aortic arteriosclerosis	1/2841 (0%)	1	0/2902 (0%)	0
Aortic dilatation	1/2841 (0%)	1	1/2902 (0%)	1
Arterial thrombosis	1/2841 (0%)	1	0/2902 (0%)	0
Arteriosclerosis	0/2841 (0%)	0	1/2902 (0%)	1
Arteriovenous fistula	0/2841 (0%)	0	1/2902 (0%)	1
Axillary vein thrombosis	1/2841 (0%)	1	0/2902 (0%)	0
Bleeding varicose vein	0/2841 (0%)	0	1/2902 (0%)	1
Blood pressure inadequately controlled	0/2841 (0%)	0	1/2902 (0%)	1
Capillary fragility	5/2841 (0.2%)	5	1/2902 (0%)	1
Deep vein thrombosis	9/2841 (0.3%)	9	5/2902 (0.2%)	8
Embolism	9/2841 (0.3%)	9	3/2902 (0.1%)	4
Essential hypertension	0/2841 (0%)	0	1/2902 (0%)	2
Flushing	15/2841 (0.5%)	20	24/2902 (0.8%)	33
Haematoma	20/2841 (0.7%)	20	7/2902 (0.2%)	7
Hot flush	702/2841 (24.7%)	887	849/2902 (29.3%)	1066
Hypertension	205/2841 (7.2%)	363	227/2902 (7.8%)	382
Hypertensive crisis	2/2841 (0.1%)	3	1/2902 (0%)	1
Hypotension	28/2841 (1%)	31	16/2902 (0.6%)	16
Intermittent claudication	1/2841 (0%)	1	0/2902 (0%)	0
Lymphocele	1/2841 (0%)	1	0/2902 (0%)	0
Lymphoedema	336/2841 (11.8%)	395	268/2902 (9.2%)	303
Orthostatic hypotension	1/2841 (0%)	1	2/2902 (0.1%)	2
Peripheral coldness	3/2841 (0.1%)	3	3/2902 (0.1%)	3
Peripheral venous disease	6/2841 (0.2%)	7	2/2902 (0.1%)	2
Phlebitis	6/2841 (0.2%)	7	6/2902 (0.2%)	8
Poor peripheral circulation	2/2841 (0.1%)	2	0/2902 (0%)	0
Post thrombotic syndrome	1/2841 (0%)	1	0/2902 (0%)	0
Prehypertension	0/2841 (0%)	0	1/2902 (0%)	1
Raynaud's phenomenon	3/2841 (0.1%)	4	1/2902 (0%)	1
Subclavian vein thrombosis	2/2841 (0.1%)	2	0/2902 (0%)	0
Thrombophlebitis	5/2841 (0.2%)	7	3/2902 (0.1%)	3
Thrombophlebitis superficial	5/2841 (0.2%)	6	5/2902 (0.2%)	5
Thrombosis	8/2841 (0.3%)	11	2/2902 (0.1%)	2
Varicophlebitis	1/2841 (0%)	1	0/2902 (0%)	0
Varicose vein	4/2841 (0.1%)	4	4/2902 (0.1%)	5
Venous thrombosis	1/2841 (0%)	2	0/2902 (0%)	0
White coat hypertension	0/2841 (0%)	0	2/2902 (0.1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title	Erica L. Mayer, MD, MPH
Organization	Dana-Farber Cancer Institute
Phone	617-632-3800
Email	emayer@partners.org

Responsible Party:

Alliance Foundation Trials, LLC.

ClinicalTrials.gov Identifier:

NCT02513394

Other Study ID Numbers:

AFT-05
ABCSG 42
BIG 14-03
2014-005181-30

First Posted:

Jul 31, 2015

Last Update Posted:

Apr 13, 2022

Last Verified:

Mar 1, 2022

PALLAS: PALbociclib CoLlaborative Adjuvant Study

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact