ALTTO (Adjuvant Lapatinib And/Or Trastuzumab Treatment Optimisation) Study; BIG 2-06/N063D

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00490139

Collaborator

North Central Cancer Treatment Group (Other), National Cancer Institute (NCI) (NIH), Breast International Group (Other), Canadian Cancer Trials Group (Other)

8,382

Enrollment

1412

Locations

Arms

169.5

Actual Duration (Months)

5.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomised, open label multi-centre phase III study comparing the activity of lapatinib alone versus trastuzumab alone versus trastuzumab followed by lapatinib versus lapatinib concomitantly with trastuzumab in the adjuvant treatment of patients with ErbB2 overexpressing and/or amplified breast cancer. Patients will be enrolled according to one of two design schemas, with Design 2 having two chemotherapy options (Design 2 and 2B), and will be randomised to one of four treatment regimens within each design schema.

The primary objective of this study is to compare disease-free survival (DFS) in patients with HER2 overexpressing and/or amplified breast cancer randomised to trastuzumab for one year versus lapatinib for one year versus trastuzumab (12 or 18 weeks, according to assigned design) followed by a six-week treatment-free interval followed by lapatinib (28 or 34 weeks, according to assigned design) versus trastuzumab in combination with lapatinib for one year (52 weeks). Secondary objectives include treatment comparisons with respect to overall survival, time to recurrence, time to distant recurrence, safety and tolerability, incidence of brain metastasis, and analyses conducted separately for cohorts of patients defined by presence or absence of cMyc oncogene amplification, expression level of PTEN and presence or absence of the p95HER2 receptor. On August 18, 2011, the ALTTO Independent Data Monitoring Committee (IDMC) met to review the first planned interim analysis. The IDMC reported that the comparison of lapatinib alone versus trastuzumab alone crossed the futility boundary, indicating that the lapatinib alone arm was unlikely to meet the pre-specified criteria to demonstrate non-inferiority to trastuzumab alone with respect to disease-free survival (DFS). The IDMC also stated that the other three arms (trastuzumab alone, sequential trastuzumab/lapatinib arm and the combination arm) should continue as planned with no changes.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms, Breast	Drug: Lapatinib Biological: Trastuzumab	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

8382 participants

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomised, Multi-centre, Open-label, Phase III Study of Adjuvant Lapatinib, Trastuzumab, Their Sequence and Their Combination in Patients With HER2/ErbB2 Positive Primary Breast Cancer

Actual Study Start Date :

May 16, 2007

Actual Primary Completion Date :

Dec 6, 2013

Actual Study Completion Date :

Jul 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1: Trastuzumab Design 1: Trastuzumab 8mg/kg IV loading dose followed by 6mg/kg IV every 3 weeks for a total of 52 weeks. Design 2: Either paclitaxel 80mg/m2 IV weekly for 12 weeks OR docetaxel 75mg/m2 IV every 3 weeks for 4 cycles administered concomitantly with trastuzumab 4mg/kg IV loading dose followed by 2mg/kg IV weekly. After completion of chemotherapy, trastuzumab administered every 3 weeks (6mg/kg IV without loading dose) for an additional 40 weeks (52 weeks total). Design 2B: Docetaxel 75mg/m2 and carboplatin AUC 6 every 3 weeks for 6 cycles (18 weeks) administered concomitantly with trastuzumab 4mg/kg IV loading dose followed by 2mg/kg IV weekly. After completion of chemotherapy, trastuzumab (6mg/kg without loading dose) every 3 weeks for an additional 40 weeks (52 weeks total).	Biological: Trastuzumab Antibody
Experimental: Arm 2: Lapatinib Based on the IDMC results from 18 August 2011, any patient enrolled onto Arm 2 should be considered for a new treatment strategy based on discussion with their physician. Design 1: Lapatinib 1500mg oral daily for a total of 52 weeks. Design 2: Either paclitaxel 80mg/m2 IV weekly for 12 weeks OR docetaxel 75mg/m2 IV every 3 weeks for 4 cycles administered concomitantly with oral lapatinib at 750mg daily. After completion of chemotherapy, oral lapatinib administered at 1500mg daily for an additional 40 weeks (52 weeks total). Design 2B: Docetaxel 75mg/m2 and carboplatin AUC 6 every 3 weeks for 6 cycles (18 weeks) administered concomitantly with oral lapatinib at 750mg daily. After completion of chemotherapy, the dose of lapatinib will be increased to 1500mg oral daily for an additional 40 weeks (52 weeks total).	Drug: Lapatinib Small molecule inhibitor
Experimental: Arm 3: Trastuzumab followed by Lapatinib Design 1: Trastuzumab (4mg/kg IV loading dose followed by 2mg/kg IV weekly) for 12 weeks followed by a 6 week treatment-free interval followed by oral lapatinib 1500mg daily for 34 weeks (52 weeks total). Design 2: Trastuzumab (4mg/kg IV loading dose followed by 2mg/kg IV weekly) for 12 weeks administered concomitantly and either paclitaxel 80mg/m2 IV weekly for 12 weeks OR docetaxel 75mg/m2 every 21 days for 4 cycles; followed by a 6 week treatment-free interval followed by oral lapatinib 1500mg daily for 34 weeks (52 weeks total). Design 2B: Docetaxel 75mg/m2 and carboplatin AUC 6 every 3 weeks for 6 cycles (18 weeks) administered concomitantly with trastuzumab (4mg/kg IV loading dose followed by 2mg/kg IV weekly) followed by a 6 week treatment-free interval followed by oral lapatinib 1500 mg daily for 28 weeks (52 weeks total).	Drug: Lapatinib Small molecule inhibitor Biological: Trastuzumab Antibody
Experimental: Arm 4: Lapatinib in combination with Trastuzumab Design 1: Oral lapatinib 1000 mg daily concurrent with trastuzumab 8 mg/kg IV loading dose followed by 6mg/kg IV every 3 weeks (52 weeks total). Design 2: Trastuzumab (4mg/kg loading dose followed by 2mg/kg IV weekly) concurrent with oral lapatinib 750 mg daily and either paclitaxel 80mg/m2 IV weekly for 12 weeks OR docetaxel 75mg/m2 every 21 days for 4 cycles (12 weeks). After completion of chemotherapy, the dose of lapatinib will be increased to 1000mg daily concurrently with trastuzumab every 3 weeks (6mg/kg without loading dose) for an additional 40 weeks (52 weeks total). Design 2B: Docetaxel 75mg/m2 and carboplatin AUC 6 every 3 weeks for 6 cycles (18 weeks) administered concurrently with oral lapatinib 750mg plus weekly trastuzumab (4mg/kg IV loading dose followed by 2mg/kg IV. After the completion of chemotherapy, trastuzumab will be administered every 3 weeks (6mg/kg without loading dose) concurrent with lapatinib 1000mg daily for an additional 40 weeks (52 weeks total).	Drug: Lapatinib Small molecule inhibitor Biological: Trastuzumab Antibody

Outcome Measures

Primary Outcome Measures

Disease-free Survival (DFS) [From randomization until the date of the first occurrence of disease recurrence, a contralateral invasive breast cancer, a second primary cancer, or death from any cause (median follow-up of 4.5 years)]
Disease-free survival is defined as the interval between randomization and the date of the first occurence of disease recurrence (local, regional or distant), a contralateral invasive breast cancer, a second primary cancer (SPC), or death from any cause. DFS was estimated using the Kaplan Meier method.The percentile data values presented here indicate the percentage (95, 90, 85, 80 and 75 percent) of participants who had disease free survival for the indicated years.

Secondary Outcome Measures

Overall Survival (OS) [From randomization until death due to any cause (median follow-up of 4.5 years)]
Overall survival is defined as the time from randomization until death due to any cause. Overall survival was calculated in years as (date of death minus the date of randomization +1) divided by 365.25. The percentile data values presented here indicate the percentage (99, 98, 97, 96, 95 and 90 percent) of participants who survived for the indicated years.
Time to Recurrence [From randomization until the date of the first occurrence of a disease recurrence (median follow-up of 4.5 years)]
Time to recurrence is defined as the interval between the date of randomization and the date of the first occurrence of a disease recurrence (local, regional or distant). The percentile data values presented here indicate the percentage (95, 90, 85, and 80 percent) of participants who did not have disease recurrence for the indicated years. IDMC=Independent Data Monitoring Committee.
Time to Distant Recurrence [From randomization until the date of the first occurrence of distant recurrence (median follow-up of 4.5 years)]
Time to distant recurrence is defined as the interval between the date of randomization and the date of the first occurrence of distant recurrence (including central nervous system recurrence). The percentile data values presented here indicate the percentage (95, 90, 85 and 80 percent) of participants who did not have distant recurrence for the indicated years.
Time to Central Nervous System Recurrence [From randomization until the first central nervous system recurrence (median follow-up of 4.5 years)]
Time to central nervous system recurrence is defined as the time from randomization until the first central nervous system recurrence. Both brain metastasis and meningitis carcinomatosa were considered.The percentile data values presented here indicate that 95 percent of participants did not have central nervous system recurrence for the indicated years.
DFS Ignoring Non-breast Second Primary Malignancies [From randomization until the date of the first occurrence of disease recurrence, a contralateral invasive breast cancer, a second primary cancer, or death from any cause (median follow-up of 4.5 years)]
Disease-free survival is defined as the interval between randomization and the date of the first occurence of disease recurrence (local, regional or distant), a contralateral invasive breast cancer, a second primary cancer, or death from any cause. DFS was estimated using the Kaplan Meier method. The non-breast second primary malignancies were not considered events.The percentile data values presented here indicate the percentage (95, 90, 85, 80 and 75 percent) of participants who did not have DFS ignoring non-breast second primary malignancies for the indicated years. Zero participants were analyzed in the lapatinib arm, as the IDMC discontinued the lapatinib-alone arm due to futility at the time of the first interim analysis (lapatinib participants were then offered trastuzumab).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1;
Non-metastatic operable primary invasive adenocarcinoma of the breast fulfilling the following:

Histologically confirmed
Adequately excised (exceptions: patients who have 'non-resectable' deep margin invasion are eligible provided they have had or will receive radiotherapy encompassing the region concerned; patients with histologically documented infiltration of the skin (pT4) are eligible provided they have undergone or will receive radiotherapy encompassing the tumour bed);
Axilla dissected; sentinel node sampling is allowed provided that axillary dissection follows confirmation of a positive sentinel node; sentinel node sampling alone is NOT acceptable after neoadjuvant chemotherapy (in patients receiving neoadjuvant chemotherapy lymph node status will be considered unknown, regardless of the results of post-chemotherapy axillary dissection);
Axillary node positive patient OR node negative patient with a tumour greater than or equal to 1.0 cm in greatest diameter. For clarification, isolated tumour cells (ITC) are considered pN0 and micrometastases are considered pN1

Known hormone receptor status (ER/PgR or ER alone)
For Designs 1 and 2: Patients must have received at least four cycles of an approved anthracycline-based (neo-) adjuvant chemotherapy regimen or listed as an exception in Table 5 of the protocol.

For Design 1: Randomization must be performed no longer than 12 weeks from day 1 of the last chemotherapy cycle after obtaining a post-chemotherapy LVEF ≥ 50. Study treatment must start no more than 14 days after randomization For Design 2: Randomization must be performed no longer than 6 weeks from day 1 of the last anthracycline-containing chemotherapy cycle after obtaining a post-anthracycline chemotherapy LVEF ≥ 50. Study treatment must start no more than 14 days after randomization and must be concurrent with taxanes.

For Design 2B: Randomisation must be performed no longer than 8 weeks from definitive surgery. Non-anthracycline platinum containing regimen (docetaxel and carboplatin) and study treatment must start concomitantly and no more than 14 days after randomisation.

Baseline LVEF ≥50% measured by echocardiography or MUGA scan. For Design 1 and Design 2 - after completion of all anthracycline-based (neo-) adjuvant chemotherapy and prior to the targeted therapy(ies); for Design 2B - prior to targeted therapy(ies) and chemotherapy (docetaxel and carboplatin)
Over expression and/or amplification of HER2 in the invasive component of the primary tumour (in case of neoadjuvant treatment, tissue sample used for HER2 testing should be collected before neoadjuvant treatment starts), according to one of the following definitions [Wolff et al 2007] and confirmed by central laboratory prior to randomization:
3+ over expression by IHC (> 30% of invasive tumour cells);
2+ or 3+ (in 30% or less neoplastic cells) over expression by IHC AND in situ hybridization (FISH/CISH) test demonstrating HER2 gene amplification;
HER2 gene amplification by FISH/CISH ( > 6 HER2 gene copies per nucleus, or a FISH ratio [HER2 gene copies to chromosome 17 signals] of > than 2.2.) Patients with a negative or equivocal overall result (FISH test ratio of ≤ 2.2, ≤ 6.0 HER2 gene copies per nucleus) and staining scores of 0, 1+, 2+ or 3+ (in 30% or less neoplastic cells) by IHC are not eligible for participation in the trial.

Equivocal local results may be submitted for a final determination by the central laboratory.

Completion of all necessary baseline laboratory and radiological investigations
Signed written informed consent (approved by an Independent Ethics Committee (IEC) and obtained prior to any study specific screening procedures).

Exclusion Criteria:

History of any prior (ipsi- and/or contralateral) invasive breast carcinoma;
Past (less than 10 years) or current history of malignant neoplasms, except for curatively treated 1) basal and squamous cell carcinoma of the skin or 2) carcinoma in situ of the cervix.

NOTE: Patients with a prior malignancy diagnosed greater than 10 years in the past who have been curatively treated with surgery ONLY, WITHOUT radiation therapy or systemic therapy (chemotherapy or endocrine) are eligible for the study. Patients with any prior diagnosis of breast cancer or melanoma, at any time, are excluded from this study.

Any clinically staged T4 tumour, including inflammatory breast cancer;
Bilateral tumours;
This exclusion criterion has been removed as of protocol amendment 1.

NOTE: multifocal/multicentric tumours are permitted:

If the patient is node-negative: one of the lesions must be equal or greater than 1.0 cm (sum of the lesion diameters is not acceptable) AND must have positive HER2 status centrally-confirmed;
If patient is node-positive: lesion size does not matter BUT one of the lesions must have HER2 positivity centrally-confirmed. If several lesions are found to be HER2 positive locally, the largest lesion should be considered for central review.
Maximum cumulative dose of doxorubicin >360mg/m² or maximum cumulative dose of epirubicin >720mg/m² or any prior anthracyclines unrelated to the present breast cancer;
(Neo-) or adjuvant chemotherapy using peripheral stem cell or bone marrow stem cell support;
Any prior mediastinal irradiation except internal mammary node irradiation for the present breast cancer;
Patients with positive or suspicious internal mammary nodes identified by sentinel node technique which have not been irradiated or will not be irradiated, or patients with supraclavicular lymph node involvement (confirmed by fine needle aspirate or biopsy);
Prior use of anti-HER2 therapy for any reason or other prior biologic or immunotherapy for breast cancer;
Concurrent anti-cancer treatment, except hormonal therapy or radiotherapy for the present breast cancer;
Concurrent anti-cancer treatment in another investigational trial with hormone therapy or immunotherapy unless approved by the Executive Committee:
Serious cardiac illness or medical conditions including but not confined to:

History of documented congestive heart failure (CHF) or systolic dysfunction (LVEF <50%); High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV-block, supraventricular arrhythmias which are not adequately rate-controlled); Angina pectoris requiring antianginal medication; Clinically significant valvular heart disease; Evidence of transmural infarction on ECG; Poorly controlled hypertension (e.g. systolic >180mm Hg or diastolic >100mm Hg);

Other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness;
Any of the following abnormal laboratory tests immediately prior to randomization:

serum total bilirubin >1.5 x upper limit of normal (ULN), in the case of known Gilbert's syndrome, a higher serum total bilirubin (<2 X ULN) is allowed; alanine amino transferase (ALAT) or aspartate amino transferase (ASAT) >2.5 x ULN; alkaline phosphatase (ALP) > 2.5 x ULN; serum creatinine >2.0 x ULN; total white blood cell count (WBC) <2.5 x 10^{9/L;
absolute neutrophil count <1.5 x 10}9/L; platelets <100 x 10^9/L.

Unresolved or unstable serious adverse events from prior adjuvant chemotherapy or radiotherapy;
Malabsorption syndrome, any disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, or persons unable to swallow oral medication. Subjects with ulcerative colitis are also excluded;
Pregnant, lactating or women of childbearing potential without a negative pregnancy test - urine or serum - within 7 days prior to randomization, irrespective of the method of contraception used, including tubal ligation;
Women of childbearing potential and male participants with partners of child bearing potential, including women whose last menstrual period was <12 months ago (unless surgically sterile) who are unable or unwilling to use adequate contraceptive measures during study treatment (adequate contraceptive measures: intra-uterine device, barrier method - condoms, diaphragm - also in conjunction with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not indicated in this patient population);
Concomitant use of CYP3A4 inhibitors or inducers.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Mobile	Alabama	United States	36608
2	Novartis Investigative Site	Anchorage	Alaska	United States	99508
3	Novartis Investigative Site	Fairbanks	Alaska	United States	99701
4	Novartis Investigative Site	Phoenix	Arizona	United States	85012
5	Novartis Investigative Site	Tucson	Arizona	United States	85704
6	Novartis Investigative Site	Tucson	Arizona	United States	85715
7	Novartis Investigative Site	Jonesboro	Arkansas	United States	72401
8	Novartis Investigative Site	Berkeley	California	United States	94705
9	Novartis Investigative Site	Burlingame	California	United States	94010
10	Novartis Investigative Site	Castro Valley	California	United States	94546
11	Novartis Investigative Site	Duarte	California	United States	91010
12	Novartis Investigative Site	Fairfield	California	United States	94533
13	Novartis Investigative Site	Fremont	California	United States	94538
14	Novartis Investigative Site	Fresno	California	United States	93720
15	Novartis Investigative Site	Glendale	California	United States	91204
16	Novartis Investigative Site	Greenbrae	California	United States	94904
17	Novartis Investigative Site	La Jolla	California	United States	92093-0987
18	Novartis Investigative Site	La Jolla	California	United States	92093
19	Novartis Investigative Site	Loma Linda	California	United States	92534
20	Novartis Investigative Site	Martinez	California	United States	94553-3156
21	Novartis Investigative Site	Marysville	California	United States	95901
22	Novartis Investigative Site	Monterey	California	United States	93940
23	Novartis Investigative Site	Mountain View	California	United States	94040
24	Novartis Investigative Site	Murrieta	California	United States	92562
25	Novartis Investigative Site	Oakland	California	United States	94602
26	Novartis Investigative Site	Oakland	California	United States	94609
27	Novartis Investigative Site	Orange	California	United States	92868
28	Novartis Investigative Site	Palm Springs	California	United States	92262
29	Novartis Investigative Site	Palo Alto	California	United States	94301
30	Novartis Investigative Site	Pismo Beach	California	United States	93449
31	Novartis Investigative Site	Pleasanton	California	United States	94588
32	Novartis Investigative Site	Sacramento	California	United States	95817
33	Novartis Investigative Site	San Francisco	California	United States	94110
34	Novartis Investigative Site	San Francisco	California	United States	94115
35	Novartis Investigative Site	San Francisco	California	United States	94118
36	Novartis Investigative Site	San Leandro	California	United States	94578
37	Novartis Investigative Site	Vallejo	California	United States	94589
38	Novartis Investigative Site	Aurora	Colorado	United States	80012
39	Novartis Investigative Site	Boulder	Colorado	United States	80301
40	Novartis Investigative Site	Colorado Springs	Colorado	United States	80907
41	Novartis Investigative Site	Denver	Colorado	United States	80204
42	Novartis Investigative Site	Denver	Colorado	United States	80210
43	Novartis Investigative Site	Denver	Colorado	United States	80217-3364
44	Novartis Investigative Site	Denver	Colorado	United States	80218
45	Novartis Investigative Site	Denver	Colorado	United States	80220
46	Novartis Investigative Site	Denver	Colorado	United States	80224
47	Novartis Investigative Site	Edwards	Colorado	United States	81632
48	Novartis Investigative Site	Englewood	Colorado	United States	80110
49	Novartis Investigative Site	Fort Collins	Colorado	United States	80524
50	Novartis Investigative Site	Fort Collins	Colorado	United States	80528
51	Novartis Investigative Site	Glenwood Springs	Colorado	United States	81601
52	Novartis Investigative Site	Grand Junction	Colorado	United States	81502
53	Novartis Investigative Site	Greeley	Colorado	United States	80631
54	Novartis Investigative Site	Lone Tree	Colorado	United States	80124
55	Novartis Investigative Site	Longmont	Colorado	United States	80502
56	Novartis Investigative Site	Loveland	Colorado	United States	80539
57	Novartis Investigative Site	Montrose	Colorado	United States	81401
58	Novartis Investigative Site	Pueblo	Colorado	United States	81004
59	Novartis Investigative Site	Thornton	Colorado	United States	80229
60	Novartis Investigative Site	Wheat Ridge	Colorado	United States	80033
61	Novartis Investigative Site	Hartford	Connecticut	United States	06105
62	Novartis Investigative Site	New Haven	Connecticut	United States	06520
63	Novartis Investigative Site	Stamford	Connecticut	United States	06904
64	Novartis Investigative Site	Torrington	Connecticut	United States	06790
65	Novartis Investigative Site	Dover	Delaware	United States	19901
66	Novartis Investigative Site	Milford	Delaware	United States	19963
67	Novartis Investigative Site	Washington	District of Columbia	United States	20007
68	Novartis Investigative Site	Washington	District of Columbia	United States	20307
69	Novartis Investigative Site	Boca Raton	Florida	United States	33486
70	Novartis Investigative Site	Fort Lauderdale	Florida	United States	33308
71	Novartis Investigative Site	Fort Myers	Florida	United States	33916
72	Novartis Investigative Site	Hollywood	Florida	United States	33021
73	Novartis Investigative Site	Jacksonville	Florida	United States	32207
74	Novartis Investigative Site	Jacksonville	Florida	United States	32224
75	Novartis Investigative Site	Jupiter	Florida	United States	33458
76	Novartis Investigative Site	Lakeland	Florida	United States	33805
77	Novartis Investigative Site	Miami Beach	Florida	United States	33140
78	Novartis Investigative Site	New Port Richey	Florida	United States	34655
79	Novartis Investigative Site	Ocala	Florida	United States	34474
80	Novartis Investigative Site	Orange Park	Florida	United States	32073
81	Novartis Investigative Site	Orlando	Florida	United States	32803
82	Novartis Investigative Site	Orlando	Florida	United States	32806
83	Novartis Investigative Site	Titusville	Florida	United States	32796
84	Novartis Investigative Site	Weston	Florida	United States	33331
85	Novartis Investigative Site	Athens	Georgia	United States	30607
86	Novartis Investigative Site	Atlanta	Georgia	United States	30309
87	Novartis Investigative Site	Atlanta	Georgia	United States	30342
88	Novartis Investigative Site	Augusta	Georgia	United States	30901
89	Novartis Investigative Site	Augusta	Georgia	United States	30912
90	Novartis Investigative Site	Austell	Georgia	United States	30106
91	Novartis Investigative Site	Columbus	Georgia	United States	31904
92	Novartis Investigative Site	Decatur	Georgia	United States	30033
93	Novartis Investigative Site	Fort Gordon	Georgia	United States	30905-5650
94	Novartis Investigative Site	Gainesville	Georgia	United States	30501
95	Novartis Investigative Site	Lawrenceville	Georgia	United States	30045
96	Novartis Investigative Site	Marietta	Georgia	United States	30060
97	Novartis Investigative Site	Riverdale	Georgia	United States	30274
98	Novartis Investigative Site	Rome	Georgia	United States	30165
99	Novartis Investigative Site	Savannah	Georgia	United States	31405
100	Novartis Investigative Site	Valdosta	Georgia	United States	31603
101	Novartis Investigative Site	'Aiea	Hawaii	United States	96701
102	Novartis Investigative Site	Honolulu	Hawaii	United States	96813
103	Novartis Investigative Site	Honolulu	Hawaii	United States	96817
104	Novartis Investigative Site	Honolulu	Hawaii	United States	96826
105	Novartis Investigative Site	Honolulu	Hawaii	United States	96859
106	Novartis Investigative Site	Lihue	Hawaii	United States	96766
107	Novartis Investigative Site	Wailuku	Hawaii	United States	96793
108	Novartis Investigative Site	Boise	Idaho	United States	83706
109	Novartis Investigative Site	Boise	Idaho	United States	83712
110	Novartis Investigative Site	Alton	Illinois	United States	62002
111	Novartis Investigative Site	Aurora	Illinois	United States	60504
112	Novartis Investigative Site	Berwyn	Illinois	United States	60402
113	Novartis Investigative Site	Bloomington	Illinois	United States	61701
114	Novartis Investigative Site	Canton	Illinois	United States	61520
115	Novartis Investigative Site	Carthage	Illinois	United States	62321
116	Novartis Investigative Site	Chicago	Illinois	United States	60611
117	Novartis Investigative Site	Chicago	Illinois	United States	60657
118	Novartis Investigative Site	Eureka	Illinois	United States	61530
119	Novartis Investigative Site	Evanston	Illinois	United States	60201
120	Novartis Investigative Site	Galesburg	Illinois	United States	61401
121	Novartis Investigative Site	Harvey	Illinois	United States	60426
122	Novartis Investigative Site	Havana	Illinois	United States	62644
123	Novartis Investigative Site	Highland Park	Illinois	United States	60035
124	Novartis Investigative Site	Hopedale	Illinois	United States	61747
125	Novartis Investigative Site	Joliet	Illinois	United States	60432
126	Novartis Investigative Site	Joliet	Illinois	United States	60435
127	Novartis Investigative Site	Kankakee	Illinois	United States	60901
128	Novartis Investigative Site	Kewanee	Illinois	United States	61443
129	Novartis Investigative Site	La Grange	Illinois	United States	60525
130	Novartis Investigative Site	Libertyville	Illinois	United States	60048
131	Novartis Investigative Site	Macomb	Illinois	United States	61455
132	Novartis Investigative Site	Maywood	Illinois	United States	60153
133	Novartis Investigative Site	Moline	Illinois	United States	61265
134	Novartis Investigative Site	Monmouth	Illinois	United States	61462
135	Novartis Investigative Site	Mount Vernon	Illinois	United States	62864
136	Novartis Investigative Site	Naperville	Illinois	United States	60563
137	Novartis Investigative Site	Niles	Illinois	United States	60714
138	Novartis Investigative Site	Normal	Illinois	United States	61761
139	Novartis Investigative Site	Oak Lawn	Illinois	United States	60453-2699
140	Novartis Investigative Site	Ottawa	Illinois	United States	61350
141	Novartis Investigative Site	Park Ridge	Illinois	United States	60068
142	Novartis Investigative Site	Pekin	Illinois	United States	61554
143	Novartis Investigative Site	Pekin	Illinois	United States	61603
144	Novartis Investigative Site	Peoria	Illinois	United States	61603
145	Novartis Investigative Site	Peoria	Illinois	United States	61614
146	Novartis Investigative Site	Peoria	Illinois	United States	61615-7822
147	Novartis Investigative Site	Peoria	Illinois	United States	61615
148	Novartis Investigative Site	Peoria	Illinois	United States	61637
149	Novartis Investigative Site	Peru	Illinois	United States	61354
150	Novartis Investigative Site	Princeton	Illinois	United States	61356
151	Novartis Investigative Site	Rockford	Illinois	United States	61114
152	Novartis Investigative Site	Skokie	Illinois	United States	60077
153	Novartis Investigative Site	Spring Valley	Illinois	United States	61362
154	Novartis Investigative Site	Springfield	Illinois	United States	62781-0001
155	Novartis Investigative Site	Urbana	Illinois	United States	61801
156	Novartis Investigative Site	Warrenville	Illinois	United States	60555
157	Novartis Investigative Site	Winfield	Illinois	United States	60190
158	Novartis Investigative Site	Beech Grove	Indiana	United States	46107
159	Novartis Investigative Site	Elkhart	Indiana	United States	46515
160	Novartis Investigative Site	Fort Wayne	Indiana	United States	46815
161	Novartis Investigative Site	Indianapolis	Indiana	United States	46202
162	Novartis Investigative Site	Indianapolis	Indiana	United States	46260
163	Novartis Investigative Site	Kokomo	Indiana	United States	46904
164	Novartis Investigative Site	La Porte	Indiana	United States	46350
165	Novartis Investigative Site	Michigan City	Indiana	United States	46360
166	Novartis Investigative Site	Mishawaka	Indiana	United States	46545
167	Novartis Investigative Site	Muncie	Indiana	United States	47303
168	Novartis Investigative Site	Richmond	Indiana	United States	47374
169	Novartis Investigative Site	South Bend	Indiana	United States	46601
170	Novartis Investigative Site	South Bend	Indiana	United States	46617
171	Novartis Investigative Site	Ames	Iowa	United States	50010
172	Novartis Investigative Site	Bettendorf	Iowa	United States	52722
173	Novartis Investigative Site	Cedar Rapids	Iowa	United States	52402
174	Novartis Investigative Site	Cedar Rapids	Iowa	United States	52403
175	Novartis Investigative Site	Des Moines	Iowa	United States	50307
176	Novartis Investigative Site	Des Moines	Iowa	United States	50309
177	Novartis Investigative Site	Des Moines	Iowa	United States	50314
178	Novartis Investigative Site	Des Moines	Iowa	United States	50316
179	Novartis Investigative Site	Mason City	Iowa	United States
180	Novartis Investigative Site	Ottumwa	Iowa	United States	52501
181	Novartis Investigative Site	Sioux City	Iowa	United States	51101-1733
182	Novartis Investigative Site	Sioux City	Iowa	United States	51104
183	Novartis Investigative Site	Waterloo	Iowa	United States	50701
184	Novartis Investigative Site	Waterloo	Iowa	United States	50702
185	Novartis Investigative Site	Anthony	Kansas	United States	67003
186	Novartis Investigative Site	Chanute	Kansas	United States	66720
187	Novartis Investigative Site	Dodge City	Kansas	United States	67801
188	Novartis Investigative Site	El Dorado	Kansas	United States	67042
189	Novartis Investigative Site	Fort Scott	Kansas	United States	66701
190	Novartis Investigative Site	Independence	Kansas	United States	67301
191	Novartis Investigative Site	Kansas City	Kansas	United States	66160
192	Novartis Investigative Site	Kingman	Kansas	United States	67068
193	Novartis Investigative Site	Lawrence	Kansas	United States	66044
194	Novartis Investigative Site	Liberal	Kansas	United States	67901
195	Novartis Investigative Site	Newton	Kansas	United States	67114
196	Novartis Investigative Site	Olathe	Kansas	United States	66061
197	Novartis Investigative Site	Overland Park	Kansas	United States	66209
198	Novartis Investigative Site	Overland Park	Kansas	United States	66210
199	Novartis Investigative Site	Overland Park	Kansas	United States	66213
200	Novartis Investigative Site	Parsons	Kansas	United States	67357
201	Novartis Investigative Site	Prairie Village	Kansas	United States	66208
202	Novartis Investigative Site	Pratt	Kansas	United States	67124
203	Novartis Investigative Site	Salina	Kansas	United States	67042
204	Novartis Investigative Site	Shawnee Mission	Kansas	United States	66204
205	Novartis Investigative Site	Topeka	Kansas	United States	66604
206	Novartis Investigative Site	Topeka	Kansas	United States	66606
207	Novartis Investigative Site	Wellington	Kansas	United States	67152
208	Novartis Investigative Site	Wichita	Kansas	United States	67203
209	Novartis Investigative Site	Wichita	Kansas	United States	67208
210	Novartis Investigative Site	Wichita	Kansas	United States	67214
211	Novartis Investigative Site	Winfield	Kansas	United States	67156
212	Novartis Investigative Site	Louisville	Kentucky	United States	40292
213	Novartis Investigative Site	Baton Rouge	Louisiana	United States	70806
214	Novartis Investigative Site	Baton Rouge	Louisiana	United States	70809
215	Novartis Investigative Site	Houma	Louisiana	United States	70360
216	Novartis Investigative Site	New Orleans	Louisiana	United States	70112
217	Novartis Investigative Site	New Orleans	Louisiana	United States	70121
218	Novartis Investigative Site	Portland	Maine	United States	04101
219	Novartis Investigative Site	Scarborough	Maine	United States	04074
220	Novartis Investigative Site	Baltimore	Maryland	United States	21201
221	Novartis Investigative Site	Baltimore	Maryland	United States	21287-8936
222	Novartis Investigative Site	Bethesda	Maryland	United States	20889-5600
223	Novartis Investigative Site	Easton	Maryland	United States	21601
224	Novartis Investigative Site	Frederick	Maryland	United States	21701
225	Novartis Investigative Site	Hagerstown	Maryland	United States	21740
226	Novartis Investigative Site	Silver Spring	Maryland	United States	20910
227	Novartis Investigative Site	Towson	Maryland	United States	21204
228	Novartis Investigative Site	Westminster	Maryland	United States	21157
229	Novartis Investigative Site	Boston	Massachusetts	United States	02114
230	Novartis Investigative Site	Boston	Massachusetts	United States	02115
231	Novartis Investigative Site	Boston	Massachusetts	United States	02135
232	Novartis Investigative Site	Boston	Massachusetts	United States	02215
233	Novartis Investigative Site	Burlington	Massachusetts	United States	01805
234	Novartis Investigative Site	Gloucester	Massachusetts	United States	01930
235	Novartis Investigative Site	Hyannis	Massachusetts	United States	02601
236	Novartis Investigative Site	Lowell	Massachusetts	United States
237	Novartis Investigative Site	Peabody	Massachusetts	United States	01960
238	Novartis Investigative Site	Adrian	Michigan	United States	49221
239	Novartis Investigative Site	Ann Arbor	Michigan	United States	48106-0995
240	Novartis Investigative Site	Ann Arbor	Michigan	United States	48106
241	Novartis Investigative Site	Ann Arbor	Michigan	United States	48109
242	Novartis Investigative Site	Battle Creek	Michigan	United States	49016
243	Novartis Investigative Site	Big Rapids	Michigan	United States
244	Novartis Investigative Site	Byron Center	Michigan	United States	49519
245	Novartis Investigative Site	Dearborn	Michigan	United States	48123
246	Novartis Investigative Site	Detroit	Michigan	United States	48202
247	Novartis Investigative Site	Detroit	Michigan	United States	48236
248	Novartis Investigative Site	Escanaba	Michigan	United States	49431
249	Novartis Investigative Site	Flint	Michigan	United States	48502
250	Novartis Investigative Site	Flint	Michigan	United States	48532
251	Novartis Investigative Site	Grand Rapids	Michigan	United States	49503
252	Novartis Investigative Site	Iron Mountain	Michigan	United States	49801
253	Novartis Investigative Site	Jackson	Michigan	United States	49201
254	Novartis Investigative Site	Kalamazoo	Michigan	United States	49001
255	Novartis Investigative Site	Kalamazoo	Michigan	United States	49007
256	Novartis Investigative Site	Lansing	Michigan	United States	48912
257	Novartis Investigative Site	Livonia	Michigan	United States	48154
258	Novartis Investigative Site	Monroe	Michigan	United States	48162
259	Novartis Investigative Site	Muskegon	Michigan	United States	49444
260	Novartis Investigative Site	Pontiac	Michigan	United States	48341-2985
261	Novartis Investigative Site	Port Huron	Michigan	United States	48060
262	Novartis Investigative Site	Saginaw	Michigan	United States	48601
263	Novartis Investigative Site	Saint Joseph	Michigan	United States	49085
264	Novartis Investigative Site	Saint Joseph	Michigan	United States
265	Novartis Investigative Site	Southfield	Michigan	United States	48075
266	Novartis Investigative Site	Traverse City	Michigan	United States	49684
267	Novartis Investigative Site	Warren	Michigan	United States	48093
268	Novartis Investigative Site	Albert Lea	Minnesota	United States	56007
269	Novartis Investigative Site	Alexandria	Minnesota	United States	56308
270	Novartis Investigative Site	Bemidji	Minnesota	United States	56601
271	Novartis Investigative Site	Burnsville	Minnesota	United States	55337
272	Novartis Investigative Site	Coon Rapids	Minnesota	United States	55433
273	Novartis Investigative Site	Duluth	Minnesota	United States	55805
274	Novartis Investigative Site	Edina	Minnesota	United States	55435
275	Novartis Investigative Site	Fergus Falls	Minnesota	United States	56537
276	Novartis Investigative Site	Fridley	Minnesota	United States	55432
277	Novartis Investigative Site	Hutchinson	Minnesota	United States	55350
278	Novartis Investigative Site	Litchfield	Minnesota	United States	55355
279	Novartis Investigative Site	Mankato	Minnesota	United States	56002
280	Novartis Investigative Site	Maplewood	Minnesota	United States	55109
281	Novartis Investigative Site	Minneapolis	Minnesota	United States	55407-3799
282	Novartis Investigative Site	Minneapolis	Minnesota	United States	55415
283	Novartis Investigative Site	Minneapolis	Minnesota	United States	55455
284	Novartis Investigative Site	Robbinsdale	Minnesota	United States	55422
285	Novartis Investigative Site	Saint Cloud	Minnesota	United States	56303
286	Novartis Investigative Site	Saint Louis Park	Minnesota	United States	55416
287	Novartis Investigative Site	Saint Paul	Minnesota	United States	55101
288	Novartis Investigative Site	Saint Paul	Minnesota	United States	55102
289	Novartis Investigative Site	Shakopee	Minnesota	United States	55379
290	Novartis Investigative Site	Waconia	Minnesota	United States	55387
291	Novartis Investigative Site	Willmar	Minnesota	United States	56201
292	Novartis Investigative Site	Woodbury	Minnesota	United States	55125
293	Novartis Investigative Site	Jackson	Mississippi	United States	39216-4505
294	Novartis Investigative Site	Keesler Air Force Base	Mississippi	United States	39534
295	Novartis Investigative Site	Pascagoula	Mississippi	United States	39581
296	Novartis Investigative Site	Bolivar	Missouri	United States	65613
297	Novartis Investigative Site	Cape Girardeau	Missouri	United States	63701
298	Novartis Investigative Site	Cape Girardeau	Missouri	United States	63703
299	Novartis Investigative Site	Independence	Missouri	United States	64050
300	Novartis Investigative Site	Joplin	Missouri	United States	64804
301	Novartis Investigative Site	Kansas City	Missouri	United States	64108
302	Novartis Investigative Site	Kansas City	Missouri	United States	64111
303	Novartis Investigative Site	Kansas City	Missouri	United States	64114
304	Novartis Investigative Site	Kansas City	Missouri	United States	64116
305	Novartis Investigative Site	Kansas City	Missouri	United States	64118
306	Novartis Investigative Site	Kansas City	Missouri	United States	64131
307	Novartis Investigative Site	Kansas City	Missouri	United States	64132
308	Novartis Investigative Site	Kansas City	Missouri	United States	64154
309	Novartis Investigative Site	Lee's Summit	Missouri	United States	64086
310	Novartis Investigative Site	Liberty	Missouri	United States	64068
311	Novartis Investigative Site	Saint Joseph	Missouri	United States	64506
312	Novartis Investigative Site	Saint Joseph	Missouri	United States	64507
313	Novartis Investigative Site	Saint Louis	Missouri	United States	63109
314	Novartis Investigative Site	Saint Louis	Missouri	United States	63110
315	Novartis Investigative Site	Saint Louis	Missouri	United States	63131
316	Novartis Investigative Site	Saint Louis	Missouri	United States	63141
317	Novartis Investigative Site	Springfield	Missouri	United States	65802
318	Novartis Investigative Site	Springfield	Missouri	United States	65804
319	Novartis Investigative Site	Springfield	Missouri	United States	65807
320	Novartis Investigative Site	Billings	Montana	United States	59101
321	Novartis Investigative Site	Bozeman	Montana	United States	59715
322	Novartis Investigative Site	Butte	Montana	United States	59701
323	Novartis Investigative Site	Great Falls	Montana	United States	59405
324	Novartis Investigative Site	Havre	Montana	United States	59501
325	Novartis Investigative Site	Helena	Montana	United States	59601
326	Novartis Investigative Site	Kalispell	Montana	United States	59901
327	Novartis Investigative Site	Missoula	Montana	United States	59801
328	Novartis Investigative Site	Missoula	Montana	United States	59802
329	Novartis Investigative Site	Missoula	Montana	United States	59804
330	Novartis Investigative Site	Grand Island	Nebraska	United States	68803
331	Novartis Investigative Site	Lincoln	Nebraska	United States	68510
332	Novartis Investigative Site	Omaha	Nebraska	United States	68106
333	Novartis Investigative Site	Omaha	Nebraska	United States	68114
334	Novartis Investigative Site	Omaha	Nebraska	United States	68122
335	Novartis Investigative Site	Omaha	Nebraska	United States	68124
336	Novartis Investigative Site	Omaha	Nebraska	United States	68131
337	Novartis Investigative Site	Omaha	Nebraska	United States	68198
338	Novartis Investigative Site	Las Vegas	Nevada	United States	89169
339	Novartis Investigative Site	Concord	New Hampshire	United States	03301
340	Novartis Investigative Site	Exeter	New Hampshire	United States	03833
341	Novartis Investigative Site	Hooksett	New Hampshire	United States	03106
342	Novartis Investigative Site	Keene	New Hampshire	United States	03431
343	Novartis Investigative Site	Laconia	New Hampshire	United States	03246
344	Novartis Investigative Site	Lebanon	New Hampshire	United States	03756
345	Novartis Investigative Site	Manchester	New Hampshire	United States	03104
346	Novartis Investigative Site	Portsmouth	New Hampshire	United States	03802
347	Novartis Investigative Site	Hackensack	New Jersey	United States	07601
348	Novartis Investigative Site	Hamilton	New Jersey	United States	08690
349	Novartis Investigative Site	Livingston	New Jersey	United States	07039
350	Novartis Investigative Site	Marlton	New Jersey	United States	08053
351	Novartis Investigative Site	Morristown	New Jersey	United States	07962
352	Novartis Investigative Site	Mount Holly	New Jersey	United States	08060
353	Novartis Investigative Site	Neptune	New Jersey	United States	7754
354	Novartis Investigative Site	New Brunswick	New Jersey	United States	08901
355	Novartis Investigative Site	Pomona	New Jersey	United States	08240
356	Novartis Investigative Site	Princeton	New Jersey	United States	24740
357	Novartis Investigative Site	Ridgewood	New Jersey	United States	07450
358	Novartis Investigative Site	Somerville	New Jersey	United States	08876
359	Novartis Investigative Site	Sparta	New Jersey	United States	07871
360	Novartis Investigative Site	Summit	New Jersey	United States	07902
361	Novartis Investigative Site	Vineland	New Jersey	United States	08360
362	Novartis Investigative Site	Voorhees	New Jersey	United States	08043
363	Novartis Investigative Site	Albuquerque	New Mexico	United States	87106
364	Novartis Investigative Site	Albuquerque	New Mexico	United States	87110
365	Novartis Investigative Site	Las Cruces	New Mexico	United States	88011
366	Novartis Investigative Site	Bronx	New York	United States	10461
367	Novartis Investigative Site	Bronx	New York	United States	10466
368	Novartis Investigative Site	Bronx	New York	United States	10467-2490
369	Novartis Investigative Site	Buffalo	New York	United States	14263
370	Novartis Investigative Site	Clifton Springs	New York	United States	14432
371	Novartis Investigative Site	Cooperstown	New York	United States	13326
372	Novartis Investigative Site	East Syracuse	New York	United States	13057
373	Novartis Investigative Site	Elmhurst	New York	United States	11373
374	Novartis Investigative Site	Jamaica	New York	United States	11432
375	Novartis Investigative Site	Lake Success	New York	United States	11042
376	Novartis Investigative Site	Manhasset	New York	United States	11030
377	Novartis Investigative Site	Mineola	New York	United States	11501
378	Novartis Investigative Site	New Hyde Park	New York	United States	11042
379	Novartis Investigative Site	New York	New York	United States	10003
380	Novartis Investigative Site	New York	New York	United States	10011
381	Novartis Investigative Site	New York	New York	United States	10016
382	Novartis Investigative Site	New York	New York	United States	10029
383	Novartis Investigative Site	New York	New York	United States	10032
384	Novartis Investigative Site	Rochester	New York	United States	14620
385	Novartis Investigative Site	Rochester	New York	United States	14623
386	Novartis Investigative Site	Rochester	New York	United States	14642
387	Novartis Investigative Site	Stony Brook	New York	United States	11794
388	Novartis Investigative Site	Syracuse	New York	United States	13210
389	Novartis Investigative Site	Utica	New York	United States	13502
390	Novartis Investigative Site	Chapel Hill	North Carolina	United States	27599
391	Novartis Investigative Site	Fayetteville	North Carolina	United States	28304
392	Novartis Investigative Site	Gastonia	North Carolina	United States	28053
393	Novartis Investigative Site	Goldsboro	North Carolina	United States	27534
394	Novartis Investigative Site	Hendersonville	North Carolina	United States	28791
395	Novartis Investigative Site	Kinston	North Carolina	United States	28501
396	Novartis Investigative Site	Raleigh	North Carolina	United States	27607
397	Novartis Investigative Site	Rutherfordton	North Carolina	United States	28139
398	Novartis Investigative Site	Statesville	North Carolina	United States	28677
399	Novartis Investigative Site	Washington	North Carolina	United States	27889
400	Novartis Investigative Site	Winston-Salem	North Carolina	United States	27157
401	Novartis Investigative Site	Bismarck	North Dakota	United States	58501
402	Novartis Investigative Site	Fargo	North Dakota	United States	58122
403	Novartis Investigative Site	Grand Forks	North Dakota	United States	58201
404	Novartis Investigative Site	Minot	North Dakota	United States	58701
405	Novartis Investigative Site	Beachwood	Ohio	United States	44122
406	Novartis Investigative Site	Bellefontaine	Ohio	United States	43311
407	Novartis Investigative Site	Bowling Green	Ohio	United States	43402
408	Novartis Investigative Site	Canton	Ohio	United States	44708
409	Novartis Investigative Site	Canton	Ohio	United States	44710
410	Novartis Investigative Site	Chillicothe	Ohio	United States	54601
411	Novartis Investigative Site	Cincinnati	Ohio	United States	45242
412	Novartis Investigative Site	Cincinnati	Ohio	United States	45267
413	Novartis Investigative Site	Cleveland	Ohio	United States	44111
414	Novartis Investigative Site	Cleveland	Ohio	United States	44195
415	Novartis Investigative Site	Clyde	Ohio	United States	43410
416	Novartis Investigative Site	Columbia	Ohio	United States	43215
417	Novartis Investigative Site	Columbus	Ohio	United States	43210
418	Novartis Investigative Site	Columbus	Ohio	United States	43214
419	Novartis Investigative Site	Columbus	Ohio	United States	43215
420	Novartis Investigative Site	Columbus	Ohio	United States	43222
421	Novartis Investigative Site	Columbus	Ohio	United States	43228
422	Novartis Investigative Site	Dayton	Ohio	United States	45405
423	Novartis Investigative Site	Dayton	Ohio	United States	45406
424	Novartis Investigative Site	Dayton	Ohio	United States	45409
425	Novartis Investigative Site	Dayton	Ohio	United States	45415
426	Novartis Investigative Site	Dayton	Ohio	United States	45429
427	Novartis Investigative Site	Delaware	Ohio	United States	43015
428	Novartis Investigative Site	Elyria	Ohio	United States	44035
429	Novartis Investigative Site	Findlay	Ohio	United States	45840
430	Novartis Investigative Site	Franklin	Ohio	United States	45005-1066
431	Novartis Investigative Site	Greenville	Ohio	United States	45331
432	Novartis Investigative Site	Independence	Ohio	United States	44131
433	Novartis Investigative Site	Kettering	Ohio	United States	45429
434	Novartis Investigative Site	Lambertville	Ohio	United States	48144
435	Novartis Investigative Site	Lima	Ohio	United States	45804
436	Novartis Investigative Site	Marietta	Ohio	United States	45750
437	Novartis Investigative Site	Maumee	Ohio	United States	43537
438	Novartis Investigative Site	Maumee	Ohio	United States	43623
439	Novartis Investigative Site	Mayfield Heights	Ohio	United States	44124
440	Novartis Investigative Site	Newark	Ohio	United States	43055
441	Novartis Investigative Site	Oregon	Ohio	United States	43616
442	Novartis Investigative Site	Sandusky	Ohio	United States	44870
443	Novartis Investigative Site	Springfield	Ohio	United States	45504
444	Novartis Investigative Site	Springfield	Ohio	United States	45505
445	Novartis Investigative Site	Sylvania	Ohio	United States	43560
446	Novartis Investigative Site	Tiffin	Ohio	United States	44883
447	Novartis Investigative Site	Toledo	Ohio	United States	43606
448	Novartis Investigative Site	Toledo	Ohio	United States	43608
449	Novartis Investigative Site	Toledo	Ohio	United States	43614
450	Novartis Investigative Site	Toledo	Ohio	United States	43617
451	Novartis Investigative Site	Toledo	Ohio	United States	43623
452	Novartis Investigative Site	Troy	Ohio	United States	45373
453	Novartis Investigative Site	Wauseon	Ohio	United States	43567
454	Novartis Investigative Site	Westerville	Ohio	United States	43081
455	Novartis Investigative Site	Wilmington	Ohio	United States	45177
456	Novartis Investigative Site	Wooster	Ohio	United States	44691
457	Novartis Investigative Site	Wright-Patterson Air Force Base	Ohio	United States	45433
458	Novartis Investigative Site	Xenia	Ohio	United States	45385
459	Novartis Investigative Site	Zanesville	Ohio	United States	43701
460	Novartis Investigative Site	Oklahoma City	Oklahoma	United States	73104
461	Novartis Investigative Site	Oklahoma City	Oklahoma	United States	73112
462	Novartis Investigative Site	Oklahoma City	Oklahoma	United States	73120
463	Novartis Investigative Site	Tulsa	Oklahoma	United States	74136
464	Novartis Investigative Site	Coos Bay	Oregon	United States	97420
465	Novartis Investigative Site	Eugene	Oregon	United States	97401
466	Novartis Investigative Site	Gresham	Oregon	United States	97030
467	Novartis Investigative Site	Hillsboro	Oregon	United States	97123
468	Novartis Investigative Site	Klamath Falls	Oregon	United States	97601
469	Novartis Investigative Site	Milwaukie	Oregon	United States	97222
470	Novartis Investigative Site	Portland	Oregon	United States	97210
471	Novartis Investigative Site	Portland	Oregon	United States	97213
472	Novartis Investigative Site	Portland	Oregon	United States	97216
473	Novartis Investigative Site	Portland	Oregon	United States	97225
474	Novartis Investigative Site	Portland	Oregon	United States	97227
475	Novartis Investigative Site	Portland	Oregon	United States	97239
476	Novartis Investigative Site	Tualatin	Oregon	United States	97062
477	Novartis Investigative Site	Abington	Pennsylvania	United States	19001-3788
478	Novartis Investigative Site	Bethlehem	Pennsylvania	United States	18015
479	Novartis Investigative Site	Bryn Mawr	Pennsylvania	United States	19010
480	Novartis Investigative Site	Butler	Pennsylvania	United States	16001
481	Novartis Investigative Site	Danville	Pennsylvania	United States	17822-2001
482	Novartis Investigative Site	Ephrata	Pennsylvania	United States	17522
483	Novartis Investigative Site	Hazleton	Pennsylvania	United States	18201
484	Novartis Investigative Site	Hershey	Pennsylvania	United States	17033
485	Novartis Investigative Site	Kingston	Pennsylvania	United States	18704
486	Novartis Investigative Site	Lancaster	Pennsylvania	United States	17604
487	Novartis Investigative Site	Langhorne	Pennsylvania	United States	19047
488	Novartis Investigative Site	Lewistown	Pennsylvania	United States	17044
489	Novartis Investigative Site	Media	Pennsylvania	United States	19063
490	Novartis Investigative Site	Nashville	Pennsylvania	United States	37204
491	Novartis Investigative Site	Paoli	Pennsylvania	United States	19301
492	Novartis Investigative Site	Philadelphia	Pennsylvania	United States	19107-2568
493	Novartis Investigative Site	Philadelphia	Pennsylvania	United States	19107
494	Novartis Investigative Site	Philadelphia	Pennsylvania	United States	19111
495	Novartis Investigative Site	Philadelphia	Pennsylvania	United States	19114
496	Novartis Investigative Site	Phoenixville	Pennsylvania	United States	19460
497	Novartis Investigative Site	Pottstown	Pennsylvania	United States	19464
498	Novartis Investigative Site	Sayre	Pennsylvania	United States	18840
499	Novartis Investigative Site	Scranton	Pennsylvania	United States	18508
500	Novartis Investigative Site	Sellersville	Pennsylvania	United States	18960
501	Novartis Investigative Site	State College	Pennsylvania	United States	16801
502	Novartis Investigative Site	State College	Pennsylvania	United States	16803
503	Novartis Investigative Site	West Reading	Pennsylvania	United States	19612
504	Novartis Investigative Site	Wilkes-Barre	Pennsylvania	United States	18711
505	Novartis Investigative Site	Wilkes-Barre	Pennsylvania	United States	18765
506	Novartis Investigative Site	Wynnewood	Pennsylvania	United States	19096
507	Novartis Investigative Site	Providence	Rhode Island	United States	02903
508	Novartis Investigative Site	Providence	Rhode Island	United States	02905
509	Novartis Investigative Site	Providence	Rhode Island	United States	02906
510	Novartis Investigative Site	Warwick	Rhode Island	United States	02886
511	Novartis Investigative Site	Anderson	South Carolina	United States	29621
512	Novartis Investigative Site	Charleston	South Carolina	United States	29406
513	Novartis Investigative Site	Columbia	South Carolina	United States	29210
514	Novartis Investigative Site	Greenville	South Carolina	United States	29605
515	Novartis Investigative Site	Mount Pleasant	South Carolina	United States	29464
516	Novartis Investigative Site	Spartanburg	South Carolina	United States	29303
517	Novartis Investigative Site	Aberdeen	South Dakota	United States	57401
518	Novartis Investigative Site	Rapid City	South Dakota	United States	57701
519	Novartis Investigative Site	Sioux Falls	South Dakota	United States	57104
520	Novartis Investigative Site	Sioux Falls	South Dakota	United States	57105
521	Novartis Investigative Site	Sioux Falls	South Dakota	United States	57117-5134
522	Novartis Investigative Site	Chattanooga	Tennessee	United States	37403
523	Novartis Investigative Site	Chattanooga	Tennessee	United States	37404
524	Novartis Investigative Site	Franklin	Tennessee	United States	37067
525	Novartis Investigative Site	Germantown	Tennessee	United States	38138
526	Novartis Investigative Site	Jackson	Tennessee	United States	38301
527	Novartis Investigative Site	Knoxville	Tennessee	United States	37909
528	Novartis Investigative Site	Knoxville	Tennessee	United States	37916
529	Novartis Investigative Site	Knoxville	Tennessee	United States	37920
530	Novartis Investigative Site	Nashville	Tennessee	United States	37203
531	Novartis Investigative Site	Nashville	Tennessee	United States	37208
532	Novartis Investigative Site	Nashville	Tennessee	United States	37232
533	Novartis Investigative Site	Abilene	Texas	United States	79606-5208
534	Novartis Investigative Site	Amarillo	Texas	United States	79106
535	Novartis Investigative Site	Austin	Texas	United States	78705
536	Novartis Investigative Site	Austin	Texas	United States	78731
537	Novartis Investigative Site	Austin	Texas	United States	78745
538	Novartis Investigative Site	Austin	Texas	United States	78758
539	Novartis Investigative Site	Beaumont	Texas	United States	77702-1449
540	Novartis Investigative Site	Bedford	Texas	United States	76022
541	Novartis Investigative Site	Cedar Park	Texas	United States	78613
542	Novartis Investigative Site	Dallas	Texas	United States	75230
543	Novartis Investigative Site	Dallas	Texas	United States	75237
544	Novartis Investigative Site	Fort Sam Houston	Texas	United States	78234
545	Novartis Investigative Site	Fort Worth	Texas	United States	76104
546	Novartis Investigative Site	Houston	Texas	United States	77030
547	Novartis Investigative Site	Lackland Air Force Base	Texas	United States	78236
548	Novartis Investigative Site	Longview	Texas	United States	75601
549	Novartis Investigative Site	McAllen	Texas	United States	78503-1298
550	Novartis Investigative Site	Mesquite	Texas	United States	75150
551	Novartis Investigative Site	Midland	Texas	United States	79701
552	Novartis Investigative Site	Paris	Texas	United States	75460
553	Novartis Investigative Site	Round Rock	Texas	United States	78655
554	Novartis Investigative Site	Round Rock	Texas	United States	78681
555	Novartis Investigative Site	San Antonio	Texas	United States	78209
556	Novartis Investigative Site	San Antonio	Texas	United States	78229
557	Novartis Investigative Site	San Marcos	Texas	United States	78666
558	Novartis Investigative Site	Sherman	Texas	United States	75090
559	Novartis Investigative Site	Sugar Land	Texas	United States	77479
560	Novartis Investigative Site	Tyler	Texas	United States	75702
561	Novartis Investigative Site	Waco	Texas	United States	76712
562	Novartis Investigative Site	Wichita Falls	Texas	United States	76310
563	Novartis Investigative Site	Salt Lake City	Utah	United States	84112
564	Novartis Investigative Site	Berlin	Vermont	United States	05602
565	Novartis Investigative Site	Burlington	Vermont	United States	05401
566	Novartis Investigative Site	Saint Johnsbury	Vermont	United States	05819
567	Novartis Investigative Site	Charlottesville	Virginia	United States	22902
568	Novartis Investigative Site	Danville	Virginia	United States	24541
569	Novartis Investigative Site	Fredericksburg	Virginia	United States	22401
570	Novartis Investigative Site	Hampton	Virginia	United States	23666
571	Novartis Investigative Site	Norfolk	Virginia	United States	23502
572	Novartis Investigative Site	Richmond	Virginia	United States	23226
573	Novartis Investigative Site	Roanoke	Virginia	United States	24014
574	Novartis Investigative Site	Auburn	Washington	United States	98002
575	Novartis Investigative Site	Bellingham	Washington	United States	98225
576	Novartis Investigative Site	Bremerton	Washington	United States	98310
577	Novartis Investigative Site	Burien	Washington	United States	98166
578	Novartis Investigative Site	Centralia	Washington	United States	98531
579	Novartis Investigative Site	Federal Way	Washington	United States	98003
580	Novartis Investigative Site	Kennewick	Washington	United States	99336
581	Novartis Investigative Site	Kirkland	Washington	United States
582	Novartis Investigative Site	Mount Vernon	Washington	United States	98273
583	Novartis Investigative Site	Olympia	Washington	United States	98506
584	Novartis Investigative Site	Port Angeles	Washington	United States	98362
585	Novartis Investigative Site	Poulsbo	Washington	United States	98370
586	Novartis Investigative Site	Puyallup	Washington	United States	98372
587	Novartis Investigative Site	Renton	Washington	United States	98055
588	Novartis Investigative Site	Seattle	Washington	United States	98104
589	Novartis Investigative Site	Seattle	Washington	United States	98112
590	Novartis Investigative Site	Seattle	Washington	United States	98122-4299
591	Novartis Investigative Site	Seattle	Washington	United States	98122
592	Novartis Investigative Site	Seattle	Washington	United States	98133
593	Novartis Investigative Site	Seattle	Washington	United States	98195-6098
594	Novartis Investigative Site	Spokane	Washington	United States	99202
595	Novartis Investigative Site	Spokane	Washington	United States	99218
596	Novartis Investigative Site	Tacoma	Washington	United States	98405
597	Novartis Investigative Site	Tacoma	Washington	United States	98415
598	Novartis Investigative Site	Tacoma	Washington	United States	98499
599	Novartis Investigative Site	Vancouver	Washington	United States	98668
600	Novartis Investigative Site	Vancouver	Washington	United States	98686
601	Novartis Investigative Site	Wenatchee	Washington	United States	98801
602	Novartis Investigative Site	Charleston	West Virginia	United States	25304
603	Novartis Investigative Site	Huntington	West Virginia	United States	25701
604	Novartis Investigative Site	Wheeling	West Virginia	United States	26003
605	Novartis Investigative Site	Chippewa Falls	Wisconsin	United States	54729
606	Novartis Investigative Site	Eau Claire	Wisconsin	United States	54701
607	Novartis Investigative Site	Eau Claire	Wisconsin	United States	54702
608	Novartis Investigative Site	Green Bay	Wisconsin	United States	54301
609	Novartis Investigative Site	Green Bay	Wisconsin	United States	54303
610	Novartis Investigative Site	La Crosse	Wisconsin	United States	54601
611	Novartis Investigative Site	Madison	Wisconsin	United States	53717
612	Novartis Investigative Site	Manitowoc	Wisconsin	United States	54221
613	Novartis Investigative Site	Marinette	Wisconsin	United States	54143
614	Novartis Investigative Site	Marshfield	Wisconsin	United States	54449
615	Novartis Investigative Site	Milwaukee	Wisconsin	United States	53233
616	Novartis Investigative Site	Minocqua	Wisconsin	United States	54548
617	Novartis Investigative Site	Oconto Falls	Wisconsin	United States	54154
618	Novartis Investigative Site	Oshkosh	Wisconsin	United States	54904
619	Novartis Investigative Site	Rhinelander	Wisconsin	United States	54501
620	Novartis Investigative Site	Rice Lake	Wisconsin	United States	54868
621	Novartis Investigative Site	Stevens Point	Wisconsin	United States	54481
622	Novartis Investigative Site	Sturgeon Bay	Wisconsin	United States	54235
623	Novartis Investigative Site	Weston	Wisconsin	United States	54476
624	Novartis Investigative Site	Wisconsin Rapids	Wisconsin	United States	54494
625	Novartis Investigative Site	Casper	Wyoming	United States	82609
626	Novartis Investigative Site	Sheridan	Wyoming	United States	82801
627	Novartis Investigative Site	Berazategui	Buenos Aires	Argentina	B1880BBF
628	Novartis Investigative Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1125ABD
629	Novartis Investigative Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1185AAT
630	Novartis Investigative Site	Rosario	Santa Fe	Argentina	S2000KZE
631	Novartis Investigative Site	Ciudad Autonoma de Buenos Aires		Argentina	C1417DTN
632	Novartis Investigative Site	Mendoza		Argentina	M5500AYB
633	Novartis Investigative Site	Quilmes		Argentina	1878
634	Novartis Investigative Site	Santa Fe		Argentina	3000
635	Novartis Investigative Site	Tucuman		Argentina	4000
636	Novartis Investigative Site	Camperdown	New South Wales	Australia	2050
637	Novartis Investigative Site	Coffs Harbour	New South Wales	Australia	2450
638	Novartis Investigative Site	Concord	New South Wales	Australia	2139
639	Novartis Investigative Site	Kingswood	New South Wales	Australia	2747
640	Novartis Investigative Site	Liverpool	New South Wales	Australia	2170
641	Novartis Investigative Site	North Sydney	New South Wales	Australia	2060
642	Novartis Investigative Site	Port Macquarie	New South Wales	Australia	2444
643	Novartis Investigative Site	Randwick	New South Wales	Australia	2031
644	Novartis Investigative Site	Taree	New South Wales	Australia	2430
645	Novartis Investigative Site	Tweed Heads	New South Wales	Australia	2485
646	Novartis Investigative Site	Wagga Wagga	New South Wales	Australia	2650
647	Novartis Investigative Site	Waratah	New South Wales	Australia	2298
648	Novartis Investigative Site	Westmead	New South Wales	Australia	2145
649	Novartis Investigative Site	Nambour	Queensland	Australia	4560
650	Novartis Investigative Site	South Brisbane	Queensland	Australia	4101
651	Novartis Investigative Site	Woolloongabba	Queensland	Australia	4102
652	Novartis Investigative Site	Adelaide	South Australia	Australia	5000
653	Novartis Investigative Site	Bedford Park	South Australia	Australia	5042
654	Novartis Investigative Site	Woodville	South Australia	Australia	5011
655	Novartis Investigative Site	Hobart	Tasmania	Australia	7000
656	Novartis Investigative Site	Box Hill	Victoria	Australia	3128
657	Novartis Investigative Site	East Bentleigh	Victoria	Australia	3165
658	Novartis Investigative Site	East Melbourne	Victoria	Australia	3002
659	Novartis Investigative Site	Fitzroy	Victoria	Australia	3065
660	Novartis Investigative Site	Footscray	Victoria	Australia	3011
661	Novartis Investigative Site	Frankston	Victoria	Australia	3199
662	Novartis Investigative Site	Heidelberg	Victoria	Australia	3084
663	Novartis Investigative Site	Melbourne	Victoria	Australia	3002
664	Novartis Investigative Site	Parkville	Victoria	Australia	3050
665	Novartis Investigative Site	Ringwood East	Victoria	Australia	3135
666	Novartis Investigative Site	Wendouree	Victoria	Australia	3355
667	Novartis Investigative Site	Bunbury	Western Australia	Australia	6230
668	Novartis Investigative Site	Nedlands	Western Australia	Australia	6009
669	Novartis Investigative Site	Subiaco	Western Australia	Australia	6008
670	Novartis Investigative Site	Campbelltown		Australia	2560
671	Novartis Investigative Site	Lismore		Australia	2480
672	Novartis Investigative Site	Murdoch		Australia	6150
673	Novartis Investigative Site	Guessing		Austria	7540
674	Novartis Investigative Site	Linz		Austria	A-4020
675	Novartis Investigative Site	Rankweil		Austria	A-6830
676	Novartis Investigative Site	Salzburg		Austria	A-5020
677	Novartis Investigative Site	Steyr		Austria	4400
678	Novartis Investigative Site	Vienna		Austria	1140
679	Novartis Investigative Site	Villach		Austria	9500
680	Novartis Investigative Site	Wien		Austria	A-1090
681	Novartis Investigative Site	Wolfsberg		Austria	9400
682	Novartis Investigative Site	Aalst		Belgium	9300
683	Novartis Investigative Site	Antwerpen		Belgium	2020
684	Novartis Investigative Site	Bonheiden		Belgium	2820
685	Novartis Investigative Site	Brasschaat		Belgium	2930
686	Novartis Investigative Site	Brugge		Belgium	8000
687	Novartis Investigative Site	Brussels		Belgium	1000
688	Novartis Investigative Site	Brussels		Belgium	1070
689	Novartis Investigative Site	Brussel		Belgium	1090
690	Novartis Investigative Site	Bruxelles		Belgium	1020
691	Novartis Investigative Site	Bruxelles		Belgium	1050
692	Novartis Investigative Site	Bruxelles		Belgium	1200
693	Novartis Investigative Site	Charleroi		Belgium	6000
694	Novartis Investigative Site	Edegem		Belgium	2650
695	Novartis Investigative Site	Genk		Belgium	3600
696	Novartis Investigative Site	Gent		Belgium	9000
697	Novartis Investigative Site	Haine Saint Paul		Belgium	7100
698	Novartis Investigative Site	Hasselt		Belgium	3500
699	Novartis Investigative Site	Huy		Belgium	4500
700	Novartis Investigative Site	Kortrijk		Belgium	8500
701	Novartis Investigative Site	Leuven		Belgium	3000
702	Novartis Investigative Site	Liege		Belgium	4000
703	Novartis Investigative Site	Mons		Belgium	7000
704	Novartis Investigative Site	Namur		Belgium	5000
705	Novartis Investigative Site	Roeselare		Belgium	8800
706	Novartis Investigative Site	Sint-Niklaas		Belgium	9100
707	Novartis Investigative Site	Tournai		Belgium	7500
708	Novartis Investigative Site	Turnhout		Belgium	2300
709	Novartis Investigative Site	Verviers		Belgium	4800
710	Novartis Investigative Site	Wilrijk		Belgium	2610
711	Novartis Investigative Site	Yvoir		Belgium	5530
712	Novartis Investigative Site	Salvador	Bahía	Brazil	40.050-410
713	Novartis Investigative Site	Belo Horizonte	Minas Gerais	Brazil	30150-270
714	Novartis Investigative Site	Porte Alegre	Rio Grande Do Sul	Brazil	90430-001
715	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul	Brazil	90035-003
716	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul	Brazil	90035-903
717	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul	Brazil	90050-170
718	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul	Brazil	90430-090
719	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul	Brazil	90560-030
720	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul	Brazil	90610000
721	Novartis Investigative Site	Jau	São Paulo	Brazil	17210-120
722	Novartis Investigative Site	Santo Andre	São Paulo	Brazil	09060-650
723	Novartis Investigative Site	Rio de Janeiro		Brazil	20560-120
724	Novartis Investigative Site	Shumen		Bulgaria	9700
725	Novartis Investigative Site	Sofia		Bulgaria	1527
726	Novartis Investigative Site	Sofia		Bulgaria	1756
727	Novartis Investigative Site	Varna		Bulgaria	9010
728	Novartis Investigative Site	Kelowna	British Columbia	Canada	V1Y 5L3
729	Novartis Investigative Site	Vancouver	British Columbia	Canada	V5Z 4E6
730	Novartis Investigative Site	Moncton	New Brunswick	Canada	E1C 8X3
731	Novartis Investigative Site	Saint John	New Brunswick	Canada	E2L 4L2
732	Novartis Investigative Site	Barrie	Ontario	Canada	L4M 6M2
733	Novartis Investigative Site	London	Ontario	Canada	N6A 4L6
734	Novartis Investigative Site	Sault Ste. Marie	Ontario	Canada	P6A 2C4
735	Novartis Investigative Site	St Catharines	Ontario	Canada	L2R 7C6
736	Novartis Investigative Site	Toronto	Ontario	Canada	M4C 3E7
737	Novartis Investigative Site	Toronto	Ontario	Canada	M4N 3M5
738	Novartis Investigative Site	Charlottetown	Prince Edward Island	Canada	C1A 8T5
739	Novartis Investigative Site	Montreal	Quebec	Canada	H2W 1S6
740	Novartis Investigative Site	Sherbrooke	Quebec	Canada	J1H 5N4
741	Novartis Investigative Site	Regina	Saskatchewan	Canada	S4T 7T1
742	Novartis Investigative Site	Saskatoon	Saskatchewan	Canada	S7N 4H4
743	Novartis Investigative Site	Temuco	Región De La Araucania	Chile	481-0469
744	Novartis Investigative Site	Valdivia	Región De Los Lagos	Chile	5090145
745	Novartis Investigative Site	Santiago	Región Metro De Santiago	Chile	7500921
746	Novartis Investigative Site	Santiago	Región Metro De Santiago	Chile	7650635
747	Novartis Investigative Site	Santiago	Región Metro De Santiago	Chile	8360160
748	Novartis Investigative Site	Santiago	Región Metro De Santiago	Chile	8380455
749	Novartis Investigative Site	Valparaiso	Valparaíso	Chile	2341131
750	Novartis Investigative Site	Vina del Mar	Valparaíso	Chile	254-0364
751	Novartis Investigative Site	Arica		Chile	1000871
752	Novartis Investigative Site	Guangzhou	Guangdong	China	510060
753	Novartis Investigative Site	Beijing		China	100021
754	Novartis Investigative Site	Beijing		China	100071
755	Novartis Investigative Site	Shanghai		China	200032
756	Novartis Investigative Site	Tianjin		China	300060
757	Novartis Investigative Site	Varazdin		Croatia
758	Novartis Investigative Site	Zagreb		Croatia	10 000
759	Novartis Investigative Site	Zagreb		Croatia	10000
760	Novartis Investigative Site	Brno		Czechia	625 00
761	Novartis Investigative Site	Brno		Czechia	656 53
762	Novartis Investigative Site	Brno		Czechia	656 91
763	Novartis Investigative Site	Ceske Budejovice		Czechia	370 87
764	Novartis Investigative Site	Chomutov		Czechia	43012
765	Novartis Investigative Site	Jihlava		Czechia	586 01
766	Novartis Investigative Site	Novy Jicin		Czechia	741 01
767	Novartis Investigative Site	Olomouc		Czechia	775 20
768	Novartis Investigative Site	Pardubice		Czechia	532 03
769	Novartis Investigative Site	Praha 10		Czechia	100 34
770	Novartis Investigative Site	Praha 2		Czechia	12808
771	Novartis Investigative Site	Praha 4		Czechia	140 59
772	Novartis Investigative Site	Praha 5		Czechia	150 08
773	Novartis Investigative Site	Praha 8		Czechia	180 00
774	Novartis Investigative Site	Usti nad Labem		Czechia	40113
775	Novartis Investigative Site	Aalborg		Denmark	9100
776	Novartis Investigative Site	Arhus C		Denmark	8000
777	Novartis Investigative Site	Esbjerg		Denmark	6700
778	Novartis Investigative Site	Herlev		Denmark	DK-2730
779	Novartis Investigative Site	Hilleroed		Denmark	3400
780	Novartis Investigative Site	Koebenhavn Oe		Denmark	2100
781	Novartis Investigative Site	Naestved		Denmark	4700
782	Novartis Investigative Site	Odense		Denmark	5000
783	Novartis Investigative Site	Roskilde		Denmark	4000
784	Novartis Investigative Site	Vejle		Denmark	7100
785	Novartis Investigative Site	Viborg		Denmark	8800
786	Novartis Investigative Site	Tallinn		Estonia	13419
787	Novartis Investigative Site	Tartu		Estonia	51014
788	Novartis Investigative Site	ANGERS Cedex 2		France	49055
789	Novartis Investigative Site	Annecy		France	74000
790	Novartis Investigative Site	Avignon		France	84000
791	Novartis Investigative Site	Bayonne		France	64100
792	Novartis Investigative Site	Bethune		France	62400
793	Novartis Investigative Site	Bordeaux		France	33000
794	Novartis Investigative Site	Brive La Gaillarde		France	19100
795	Novartis Investigative Site	Bron		France	69677
796	Novartis Investigative Site	Caen Cedex 05		France	14076
797	Novartis Investigative Site	Caen		France	14000
798	Novartis Investigative Site	Clermont Ferrand		France	63000
799	Novartis Investigative Site	Coudekerque Branche		France	59210
800	Novartis Investigative Site	Dijon Cedex		France	21079
801	Novartis Investigative Site	Dijon		France	21000
802	Novartis Investigative Site	Draguignan		France	83007
803	Novartis Investigative Site	Grenoble Cedex 9		France	38043
804	Novartis Investigative Site	Grenoble Cedex		France	38028
805	Novartis Investigative Site	Hyeres		France	83400
806	Novartis Investigative Site	La Seyne Sur Mer		France	83500
807	Novartis Investigative Site	Le Chesnay		France	78157
808	Novartis Investigative Site	Le Havre		France	76600
809	Novartis Investigative Site	Le Mans		France	72000
810	Novartis Investigative Site	Lille		France	59000
811	Novartis Investigative Site	Lyon		France	69008
812	Novartis Investigative Site	Lyon		France	69337
813	Novartis Investigative Site	Lyon		France	69373
814	Novartis Investigative Site	Marseille Cedex 09		France	13273
815	Novartis Investigative Site	Marseille cedex 5		France	13385
816	Novartis Investigative Site	Marseille		France	13285
817	Novartis Investigative Site	Metz cedex 01		France	57045
818	Novartis Investigative Site	Mont de Marsan		France	40024
819	Novartis Investigative Site	Montauban		France	82000
820	Novartis Investigative Site	Montbeliard		France	25200
821	Novartis Investigative Site	Mulhouse		France	68070
822	Novartis Investigative Site	Nancy		France	54100
823	Novartis Investigative Site	Nice Cedex 2		France	06189
824	Novartis Investigative Site	Nimes cedex 9		France	30029
825	Novartis Investigative Site	Paris Cedex 10		France	75475
826	Novartis Investigative Site	Paris Cedex 14		France	75674
827	Novartis Investigative Site	Paris Cedex 5		France	75248
828	Novartis Investigative Site	Perigueux		France	24004
829	Novartis Investigative Site	Perin Sur Mer		France	22190
830	Novartis Investigative Site	Perpignan		France	66000
831	Novartis Investigative Site	Reims		France	51100
832	Novartis Investigative Site	Rouen cedex 1		France	76038
833	Novartis Investigative Site	Rouen		France	76000
834	Novartis Investigative Site	Saint Gregoire		France	35760
835	Novartis Investigative Site	Saint Jean		France	31240
836	Novartis Investigative Site	Saint-Cloud		France	92210
837	Novartis Investigative Site	Saint-Herblain		France	44805
838	Novartis Investigative Site	Saint-Martin Boulogne		France	62280
839	Novartis Investigative Site	Saint-Priest en Jarez Cedex		France	42271
840	Novartis Investigative Site	Strasbourg		France	67000
841	Novartis Investigative Site	Strasbourg		France	67085
842	Novartis Investigative Site	Toulouse		France	31077
843	Novartis Investigative Site	Toulouse		France	31300
844	Novartis Investigative Site	Tours cedex		France	37044
845	Novartis Investigative Site	Valenciennes		France	59322
846	Novartis Investigative Site	Vandoeuvre-Les-Nancy		France	54511
847	Novartis Investigative Site	Villejuif Cedex		France	94805
848	Novartis Investigative Site	Aalen	Baden-Wuerttemberg	Germany	73430
849	Novartis Investigative Site	Baden-Baden	Baden-Wuerttemberg	Germany	76532
850	Novartis Investigative Site	Boeblingen	Baden-Wuerttemberg	Germany	71032
851	Novartis Investigative Site	Emmendingen	Baden-Wuerttemberg	Germany	79312
852	Novartis Investigative Site	Esslingen	Baden-Wuerttemberg	Germany	73730
853	Novartis Investigative Site	Freiburg	Baden-Wuerttemberg	Germany	79106
854	Novartis Investigative Site	Goeppingen	Baden-Wuerttemberg	Germany	73035
855	Novartis Investigative Site	Heidelberg	Baden-Wuerttemberg	Germany	69115
856	Novartis Investigative Site	Heidelberg	Baden-Wuerttemberg	Germany	69120
857	Novartis Investigative Site	Karlsruhe	Baden-Wuerttemberg	Germany	76133
858	Novartis Investigative Site	Karlsruhe	Baden-Wuerttemberg	Germany	76135
859	Novartis Investigative Site	Karlsruhe	Baden-Wuerttemberg	Germany	76199
860	Novartis Investigative Site	Konstanz	Baden-Wuerttemberg	Germany	78464
861	Novartis Investigative Site	Loerrach	Baden-Wuerttemberg	Germany	79539
862	Novartis Investigative Site	Ludwigsburg	Baden-Wuerttemberg	Germany	71640
863	Novartis Investigative Site	Mannheim	Baden-Wuerttemberg	Germany	68165
864	Novartis Investigative Site	Mannheim	Baden-Wuerttemberg	Germany	68167
865	Novartis Investigative Site	Mutlangen	Baden-Wuerttemberg	Germany	73557
866	Novartis Investigative Site	Ostfildern	Baden-Wuerttemberg	Germany	73760
867	Novartis Investigative Site	Ravensburg	Baden-Wuerttemberg	Germany	88212
868	Novartis Investigative Site	Reutlingen	Baden-Wuerttemberg	Germany	72764
869	Novartis Investigative Site	Rheinfelden	Baden-Wuerttemberg	Germany	79618
870	Novartis Investigative Site	Schwaebisch Hall	Baden-Wuerttemberg	Germany	74523
871	Novartis Investigative Site	Schwetzingen	Baden-Wuerttemberg	Germany	68723
872	Novartis Investigative Site	Sigmaringen	Baden-Wuerttemberg	Germany	72488
873	Novartis Investigative Site	Stuttgart	Baden-Wuerttemberg	Germany	70174
874	Novartis Investigative Site	Stuttgart	Baden-Wuerttemberg	Germany	70376
875	Novartis Investigative Site	Tuebingen	Baden-Wuerttemberg	Germany	72076
876	Novartis Investigative Site	Tuttlingen	Baden-Wuerttemberg	Germany	78532
877	Novartis Investigative Site	Ulm	Baden-Wuerttemberg	Germany	89075
878	Novartis Investigative Site	Villingen-Schwenningen	Baden-Wuerttemberg	Germany	78050
879	Novartis Investigative Site	Ansbach	Bayern	Germany	91522
880	Novartis Investigative Site	Aschaffenburg	Bayern	Germany	63739
881	Novartis Investigative Site	Augsburg	Bayern	Germany	86156
882	Novartis Investigative Site	Bad Reichenhall	Bayern	Germany	83435
883	Novartis Investigative Site	Bayreuth	Bayern	Germany	95445
884	Novartis Investigative Site	Coburg	Bayern	Germany	96450
885	Novartis Investigative Site	Dachau	Bayern	Germany	85221
886	Novartis Investigative Site	Deggendorf	Bayern	Germany	94469
887	Novartis Investigative Site	Donauwoerth	Bayern	Germany	86609
888	Novartis Investigative Site	Ebersberg	Bayern	Germany	85560
889	Novartis Investigative Site	Eggenfelden	Bayern	Germany	84307
890	Novartis Investigative Site	Erlangen	Bayern	Germany	91054
891	Novartis Investigative Site	Forchheim	Bayern	Germany	91301
892	Novartis Investigative Site	Freising	Bayern	Germany	85354
893	Novartis Investigative Site	Fuerth	Bayern	Germany	90766
894	Novartis Investigative Site	Garmisch-Partenkirchen	Bayern	Germany	82467
895	Novartis Investigative Site	Kempten	Bayern	Germany	87439
896	Novartis Investigative Site	Kronach	Bayern	Germany	96317
897	Novartis Investigative Site	Landshut	Bayern	Germany	84034
898	Novartis Investigative Site	Landshut	Bayern	Germany	84036
899	Novartis Investigative Site	Marktredwitz	Bayern	Germany	95615
900	Novartis Investigative Site	Memmingen	Bayern	Germany	87700
901	Novartis Investigative Site	Muenchen	Bayern	Germany	80331
902	Novartis Investigative Site	Muenchen	Bayern	Germany	80335
903	Novartis Investigative Site	Muenchen	Bayern	Germany	80337
904	Novartis Investigative Site	Muenchen	Bayern	Germany	80637
905	Novartis Investigative Site	Muenchen	Bayern	Germany	81675
906	Novartis Investigative Site	Muenchen	Bayern	Germany	81925
907	Novartis Investigative Site	Muhr	Bayern	Germany	91735
908	Novartis Investigative Site	Munchen	Bayern	Germany	80638
909	Novartis Investigative Site	Nuernberg	Bayern	Germany	90449
910	Novartis Investigative Site	Nuernberg	Bayern	Germany	90491
911	Novartis Investigative Site	Regensburg	Bayern	Germany	93053
912	Novartis Investigative Site	Rosenheim	Bayern	Germany	83022
913	Novartis Investigative Site	Roth	Bayern	Germany	91154
914	Novartis Investigative Site	Schwandorf	Bayern	Germany	92421
915	Novartis Investigative Site	Traunstein	Bayern	Germany	83278
916	Novartis Investigative Site	Waldmuenchen	Bayern	Germany	93449
917	Novartis Investigative Site	Weiden	Bayern	Germany	92637
918	Novartis Investigative Site	Fuerstenwalde	Brandenburg	Germany	15517
919	Novartis Investigative Site	Koenigs Wusterhausen	Brandenburg	Germany	15711
920	Novartis Investigative Site	Luckenwalde	Brandenburg	Germany	14943
921	Novartis Investigative Site	Ludwigsfelde	Brandenburg	Germany	14974
922	Novartis Investigative Site	Bremerhaven	Bremen	Germany	27574
923	Novartis Investigative Site	Bad Soden	Hessen	Germany	65812
924	Novartis Investigative Site	Frankfurt am Main	Hessen	Germany	60590
925	Novartis Investigative Site	Frankfurt	Hessen	Germany	60389
926	Novartis Investigative Site	Frankfurt	Hessen	Germany	60596
927	Novartis Investigative Site	Frankfurt	Hessen	Germany	65929
928	Novartis Investigative Site	Fulda	Hessen	Germany	36043
929	Novartis Investigative Site	Hanau	Hessen	Germany	63450
930	Novartis Investigative Site	Kassel	Hessen	Germany	34117
931	Novartis Investigative Site	Kassel	Hessen	Germany	34125
932	Novartis Investigative Site	Limburg	Hessen	Germany	65549
933	Novartis Investigative Site	Marburg	Hessen	Germany	35043
934	Novartis Investigative Site	Offenbach	Hessen	Germany	63069
935	Novartis Investigative Site	Wiesbaden	Hessen	Germany	65189
936	Novartis Investigative Site	Wiesbaden	Hessen	Germany	65191
937	Novartis Investigative Site	Wiesbaden	Hessen	Germany	65199
938	Novartis Investigative Site	Greifswald	Mecklenburg-Vorpommern	Germany	17487
939	Novartis Investigative Site	Guestrow	Mecklenburg-Vorpommern	Germany	18273
940	Novartis Investigative Site	Rostock	Mecklenburg-Vorpommern	Germany	18059
941	Novartis Investigative Site	Schwerin	Mecklenburg-Vorpommern	Germany	19055
942	Novartis Investigative Site	Stralsund	Mecklenburg-Vorpommern	Germany	18435
943	Novartis Investigative Site	Aurich	Niedersachsen	Germany	26603
944	Novartis Investigative Site	Braunschweig	Niedersachsen	Germany	38100
945	Novartis Investigative Site	Celle	Niedersachsen	Germany	29223
946	Novartis Investigative Site	Cuxhaven	Niedersachsen	Germany	27474
947	Novartis Investigative Site	Georgsmarienhuette	Niedersachsen	Germany	49124
948	Novartis Investigative Site	Goettingen	Niedersachsen	Germany	37075
949	Novartis Investigative Site	Goslar	Niedersachsen	Germany	38642
950	Novartis Investigative Site	Hameln	Niedersachsen	Germany	31785
951	Novartis Investigative Site	Hannover	Niedersachsen	Germany	30177
952	Novartis Investigative Site	Hannover	Niedersachsen	Germany	30559
953	Novartis Investigative Site	Hannover	Niedersachsen	Germany	30625
954	Novartis Investigative Site	Leer	Niedersachsen	Germany	26789
955	Novartis Investigative Site	Oldenburg	Niedersachsen	Germany	26121
956	Novartis Investigative Site	Oldenburg	Niedersachsen	Germany	26133
957	Novartis Investigative Site	Osnabrueck	Niedersachsen	Germany	49074
958	Novartis Investigative Site	Rotenburg (Wuemme)	Niedersachsen	Germany	27356
959	Novartis Investigative Site	Stade	Niedersachsen	Germany	21680
960	Novartis Investigative Site	Stadthagen	Niedersachsen	Germany	31655
961	Novartis Investigative Site	Vechta	Niedersachsen	Germany	49377
962	Novartis Investigative Site	Westerstede	Niedersachsen	Germany	26655
963	Novartis Investigative Site	Bergisch Gladbach	Nordrhein-Westfalen	Germany	51465
964	Novartis Investigative Site	Bielefeld	Nordrhein-Westfalen	Germany	33604
965	Novartis Investigative Site	Bochum	Nordrhein-Westfalen	Germany	44787
966	Novartis Investigative Site	Bochum	Nordrhein-Westfalen	Germany	44791
967	Novartis Investigative Site	Bonn	Nordrhein-Westfalen	Germany	53113
968	Novartis Investigative Site	Bonn	Nordrhein-Westfalen	Germany	53127
969	Novartis Investigative Site	Bonn	Nordrhein-Westfalen	Germany	53129
970	Novartis Investigative Site	Duesseldorf	Nordrhein-Westfalen	Germany	40225
971	Novartis Investigative Site	Duesseldorf	Nordrhein-Westfalen	Germany	40325
972	Novartis Investigative Site	Duisburg	Nordrhein-Westfalen	Germany	47166
973	Novartis Investigative Site	Eschweiler	Nordrhein-Westfalen	Germany	52249
974	Novartis Investigative Site	Essen	Nordrhein-Westfalen	Germany	45122
975	Novartis Investigative Site	Essen	Nordrhein-Westfalen	Germany	45130
976	Novartis Investigative Site	Essen	Nordrhein-Westfalen	Germany	45131
977	Novartis Investigative Site	Essen	Nordrhein-Westfalen	Germany	45136
978	Novartis Investigative Site	Gummersbach	Nordrhein-Westfalen	Germany	51643
979	Novartis Investigative Site	Hamm-Heessen	Nordrhein-Westfalen	Germany	59073
980	Novartis Investigative Site	Herne	Nordrhein-Westfalen	Germany	44623
981	Novartis Investigative Site	Koeln	Nordrhein-Westfalen	Germany	50677
982	Novartis Investigative Site	Koeln	Nordrhein-Westfalen	Germany	50935
983	Novartis Investigative Site	Koeln	Nordrhein-Westfalen	Germany	50937
984	Novartis Investigative Site	Krefeld	Nordrhein-Westfalen	Germany	47805
985	Novartis Investigative Site	Leverkusen	Nordrhein-Westfalen	Germany	51375
986	Novartis Investigative Site	Minden	Nordrhein-Westfalen	Germany	32429
987	Novartis Investigative Site	Moenchengladbach	Nordrhein-Westfalen	Germany	41061
988	Novartis Investigative Site	Muelheim	Nordrhein-Westfalen	Germany	45473
989	Novartis Investigative Site	Muenster	Nordrhein-Westfalen	Germany	48149
990	Novartis Investigative Site	Muenster	Nordrhein-Westfalen	Germany	48153
991	Novartis Investigative Site	Olpe	Nordrhein-Westfalen	Germany	57462
992	Novartis Investigative Site	Porta Westfalica	Nordrhein-Westfalen	Germany	32457
993	Novartis Investigative Site	Solingen	Nordrhein-Westfalen	Germany	42697
994	Novartis Investigative Site	Troisdorf	Nordrhein-Westfalen	Germany	53840
995	Novartis Investigative Site	Velbert	Nordrhein-Westfalen	Germany	42551
996	Novartis Investigative Site	Wesel	Nordrhein-Westfalen	Germany	46485
997	Novartis Investigative Site	Witten	Nordrhein-Westfalen	Germany	58452
998	Novartis Investigative Site	Wuerselen	Nordrhein-Westfalen	Germany	52146
999	Novartis Investigative Site	Wuppertal	Nordrhein-Westfalen	Germany	42105
1000	Novartis Investigative Site	Wuppertal	Nordrhein-Westfalen	Germany	42109
1001	Novartis Investigative Site	Wuppertal	Nordrhein-Westfalen	Germany	42283
1002	Novartis Investigative Site	Ludwigshafen	Rheinland-Pfalz	Germany	67063
1003	Novartis Investigative Site	Mainz	Rheinland-Pfalz	Germany	55131
1004	Novartis Investigative Site	Trier	Rheinland-Pfalz	Germany	54290
1005	Novartis Investigative Site	Homburg/Saar	Saarland	Germany	66421
1006	Novartis Investigative Site	Landstuhl	Saarland	Germany	66849
1007	Novartis Investigative Site	Neunkirchen	Saarland	Germany	66539
1008	Novartis Investigative Site	Saarbruecken	Saarland	Germany	66113
1009	Novartis Investigative Site	Aschersleben	Sachsen-Anhalt	Germany	06449
1010	Novartis Investigative Site	Halle	Sachsen-Anhalt	Germany	06110
1011	Novartis Investigative Site	Halle	Sachsen-Anhalt	Germany	06120
1012	Novartis Investigative Site	Magdeburg	Sachsen-Anhalt	Germany	39108
1013	Novartis Investigative Site	Magdeburg	Sachsen-Anhalt	Germany	39130
1014	Novartis Investigative Site	Stendal	Sachsen-Anhalt	Germany	39576
1015	Novartis Investigative Site	Weissenfels	Sachsen-Anhalt	Germany	06667
1016	Novartis Investigative Site	Chemnitz	Sachsen	Germany	09116
1017	Novartis Investigative Site	Dresden	Sachsen	Germany	01127
1018	Novartis Investigative Site	Dresden	Sachsen	Germany	01307
1019	Novartis Investigative Site	Hoyerswerda	Sachsen	Germany	02977
1020	Novartis Investigative Site	Leipzig	Sachsen	Germany	04129
1021	Novartis Investigative Site	Leipzig	Sachsen	Germany	04277
1022	Novartis Investigative Site	Radebeul	Sachsen	Germany	01445
1023	Novartis Investigative Site	Rodewisch	Sachsen	Germany	08228
1024	Novartis Investigative Site	Schkeuditz	Sachsen	Germany	04435
1025	Novartis Investigative Site	Torgau	Sachsen	Germany	04860
1026	Novartis Investigative Site	Zittau	Sachsen	Germany	02763
1027	Novartis Investigative Site	Zwickau	Sachsen	Germany	08060
1028	Novartis Investigative Site	Bad Oldesloe	Schleswig-Holstein	Germany	23843
1029	Novartis Investigative Site	Flensburg	Schleswig-Holstein	Germany	24939
1030	Novartis Investigative Site	Geesthacht	Schleswig-Holstein	Germany	21502
1031	Novartis Investigative Site	Heide	Schleswig-Holstein	Germany	25746
1032	Novartis Investigative Site	Itzehoe	Schleswig-Holstein	Germany	25524
1033	Novartis Investigative Site	Kiel	Schleswig-Holstein	Germany	24103
1034	Novartis Investigative Site	Kiel	Schleswig-Holstein	Germany	24105
1035	Novartis Investigative Site	Luebeck	Schleswig-Holstein	Germany	23538
1036	Novartis Investigative Site	Neumuenster	Schleswig-Holstein	Germany	24534
1037	Novartis Investigative Site	Rendsburg	Schleswig-Holstein	Germany	24768
1038	Novartis Investigative Site	Erfurt	Thueringen	Germany	99085
1039	Novartis Investigative Site	Gera	Thueringen	Germany	07548
1040	Novartis Investigative Site	Jena	Thueringen	Germany	07743
1041	Novartis Investigative Site	Meiningen	Thueringen	Germany	98617
1042	Novartis Investigative Site	Muehlhausen	Thueringen	Germany	99974
1043	Novartis Investigative Site	Berlin		Germany	10117
1044	Novartis Investigative Site	Berlin		Germany	10317
1045	Novartis Investigative Site	Berlin		Germany	10365
1046	Novartis Investigative Site	Berlin		Germany	10367
1047	Novartis Investigative Site	Berlin		Germany	10713
1048	Novartis Investigative Site	Berlin		Germany	10967
1049	Novartis Investigative Site	Berlin		Germany	12559
1050	Novartis Investigative Site	Berlin		Germany	13125
1051	Novartis Investigative Site	Berlin		Germany	13589
1052	Novartis Investigative Site	Berlin		Germany	14169
1053	Novartis Investigative Site	Berlin		Germany	14197
1054	Novartis Investigative Site	Brandenburg		Germany	14770
1055	Novartis Investigative Site	Bremen		Germany	28209
1056	Novartis Investigative Site	Bremen		Germany	28239
1057	Novartis Investigative Site	Friedrichshafen		Germany	88048
1058	Novartis Investigative Site	Hamburg		Germany	20246
1059	Novartis Investigative Site	Hamburg		Germany	20259
1060	Novartis Investigative Site	Hamburg		Germany	20357
1061	Novartis Investigative Site	Hamburg		Germany	22081
1062	Novartis Investigative Site	Hamburg		Germany	22359
1063	Novartis Investigative Site	Hamburg		Germany	22457
1064	Novartis Investigative Site	Wuerzburg		Germany	97080
1065	Novartis Investigative Site	Athens		Greece	115 22
1066	Novartis Investigative Site	Athens		Greece	115 27
1067	Novartis Investigative Site	Athens		Greece	151 23
1068	Novartis Investigative Site	Athens		Greece	15123
1069	Novartis Investigative Site	Athens		Greece	18547
1070	Novartis Investigative Site	Heraklion,Crete		Greece	71110
1071	Novartis Investigative Site	Patra		Greece	26504
1072	Novartis Investigative Site	Thessaloniki		Greece	546 45
1073	Novartis Investigative Site	Kowloon		Hong Kong
1074	Novartis Investigative Site	Tuen Mun		Hong Kong
1075	Novartis Investigative Site	Budapest		Hungary	1032
1076	Novartis Investigative Site	Budapest		Hungary	1082
1077	Novartis Investigative Site	Budapest		Hungary	1145
1078	Novartis Investigative Site	Budapest		Hungary	H-1122
1079	Novartis Investigative Site	Gyor		Hungary	9023
1080	Novartis Investigative Site	Szeged		Hungary	6720
1081	Novartis Investigative Site	Szombathely		Hungary	9700
1082	Novartis Investigative Site	Gurgaon		India	122002
1083	Novartis Investigative Site	Hyderabad		India	500082
1084	Novartis Investigative Site	Kolkatta (w.b.)		India	700016
1085	Novartis Investigative Site	Mangalore		India	575001
1086	Novartis Investigative Site	Mumbai		India	400012
1087	Novartis Investigative Site	Nagpur		India	440010
1088	Novartis Investigative Site	New Delhi		India	110029
1089	Novartis Investigative Site	New Delhi		India	110076
1090	Novartis Investigative Site	Trivandrum		India	695011
1091	Novartis Investigative Site	Dublin		Ireland	7
1092	Novartis Investigative Site	Dublin		Ireland	8
1093	Novartis Investigative Site	Dublin		Ireland	9
1094	Novartis Investigative Site	Galway		Ireland
1095	Novartis Investigative Site	Limerick		Ireland
1096	Novartis Investigative Site	Sligo		Ireland
1097	Novartis Investigative Site	Tallaght, Dublin		Ireland	24
1098	Novartis Investigative Site	Wilton, Cork		Ireland
1099	Novartis Investigative Site	Beer-Sheva		Israel	84101
1100	Novartis Investigative Site	Haifa		Israel	31096
1101	Novartis Investigative Site	Holon		Israel	58100
1102	Novartis Investigative Site	Jerusalem		Israel	91031
1103	Novartis Investigative Site	Kfar Saba		Israel	44281
1104	Novartis Investigative Site	Netanya		Israel	52621
1105	Novartis Investigative Site	Ramat Gan		Israel	52621
1106	Novartis Investigative Site	Rehovot		Israel	76100
1107	Novartis Investigative Site	Tel Aviv		Israel	64239
1108	Novartis Investigative Site	Potenza	Basilicata	Italy	85100
1109	Novartis Investigative Site	Avellino	Campania	Italy	83100
1110	Novartis Investigative Site	Carpi (MO)	Emilia-Romagna	Italy	41012
1111	Novartis Investigative Site	Lugo (Ravenna)	Emilia-Romagna	Italy	48022
1112	Novartis Investigative Site	Meldola (FC)	Emilia-Romagna	Italy	47014
1113	Novartis Investigative Site	Ravenna	Emilia-Romagna	Italy	48100
1114	Novartis Investigative Site	Rimini	Emilia-Romagna	Italy	47900
1115	Novartis Investigative Site	Aviano (PN)	Friuli-Venezia-Giulia	Italy	33081
1116	Novartis Investigative Site	Udine	Friuli-Venezia-Giulia	Italy	33100
1117	Novartis Investigative Site	Roma	Lazio	Italy	00135
1118	Novartis Investigative Site	Roma	Lazio	Italy	00144
1119	Novartis Investigative Site	Roma	Lazio	Italy	00168
1120	Novartis Investigative Site	Viterbo	Lazio	Italy	01100
1121	Novartis Investigative Site	Genova	Liguria	Italy	16132
1122	Novartis Investigative Site	Alzano Lombardo (BG)	Lombardia	Italy	24022
1123	Novartis Investigative Site	Bergamo	Lombardia	Italy	24127
1124	Novartis Investigative Site	Brescia	Lombardia	Italy	25123
1125	Novartis Investigative Site	Brescia	Lombardia	Italy	25124
1126	Novartis Investigative Site	Cremona	Lombardia	Italy	26100
1127	Novartis Investigative Site	Lecco	Lombardia	Italy	23900
1128	Novartis Investigative Site	Mantova	Lombardia	Italy	46100
1129	Novartis Investigative Site	Milano	Lombardia	Italy	20141
1130	Novartis Investigative Site	Milano	Lombardia	Italy	20142
1131	Novartis Investigative Site	Milano	Lombardia	Italy	20162
1132	Novartis Investigative Site	Monza	Lombardia	Italy	20052
1133	Novartis Investigative Site	Pavia	Lombardia	Italy	27100
1134	Novartis Investigative Site	Rozzano (MI)	Lombardia	Italy	20089
1135	Novartis Investigative Site	San Fermo Della Battaglia (Co)	Lombardia	Italy	22020
1136	Novartis Investigative Site	Saronno (VA)	Lombardia	Italy	21047
1137	Novartis Investigative Site	Treviglio (BG)	Lombardia	Italy	24047
1138	Novartis Investigative Site	Varese	Lombardia	Italy	21100
1139	Novartis Investigative Site	Fano (Pesaro Urbino)	Marche	Italy	61032
1140	Novartis Investigative Site	Fermo (AP)	Marche	Italy	63023
1141	Novartis Investigative Site	Asti	Piemonte	Italy	14100
1142	Novartis Investigative Site	Biella	Piemonte	Italy	13900
1143	Novartis Investigative Site	Candiolo (TO)	Piemonte	Italy	10060
1144	Novartis Investigative Site	Brindisi	Puglia	Italy	72100
1145	Novartis Investigative Site	Lecce	Puglia	Italy	73100
1146	Novartis Investigative Site	Monserrato (CA)	Sardegna	Italy	09042
1147	Novartis Investigative Site	Sassari	Sardegna	Italy	07100
1148	Novartis Investigative Site	Palermo	Sicilia	Italy	90127
1149	Novartis Investigative Site	Palermo	Sicilia	Italy	90146
1150	Novartis Investigative Site	Ragusa	Sicilia	Italy	97100
1151	Novartis Investigative Site	Firenze	Toscana	Italy	50134
1152	Novartis Investigative Site	Firenze	Toscana	Italy	50139
1153	Novartis Investigative Site	Lido Di Camaiore (LU)	Toscana	Italy	55043
1154	Novartis Investigative Site	Livorno	Toscana	Italy	57123
1155	Novartis Investigative Site	Montepulciano (Siena	Toscana	Italy	53045
1156	Novartis Investigative Site	Pisa	Toscana	Italy	56126
1157	Novartis Investigative Site	Poggibonsi (Siena)	Toscana	Italy	53036
1158	Novartis Investigative Site	Prato	Toscana	Italy	59100
1159	Novartis Investigative Site	Trento	Trentino-Alto Adige	Italy	38122
1160	Novartis Investigative Site	Chieti		Italy	66100
1161	Novartis Investigative Site	Cosenza		Italy	87100
1162	Novartis Investigative Site	Aichi		Japan	464-8681
1163	Novartis Investigative Site	Chiba		Japan	277-8577
1164	Novartis Investigative Site	Ehime		Japan	791-0280
1165	Novartis Investigative Site	Fukuoka		Japan	811-1395
1166	Novartis Investigative Site	Ibaraki		Japan	305-8576
1167	Novartis Investigative Site	Kanagawa		Japan	259-1143
1168	Novartis Investigative Site	Kyoto		Japan	606-8507
1169	Novartis Investigative Site	Osaka		Japan	530-8480
1170	Novartis Investigative Site	Osaka		Japan	540-0006
1171	Novartis Investigative Site	Saitama		Japan	350-1298
1172	Novartis Investigative Site	Tokyo		Japan	101-8643
1173	Novartis Investigative Site	Tokyo		Japan	104-0045
1174	Novartis Investigative Site	Tokyo		Japan	104-8560
1175	Novartis Investigative Site	Tokyo		Japan	113-8677
1176	Novartis Investigative Site	Tokyo		Japan	135-8550
1177	Novartis Investigative Site	Gyeonggi-do		Korea, Republic of	10408
1178	Novartis Investigative Site	Incheon		Korea, Republic of	400-711
1179	Novartis Investigative Site	Seoul		Korea, Republic of	003722
1180	Novartis Investigative Site	Seoul		Korea, Republic of	03080
1181	Novartis Investigative Site	Seoul		Korea, Republic of	06351
1182	Novartis Investigative Site	Seoul		Korea, Republic of	138-736
1183	Novartis Investigative Site	Suwon-si, Gyeonggi-do		Korea, Republic of	443-380
1184	Novartis Investigative Site	Kubang Kerian		Malaysia	16150
1185	Novartis Investigative Site	Sarawak		Malaysia	93586
1186	Novartis Investigative Site	Toluca	Estado De México	Mexico	50080
1187	Novartis Investigative Site	Merida	Yucatán	Mexico	97500
1188	Novartis Investigative Site	Chihuahua		Mexico	31000
1189	Novartis Investigative Site	Mexico City		Mexico	CP 14080
1190	Novartis Investigative Site	Mexico D.F.		Mexico	11000
1191	Novartis Investigative Site	Mexico DF		Mexico	01120
1192	Novartis Investigative Site	Amersfoort		Netherlands	3818 ES
1193	Novartis Investigative Site	Amsterdam		Netherlands	1066 CX
1194	Novartis Investigative Site	Amsterdam		Netherlands	1081 HV
1195	Novartis Investigative Site	Arnhem		Netherlands	6815 AD
1196	Novartis Investigative Site	Blaricum		Netherlands	1261 AN
1197	Novartis Investigative Site	Delft		Netherlands	2625 AD
1198	Novartis Investigative Site	Den Haag		Netherlands	2512 VA
1199	Novartis Investigative Site	Den Haag		Netherlands	2545CH
1200	Novartis Investigative Site	Eindhoven		Netherlands	5623 EJ
1201	Novartis Investigative Site	Gouda		Netherlands	2803 HH
1202	Novartis Investigative Site	Hoofddorp		Netherlands	2130 AT
1203	Novartis Investigative Site	Leeuwarden		Netherlands	8934 AD
1204	Novartis Investigative Site	Leiden		Netherlands	2333 ZA
1205	Novartis Investigative Site	Leidschendam		Netherlands	2262 BA
1206	Novartis Investigative Site	Purmerend		Netherlands	1441 RN
1207	Novartis Investigative Site	Rotterdam		Netherlands	3075 EA
1208	Novartis Investigative Site	Rotterdam		Netherlands	3083 AN
1209	Novartis Investigative Site	Sittard-geleen		Netherlands	6162 BG
1210	Novartis Investigative Site	Tilburg		Netherlands	5022 GC
1211	Novartis Investigative Site	Utrecht		Netherlands	3582 KE
1212	Novartis Investigative Site	Hamilton		New Zealand	2001
1213	Novartis Investigative Site	Palmerston North		New Zealand	4414
1214	Novartis Investigative Site	Wellington		New Zealand	6021
1215	Novartis Investigative Site	Forde		Norway	6807
1216	Novartis Investigative Site	Oslo		Norway	0310
1217	Novartis Investigative Site	Oslo		Norway	0407
1218	Novartis Investigative Site	Tromso		Norway	9038
1219	Novartis Investigative Site	Karachi		Pakistan	74800
1220	Novartis Investigative Site	Karachi		Pakistan
1221	Novartis Investigative Site	Lahore		Pakistan	53400
1222	Novartis Investigative Site	Lahore		Pakistan	54600
1223	Novartis Investigative Site	Rawalpindi		Pakistan	1590
1224	Novartis Investigative Site	Callao		Peru	Callao 2
1225	Novartis Investigative Site	Lima		Peru	Lima 11
1226	Novartis Investigative Site	Lima		Peru	Lima 13
1227	Novartis Investigative Site	Lima		Peru	Lima 34
1228	Novartis Investigative Site	Cebu		Philippines	6000
1229	Novartis Investigative Site	Quezon City		Philippines	1102
1230	Novartis Investigative Site	Sampaloc Manila		Philippines	1008
1231	Novartis Investigative Site	San Juan		Philippines	1502
1232	Novartis Investigative Site	Bydgoszcz		Poland	85-796
1233	Novartis Investigative Site	Elblag		Poland	82-300
1234	Novartis Investigative Site	Gdansk		Poland	80-210
1235	Novartis Investigative Site	Gdansk		Poland	80-211
1236	Novartis Investigative Site	Gliwice		Poland	44-101
1237	Novartis Investigative Site	Krakow		Poland	31-108
1238	Novartis Investigative Site	Krakow		Poland	31-115
1239	Novartis Investigative Site	Olsztyn		Poland	10-226
1240	Novartis Investigative Site	Olsztyn		Poland	10-228
1241	Novartis Investigative Site	Opole		Poland	45-060
1242	Novartis Investigative Site	Rzeszow		Poland	35-021
1243	Novartis Investigative Site	Szczecin		Poland	71-730
1244	Novartis Investigative Site	Warszawa		Poland	02-781
1245	Novartis Investigative Site	Wroclaw		Poland	53-413
1246	Novartis Investigative Site	Bucharest		Romania	022328
1247	Novartis Investigative Site	Bucharest		Romania	050098
1248	Novartis Investigative Site	Bucuresti		Romania	022328
1249	Novartis Investigative Site	Cluj-Napoca		Romania	400015
1250	Novartis Investigative Site	Iasi		Romania	700106
1251	Novartis Investigative Site	Arkhangelsk		Russian Federation	163045
1252	Novartis Investigative Site	Chelyabinsk		Russian Federation	454087
1253	Novartis Investigative Site	Irkutsk		Russian Federation	664035
1254	Novartis Investigative Site	Kazan		Russian Federation	420029
1255	Novartis Investigative Site	Kirov		Russian Federation	610021
1256	Novartis Investigative Site	Moscow		Russian Federation	115 478
1257	Novartis Investigative Site	Moscow		Russian Federation	115478
1258	Novartis Investigative Site	Moscow		Russian Federation	121359
1259	Novartis Investigative Site	Moscow		Russian Federation	129 128
1260	Novartis Investigative Site	Novosibirsk		Russian Federation	630047
1261	Novartis Investigative Site	Omsk		Russian Federation	644013
1262	Novartis Investigative Site	Orenburg		Russian Federation	460021
1263	Novartis Investigative Site	Ryazan		Russian Federation	390011
1264	Novartis Investigative Site	Samara		Russian Federation	443031
1265	Novartis Investigative Site	St. Petersburg		Russian Federation	197022
1266	Novartis Investigative Site	St. Petersburg		Russian Federation	197758
1267	Novartis Investigative Site	Voronezh		Russian Federation	394062
1268	Novartis Investigative Site	Singapore		Singapore	119074
1269	Novartis Investigative Site	Singapore		Singapore	119082
1270	Novartis Investigative Site	Bratislava		Slovakia	812 50
1271	Novartis Investigative Site	Bratislava		Slovakia	833 10
1272	Novartis Investigative Site	Kosice		Slovakia	041 91
1273	Novartis Investigative Site	Poprad		Slovakia	058 01
1274	Novartis Investigative Site	Rimavska Sobota		Slovakia	979 01
1275	Novartis Investigative Site	Zilina		Slovakia	010 01
1276	Novartis Investigative Site	Ljubljana		Slovenia	1000
1277	Novartis Investigative Site	Capital Park		South Africa	0002
1278	Novartis Investigative Site	Groenkloof, Pretoria, 0001		South Africa	0081
1279	Novartis Investigative Site	Johannesburg		South Africa	2199
1280	Novartis Investigative Site	Observatory		South Africa	7925
1281	Novartis Investigative Site	Panorama		South Africa	7500
1282	Novartis Investigative Site	Parktown		South Africa	2193
1283	Novartis Investigative Site	Pretoria		South Africa	0041
1284	Novartis Investigative Site	Pretoria		South Africa	0081
1285	Novartis Investigative Site	Saxonwold, Johannesburg		South Africa	2196
1286	Novartis Investigative Site	Alcoy/Alicante		Spain	03804
1287	Novartis Investigative Site	Barakaldo (Vizcaya)		Spain	48903
1288	Novartis Investigative Site	Barcelona		Spain	08035
1289	Novartis Investigative Site	Burgos		Spain	09006
1290	Novartis Investigative Site	Cadiz		Spain	11009
1291	Novartis Investigative Site	Castellon		Spain	12002
1292	Novartis Investigative Site	Cordoba		Spain	14004
1293	Novartis Investigative Site	Coria		Spain	10800
1294	Novartis Investigative Site	Elda		Spain	03600
1295	Novartis Investigative Site	Granada		Spain	18014
1296	Novartis Investigative Site	Hospitalet de Llobregat (Barcelona)		Spain	08907
1297	Novartis Investigative Site	Huesca		Spain	22300
1298	Novartis Investigative Site	La Laguna (Santa Cruz De Tenerife)		Spain	38320
1299	Novartis Investigative Site	Lerida		Spain	25198
1300	Novartis Investigative Site	Lugo		Spain	27003
1301	Novartis Investigative Site	Madrid		Spain	28006
1302	Novartis Investigative Site	Madrid		Spain	28007
1303	Novartis Investigative Site	Madrid		Spain	28033
1304	Novartis Investigative Site	Madrid		Spain	28034
1305	Novartis Investigative Site	Madrid		Spain	28041
1306	Novartis Investigative Site	Madrid		Spain	28046
1307	Novartis Investigative Site	Malaga		Spain	29010
1308	Novartis Investigative Site	Mataro		Spain	08034
1309	Novartis Investigative Site	Mostoles (Madrid)		Spain	28460
1310	Novartis Investigative Site	Murcia		Spain	30008
1311	Novartis Investigative Site	Murcia		Spain	30120
1312	Novartis Investigative Site	Palma de Mallorca		Spain	07010
1313	Novartis Investigative Site	Palma de Mallorca		Spain	07198
1314	Novartis Investigative Site	Pamplona		Spain	31008
1315	Novartis Investigative Site	Salamanca		Spain	37007
1316	Novartis Investigative Site	San Sebastian		Spain	20014
1317	Novartis Investigative Site	Santander		Spain	39008
1318	Novartis Investigative Site	Santiago		Spain	15705
1319	Novartis Investigative Site	Segovia		Spain	40002
1320	Novartis Investigative Site	Sevilla		Spain	41009
1321	Novartis Investigative Site	Sevilla		Spain	41014
1322	Novartis Investigative Site	Tarrasa, Barcelona		Spain	08221
1323	Novartis Investigative Site	Toledo		Spain	45004
1324	Novartis Investigative Site	Valencia		Spain	46014
1325	Novartis Investigative Site	Valencia		Spain	46017
1326	Novartis Investigative Site	Zamora		Spain
1327	Novartis Investigative Site	Zaragoza		Spain	50009
1328	Novartis Investigative Site	Aarau		Switzerland	5001
1329	Novartis Investigative Site	Basel		Switzerland	4031
1330	Novartis Investigative Site	Bellinzona		Switzerland	6500
1331	Novartis Investigative Site	Bern		Switzerland	3010
1332	Novartis Investigative Site	Chur		Switzerland	7000
1333	Novartis Investigative Site	Lausanne		Switzerland	1005
1334	Novartis Investigative Site	Locarno		Switzerland	6600
1335	Novartis Investigative Site	St Gallen		Switzerland	9007
1336	Novartis Investigative Site	Thun		Switzerland	3600
1337	Novartis Investigative Site	Zuerich		Switzerland	8091
1338	Novartis Investigative Site	Zurich		Switzerland	8008
1339	Novartis Investigative Site	Kaohsiung		Taiwan	807
1340	Novartis Investigative Site	Taichung		Taiwan	404
1341	Novartis Investigative Site	Tainan County		Taiwan	736
1342	Novartis Investigative Site	Taipei		Taiwan	100
1343	Novartis Investigative Site	Taipei		Taiwan	104
1344	Novartis Investigative Site	Taipei		Taiwan	105
1345	Novartis Investigative Site	Taipei		Taiwan	112
1346	Novartis Investigative Site	Taipei		Taiwan	114
1347	Novartis Investigative Site	Bangkok		Thailand	10330
1348	Novartis Investigative Site	Bangkok		Thailand	10400
1349	Novartis Investigative Site	Bangkok		Thailand	10700
1350	Novartis Investigative Site	Chiangmai		Thailand	50200
1351	Novartis Investigative Site	Hatyai, Songkhla		Thailand	90110
1352	Novartis Investigative Site	Khon Kaen		Thailand	40002
1353	Novartis Investigative Site	Phitsanulok		Thailand	65000
1354	Novartis Investigative Site	Chernivtsi		Ukraine	58013
1355	Novartis Investigative Site	Donetsk		Ukraine	83092
1356	Novartis Investigative Site	Ivano-Frankivsk		Ukraine	76018
1357	Novartis Investigative Site	Kharkiv		Ukraine	61024
1358	Novartis Investigative Site	Kyiv		Ukraine	03115
1359	Novartis Investigative Site	Lviv		Ukraine	79031
1360	Novartis Investigative Site	Simferopol		Ukraine	95023
1361	Novartis Investigative Site	Uzhgorod		Ukraine	88014
1362	Novartis Investigative Site	Uzhorod		Ukraine	88000
1363	Novartis Investigative Site	Chelmsford	Essex	United Kingdom	CM1 7ET
1364	Novartis Investigative Site	Epping	Essex	United Kingdom	CM16 6TN
1365	Novartis Investigative Site	Prittlewell Chase	Essex	United Kingdom	SS0 0RY
1366	Novartis Investigative Site	Nottingham	Gloucestershire	United Kingdom	NG5 1PB
1367	Novartis Investigative Site	Canterbury	Kent	United Kingdom	CT1 3NG
1368	Novartis Investigative Site	Manchester	Lancashire	United Kingdom	M20 4BX
1369	Novartis Investigative Site	Preston	Lancashire	United Kingdom	PR2 9HT
1370	Novartis Investigative Site	Northwood	Middlesex	United Kingdom	HA6 2RN
1371	Novartis Investigative Site	Edinburgh	Midlothian	United Kingdom	EH4 2XU
1372	Novartis Investigative Site	Headington, Oxford	Oxfordshire	United Kingdom	OX3 7LJ
1373	Novartis Investigative Site	Ashford		United Kingdom	TN24 0LZ
1374	Novartis Investigative Site	Blackpool		United Kingdom	FY3 8NR
1375	Novartis Investigative Site	Bournemouth		United Kingdom	BH7 7DW
1376	Novartis Investigative Site	Brighton		United Kingdom	BN2 5BE
1377	Novartis Investigative Site	Cheltenham		United Kingdom	GL53 7AN
1378	Novartis Investigative Site	Cottingham		United Kingdom	HU16 5JQ
1379	Novartis Investigative Site	Dorchester		United Kingdom	DT1 2JY
1380	Novartis Investigative Site	Exeter		United Kingdom	EX2 5DW
1381	Novartis Investigative Site	Grimsby		United Kingdom	DN33 2BA
1382	Novartis Investigative Site	Guildford		United Kingdom	GU2 7XX
1383	Novartis Investigative Site	Gwynedd		United Kingdom	LL57 2PW
1384	Novartis Investigative Site	Ipswich		United Kingdom	IP4 5PD
1385	Novartis Investigative Site	Lancaster		United Kingdom	LA1 4RP
1386	Novartis Investigative Site	Leeds		United Kingdom	LS9 7TF
1387	Novartis Investigative Site	Lindley, Huddersfield		United Kingdom	HD3 3EA
1388	Novartis Investigative Site	Liverpool		United Kingdom	L7 8XP
1389	Novartis Investigative Site	London		United Kingdom	EC1A 7BE
1390	Novartis Investigative Site	London		United Kingdom	NW1 2PG
1391	Novartis Investigative Site	London		United Kingdom	NW3 2QG
1392	Novartis Investigative Site	London		United Kingdom	SE1 9RT
1393	Novartis Investigative Site	London		United Kingdom	SW17 0QT
1394	Novartis Investigative Site	London		United Kingdom	W2 1NY
1395	Novartis Investigative Site	London		United Kingdom	W6 8RF
1396	Novartis Investigative Site	Maidstone		United Kingdom	ME16 9QQ
1397	Novartis Investigative Site	Margate		United Kingdom	CT9 4AN
1398	Novartis Investigative Site	Newcastle upon Tyne		United Kingdom	NE7 7DN
1399	Novartis Investigative Site	Nottingham		United Kingdom	NG5 1PB
1400	Novartis Investigative Site	Plymouth		United Kingdom	PL6 8DH
1401	Novartis Investigative Site	Poole, Dorset		United Kingdom	BH15 2JB
1402	Novartis Investigative Site	Portsmouth		United Kingdom	PO6 3LY
1403	Novartis Investigative Site	Romford		United Kingdom	RM7 0AG
1404	Novartis Investigative Site	Sheffield		United Kingdom	S10 2SJ
1405	Novartis Investigative Site	Shrewsbury		United Kingdom	SY3 8XQ
1406	Novartis Investigative Site	Southport		United Kingdom	PR8 6PN
1407	Novartis Investigative Site	St Helens		United Kingdom	WA9 3DA
1408	Novartis Investigative Site	Stoke on Trent		United Kingdom	ST4 6QG
1409	Novartis Investigative Site	Sutton		United Kingdom	SM2 5PT
1410	Novartis Investigative Site	Swansea		United Kingdom	SA2 8QA
1411	Novartis Investigative Site	Whitchurch, Cardiff		United Kingdom	CF14 2TL
1412	Novartis Investigative Site	Worthing		United Kingdom	BN11 2DH

Sponsors and Collaborators

Novartis Pharmaceuticals
North Central Cancer Treatment Group
National Cancer Institute (NCI)
Breast International Group
Canadian Cancer Trials Group

Investigators

Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Novartis Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT00490139

Other Study ID Numbers:

EGF106708
CLAP016B2301
2006-000562-36
NCT00609024

First Posted:

Jun 22, 2007

Last Update Posted:

Jul 23, 2021

Last Verified:

Jul 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Novartis Pharmaceuticals

Adjuvant

ErbB2-overexpressing

Early stage breast cancer

HER2/neu gene amplified

Additional relevant MeSH terms:

Breast Neoplasms

Trastuzumab

Lapatinib

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	Treatments administered differed per timing/type of adjuvant chemotherapy. Design (D) 1: (neo) adjuvant anthracycline-based chemotherapy (AABC) prior to targeted therapy (TT); Design 2: TT concurrently with paclitaxel or docetaxel, after completion of a (neo) AABC; Design 2B: TT concurrently with chemotherapy with docetaxel and carboplatin.

Arm/Group Title	Lapatinib plusTrastuzumab	Trastuzumab Followed by Lapatinib	Lapatinib	Trastuzumab
Arm/Group Description	Participants (par.) received treatment per one of three designs. D1: oral lapatinib (OL) 1000 milligrams (mg) daily with trastuzumab (tras) (8 milligrams per kilogram [mg/kg] intravenous [IV] loading dose [LD], followed by 6 mg/kg IV every 3 weeks [E3W]) for 52 weeks (wks). D2: OL 750 mg daily plus wkly tras (4 mg/kg LD, followed by 2 mg/kg IV) concomitantly (conc.) with wkly paclitaxel (pac) 80 mg per squared meter (mg/m^2) IV or docetaxel (doc) 75 mg/m^2 IV E3W for 12 wks. After completion of pac or doc, par. received OL at an increased dose of 1000 mg daily in combination with tras (6 mg/kg without a LD) E3W for 40 wks. D2B: OL 750 mg plus wkly tras (4 mg/kg IV LD, followed by 2 mg/kg IV wkly) conc. with doc 75 mg/m^2 E3W and carboplatin (carb) AUC6 IV for 18 wks. After completion of doc and carb, par. received tras E3W (6 mg/kg without a LD) plus OL 1000 mg daily for 34 wks. Par. also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: weekly tras for 12 weeks (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly), followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks for 12 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2B: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV for 18 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 28 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: oral lap 1500 mg daily for 52 weeks. Design 2: oral lap 750 mg daily concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received oral lap at an increased dose of 1500 mg daily for 40 weeks. Design 2B: oral lap 750 mg daily concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, oral lap was given at an increased dose of 1500 mg for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: tras 8 mg/kg IV LD, followed by 6 mg/kg IV every 3 weeks for 52 weeks. Design 2: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received tras (6 mg/kg without a LD every 3 weeks for 40 weeks. Design 2B: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, participants received tras every 3 weeks (6 mg/kg without a LD) for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.
Period Title: Overall Study
STARTED	2093	2091	2100	2097
COMPLETED	1785	1816	1666	1790
NOT COMPLETED	308	275	434	307

Baseline Characteristics

Arm/Group Title	Lapatinib plusTrastuzumab	Trastuzumab Followed by Lapatinib	Lapatinib	Trastuzumab	Total
Arm/Group Description	Participants (par.) received treatment per one of three designs. D1: oral lapatinib (OL) 1000 milligrams (mg) daily with trastuzumab (tras) (8 milligrams per kilogram [mg/kg] intravenous [IV] loading dose [LD], followed by 6 mg/kg IV every 3 weeks [E3W]) for 52 weeks (wks). D2: OL 750 mg daily plus wkly tras (4 mg/kg LD, followed by 2 mg/kg IV) concomitantly (conc.) with wkly paclitaxel (pac) 80 mg per squared meter (mg/m^2) IV or docetaxel (doc) 75 mg/m^2 IV E3W for 12 wks. After completion of pac or doc, par. received OL at an increased dose of 1000 mg daily in combination with tras (6 mg/kg without a LD) E3W for 40 wks. D2B: OL 750 mg plus wkly tras (4 mg/kg IV LD, followed by 2 mg/kg IV wkly) conc. with doc 75 mg/m^2 E3W and carboplatin (carb) AUC6 IV for 18 wks. After completion of doc and carb, par. received tras E3W (6 mg/kg without a LD) plus OL 1000 mg daily for 34 wks. Par. also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: weekly tras for 12 weeks (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly), followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks for 12 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2B: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV for 18 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 28 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: oral lap 1500 mg daily for 52 weeks. Design 2: oral lap 750 mg daily concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received oral lap at an increased dose of 1500 mg daily for 40 weeks. Design 2B: oral lap 750 mg daily concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, oral lap was given at an increased dose of 1500 mg for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: tras 8 mg/kg IV LD, followed by 6 mg/kg IV every 3 weeks for 52 weeks. Design 2: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received tras (6 mg/kg without a LD every 3 weeks for 40 weeks. Design 2B: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, participants received tras every 3 weeks (6 mg/kg without a LD) for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Total of all reporting groups
Overall Participants	2093	2091	2100	2097	8381
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.9 (10.23)	50.8 (10.32)	51.2 (10.18)	51.0 (10.25)	51.0 (10.24)
Sex: Female, Male (Count of Participants)
Female	2091 99.9%	2086 99.8%	2098 99.9%	2097 100%	8372 99.9%
Male	2 0.1%	5 0.2%	2 0.1%	0 0%	9 0.1%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	48 2.3%	45 2.2%	47 2.2%	47 2.2%	187 2.2%
Asian: Central/South	107 5.1%	103 4.9%	110 5.2%	109 5.2%	429 5.1%
Asian: East	311 14.9%	312 14.9%	299 14.2%	314 15%	1236 14.7%
Asian: Japanese	33 1.6%	36 1.7%	33 1.6%	43 2.1%	145 1.7%
Asian: South East	95 4.5%	92 4.4%	107 5.1%	89 4.2%	383 4.6%
Black or African American	38 1.8%	30 1.4%	43 2%	25 1.2%	136 1.6%
Native Hawaiian (NH) or Other Pacific	2 0.1%	4 0.2%	4 0.2%	5 0.2%	15 0.2%
White: Arabic	53 2.5%	52 2.5%	62 3%	69 3.3%	236 2.8%
White: Caucasian	1392 66.5%	1402 67%	1372 65.3%	1382 65.9%	5548 66.2%
Mixed Race/Ancestry	5 0.2%	7 0.3%	10 0.5%	3 0.1%	25 0.3%
Hispanic	2 0.1%	1 0%	1 0%	3 0.1%	7 0.1%
Mestizo	1 0%	1 0%	3 0.1%	0 0%	5 0.1%
Mauritius Islander	0 0%	0 0%	0 0%	1 0%	1 0%
Coloured	1 0%	0 0%	1 0%	0 0%	2 0%
NH and White (Arabic/North African Heritage [HER])	0 0%	0 0%	1 0%	0 0%	1 0%
European Heritage and South American	1 0%	0 0%	0 0%	0 0%	1 0%
South American, African HER and European HER	0 0%	1 0%	0 0%	0 0%	1 0%
Afrikaans-South Africa	1 0%	0 0%	0 0%	0 0%	1 0%
White South African	0 0%	0 0%	0 0%	1 0%	1 0%
White South American	1 0%	0 0%	2 0.1%	0 0%	3 0%
Southeast and Northeast of South America	0 0%	0 0%	1 0%	0 0%	1 0%
Mulatto	0 0%	1 0%	0 0%	0 0%	1 0%
South American Latin American and European HER	0 0%	1 0%	0 0%	0 0%	1 0%
Black from South America	1 0%	0 0%	0 0%	0 0%	1 0%
Northeast of South America and European HER	0 0%	0 0%	1 0%	0 0%	1 0%
Asian (East), NH or Other Pacific Islander	0 0%	0 0%	0 0%	1 0%	1 0%
Peruvian	0 0%	0 0%	0 0%	1 0%	1 0%
Mexican	0 0%	0 0%	0 0%	1 0%	1 0%
American Indian or Alaska Native and White	0 0%	0 0%	1 0%	0 0%	1 0%
Caucasian and Guamanian (Chamorro)	0 0%	0 0%	1 0%	0 0%	1 0%
Unknown/Missing	1 0%	3 0.1%	1 0%	3 0.1%	8 0.1%

Outcome Measures

1. Primary Outcome

Title	Disease-free Survival (DFS)
Description	Disease-free survival is defined as the interval between randomization and the date of the first occurence of disease recurrence (local, regional or distant), a contralateral invasive breast cancer, a second primary cancer (SPC), or death from any cause. DFS was estimated using the Kaplan Meier method.The percentile data values presented here indicate the percentage (95, 90, 85, 80 and 75 percent) of participants who had disease free survival for the indicated years.
Time Frame	From randomization until the date of the first occurrence of disease recurrence, a contralateral invasive breast cancer, a second primary cancer, or death from any cause (median follow-up of 4.5 years)

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized par., except for those who withdrew their consent to use any of their data prior to receiving any study medication. Par. with no recurrence of the initial disease or SPC, or who did not die, were lost to follow-up, or were withdrawn from the study were censored at the date of last clinical contact.

Arm/Group Title	Lapatinib plusTrastuzumab	Trastuzumab Followed by Lapatinib	Lapatinib	Trastuzumab
Arm/Group Description	Participants (par.) received treatment per one of three designs. D1: oral lapatinib (OL) 1000 milligrams (mg) daily with trastuzumab (tras) (8 milligrams per kilogram [mg/kg] intravenous [IV] loading dose [LD], followed by 6 mg/kg IV every 3 weeks [E3W]) for 52 weeks (wks). D2: OL 750 mg daily plus wkly tras (4 mg/kg LD, followed by 2 mg/kg IV) concomitantly (conc.) with wkly paclitaxel (pac) 80 mg per squared meter (mg/m^2) IV or docetaxel (doc) 75 mg/m^2 IV E3W for 12 wks. After completion of pac or doc, par. received OL at an increased dose of 1000 mg daily in combination with tras (6 mg/kg without a LD) E3W for 40 wks. D2B: OL 750 mg plus wkly tras (4 mg/kg IV LD, followed by 2 mg/kg IV wkly) conc. with doc 75 mg/m^2 E3W and carboplatin (carb) AUC6 IV for 18 wks. After completion of doc and carb, par. received tras E3W (6 mg/kg without a LD) plus OL 1000 mg daily for 34 wks. Par. also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: weekly tras for 12 weeks (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly), followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks for 12 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2B: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV for 18 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 28 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: oral lap 1500 mg daily for 52 weeks. Design 2: oral lap 750 mg daily concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received oral lap at an increased dose of 1500 mg daily for 40 weeks. Design 2B: oral lap 750 mg daily concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, oral lap was given at an increased dose of 1500 mg for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: tras 8 mg/kg IV LD, followed by 6 mg/kg IV every 3 weeks for 52 weeks. Design 2: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received tras (6 mg/kg without a LD every 3 weeks for 40 weeks. Design 2B: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, participants received tras every 3 weeks (6 mg/kg without a LD) for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.
Measure Participants	2093	2091	2100	2097
95th Percentile	1.9	1.3	1.0	1.5
90th Percentile	3.2	2.8	1.8	2.6
85th Percentile	5.1	4.8	2.8	4.2
80th Percentile	6.1	NA	4.9	5.6
75th Percentile	6.1	NA	5.5	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lapatinib plusTrastuzumab, Trastuzumab
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.048
	Comments
	Method	Stratified log-rank test
	Comments	Stratification was by chemotherapy timing, hormone receptor status, and axillary lymph node status.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	() 97.5% 0.70 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimate of the treatment hazard ratio (lap plus tras versus tras) is based on the Cox's proportional hazards model adjusting for the stratification factors of chemotherapy timing, hormone receptor status, and auxillary lymph node status.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Trastuzumab Followed by Lapatinib, Trastuzumab
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.610
	Comments
	Method	Stratified log-rank test
	Comments	Stratification is by chemotherapy timing, hormone receptor status, and axillary lymph node status.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.96
	Confidence Interval	() 97.5% 0.80 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimate of the treatment hazard ratio (tras followed by lap versus tras) is based on the Cox's proportional hazards model adjusting for the stratification factors of chemotherapy timing, hormone receptor status, and auxillary lymph node status.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lapatinib, Trastuzumab
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	<0.0005
	Comments
	Method	Stratified log-rank test
	Comments	Stratification is by chemotherapy timing, hormone receptor status, and axillary lymph node status.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.34
	Confidence Interval	() 97.5% 1.13 to 1.60
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimate of the treatment hazard ratio (lap versus tras) is based on the Cox's proportional hazards model adjusting for the stratification factors of chemotherapy timing, hormone receptor status, and auxillary lymph node status.

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival is defined as the time from randomization until death due to any cause. Overall survival was calculated in years as (date of death minus the date of randomization +1) divided by 365.25. The percentile data values presented here indicate the percentage (99, 98, 97, 96, 95 and 90 percent) of participants who survived for the indicated years.
Time Frame	From randomization until death due to any cause (median follow-up of 4.5 years)

Outcome Measure Data

Analysis Population Description
ITT Population. Participants who did not die were censored at the date of last survival contact. Zero participants were analyzed in the lapatinib arm, as the Independent Data Monitoring Committee discontinued the lapatinib-alone arm due to futility at the time of the first interim analysis (lapatinib participants were then offered trastuzumab).

Arm/Group Title	Lapatinib plusTrastuzumab	Trastuzumab Followed by Lapatinib	Trastuzumab	Lapatinib
Arm/Group Description	Participants (par.) received treatment per one of three designs. D1: oral lapatinib (OL) 1000 milligrams (mg) daily with trastuzumab (tras) (8 milligrams per kilogram [mg/kg] intravenous [IV] loading dose [LD], followed by 6 mg/kg IV every 3 weeks [E3W]) for 52 weeks (wks). D2: OL 750 mg daily plus wkly tras (4 mg/kg LD, followed by 2 mg/kg IV) concomitantly (conc.) with wkly paclitaxel (pac) 80 mg per squared meter (mg/m^2) IV or docetaxel (doc) 75 mg/m^2 IV E3W for 12 wks. After completion of pac or doc, par. received OL at an increased dose of 1000 mg daily in combination with tras (6 mg/kg without a LD) E3W for 40 wks. D2B: OL 750 mg plus wkly tras (4 mg/kg IV LD, followed by 2 mg/kg IV wkly) conc. with doc 75 mg/m^2 E3W and carboplatin (carb) AUC6 IV for 18 wks. After completion of doc and carb, par. received tras E3W (6 mg/kg without a LD) plus OL 1000 mg daily for 34 wks. Par. also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: weekly tras for 12 weeks (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly), followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks for 12 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2B: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV for 18 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 28 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: tras 8 mg/kg IV LD, followed by 6 mg/kg IV every 3 weeks for 52 weeks. Design 2: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received tras (6 mg/kg without a LD every 3 weeks for 40 weeks. Design 2B: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, participants received tras every 3 weeks (6 mg/kg without a LD) for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: oral lap 1500 mg daily for 52 weeks. Design 2: oral lap 750 mg daily concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received oral lap at an increased dose of 1500 mg daily for 40 weeks. Design 2B: oral lap 750 mg daily concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, oral lap was given at an increased dose of 1500 mg for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.
Measure Participants	2093	2091	2097	0
99th Percentile	1.7	1.2	1.7
98th Percentile	2.2	1.6	2.1
97th Percentile	2.8	2.2	2.6
96th Percentile	3.4	2.9	3.0
95th Percentile	3.9	3.7	3.6
90th Percentile	NA	NA	5.9

3. Secondary Outcome

Title	Time to Recurrence
Description	Time to recurrence is defined as the interval between the date of randomization and the date of the first occurrence of a disease recurrence (local, regional or distant). The percentile data values presented here indicate the percentage (95, 90, 85, and 80 percent) of participants who did not have disease recurrence for the indicated years. IDMC=Independent Data Monitoring Committee.
Time Frame	From randomization until the date of the first occurrence of a disease recurrence (median follow-up of 4.5 years)

Outcome Measure Data

Analysis Population Description
ITT Population. Participants who did not have a recurrence of the initial disease were censored at the date of the last recorded physical or radiological examination. Death was treated as a competing risk. Zero participants were analyzed in the lapatinib arm, as the IDMC discontinued the lapatinib-alone arm due to futility at the interim analysis.

Arm/Group Title	Lapatinib plusTrastuzumab	Trastuzumab Followed by Lapatinib	Trastuzumab	Lapatinib
Arm/Group Description	Participants (par.) received treatment per one of three designs. D1: oral lapatinib (OL) 1000 milligrams (mg) daily with trastuzumab (tras) (8 milligrams per kilogram [mg/kg] intravenous [IV] loading dose [LD], followed by 6 mg/kg IV every 3 weeks [E3W]) for 52 weeks (wks). D2: OL 750 mg daily plus wkly tras (4 mg/kg LD, followed by 2 mg/kg IV) concomitantly (conc.) with wkly paclitaxel (pac) 80 mg per squared meter (mg/m^2) IV or docetaxel (doc) 75 mg/m^2 IV E3W for 12 wks. After completion of pac or doc, par. received OL at an increased dose of 1000 mg daily in combination with tras (6 mg/kg without a LD) E3W for 40 wks. D2B: OL 750 mg plus wkly tras (4 mg/kg IV LD, followed by 2 mg/kg IV wkly) conc. with doc 75 mg/m^2 E3W and carboplatin (carb) AUC6 IV for 18 wks. After completion of doc and carb, par. received tras E3W (6 mg/kg without a LD) plus OL 1000 mg daily for 34 wks. Par. also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: weekly tras for 12 weeks (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly), followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks for 12 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2B: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV for 18 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 28 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: tras 8 mg/kg IV LD, followed by 6 mg/kg IV every 3 weeks for 52 weeks. Design 2: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received tras (6 mg/kg without a LD every 3 weeks for 40 weeks. Design 2B: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, participants received tras every 3 weeks (6 mg/kg without a LD) for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: oral lap 1500 mg daily for 52 weeks. Design 2: oral lap 750 mg daily concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received oral lap at an increased dose of 1500 mg daily for 40 weeks. Design 2B: oral lap 750 mg daily concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, oral lap was given at an increased dose of 1500 mg for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.
Measure Participants	2093	2091	2097	0
95th Percentile	2.2	1.5	1.7
90th Percentile	4.5	3.7	3.2
85th Percentile	6.1	NA	NA
80th Percentile	6.1	NA	NA

4. Secondary Outcome

Title	Time to Distant Recurrence
Description	Time to distant recurrence is defined as the interval between the date of randomization and the date of the first occurrence of distant recurrence (including central nervous system recurrence). The percentile data values presented here indicate the percentage (95, 90, 85 and 80 percent) of participants who did not have distant recurrence for the indicated years.
Time Frame	From randomization until the date of the first occurrence of distant recurrence (median follow-up of 4.5 years)

Outcome Measure Data

Analysis Population Description
ITT Population. Participants who did not have a distant recurrence of the initial disease were censored at the date of the last recorded physical or radiological examination. Death was treated as a competing risk. Zero participants were analyzed in the lapatinib arm, as the IDMC discontinued the lapatinib-alone arm due to futility.

Arm/Group Title	Lapatinib plusTrastuzumab	Trastuzumab Followed by Lapatinib	Trastuzumab	Lapatinib
Arm/Group Description	Participants (par.) received treatment per one of three designs. D1: oral lapatinib (OL) 1000 milligrams (mg) daily with trastuzumab (tras) (8 milligrams per kilogram [mg/kg] intravenous [IV] loading dose [LD], followed by 6 mg/kg IV every 3 weeks [E3W]) for 52 weeks (wks). D2: OL 750 mg daily plus wkly tras (4 mg/kg LD, followed by 2 mg/kg IV) concomitantly (conc.) with wkly paclitaxel (pac) 80 mg per squared meter (mg/m^2) IV or docetaxel (doc) 75 mg/m^2 IV E3W for 12 wks. After completion of pac or doc, par. received OL at an increased dose of 1000 mg daily in combination with tras (6 mg/kg without a LD) E3W for 40 wks. D2B: OL 750 mg plus wkly tras (4 mg/kg IV LD, followed by 2 mg/kg IV wkly) conc. with doc 75 mg/m^2 E3W and carboplatin (carb) AUC6 IV for 18 wks. After completion of doc and carb, par. received tras E3W (6 mg/kg without a LD) plus OL 1000 mg daily for 34 wks. Par. also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: weekly tras for 12 weeks (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly), followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks for 12 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2B: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV for 18 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 28 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: tras 8 mg/kg IV LD, followed by 6 mg/kg IV every 3 weeks for 52 weeks. Design 2: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received tras (6 mg/kg without a LD every 3 weeks for 40 weeks. Design 2B: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, participants received tras every 3 weeks (6 mg/kg without a LD) for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: oral lap 1500 mg daily for 52 weeks. Design 2: oral lap 750 mg daily concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received oral lap at an increased dose of 1500 mg daily for 40 weeks. Design 2B: oral lap 750 mg daily concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, oral lap was given at an increased dose of 1500 mg for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.
Measure Participants	2093	2091	2097	0
95th Percentile	2.4	1.8	1.9
90th Percentile	5.5	4.2	4.1
85th Percentile	6.1	NA	NA
80th Percentile	6.1	NA	NA

5. Secondary Outcome

Title	Time to Central Nervous System Recurrence
Description	Time to central nervous system recurrence is defined as the time from randomization until the first central nervous system recurrence. Both brain metastasis and meningitis carcinomatosa were considered.The percentile data values presented here indicate that 95 percent of participants did not have central nervous system recurrence for the indicated years.
Time Frame	From randomization until the first central nervous system recurrence (median follow-up of 4.5 years)

Outcome Measure Data

Analysis Population Description
ITT Population. Participants who did not have a central nervous system recurrence were censored at the date of the last recorded physical or radiological examination. Death was treated as a competing risk. Zero participants were analyzed in the lapatinib arm, as the IDMC discontinued the lapatinib-alone arm due to futility at the interim analysis.

Arm/Group Title	Lapatinib plusTrastuzumab	Trastuzumab Followed by Lapatinib	Trastuzumab	Lapatinib
Arm/Group Description	Participants (par.) received treatment per one of three designs. D1: oral lapatinib (OL) 1000 milligrams (mg) daily with trastuzumab (tras) (8 milligrams per kilogram [mg/kg] intravenous [IV] loading dose [LD], followed by 6 mg/kg IV every 3 weeks [E3W]) for 52 weeks (wks). D2: OL 750 mg daily plus wkly tras (4 mg/kg LD, followed by 2 mg/kg IV) concomitantly (conc.) with wkly paclitaxel (pac) 80 mg per squared meter (mg/m^2) IV or docetaxel (doc) 75 mg/m^2 IV E3W for 12 wks. After completion of pac or doc, par. received OL at an increased dose of 1000 mg daily in combination with tras (6 mg/kg without a LD) E3W for 40 wks. D2B: OL 750 mg plus wkly tras (4 mg/kg IV LD, followed by 2 mg/kg IV wkly) conc. with doc 75 mg/m^2 E3W and carboplatin (carb) AUC6 IV for 18 wks. After completion of doc and carb, par. received tras E3W (6 mg/kg without a LD) plus OL 1000 mg daily for 34 wks. Par. also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: weekly tras for 12 weeks (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly), followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks for 12 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2B: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV for 18 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 28 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: tras 8 mg/kg IV LD, followed by 6 mg/kg IV every 3 weeks for 52 weeks. Design 2: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received tras (6 mg/kg without a LD every 3 weeks for 40 weeks. Design 2B: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, participants received tras every 3 weeks (6 mg/kg without a LD) for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: oral lap 1500 mg daily for 52 weeks. Design 2: oral lap 750 mg daily concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received oral lap at an increased dose of 1500 mg daily for 40 weeks. Design 2B: oral lap 750 mg daily concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, oral lap was given at an increased dose of 1500 mg for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.
Measure Participants	2093	2091	2097	0
Number [years]	5.8	NA	NA

6. Secondary Outcome

Title	DFS Ignoring Non-breast Second Primary Malignancies
Description	Disease-free survival is defined as the interval between randomization and the date of the first occurence of disease recurrence (local, regional or distant), a contralateral invasive breast cancer, a second primary cancer, or death from any cause. DFS was estimated using the Kaplan Meier method. The non-breast second primary malignancies were not considered events.The percentile data values presented here indicate the percentage (95, 90, 85, 80 and 75 percent) of participants who did not have DFS ignoring non-breast second primary malignancies for the indicated years. Zero participants were analyzed in the lapatinib arm, as the IDMC discontinued the lapatinib-alone arm due to futility at the time of the first interim analysis (lapatinib participants were then offered trastuzumab).
Time Frame	From randomization until the date of the first occurrence of disease recurrence, a contralateral invasive breast cancer, a second primary cancer, or death from any cause (median follow-up of 4.5 years)

Outcome Measure Data

Analysis Population Description
ITT Population. Participants who did not have a recurrence of the initial disease, or did not die, were lost to follow-up, or were withdrawn from the study were censored at the date of last clinical contact. Non-breast second primary cancers were ignored.

Arm/Group Title	Lapatinib plusTrastuzumab	Trastuzumab Followed by Lapatinib	Trastuzumab	Lapatinib
Arm/Group Description	Participants (par.) received treatment per one of three designs. D1: oral lapatinib (OL) 1000 milligrams (mg) daily with trastuzumab (tras) (8 milligrams per kilogram [mg/kg] intravenous [IV] loading dose [LD], followed by 6 mg/kg IV every 3 weeks [E3W]) for 52 weeks (wks). D2: OL 750 mg daily plus wkly tras (4 mg/kg LD, followed by 2 mg/kg IV) concomitantly (conc.) with wkly paclitaxel (pac) 80 mg per squared meter (mg/m^2) IV or docetaxel (doc) 75 mg/m^2 IV E3W for 12 wks. After completion of pac or doc, par. received OL at an increased dose of 1000 mg daily in combination with tras (6 mg/kg without a LD) E3W for 40 wks. D2B: OL 750 mg plus wkly tras (4 mg/kg IV LD, followed by 2 mg/kg IV wkly) conc. with doc 75 mg/m^2 E3W and carboplatin (carb) AUC6 IV for 18 wks. After completion of doc and carb, par. received tras E3W (6 mg/kg without a LD) plus OL 1000 mg daily for 34 wks. Par. also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: weekly tras for 12 weeks (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly), followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks for 12 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2B: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV for 18 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 28 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: tras 8 mg/kg IV LD, followed by 6 mg/kg IV every 3 weeks for 52 weeks. Design 2: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received tras (6 mg/kg without a LD every 3 weeks for 40 weeks. Design 2B: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, participants received tras every 3 weeks (6 mg/kg without a LD) for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.	Participants received treatment per one of the following three designs. Design 1: oral lap 1500 mg daily for 52 weeks. Design 2: oral lap 750 mg daily concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received oral lap at an increased dose of 1500 mg daily for 40 weeks. Design 2B: oral lap 750 mg daily concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, oral lap was given at an increased dose of 1500 mg for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.
Measure Participants	1155	1143	1147	0
95th Percentile	1.9	1.2	1.4
90th Percentile	3.0	2.3	2.3
85th Percentile	5.6	4.7	3.5
80th Percentile	6.1	NA	NA
75th Percentile	6.1	NA	NA

Adverse Events

	Lapatinib plusTrastuzumab		Trastuzumab Followed by Lapatinib		Lapatinib		Trastuzumab
Time Frame	Serious adverse events (SAEs) and non-serious AEs were collected from randomization until 10 years post-study entry.
Adverse Event Reporting Description	SAEs and non-serious AEs are reported for the Safety Population, comprised of all randomized participants who were administered at least one dose of investigational targeted treatment, as recorded on the "administration of study drug" Case Report Form pages, but excluding any post-event treatments and not considering compliance.

Arm/Group Title	Lapatinib plusTrastuzumab		Trastuzumab Followed by Lapatinib		Lapatinib		Trastuzumab
Arm/Group Description	Participants (par.) received treatment per one of three designs. D1: oral lapatinib (OL) 1000 milligrams (mg) daily with trastuzumab (tras) (8 milligrams per kilogram [mg/kg] intravenous [IV] loading dose [LD], followed by 6 mg/kg IV every 3 weeks [E3W]) for 52 weeks (wks). D2: OL 750 mg daily plus wkly tras (4 mg/kg LD, followed by 2 mg/kg IV) concomitantly (conc.) with wkly paclitaxel (pac) 80 mg per squared meter (mg/m^2) IV or docetaxel (doc) 75 mg/m^2 IV E3W for 12 wks. After completion of pac or doc, par. received OL at an increased dose of 1000 mg daily in combination with tras (6 mg/kg without a LD) E3W for 40 wks. D2B: OL 750 mg plus wkly tras (4 mg/kg IV LD, followed by 2 mg/kg IV wkly) conc. with doc 75 mg/m^2 E3W and carboplatin (carb) AUC6 IV for 18 wks. After completion of doc and carb, par. received tras E3W (6 mg/kg without a LD) plus OL 1000 mg daily for 34 wks. Par. also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.		Participants received treatment per one of the following three designs. Design 1: weekly tras for 12 weeks (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly), followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks for 12 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 34 weeks. Design 2B: weekly tras (4 mg/kg IV loading dose, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV for 18 weeks, followed by a 6-week washout period, followed by oral lap 1500 mg daily for 28 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.		Participants received treatment per one of the following three designs. Design 1: oral lap 1500 mg daily for 52 weeks. Design 2: oral lap 750 mg daily concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received oral lap at an increased dose of 1500 mg daily for 40 weeks. Design 2B: oral lap 750 mg daily concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, oral lap was given at an increased dose of 1500 mg for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.		Participants received treatment per one of the following three designs. Design 1: tras 8 mg/kg IV LD, followed by 6 mg/kg IV every 3 weeks for 52 weeks. Design 2: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with weekly paclitaxel 80 mg/m^2 IV or docetaxel 75 mg/m^2 IV every 3 weeks, for 12 weeks. After completion of paclitaxel or docetaxel, participants received tras (6 mg/kg without a LD every 3 weeks for 40 weeks. Design 2B: weekly tras (4 mg/kg IV LD, followed by 2 mg/kg IV weekly) concomitantly with docetaxel 75 mg/m^2 every 3 weeks and carboplatin AUC6 IV, for 18 weeks. After completion of docetaxel and carboplatin, participants received tras every 3 weeks (6 mg/kg without a LD) for 34 weeks. Participants also received adjuvant radiotherapy and adjuvant anti-estrogen therapy when clinically indicated.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Lapatinib plusTrastuzumab		Trastuzumab Followed by Lapatinib		Lapatinib		Trastuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	430/2061 (20.9%)		352/2076 (17%)		431/2057 (21%)		292/2076 (14.1%)
Blood and lymphatic system disorders
Neutropenia	37/2061 (1.8%)		21/2076 (1%)		37/2057 (1.8%)		20/2076 (1%)
Leukopenia	20/2061 (1%)		3/2076 (0.1%)		13/2057 (0.6%)		6/2076 (0.3%)
Anaemia	7/2061 (0.3%)		6/2076 (0.3%)		13/2057 (0.6%)		7/2076 (0.3%)
Febrile Neutropenia	9/2061 (0.4%)		6/2076 (0.3%)		12/2057 (0.6%)		3/2076 (0.1%)
Thrombocytopenia	2/2061 (0.1%)		1/2076 (0%)		2/2057 (0.1%)		7/2076 (0.3%)
Agranulocytosis	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Eosinophilia	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Iron Deficiency Anaemia	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Pancytopenia	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Cardiac disorders
Cardiac Failure Congestive	24/2061 (1.2%)		12/2076 (0.6%)		8/2057 (0.4%)		20/2076 (1%)
Left Ventricular Dysfunction	3/2061 (0.1%)		9/2076 (0.4%)		5/2057 (0.2%)		4/2076 (0.2%)
Atrial Fibrillation	6/2061 (0.3%)		7/2076 (0.3%)		0/2057 (0%)		3/2076 (0.1%)
Myocardial Infarction	3/2061 (0.1%)		1/2076 (0%)		2/2057 (0.1%)		3/2076 (0.1%)
Cardiac Failure	1/2061 (0%)		2/2076 (0.1%)		0/2057 (0%)		1/2076 (0%)
Myocardial Ischaemia	1/2061 (0%)		1/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Acute Coronary Syndrome	0/2061 (0%)		1/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Arrhythmia	1/2061 (0%)		1/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Cardiac Arrest	1/2061 (0%)		1/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Pericarditis	0/2061 (0%)		1/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Supraventricular Tachycardia	2/2061 (0.1%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Angina Pectoris	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Angina Unstable	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Coronary Artery Disease	0/2061 (0%)		1/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Palpitations	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Ventricular Tachycardia	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Acute Myocardial Infarction	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Aortic Valve Sclerosis	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Atrial Tachycardia	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Atrial Thrombosis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Atrioventricular Block Complete	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Cardiac Ventricular Thrombosis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Cardio-Respiratory Arrest	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Cardiomyopathy	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Intracardiac Thrombus	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Ischaemic Cardiomyopathy	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Myocarditis	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Pericardial Effusion	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Vascular Insufficiency	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Ventricular Arrhythmia	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Ventricular Extrasystoles	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Congenital, familial and genetic disorders
Gilbert's Syndrome	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Trisomy 21	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Ear and labyrinth disorders
Vertigo	2/2061 (0.1%)		2/2076 (0.1%)		0/2057 (0%)		1/2076 (0%)
Tinnitus	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Vertigo Positional	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Endocrine disorders
Autoimmune Thyroiditis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Goitre	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Hyperparathyroidism	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Hypothyroidism	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Eye disorders
Retinal Detachment	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		2/2076 (0.1%)
Diplopia	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Periorbital Oedema	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Gastrointestinal disorders
Diarrhoea	53/2061 (2.6%)		6/2076 (0.3%)		44/2057 (2.1%)		9/2076 (0.4%)
Vomiting	9/2061 (0.4%)		3/2076 (0.1%)		9/2057 (0.4%)		8/2076 (0.4%)
Nausea	5/2061 (0.2%)		3/2076 (0.1%)		7/2057 (0.3%)		6/2076 (0.3%)
Abdominal Pain	6/2061 (0.3%)		4/2076 (0.2%)		4/2057 (0.2%)		2/2076 (0.1%)
Colitis	4/2061 (0.2%)		0/2076 (0%)		2/2057 (0.1%)		1/2076 (0%)
Gastritis	2/2061 (0.1%)		2/2076 (0.1%)		1/2057 (0%)		2/2076 (0.1%)
Haemorrhoids	1/2061 (0%)		1/2076 (0%)		0/2057 (0%)		4/2076 (0.2%)
Constipation	0/2061 (0%)		0/2076 (0%)		2/2057 (0.1%)		1/2076 (0%)
Gastrointestinal Haemorrhage	1/2061 (0%)		1/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Ileus	1/2061 (0%)		1/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Intestinal Obstruction	2/2061 (0.1%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Pancreatitis	0/2061 (0%)		1/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Abdominal Pain Upper	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Duodenal Ulcer	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Enteritis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Enterocolitis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Gastrointestinal Obstruction	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Gastrointestinal Toxicity	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Oesophagitis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Pancreatitis Acute	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Stomatitis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Abdominal Distension	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Abdominal Mass	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Abdominal Pain Lower	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Anal Fissure	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Anal Fistula	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Anal Haemorrhage	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Dyspepsia	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Dysphagia	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Epiploic Appendagitis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Gastric Haemorrhage	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Gastric Ulcer	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Gastritis Erosive	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Gastrointestinal Perforation	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Gastrointestinal Ulcer	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Intestinal Haemorrhage	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Large Intestine Perforation	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Reflux Gastritis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Small Intestinal Obstruction	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Upper Gastrointestinal Haemorrhage	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Volvulus	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
General disorders
Pyrexia	11/2061 (0.5%)		16/2076 (0.8%)		14/2057 (0.7%)		5/2076 (0.2%)
Fatigue	5/2061 (0.2%)		2/2076 (0.1%)		7/2057 (0.3%)		2/2076 (0.1%)
Chest Pain	1/2061 (0%)		5/2076 (0.2%)		2/2057 (0.1%)		1/2076 (0%)
Asthenia	2/2061 (0.1%)		0/2076 (0%)		4/2057 (0.2%)		1/2076 (0%)
Mucosal Inflammation	2/2061 (0.1%)		0/2076 (0%)		3/2057 (0.1%)		0/2076 (0%)
Chills	1/2061 (0%)		1/2076 (0%)		0/2057 (0%)		2/2076 (0.1%)
Thrombosis In Device	1/2061 (0%)		2/2076 (0.1%)		1/2057 (0%)		0/2076 (0%)
Oedema Peripheral	0/2061 (0%)		2/2076 (0.1%)		0/2057 (0%)		1/2076 (0%)
Adverse Drug Reaction	2/2061 (0.1%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Death	0/2061 (0%)		1/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Device Dislocation	2/2061 (0.1%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Fat Necrosis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
General Physical Health Deterioration	0/2061 (0%)		0/2076 (0%)		2/2057 (0.1%)		0/2076 (0%)
Impaired Healing	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Malaise	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Chronic Fatigue Syndrome	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Device Expulsion	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Feeling Cold	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Granuloma	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Inflammation	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Lipogranuloma	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Local Swelling	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Necrosis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Non-Cardiac Chest Pain	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Oedema	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Sudden Death	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Hepatobiliary disorders
Hypertransaminasaemia	74/2061 (3.6%)		55/2076 (2.6%)		87/2057 (4.2%)		11/2076 (0.5%)
Hyperbilirubinaemia	6/2061 (0.3%)		12/2076 (0.6%)		18/2057 (0.9%)		1/2076 (0%)
Hepatotoxicity	3/2061 (0.1%)		3/2076 (0.1%)		4/2057 (0.2%)		0/2076 (0%)
Cholecystitis	3/2061 (0.1%)		0/2076 (0%)		2/2057 (0.1%)		3/2076 (0.1%)
Hepatic Function Abnormal	0/2061 (0%)		4/2076 (0.2%)		4/2057 (0.2%)		0/2076 (0%)
Biliary Colic	0/2061 (0%)		2/2076 (0.1%)		0/2057 (0%)		1/2076 (0%)
Cholelithiasis	1/2061 (0%)		1/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Drug-Induced Liver Injury	2/2061 (0.1%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Jaundice	1/2061 (0%)		2/2076 (0.1%)		0/2057 (0%)		0/2076 (0%)
Cystitis	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Autoimmune Hepatitis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Bile Duct Stenosis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Cholecystitis Acute	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Gallbladder Obstruction	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Hepatic Cirrhosis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Hepatic Failure	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Hepatic Lesion	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Immune system disorders
Hypersensitivity	4/2061 (0.2%)		4/2076 (0.2%)		1/2057 (0%)		4/2076 (0.2%)
Anaphylactic Reaction	3/2061 (0.1%)		1/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Drug Hypersensitivity	1/2061 (0%)		0/2076 (0%)		2/2057 (0.1%)		0/2076 (0%)
Anaphylactoid Reaction	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Sarcoidosis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Infections and infestations
Cellulitis	16/2061 (0.8%)		14/2076 (0.7%)		7/2057 (0.3%)		5/2076 (0.2%)
Pneumonia	12/2061 (0.6%)		9/2076 (0.4%)		9/2057 (0.4%)		10/2076 (0.5%)
Device Related Infection	8/2061 (0.4%)		2/2076 (0.1%)		4/2057 (0.2%)		3/2076 (0.1%)
Erysipelas	6/2061 (0.3%)		4/2076 (0.2%)		4/2057 (0.2%)		3/2076 (0.1%)
Urinary Tract Infection	2/2061 (0.1%)		6/2076 (0.3%)		2/2057 (0.1%)		7/2076 (0.3%)
Sepsis	1/2061 (0%)		3/2076 (0.1%)		5/2057 (0.2%)		5/2076 (0.2%)
Mastitis	2/2061 (0.1%)		1/2076 (0%)		6/2057 (0.3%)		3/2076 (0.1%)
Gastroenteritis	3/2061 (0.1%)		3/2076 (0.1%)		3/2057 (0.1%)		1/2076 (0%)
Lower Respiratory Tract Infection	3/2061 (0.1%)		2/2076 (0.1%)		1/2057 (0%)		1/2076 (0%)
Herpes Zoster	1/2061 (0%)		2/2076 (0.1%)		3/2057 (0.1%)		0/2076 (0%)
Bronchitis	0/2061 (0%)		2/2076 (0.1%)		1/2057 (0%)		2/2076 (0.1%)
Infection	2/2061 (0.1%)		1/2076 (0%)		2/2057 (0.1%)		0/2076 (0%)
Skin Infection	2/2061 (0.1%)		0/2076 (0%)		2/2057 (0.1%)		1/2076 (0%)
Wound Infection	0/2061 (0%)		2/2076 (0.1%)		2/2057 (0.1%)		1/2076 (0%)
Breast Cellulitis	1/2061 (0%)		0/2076 (0%)		3/2057 (0.1%)		0/2076 (0%)
Subcutaneous Abscess	0/2061 (0%)		2/2076 (0.1%)		1/2057 (0%)		1/2076 (0%)
Respiratory Tract Infection	0/2061 (0%)		1/2076 (0%)		2/2057 (0.1%)		0/2076 (0%)
Sinusitis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		2/2076 (0.1%)
Abdominal Wall Abscess	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Anal Abscess	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Bacteraemia	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Device Related Sepsis	2/2061 (0.1%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Diverticulitis	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Gastroenteritis Viral	1/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Hepatitis C	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Influenza	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Lobar Pneumonia	1/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Localised Infection	1/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Lung Infection	1/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Lymph Gland Infection	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Osteomyelitis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Otitis Media	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		2/2076 (0.1%)
Pyelonephritis	2/2061 (0.1%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Upper Respiratory Tract Infection	1/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Viral Infection	1/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Abscess	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Acute Hepatitis B	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Acute Sinusitis	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Amoebic Dysentery	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Anal Infection	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Atypical Pneumonia	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Bacterial Infection	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Bronchitis Viral	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Candida Infection	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Catheter Site Cellulitis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Chest Wall Abscess	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Chlamydial Infection	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Clostridium Difficile Colitis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Clostridium Difficile Infection	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Conjunctivitis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Diarrhoea Infectious	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Gastric Infection	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Gastrointestinal Infection	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Hepatitis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Hepatitis B	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Hepatitis Viral	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Implant Site Cellulitis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Infected Cyst	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Infected Lymphocele	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Infectious Colitis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Infective Exacerbation Of Chronic Obstructive Airways Disease	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Intervertebral Discitis	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Laryngitis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Lymph Node Abscess	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Lymphangitis	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Malaria	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Meningitis Viral	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Nail Infection	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Nasopharyngitis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Neuroborreliosis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Neutropenic Sepsis	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Oesophageal Candidiasis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Oesophageal Infection	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Ovarian Abscess	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Paronychia	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Peritonitis	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Pharyngitis	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Pneumocystis Jirovecii Infection	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Pneumonia Cytomegaloviral	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Post Procedural Pneumonia	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Progressive Multifocal Leukoencephalopathy	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Pyelonephritis Acute	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Sialoadenitis	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Soft Tissue Infection	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Staphylococcal Bacteraemia	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Staphylococcal Infection	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Streptococcal Infection	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Streptococcal Sepsis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Superinfection	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Tooth Infection	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Tuberculosis	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Tuberculous Pleurisy	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Upper Respiratory Tract Infection Bacterial	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Urosepsis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Wound Infection Bacterial	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Wound Infection Staphylococcal	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Injury, poisoning and procedural complications
Radiation Skin Injury	1/2061 (0%)		3/2076 (0.1%)		0/2057 (0%)		1/2076 (0%)
Seroma	1/2061 (0%)		2/2076 (0.1%)		1/2057 (0%)		1/2076 (0%)
Radiation Fibrosis - Lung	0/2061 (0%)		1/2076 (0%)		2/2057 (0.1%)		1/2076 (0%)
Radiation Pneumonitis	1/2061 (0%)		1/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Ankle Fracture	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		2/2076 (0.1%)
Humerus Fracture	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Upper Limb Fracture	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		2/2076 (0.1%)
Hip Fracture	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Rib Fracture	0/2061 (0%)		2/2076 (0.1%)		0/2057 (0%)		0/2076 (0%)
Tibia Fracture	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Wound Complication	0/2061 (0%)		1/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Wrist Fracture	0/2061 (0%)		0/2076 (0%)		2/2057 (0.1%)		0/2076 (0%)
Alcohol Poisoning	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Carbon Monoxide Poisoning	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Concussion	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Contusion	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Fibula Fracture	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Foot Fracture	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Foreign Body	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Fracture	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Fractured Coccyx	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Infusion Related Reaction	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Ligament Sprain	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Lower Limb Fracture	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Multiple Injuries	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Pelvic Fracture	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Radius Fracture	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Road Traffic Accident	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Spinal Compression Fracture	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Spinal Fracture	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Sternal Fracture	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Subdural Haemorrhage	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Thermal Burn	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Investigations
Gamma-Glutamyltransferase Increased	2/2061 (0.1%)		3/2076 (0.1%)		3/2057 (0.1%)		0/2076 (0%)
Blood Creatinine Increased	1/2061 (0%)		1/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Eastern Cooperative Oncology Group Performance Status Worsened	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Electrocardiogram Qt Prolonged	0/2061 (0%)		1/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Lipase	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Liver Function Test Abnormal	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Platelet Count Decreased	2/2061 (0.1%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Alanine Aminotransferase Increased	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Amylase	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Blood Alkaline Phosphatase Increased	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Blood Bilirubin Increased	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Blood Creatinine	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Blood Magnesium Decreased	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Blood Potassium Decreased	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Blood Urea Increased	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Blood Urine Present	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Coagulation Test Abnormal	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Ejection Fraction Decreased	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Electrocardiogram Abnormal	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Electrocardiogram St Segment Depression	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Electrocardiogram T Wave Inversion	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Gamma-Glutamyltransferase	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
International Normalised Ratio	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Weight Decreased	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
White Blood Cell Count Decreased	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Metabolism and nutrition disorders
Dehydration	11/2061 (0.5%)		3/2076 (0.1%)		12/2057 (0.6%)		4/2076 (0.2%)
Hypokalaemia	8/2061 (0.4%)		1/2076 (0%)		9/2057 (0.4%)		3/2076 (0.1%)
Hyperphosphatasaemia	4/2061 (0.2%)		4/2076 (0.2%)		1/2057 (0%)		0/2076 (0%)
Decreased Appetite	3/2061 (0.1%)		0/2076 (0%)		3/2057 (0.1%)		0/2076 (0%)
Hypocalcaemia	2/2061 (0.1%)		1/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Diabetes Mellitus	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		3/2076 (0.1%)
Hyperglycaemia	0/2061 (0%)		1/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Hypomagnesaemia	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Hypovolaemia	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Hypercholesterolaemia	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Hypernatraemia	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Hyperuricaemia	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Hyponatraemia	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Hypophagia	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Hypophosphataemia	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Metabolic Acidosis	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/2061 (0%)		2/2076 (0.1%)		1/2057 (0%)		0/2076 (0%)
Back Pain	4/2061 (0.2%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Costochondritis	0/2061 (0%)		1/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Myalgia	2/2061 (0.1%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Bone Pain	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Ligament Disorder	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Lumbar Spinal Stenosis	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Musculoskeletal Chest Pain	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Musculoskeletal Pain	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Myositis	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Osteoarthritis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Osteoporosis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Scleroderma	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Spondylolisthesis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Synovial Cyst	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Synovitis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Contralateral Breast Cancer	22/2061 (1.1%)		13/2076 (0.6%)		11/2057 (0.5%)		12/2076 (0.6%)
Colon Cancer	1/2061 (0%)		2/2076 (0.1%)		6/2057 (0.3%)		5/2076 (0.2%)
Breast Cancer	1/2061 (0%)		3/2076 (0.1%)		3/2057 (0.1%)		4/2076 (0.2%)
Intraductal Proliferative Breast Lesion	4/2061 (0.2%)		2/2076 (0.1%)		1/2057 (0%)		4/2076 (0.2%)
Malignant Melanoma	5/2061 (0.2%)		2/2076 (0.1%)		3/2057 (0.1%)		1/2076 (0%)
Gastric Cancer	0/2061 (0%)		3/2076 (0.1%)		4/2057 (0.2%)		3/2076 (0.1%)
Acute Myeloid Leukaemia	2/2061 (0.1%)		0/2076 (0%)		0/2057 (0%)		5/2076 (0.2%)
Ovarian Cancer	2/2061 (0.1%)		2/2076 (0.1%)		0/2057 (0%)		2/2076 (0.1%)
Papillary Thyroid Cancer	3/2061 (0.1%)		0/2076 (0%)		2/2057 (0.1%)		1/2076 (0%)
Thyroid Cancer	0/2061 (0%)		1/2076 (0%)		1/2057 (0%)		4/2076 (0.2%)
Endometrial Cancer	2/2061 (0.1%)		2/2076 (0.1%)		1/2057 (0%)		0/2076 (0%)
Lung Adenocarcinoma	2/2061 (0.1%)		3/2076 (0.1%)		0/2057 (0%)		0/2076 (0%)
Rectal Cancer	2/2061 (0.1%)		2/2076 (0.1%)		1/2057 (0%)		0/2076 (0%)
Adenocarcinoma Of Colon	1/2061 (0%)		1/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Basal Cell Carcinoma	2/2061 (0.1%)		0/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Invasive Ductal Breast Carcinoma	0/2061 (0%)		2/2076 (0.1%)		0/2057 (0%)		2/2076 (0.1%)
Acute Lymphocytic Leukaemia	3/2061 (0.1%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Lung Neoplasm Malignant	2/2061 (0.1%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Small Cell Lung Cancer	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		2/2076 (0.1%)
Uterine Leiomyoma	0/2061 (0%)		1/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Acute Promyelocytic Leukaemia	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Adenocarcinoma Gastric	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Chronic Lymphocytic Leukaemia	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Endometrial Adenocarcinoma	2/2061 (0.1%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Leukaemia	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Metastases To Central Nervous System	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Myelodysplastic Syndrome	2/2061 (0.1%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Non-Hodgkin's Lymphoma	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Transitional Cell Carcinoma	0/2061 (0%)		0/2076 (0%)		2/2057 (0.1%)		0/2076 (0%)
Uterine Cancer	0/2061 (0%)		1/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Acral Lentiginous Melanoma	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Acute Leukaemia	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Anaplastic Meningioma	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
B-Cell Lymphoma	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Benign Breast Neoplasm	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Benign Ovarian Tumour	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Bladder Neoplasm	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Bladder Transitional Cell Carcinoma	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Borderline Ovarian Tumour	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Breast Cancer In Situ	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Bronchioloalveolar Carcinoma	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Cervix Carcinoma	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Cervix Carcinoma Stage 0	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Chronic Myeloid Leukaemia	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Colon Cancer Metastatic	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Colon Neoplasm	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Colorectal Cancer	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Fallopian Tube Cancer	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Follicular Thyroid Cancer	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Gallbladder Neoplasm	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Gastric Cancer Stage I	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Gastrointestinal Carcinoma	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Gastrointestinal Stromal Tumour	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Haemangioma	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Hepatocellular Carcinoma	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Intestinal Adenocarcinoma	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Intraductal Papilloma Of Breast	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Invasive Lobular Breast Carcinoma	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Leiomyoma	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Leiomyosarcoma	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Lentigo Maligna	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Lipoma	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Malignant Melanoma In Situ	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Malignant Neoplasm Of Unknown Primary Site	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Melanocytic Naevus	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Meningioma	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Meningioma Benign	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Metastases To Meninges	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Neuroendocrine Tumour	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Nodular Melanoma	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Oropharyngeal Cancer	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Ovarian Adenoma	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Ovarian Germ Cell Teratoma Benign	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Ovarian Neoplasm	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Pancreatic Carcinoma	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Parathyroid Tumour Benign	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Plasma Cell Myeloma	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Rectal Adenocarcinoma	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Rectosigmoid Cancer	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Renal Cancer	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Second Primary Malignancy	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Small Intestine Adenocarcinoma	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Squamous Cell Carcinoma Of Skin	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Squamous Cell Carcinoma Of The Vulva	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Superficial Spreading Melanoma Stage Unspecified	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Urethral Cancer	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Nervous system disorders
Syncope	2/2061 (0.1%)		1/2076 (0%)		3/2057 (0.1%)		5/2076 (0.2%)
Neuropathy Peripheral	0/2061 (0%)		4/2076 (0.2%)		2/2057 (0.1%)		1/2076 (0%)
Headache	2/2061 (0.1%)		0/2076 (0%)		3/2057 (0.1%)		1/2076 (0%)
Convulsion	2/2061 (0.1%)		0/2076 (0%)		3/2057 (0.1%)		0/2076 (0%)
Dizziness	1/2061 (0%)		1/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Cerebrovascular Accident	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Polyneuropathy	0/2061 (0%)		0/2076 (0%)		2/2057 (0.1%)		0/2076 (0%)
Quadriparesis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Amnesia	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Amyotrophic Lateral Sclerosis	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Brain Hypoxia	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Cerebellar Ataxia	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Epilepsy	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Hypotonia	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Intracranial Aneurysm	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Migraine	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Motor Neurone Disease	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Peripheral Motor Neuropathy	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Peripheral Sensory Neuropathy	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Serotonin Syndrome	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Somnolence	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Subarachnoid Haemorrhage	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Viith Nerve Paralysis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Foetal Death	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Psychiatric disorders
Depression	3/2061 (0.1%)		2/2076 (0.1%)		1/2057 (0%)		3/2076 (0.1%)
Suicide Attempt	0/2061 (0%)		1/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Major Depression	0/2061 (0%)		1/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Abnormal Behaviour	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Alcohol Withdrawal Syndrome	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Completed Suicide	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Insomnia	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Mental Disorder	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Restlessness	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Schizophrenia	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Renal and urinary disorders
Renal Failure	1/2061 (0%)		0/2076 (0%)		2/2057 (0.1%)		1/2076 (0%)
Nephrolithiasis	0/2061 (0%)		2/2076 (0.1%)		0/2057 (0%)		0/2076 (0%)
Calculus Urinary	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Nephritic Syndrome	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Renal Colic	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Renal Failure Acute	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Urethral Obstruction	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Urinary Bladder Haemorrhage	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Reproductive system and breast disorders
Ovarian Cyst	0/2061 (0%)		4/2076 (0.2%)		1/2057 (0%)		3/2076 (0.1%)
Breast Calcifications	1/2061 (0%)		1/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Uterine Polyp	1/2061 (0%)		1/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Endometrial Hyperplasia	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Adenomyosis	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Breast Disorder	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Breast Fibrosis	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Breast Haematoma	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Breast Inflammation	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Breast Necrosis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Breast Swelling	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Metrorrhagia	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Ovarian Cyst Ruptured	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Pelvic Pain	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Postmenopausal Haemorrhage	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Vaginal Haemorrhage	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	4/2061 (0.2%)		4/2076 (0.2%)		2/2057 (0.1%)		6/2076 (0.3%)
Pulmonary Embolism	2/2061 (0.1%)		4/2076 (0.2%)		6/2057 (0.3%)		2/2076 (0.1%)
Pneumonitis	0/2061 (0%)		4/2076 (0.2%)		2/2057 (0.1%)		5/2076 (0.2%)
Interstitial Lung Disease	2/2061 (0.1%)		1/2076 (0%)		2/2057 (0.1%)		0/2076 (0%)
Lung Disorder	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		3/2076 (0.1%)
Lung Infiltration	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Bronchiectasis	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Pleural Effusion	2/2061 (0.1%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Pleuritic Pain	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		2/2076 (0.1%)
Acute Respiratory Distress Syndrome	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Atelectasis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Bronchospasm	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Cough	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Dysphonia	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Dyspnoea Exertional	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Epistaxis	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Haemoptysis	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Hypoxia	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Laryngeal Oedema	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Lung Consolidation	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Pleurisy	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Pneumonia Aspiration	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Pneumothorax	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Pulmonary Granuloma	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Pulmonary Mass	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Pulmonary Oedema	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Pulmonary Thrombosis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Respiratory Failure	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Skin and subcutaneous tissue disorders
Rash	4/2061 (0.2%)		4/2076 (0.2%)		7/2057 (0.3%)		0/2076 (0%)
Dermatitis Acneiform	0/2061 (0%)		1/2076 (0%)		2/2057 (0.1%)		0/2076 (0%)
Acne	2/2061 (0.1%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Angioedema	0/2061 (0%)		0/2076 (0%)		2/2057 (0.1%)		0/2076 (0%)
Erythema	1/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Nail Disorder	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		1/2076 (0%)
Photosensitivity Reaction	0/2061 (0%)		1/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Pruritus	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Urticaria	1/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Angiodermatitis	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Exfoliative Rash	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Hypersensitivity Vasculitis	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Hypertrophic Scar	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Palmar-Plantar Erythrodysaesthesia Syndrome	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Rash Maculo-Papular	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Skin Necrosis	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Skin Swelling	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Skin Ulcer	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Toxic Epidermal Necrolysis	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Surgical and medical procedures
Abortion Induced	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Vascular disorders
Hypotension	2/2061 (0.1%)		1/2076 (0%)		2/2057 (0.1%)		3/2076 (0.1%)
Thrombosis	2/2061 (0.1%)		2/2076 (0.1%)		2/2057 (0.1%)		2/2076 (0.1%)
Deep Vein Thrombosis	2/2061 (0.1%)		2/2076 (0.1%)		2/2057 (0.1%)		0/2076 (0%)
Hypertension	2/2061 (0.1%)		2/2076 (0.1%)		0/2057 (0%)		1/2076 (0%)
Hypertensive Crisis	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Jugular Vein Thrombosis	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Venous Thrombosis Limb	1/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Circulatory Collapse	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Embolism Venous	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Flushing	1/2061 (0%)		0/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Orthostatic Hypotension	0/2061 (0%)		1/2076 (0%)		0/2057 (0%)		0/2076 (0%)
Rheumatoid Vasculitis	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Subclavian Vein Thrombosis	0/2061 (0%)		0/2076 (0%)		0/2057 (0%)		1/2076 (0%)
Thrombophlebitis Superficial	0/2061 (0%)		0/2076 (0%)		1/2057 (0%)		0/2076 (0%)
Other (Not Including Serious) Adverse Events
	Lapatinib plusTrastuzumab		Trastuzumab Followed by Lapatinib		Lapatinib		Trastuzumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1928/2061 (93.5%)		1861/2076 (89.6%)		1887/2057 (91.7%)		1652/2076 (79.6%)
Blood and lymphatic system disorders
Neutropenia	233/2061 (11.3%)		175/2076 (8.4%)		221/2057 (10.7%)		179/2076 (8.6%)
Anaemia	226/2061 (11%)		168/2076 (8.1%)		170/2057 (8.3%)		223/2076 (10.7%)
Leukopenia	172/2061 (8.3%)		136/2076 (6.6%)		153/2057 (7.4%)		164/2076 (7.9%)
Cardiac disorders
Left Ventricular Dysfunction	69/2061 (3.3%)		56/2076 (2.7%)		54/2057 (2.6%)		116/2076 (5.6%)
Gastrointestinal disorders
Diarrhoea	1514/2061 (73.5%)		1038/2076 (50%)		1278/2057 (62.1%)		401/2076 (19.3%)
Nausea	394/2061 (19.1%)		393/2076 (18.9%)		381/2057 (18.5%)		286/2076 (13.8%)
Vomiting	251/2061 (12.2%)		181/2076 (8.7%)		215/2057 (10.5%)		151/2076 (7.3%)
Stomatitis	203/2061 (9.8%)		141/2076 (6.8%)		161/2057 (7.8%)		98/2076 (4.7%)
Constipation	120/2061 (5.8%)		183/2076 (8.8%)		133/2057 (6.5%)		156/2076 (7.5%)
Dyspepsia	175/2061 (8.5%)		140/2076 (6.7%)		156/2057 (7.6%)		116/2076 (5.6%)
Abdominal Pain	146/2061 (7.1%)		108/2076 (5.2%)		149/2057 (7.2%)		79/2076 (3.8%)
Abdominal Pain Upper	137/2061 (6.6%)		111/2076 (5.3%)		110/2057 (5.3%)		77/2076 (3.7%)
General disorders
Fatigue	511/2061 (24.8%)		517/2076 (24.9%)		443/2057 (21.5%)		438/2076 (21.1%)
Asthenia	202/2061 (9.8%)		178/2076 (8.6%)		175/2057 (8.5%)		171/2076 (8.2%)
Pyrexia	227/2061 (11%)		188/2076 (9.1%)		131/2057 (6.4%)		171/2076 (8.2%)
Mucosal Inflammation	227/2061 (11%)		149/2076 (7.2%)		164/2057 (8%)		114/2076 (5.5%)
Oedema Peripheral	145/2061 (7%)		149/2076 (7.2%)		137/2057 (6.7%)		161/2076 (7.8%)
Hepatobiliary disorders
Hypertransaminasaemia	351/2061 (17%)		380/2076 (18.3%)		367/2057 (17.8%)		281/2076 (13.5%)
Hyperbilirubinaemia	97/2061 (4.7%)		103/2076 (5%)		121/2057 (5.9%)		32/2076 (1.5%)
Infections and infestations
Paronychia	260/2061 (12.6%)		165/2076 (7.9%)		206/2057 (10%)		22/2076 (1.1%)
Nasopharyngitis	130/2061 (6.3%)		113/2076 (5.4%)		95/2057 (4.6%)		152/2076 (7.3%)
Upper Respiratory Tract Infection	117/2061 (5.7%)		96/2076 (4.6%)		92/2057 (4.5%)		118/2076 (5.7%)
Injury, poisoning and procedural complications
Radiation Skin Injury	96/2061 (4.7%)		134/2076 (6.5%)		83/2057 (4%)		138/2076 (6.6%)
Metabolism and nutrition disorders
Decreased Appetite	224/2061 (10.9%)		172/2076 (8.3%)		187/2057 (9.1%)		143/2076 (6.9%)
Hyperphosphatasaemia	82/2061 (4%)		110/2076 (5.3%)		120/2057 (5.8%)		77/2076 (3.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	306/2061 (14.8%)		311/2076 (15%)		290/2057 (14.1%)		402/2076 (19.4%)
Myalgia	213/2061 (10.3%)		215/2076 (10.4%)		174/2057 (8.5%)		253/2076 (12.2%)
Pain In Extremity	135/2061 (6.6%)		125/2076 (6%)		99/2057 (4.8%)		175/2076 (8.4%)
Back Pain	129/2061 (6.3%)		135/2076 (6.5%)		119/2057 (5.8%)		128/2076 (6.2%)
Bone Pain	88/2061 (4.3%)		110/2076 (5.3%)		91/2057 (4.4%)		123/2076 (5.9%)
Musculoskeletal Pain	79/2061 (3.8%)		97/2076 (4.7%)		70/2057 (3.4%)		110/2076 (5.3%)
Nervous system disorders
Headache	193/2061 (9.4%)		240/2076 (11.6%)		161/2057 (7.8%)		262/2076 (12.6%)
Neuropathy peripheral	179/2061 (8.7%)		182/2076 (8.8%)		174/2057 (8.5%)		178/2076 (8.6%)
Peripheral Sensory Neuropathy	166/2061 (8.1%)		161/2076 (7.8%)		162/2057 (7.9%)		195/2076 (9.4%)
Dysgeusia	138/2061 (6.7%)		119/2076 (5.7%)		119/2057 (5.8%)		106/2076 (5.1%)
Paraesthesia	125/2061 (6.1%)		111/2076 (5.3%)		107/2057 (5.2%)		130/2076 (6.3%)
Dizziness	104/2061 (5%)		128/2076 (6.2%)		115/2057 (5.6%)		118/2076 (5.7%)
Psychiatric disorders
Insomnia	168/2061 (8.2%)		172/2076 (8.3%)		153/2057 (7.4%)		190/2076 (9.2%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	319/2061 (15.5%)		214/2076 (10.3%)		244/2057 (11.9%)		165/2076 (7.9%)
Cough	218/2061 (10.6%)		202/2076 (9.7%)		152/2057 (7.4%)		242/2076 (11.7%)
Dyspnoea	146/2061 (7.1%)		147/2076 (7.1%)		105/2057 (5.1%)		171/2076 (8.2%)
Skin and subcutaneous tissue disorders
Rash	757/2061 (36.7%)		673/2076 (32.4%)		753/2057 (36.6%)		221/2076 (10.6%)
Nail Disorder	359/2061 (17.4%)		280/2076 (13.5%)		295/2057 (14.3%)		221/2076 (10.6%)
Pruritus	287/2061 (13.9%)		249/2076 (12%)		313/2057 (15.2%)		124/2076 (6%)
Dry Skin	262/2061 (12.7%)		245/2076 (11.8%)		280/2057 (13.6%)		86/2076 (4.1%)
Alopecia	109/2061 (5.3%)		136/2076 (6.6%)		110/2057 (5.3%)		151/2076 (7.3%)
Palmar-Plantar Erythrodysaesthesia Syndrome	181/2061 (8.8%)		106/2076 (5.1%)		126/2057 (6.1%)		47/2076 (2.3%)
Erythema	122/2061 (5.9%)		104/2076 (5%)		92/2057 (4.5%)		87/2076 (4.2%)
Acne	134/2061 (6.5%)		138/2076 (6.6%)		112/2057 (5.4%)		20/2076 (1%)
Skin Fissures	145/2061 (7%)		98/2076 (4.7%)		124/2057 (6%)		7/2076 (0.3%)
Dermatitis Acneiform	116/2061 (5.6%)		96/2076 (4.6%)		124/2057 (6%)		19/2076 (0.9%)
Vascular disorders
Hot Flush	214/2061 (10.4%)		226/2076 (10.9%)		191/2057 (9.3%)		274/2076 (13.2%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.

Results Point of Contact

Name/Title	Clinical Disclosure Office
Organization	Novartis Pharmaceuticals
Phone	862-778-8300
Email

Responsible Party:

Novartis Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT00490139

Other Study ID Numbers:

EGF106708
CLAP016B2301
2006-000562-36
NCT00609024

First Posted:

Jun 22, 2007

Last Update Posted:

Jul 23, 2021

Last Verified:

Jul 1, 2021

ALTTO (Adjuvant Lapatinib And/Or Trastuzumab Treatment Optimisation) Study; BIG 2-06/N063D

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:

NOTE: multifocal/multicentric tumours are permitted:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

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Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact