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A Study Of PF-05280586 (Rituximab-Pfizer) Or MabThera® (Rituximab-EU) For The First-Line Treatment Of Patients With CD20-Positive, Low Tumor Burden, Follicular Lymphoma (REFLECTIONS B328-06)

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT02213263
Collaborator
(none)
394
Enrollment
423
Locations
2
Arms
42.6
Actual Duration (Months)
0.9
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will compare the safety and effectiveness of PF-05280586 versus rituximab-EU in patients with CD20-positive, low tumor burden follicular lymphoma. The primary hypothesis to be tested in this study is that the effectiveness of PF-05280586, as measured by the Overall Response Rate, is similar to that of rituximab-EU.

Condition or Disease Intervention/Treatment Phase
  • Biological: PF-05280586
  • Biological: MabThera®
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
394 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A PHASE 3, RANDOMIZED, DOUBLE-BLIND STUDY OF PF-05280586 VERSUS RITUXIMAB FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH CD20-POSITIVE, LOW TUMOR BURDEN, FOLLICULAR LYMPHOMA
Actual Study Start Date :
Sep 30, 2014
Actual Primary Completion Date :
Oct 23, 2017
Actual Study Completion Date :
Apr 19, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: PF-05280586

Biological: PF-05280586
PF-05280586 (rituximab-Pfizer) concentrate for solution for infusion 375mg/m2 administered via IV infusion on Days 1, 8, 15, and 22
Active Comparator: MabThera®

Biological: MabThera®
MabThera® (rituximab-EU) concentrate for solution for infusion 375mg/m2 administered via IV infusion on Days 1, 8, 15, and 22

Outcome Measures

Primary Outcome Measures

  1. Overall Response Rate (ORR): Percentage of Participants With Overall Response (OR) at Week 26 [Week 26]

    ORR was defined as the percentage of participants who achieved complete response (CR) or partial response (PR) in accordance with the revised response criteria for malignant lymphoma (Cheson 2007). CR was defined as disappearance of all evidence of disease. PR was defined as regression of measureable disease and no new sites.

Secondary Outcome Measures

  1. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline up to Week 52]

    An AE was any untoward medical occurrence in participants who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious.

  2. Number of Participants With Treatment Related Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline up to Week 52]

    Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state. Relatedness to treatment was assessed by investigator. AEs included both serious and non-serious AEs.

  3. Number of Participants With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 [Baseline up to Week 52]

    An AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Grade 1=Mild, asymptomatic or mild symptoms, Grade 2=Moderate; minimal, local or noninvasive intervention indicated, Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life threatening) events caused participant to be in imminent danger of death. Grade 5 = death. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state.

  4. Number of Participants With Grade 3 or Higher Treatment-Related Treatment-Emergent Adverse Events (AEs) as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 [Baseline up to Week 52]

    Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Grade 1=Mild, asymptomatic or mild symptoms, Grade 2=Moderate; minimal, local or noninvasive intervention indicated; Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 = death. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state.

  5. Number of Participants With Clinically Significant Laboratory Abnormalities [Baseline up to Week 52]

    Criteria for clinically significant laboratory abnormalities included total bilirubin (TB) less than (<) 2*upper limit of normal (ULN), alanine aminotransferase (ALT)<3*ULN; TB<2*ULN, ALT more than (>) 3 equal to (=) *ULN; TB<2*ULN, aspartate aminotransferase (AST)<3*ULN; TB<2*ULN, AST>=3*ULN. Data for only those categories are reported for which at least one participant had clinically significant laboratory abnormality.

  6. Time to Treatment Failure (TTF) [From randomization until disease progression, death or permanent discontinuation from treatment/study due to any reason, or up to Week 52]

    TTF was defined as the time (in months) from date of randomization to first progression of disease based on central review, death due to any cause, or permanent discontinuation from treatment, or discontinuation from study for any reason, whichever came first. Progression was defined as any new lesion or increase by greater than or equal to (>=) 50% of previously involved sites from nadir. TTF was calculated using Kaplan-Meier method.

  7. Progression-Free Survival (PFS) [From randomization until disease progression or death due to any cause or up to Week 52]

    PFS was defined as the time (in months) from date of randomization to first progression of disease (PD) based on central review or death due to any cause in the absence of documented PD. PD was defined as any new lesion or increase by >=50% of previously involved sites from nadir. PFS was calculated using Kaplan-Meier method.

  8. Percentage of Participants With Complete Remission (CR) at Week 26 [Week 26]

    Complete Remission (CR) was defined as disappearance of all evidence of disease. CR was assessed by central review based on scans done at Week 26.

  9. Duration of Response (DOR) [From date of first documentation of overall response to first documentation of PD or to death due to any cause in absence of PD or up to Week 52]

    DOR was defined as the time (in months) from date of the first documentation of overall response (CR or PR) to the first documentation of progressive disease (PD) based on central review or to death due to any cause in the absence of documented PD. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measureable disease and no new sites. PD was defined as any new lesion or increase by >=50% of previously involved sites from nadir. DOR was calculated using Kaplan-Meier method.

  10. Overall Survival [From randomization until death due to any cause or up to Week 52]

    Overall survival was defined as the time (in months) from date of randomization to death due to any cause. For participants who were alive, overall survival was censored at the last contact. Overall survival was calculated using Kaplan-Meier method.

  11. Maximum Observed Serum Concentration (Cmax) of PF-05280586 and Rituximab-EU [Predose (within 4 hours prior to start of infusion) on Days 1, 8, 15 and 22; within 15 minutes prior to end of infusion on Days 1 and 22]

  12. Minimum Observed (Trough) Serum Concentration (Ctrough) of PF-05280586 and Rituximab-EU [Predose (within 4 hours prior to the start of dosing) on Day 1, 8, 15, and 22]

  13. Cluster of Differentiation (CD) 19-Positive B-Cell Counts [Baseline, Week 2, 3, 4, 5, 13, 26, 39, 52]

  14. Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) [Baseline up to Week 52]

    Human serum ADA samples were analyzed for the presence or absence of anti-rituximab antibodies or anti-PF-05280586 antibodies using the validated drug-specific assay with a tiered approach using screening, confirmation and titer/quantitation. Human NAb serum samples testing ADA positive were analyzed for the presence or absence of neutralizing anti-rituximab antibody and neutralizing anti-PF-05280586 antibody using the validated drug-specific assay with a tiered approach using screening, confirmation and titer/quantitation. Participants with their ADA titer >= 1.88 were considered to be ADA positive. Only participants with a positive ADA result were further tested for NAb.

  15. Number of Participants Reporting Immune-Based Adverse Effects [Baseline up to Week 52]

    Immune-based adverse effects included infusion related reaction (IRR), adverse events which fulfill Sampson's criteria, and adverse events which belong to the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) anaphylaxis or hypersensitivity reactions. Potential allergic and anaphylactic reactions were identified programmatically based on the criteria of Sampson et al, (2006).

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Confirmed diagnosis of low tumor burden, CD20-positive follicular lymphoma

  • Ann Arbor Stage II, III, or IV

Exclusion Criteria:

  • Not a candidate for treatment with rituximab as a single-agent

  • Evidence of transformation to a high grade or diffuse large B-cell lymphoma

  • Any previous systemic therapy for B-cell NHL, including chemotherapy, immunotherapy, or steroids

  • Any prior treatment with rituximab

  • Active, uncontrolled infection

Contacts and Locations

Locations

Site City State Country Postal Code
1 Pacific Cancer Medical Center, Inc. Anaheim California United States 92801
2 The Oncology Institute of Hope and Innovation Anaheim California United States 92801
3 Compassionate Care Research Group, Inc., at Compassionate Cancer Care Medical Group, Inc. Corona California United States 92879
4 The Oncology Institute of Hope and Innovation Downey California United States 90241
5 Compassionate Care Research Group, Inc., at Compassionate Cancer Care Medical Group, Inc. Fountain Valley California United States 92708
6 Global Cancer Research Institute (GCRI), Inc Gilroy California United States 95020
7 Saint Louise Regional Hospital Radiology Department (Radiology Only) Gilroy California United States 95020
8 South Valley Imaging Center (Imaging Only) Gilroy California United States 95020
9 Los Angeles Hematology Oncology Medical Group Glendale California United States 91204
10 The Oncology Institute of Hope and Innovation Glendale California United States 91204
11 Los Angeles Hematology Oncology Medical Group Glendale California United States 91206
12 The Oncology Institute of Hope and Innovation Long Beach California United States 90805
13 Los Angeles Hematology Oncology Medical Group Los Angeles California United States 90017
14 Los Angeles Hematology Oncology Medical Group Los Angeles California United States 90057
15 The Oncology Institute of Hope and Innovation Lynwood California United States 90262
16 The Oncology Institute of Hope and Innovation Montebello California United States 90640
17 Comprehensive Cancer Center at Desert Regional Medical Center Palm Springs California United States 92262
18 Torrance Health Association DBA, Torrance Memorial Physician, Network/Cancer Care Associates Redondo Beach California United States 90277
19 Compassionate Care Research Group, Inc., at Compassionate Cancer Care Medical Group, Inc. Riverside California United States 92501
20 Global Cancer Research Institute, Inc. San Jose California United States 95124
21 O'Connor Hospital San Jose California United States 95128
22 PET Imaging of San Jose (Imaging Only) San Jose California United States 95128
23 The Oncology Institute of Hope and Innovation Santa Ana California United States 92705
24 Torrance Memorial Medical Center Torrance California United States 90505
25 The Oncology Institute of Hope and Innovation Whittier California United States 90602
26 Innovative Clinical Research Institute (ICRI) Whittier California United States 90603
27 Rocky Mountain Cancer Centers Aurora Colorado United States 80012
28 Rocky Mountain Cancer Centers Boulder Colorado United States 80303
29 Rocky Mountain Cancer Centers Denver Colorado United States 80218
30 Rocky Mountain Cancer Center-Lakewood (Laboratory) Lakewood Colorado United States 80228
31 Rocky Mountain Cancer Centers (RMCC) - Lakewood - St Anthony Lakewood Colorado United States 80228
32 Rocky Mountain Cancer Centers Lone Tree Colorado United States 80124
33 Rocky Mountain Cancer Center Pueblo Pueblo Colorado United States 81008
34 John D. Archbold Memorial Hospital Thomasville Georgia United States 31792
35 Lewis Hall Singletary Oncology Center At John D. Archbold Memorial Hospital Thomasville Georgia United States 31792
36 Northwestern Medicine West Region DeKalb Illinois United States 60115
37 Cancer Center,Northwestern Medicine, West Region Geneva Illinois United States 60134
38 Cancer Center of Kansas Chanute Kansas United States 66720
39 Cancer Center of Kansas Dodge City Kansas United States 67801
40 Cancer Center of Kansas El Dorado Kansas United States 67042
41 Cancer Center of Kansas Independence Kansas United States 67301
42 Cancer Center of Kansas Kingman Kansas United States 67068
43 Cancer Center of Kansas Liberal Kansas United States 67905
44 Cancer Center of Kansas McPherson Kansas United States 67460
45 Cancer Center of Kansas Newton Kansas United States 67114
46 The University of Kansas Cancer Center Overland Park Kansas United States 66210
47 Cancer Center of Kansas Parsons Kansas United States 67357
48 Cancer Center of Kansas Salina Kansas United States 67401
49 Cancer Center of Kansas Wellington Kansas United States 67152
50 Cancer Center of Kansas Wichita Kansas United States 67208
51 Cancer Center of Kansas Wichita Kansas United States 67214
52 Cancer Center Of Kansas Winfield Kansas United States 67156
53 PET/CT facility Seton Imaging Center Baltimore Maryland United States 21229
54 Saint Agnes Hospital Baltimore Maryland United States 21229
55 Rcca Md Llc Bethesda Maryland United States 20817
56 Holy Cross Hospital Resource Center Silver Spring Maryland United States 20902
57 Holy Cross Hospital Hospital Pharmacy Silver Spring Maryland United States 20910
58 Holy Cross Hospital Silver Spring Maryland United States 20910
59 Maryland Oncology Hematology, P.A. Wheaton Maryland United States 20902
60 The University of Kansas Cancer Center Kansas City Missouri United States 64131
61 The University of Kansas Cancer Center Kansas City Missouri United States 64154
62 The University of Kansas Cancer Center Lee's Summit Missouri United States 64064
63 Saint Francis Medical Center, Saint Francis Cancer Treatment Center Grand Island Nebraska United States 68803
64 Saint Francis Medical Center Grand Island Nebraska United States 68803
65 Saint Francis Medical Center, Saint Francis Cancer Treatment Center Hastings Nebraska United States 68901
66 Comprehensive Cancer Centers of Nevada Henderson Nevada United States 89052
67 Comprehensive Cancer Centers of Nevada Henderson Nevada United States 89074
68 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States 89128
69 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States 89148
70 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States 89169
71 Brody School of Medicine at East Carolina University Greenville North Carolina United States 27834
72 Vidant Medical Center Pharmacy Greenville North Carolina United States 27834
73 Vidant Medical Center Greenville North Carolina United States 27834
74 Toledo Clinic Cancer Center - Maumee Maumee Ohio United States 43537
75 Toledo Clinic Cancer Center - Toledo Toledo Ohio United States 43623
76 Toledo Clinic, Inc. Toledo Ohio United States 43623
77 Willamette Valley Cancer Institute and Research Center Eugene Oregon United States 97401
78 University of Tennessee Medical Center Knoxville Tennessee United States 37920
79 San Antonio Military Medical Center- Department of Pharmacy Fort Sam Houston Texas United States 78234
80 San Antonio Military Medical Center- Department of Radiology Fort Sam Houston Texas United States 78234
81 San Antonio Military Medical Center Fort Sam Houston Texas United States 78234
82 Investigational Products Center (I PC) Fort Worth Texas United States 76177
83 Investigational Products Center (IPC) Fort Worth Texas United States 76177
84 Millennium Oncology Houston Texas United States 77090
85 US Oncology Investigational Products Center (IPC) Irving Texas United States 75063
86 Millennium Oncology Kingwood Texas United States 77339
87 Texas Oncology - Longview Cancer Center Longview Texas United States 75601
88 Millennium Oncology Shenandoah Texas United States 77384
89 Millennium Oncology The Woodlands Texas United States 77380
90 Texas Oncology-Tyler Tyler Texas United States 75702
91 Yakima Valley Memorial Hospital/North Star Lodge Cancer Center Yakima Washington United States 98902
92 Krankenhaus der Barmherzigen Schwestern Linz Linz Austria 4010
93 Kepler Universitaetsklinikum GmbH Linz Austria 4020
94 Kepler Universitaetsklinikum GmbH Linz Austria 4021
95 SI 'Republican Research and Practice Centre of Oncology and Medical Radiology n.a. N.N. Alexandrov' Lesnoy Minsk Region Belarus 220013
96 SI 'Republican Research and Practice Centre of Oncology and Medical Radiology n.a. N.N. Alexandrov' Lesnoy Minsk Region Belarus 223040
97 Healthcare Institution "Brest Regional Oncologic Dispensary" Brest Belarus 224027
98 Healthcare Institution 'Minsk City Clinical Oncology Dispensary' Minsk Belarus 220013
99 SI Republican Research and Practice Centre of oncology and medical radiology n.a N.N Alexandrov Republic Of Belarus Belarus 223040
100 Hopital Erasme Brussels Belgium 1070
101 Nuclear Medicine Department Brussels Belgium 1200
102 Grand Hopital de Charleroi-Site Notre-Dame Charleroi Belgium 6000
103 PET/CT facility: Grand Hopital de Charleroi (GHdC) - site Notre-Dame Charleroi Belgium 6000
104 Pharmacy Department: Grand Hopital de Charleroi (GHdC) - site Notre-Dame Charleroi Belgium 6000
105 Pharmacy Department, Centre Hospitalier De Jolimont - Lobbes La Louviere (Haine-Saint Paul) Belgium 7100
106 Centre Hospitalier de Jolimont - Lobbes La Louviere (Haine-Saint-Paul) Belgium 7100
107 Radiology Department La Louviere (Haine-Saint-Paul) Belgium 7100
108 C.H.U. Ambroise Pare Mons Belgium 7000
109 Pharmacy Department, CHU Ambroise Pare Mons Belgium 7000
110 Hospital Santa Izabel - Setor de Bioimagem Salvador Bahia Brazil 40050-410
111 Hospital Santa Izabel / Santa Casa de Misericordia da Bahia Salvador Bahia Brazil 40050-410
112 Clinica Multimagem Goiania GO Brazil 74175-150
113 Hospital das Clinicas da Universidade Federal de Goias \ Centro de Pesquisa Clinica Goiania GO Brazil 74605-020
114 Centro de Imagens da Faculdade de Medicina - INCT Medicina Nuclear - PET/CT Belo Horizonte MG Brazil 30130-100
115 Unidade Funcional Apoio Diagnostico e terapeutica por Imagem do HC/UFMG - CT Scan Belo Horizonte MG Brazil 30130-100
116 Hospital das Clinicas Universidade Federal de Minas Gerais Belo Horizonte Minas Gerais Brazil 30130-100
117 Central de Misturas Intravenosas do Hospital de Clinicas de Porto Alegre Porto Alegre RIO Grande DO SUL Brazil 90035-903
118 Hospital de Clinicas de Porto Alegre - Centro de Pesquisa Clinica Porto Alegre RIO Grande DO SUL Brazil 90035-903
119 Hospital de Clinicas de Porto Alegre Porto Alegre RIO Grande DO SUL Brazil 90035-903
120 Servico de Radiologia do Hospital de Clinicas de Porto Alegre Porto Alegre RIO Grande DO SUL Brazil 90035-903
121 CDI - Centro de Diagnostico por Imagem do Hospital Sao Lucas da PUCRS Porto Alegre RS Brazil 90610-000
122 InsCer - Instituto do Cerebro do Rio Grande do Sul - PUCRS Porto Alegre RS Brazil 90610-000
123 Uniao Brasileira de Educacao e Assistencia (UBEA) - Hospital Sao Lucas da PUCRS - Porto Alegre RS Brazil 90610-000
124 Fundacao Amaral Carvalho / Fundacao Dr. Amaral Carvalho Jau SAO Paulo Brazil 17210-080
125 Fundacao Amaral Carvalho / Fundacao Dr. Amaral Carvalho Jau SAO Paulo Brazil 17210-120
126 Unidade de Quimioterapia Jaú SAO Paulo Brazil 17210-120
127 Casa da Esperanca Santo Andre SAO Paulo Brazil 09030-340
128 Tecnolab Sao Bernardo do Campo SAO Paulo Brazil 09750-670
129 CEMEDI Campinas SP Brazil 13075-460
130 Instituto Radium Campinas SP Brazil 13075-460
131 CAEP - Centro Avancado de Estudos e Pesquisas LTDA Campinas SP Brazil 13087-567
132 Hospital e Maternidade Madre Theodora LTDA Campinas SP Brazil 13087-567
133 CENNI Oncologia Campinas SP Brazil 13092-132
134 Fundacao do ABC - FMABC/ Faculdade de Medicina ABC ( CEPHO - Centro de Estudos e Pesquisas de Santo Andre SP Brazil 09060-650
135 Hospital Bandeirantes Sao Paulo SP Brazil 01506-000
136 Hospital das Clinicas da Faculdade de Medicina da USP / Fundacao Faculdade de Medicina MEC MPAS Sao Paulo SP Brazil 05403-000
137 Casa de Saude Santa Marcelina (Centro de Pesquisa Santa Marcelina) Sao Paulo SP Brazil 08270-070
138 IEP São Lucas (Pharmacy) São Paulo SP Brazil 01242-020
139 IEP Sao Lucas - Instituto de Ensino e Pesquisa Sao Lucas / HEMOMED - Instituto de Oncologia e Sao Paulo Brazil 01236-030
140 Fleury Sao Paulo Brazil 01333-910
141 University Hospital Center Zagreb, Department of Nuclear Medicine and Radiation Protection Zagreb Croatia 10 000
142 University Hospital Center Zagreb, Department of Pathology and Cytology Zagreb Croatia 10 000
143 University Hospital Center Zagreb, Department of Radiology Zagreb Croatia 10 000
144 University Hospital Centre "Sestre Milosrdnice" Zagreb Croatia 10000
145 University Hospital Centre Zagreb Zagreb Croatia 10000
146 CHU Marseille Hopital de La Conception Marseille Marseille Cedex 05 France 13385
147 CH de Mulhouse, Hopital Emile Muller Mulhouse Mulhouse Cedex France 68100
148 Hopital Duchenne Chu - Boulogne Sur Mer Boulogne Sur Mer NAP France 62321
149 Hopital Duchenne Chu - Boulogne Sur Mer Boulogne Sur Mer France 62321
150 Centre Hospitalier De Bourg En Bresse Bourg En Bresse Cedex France 01012
151 Hopital Morvan-CHU Brest- Service Hematologie Clinique Brest France 29609
152 Centre Hospitalier Universitaire Cote de Nacre Caen France 14033
153 Centre Hospitalier du Mans Le Mans France 72037
154 Clinique de la Sauvegarde Lyon France 69009
155 "LTD ""M. Zodelava's Hematology Centre""" Tbilisi Georgia 0112
156 LTD "Research Institute of Clinical Medicine" Tbilisi Georgia 0112
157 High Technology Medical Center, University Clinic Tbilisi Georgia 0144
158 Charite - Universitaetsmedizin Berlin Berlin Germany 12200
159 Charite - Universitatsmedizin Berlin - Campus Benjamin Franklin Berlin Germany 12200
160 Charite - Universitaetsmedizin Berlin, Campus Virchow-Klinikum Berlin Germany 13353
161 Charite - Universitatsmedizin Berlin, Campus Virchow-Klinikum Berlin Germany 13353
162 Charite - Universitatsmedizin Berlin Berlin Germany 13353
163 Klinikum Chemnitz gGmbH - Institut fuer Interventionelle Radiologie und Neuroradiologie Chemnitz Germany 09113
164 Klinikum Chemnitz gGmbH Chemnitz Germany 09113
165 Klinikum Chemnitz gGmbH - Klinik fuer Nuklearmedizin Chemnitz Germany 09116
166 Klinikum Chemnitz gGmbH - Zentralapotheke Chemnitz Germany 09116
167 Universitaetsklinikum Essen (AoeR) Essen Germany 45147
168 Universitatsklinikum Essen (AoR) Essen Germany 45147
169 DokuSan Gesellschaft fuer Medizinische Studien mbH & Co. KG Herne Germany 44623
170 Apotheke des St. Anna Hospital Herne Germany 44649
171 EVK Eickel Herne Germany 44651
172 Praxis im Koeln Triangle Koeln Germany 50679
173 Gemeinschaftspraxis fuer Diagnostische Radiologie und Nuklearmedizin Mutlangen Germany 73557
174 Kliniken Ostalb, Stauferklinikum Schwaebisch Gmuend, Zentrum fuer Innere Medizin Mutlangen Germany 73557
175 Stauferklinikum Schwaebisch Gmuend, Apotheke Mutlangen Germany 73557
176 Universitaetsmedizin Rostock Rostock Germany 18057
177 Klinikum Stuttgart, Klinik fuer Nuklearmedizin Stuttgart Germany 70174
178 Vinzenz von Paul Kliniken gGmbH Stuttgart Germany 70199
179 Radiologie Rhein-Sieg Troisdorf Germany 53840
180 Ueberoertliche Berufsausuebungsgemeinschaft Drs. med. Helmut Forstbauer Troisdorf Germany 53840
181 Zentralapotheke Troisdorf Germany 53842
182 Gen. Hosp. of Athens "Evangelismos - Eye Hosp.- Polikliniki" Athens Greece 10676
183 Gen. Hosp. of Athens "Evangelismos-Eye Hosp. - Polikliniki" Athens Greece 10676
184 Gen. Hosp. of Athens "Evangelismos-Eye Hosp.-Polikliniki" Athens Greece 10676
185 Gen.Hosp.of Athens "Evangelismos-Eye Hosp.-polikiliniki" Athens Greece 10676
186 General Hospital of Athens "Evangelismos - Eye Hosp. - Polikliniki" Athens Greece 10676
187 Bioiatriki S.A. Athens Greece 11526
188 Bioiatriki Athens Greece 11526
189 General Hospital of Athens 'Laiko' Athens Greece 11527
190 """ATTIKON"" Gen. Univ. Hosp" Athens Greece 12462
191 "ATTIKON'' Gen. Univ. Hosp. Chaidari, Athens Greece 12462
192 Magnitiki Patron Patras Greece 26222
193 University General Hospital of Patras Patras Greece 26504
194 Super Scan Imaging Centre Surat Gujarat India 395001
195 Pathology Department, Unique Hospital Multispeciality & Research Institute Surat Gujarat India 395002
196 Zircon- BIC Imaging Centre Surat Gujarat India 395002
197 Mangalore Institute of Oncology Mangalore Karanataka India 575002
198 HealthCare Global Enterprises Limited Bangalore Karnataka India 560027
199 Kasturba Medical College and Hospital Manipal Karnataka India 576104
200 Curie Manavata Cancer Centre Nashik Maharashtra India 422004
201 Department of Radiology, Curie Manavata Cancer Centre Nashik Maharashtra India 422004
202 Department of Radiology Pune Maharashtra India 411001
203 Jehangir Clinical Development Centre Pvt. Ltd. Pune Maharashtra India 411001
204 Ruby Hall clinic Pune Maharashtra India 411001
205 R.K. Birla Cancer Center, Sawai Man Singh Hospital Jaipur Rajasthan India 302004
206 Apollo Speciality Hospital Chennai Tamilnadu India 600035
207 Department of Radiology Chennai Tamilnadu India 600035
208 Global Hospitals Hyderabad Telangana India 500 004
209 Vijaya Diagnostic Centre Hyderabad Telangana India 500029
210 N.R.S Medical College and Hospital Kolkata WEST Bengal India 700014
211 Spandan PET-CT Unit Kolkata WEST Bengal India 700014
212 Rajiv Gandhi Cancer Institute & Research Center (RGCIRC) New Delhi India 110 085
213 U.O. di Ematologia e CTMO - Istituti Ospedalieri di Cremona Cremona CR Italy 26100
214 IRST - IRCCS U. O. Oncologia Medica Meldola FC Italy 47014
215 U.O. Ematologia 1 - IRCCS AOU San Martino-IST Genova GE Italy 16132
216 Unita di Ricerca Clinica Monza MB Italy 20900
217 Istituto Europeo di Oncologia Milano MI Italy 20141
218 Unità semplice di Medicina Nucleare Latina NAP Italy 04100
219 Clinica Ematologica - A.O.U. Ospedali Riuniti di Ancona Torrette Ancona Palermo Italy 60121
220 Az Ospedaliera Santa Maria Terni PG Italy 05100
221 Medicina nucleare Reggio Emilia Reggio Italy 42123
222 Radiologia Reggio Emilia Reggio Italy 42123
223 SC Ematologia - SC Ematologia - Arcispedale Santa Maria Nuova - IRCCS Reggio Emilia Reggio Italy 42123
224 "Dipartimento di Biotecnologie Cellulari ed Ematologia, Universita ""Sapienza"" Rome Rome Rm Italy 00161
225 IRCSS A.O.U. San Martino - IST - UO Clinica Ematologica Genova Italy 16132
226 SC Ematologia, Fondazione IRCCS Ist Nazionale dei Tumori Milano Italy 20133
227 Padiglione 1, Torre delle medicine, 6 piano Parma Italy 43100
228 Ematologia e Centro Trapianti - AZ Osp. Ospedali Riuniti Marche Nord (AORMN) - Presidio S. Salvatore Pesaro Italy 61122
229 U.O. Ematologia Universitaria - Dip. Di Oncologia dei Trapianti - AOU Pisana Pisa Italy 56126
230 Policlinico Universitario Campus Bio- Medico-U.O.C. di Ematologia Trapianto Cellule Staminali Roma Italy 00128
231 East Nagoya Imaging Diagnosis Center Nagoya Aichi Japan 464-0044
232 Nagoya Daini Red Cross Hospital Nagoya Aichi Japan 466-8650
233 Akita University Hospital Akita City Akita Japan 010-8543
234 Chiba Cancer Center Chiba-shi Chiba Japan 260-8717
235 National Hospital Organization Kyushu Medical Center Fukuoka-shi Fukuoka Japan 810-8563
236 National Hospital Organization Kyushu Cancer Center Fukuoka-Shi Fukuoka Japan 811-1395
237 Kobe City Medical Center General Hospital Kobe-City Hyogo Japan 650-0047
238 National Hospital Organization Kanazawa Medical Center Kanazawa Ishikawa Japan 920-8650
239 Kanazawa Advanced Medical Center Kanazawa Ishikawa Japan 9200934
240 Showa University Northern Yokohama Hospital Yokohama-shi Kanagawa-ken Japan 224-8503
241 Kochi Medical School Hospital Okocho, Nankoku Kochi Japan 783-8505
242 National Hospital Organization Kumamoto Medical Center Kumamoto-shi Kumamoto-ken Japan 860-0008
243 Uozumi Clinic Kumamoto-shi Kumamoto-ken Japan 862-0941
244 Sendai Kousei Hospital Sendai-shi Miyagi Japan 980-0873
245 National Hospital Organization Sendai Medical Center Sendai-shi Miyagi Japan 983-8520
246 Aizawa Hospital Matsumoto-shi Nagano Japan 390-8510
247 Nagano Red Cross Hospital Nagano-shi Nagano Japan 380-8582
248 National Hospital Organization Nagasaki Medical Center Omura Nagasaki Japan 856-8562
249 National Hospital Organization Osaka Minami Medical Center Kawachinagano Osaka Japan 586-8521
250 Hanwa Dai 2 Senboku Hospital Naka-ku Sakai Osaka Japan 599-8271
251 Osaka City University Hospital Osaka-City Osaka Japan 545-8586
252 Tokushima University Hospital Tokushima-Shi Tokushima Japan 770-8503
253 National Hospital Organization Tokyo Medical Center Meguro-Ku Tokyo Japan 152-8902
254 Showa University Hospital Shinagawa-ku Tokyo Japan 142-8666
255 National Hospital Organization Disaster Medical Center Tachikawa Tokyo Japan 190-0014
256 Yamagata University Hospital Yamagata-Shi Yamagata Japan 990-9585
257 Fukuoka Wajiro PET Diagnostic Imaging Clinic Fukuoka Japan 811-0213
258 National Hospital Organization Matsumoto Medical Center Nagano Japan 399-8701
259 Musashimurayama Hospital Tokyo Japan 2080022
260 Hallym University Sacred Heart Hospital Anyang-si Gyeonggi-do Korea, Republic of 14068
261 Seoul National University Bundang Hospital Seongnam-si Gyeonggi-do Korea, Republic of 463-707
262 Chonbuk National University Hospital Jeonju-si Jeollabuk-do Korea, Republic of 54907
263 Ulsan University Hospital Ulsan Korea Korea, Republic of 44033
264 Inje University Busan Paik Hospital Busan Korea, Republic of 47392
265 Seoul National University Hospital Seoul Korea, Republic of 03080
266 Samsung Medical Center Seoul Korea, Republic of 06351
267 Hammoud Hospital, University Medical Center Saida Southern Governate Lebanon
268 Doctors Center Radiology Beirut Lebanon
269 Mount Lebanon Hospital Beirut Lebanon
270 Middle East Institute Of Health El Metn Lebanon
271 Ain Wazein Hospital Mount Lebanon Lebanon
272 Grupo Medico Camino S.C. Mexico City Distrito Federal Mexico 03310
273 Imagenus Mexico City Distrito Federal Mexico 03340
274 Isos Pharmacorp, S.A. de C.V. Mexico City Distrito Federal Mexico 06700
275 Vely Grupo Medico Quirurgico, S.A. de C.V. Cuautitlan Izacalli Estado DE Mexico Mexico 54750
276 Phylasis Clinicas Research S. de R.L. de C.V. Cuautitlan Izcalli Estado DE Mexico Mexico 54769
277 Centro Universitario de Imagen Diagnostica, Radiologia e Imagen del Hospital Universitario Monterrey Nuevo LEON Mexico 64460
278 Hospital Universitario "Dr. Jose Eleuterio Gonzalez" Monterrey Nuevo LEON Mexico 64460
279 Cirurgia y Ginecobstetricia de Oaxaca, S.A de C.V. Oaxaca Mexico 68000
280 Oaxaca Site Management Organization S.C. Oaxaca Mexico 68000
281 Hospital Angeles Puebla Puebla Mexico 72190
282 Cancerologia de Queretaro S.C. Queretaro Mexico 76090
283 Hospital Infantil Teleton de Oncologia Queretaro Mexico 76140
284 Hospital San Jose Norte Queretaro Mexico 76158
285 Instituto Nacional de Enfermedades Neoplasicas Surquillo Lima Peru 34
286 Pet Scan Peru Lima Peru 18
287 Resocentro Lima Peru 18
288 University of Philippines Manila-Philippine General Hospital Manila Metro Manila Philippines 1000
289 St. Luke's Medical Center Quezon City Philippines 1102
290 Klinika Nowotworow Ukladu Chlonnego Centrum Onkologii - Instytut im. M. Sklodowskiej-Curie Warszawa Poland 02-781
291 Euromedic Wroclawskie Centrum Medyczne II Wroclaw Poland 50-420
292 Euromedic Wroclawskie Centrum Medyczne III Wroclaw Poland 50-557
293 Dolnoslaskie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku Wroclaw Poland 53-439
294 Euromedic Wroclawskie Centrum Medyczne I Wroclaw Poland 53-439
295 Apteka Dolnoslaskiego Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku Wroclaw Poland 54-424
296 Unidade Local de Saude de Matosinhos E.P.E. - Hospital Pedro Hispano S.A. Matosinhos Porto Portugal 4464-513
297 Hospital de Braga Braga Portugal 4710-243
298 Hospital CUF Descobertas Lisboa Portugal 1998-018
299 CIMC Porto Portugal 4050-075
300 Dr. Campos Costa Clinic Porto Portugal 4050-075
301 Centro Hospitalar do Porto-Hospital de Santo Antonio E.P.E. Porto Portugal 4099 - 001
302 Instituto Portugues de Oncologia do Porto Francisco Gentil E.P.E Porto Portugal 4200-072
303 Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E. Vila Nova de Gaia Portugal 4434-502
304 Modern Radiology, PSC Coto Laurel Puerto Rico 00780
305 Ad-Vance Medical Research, LLC Ponce Puerto Rico 00717
306 Caribe MRI and CT Ponce Puerto Rico 00717
307 Policlinica de Diagnostic Rapid, Hematologie Brasov Romania 500152
308 Policlinica de Diagnostic Rapid SA Brasov Romania 500366
309 Spitalul Clinic Colentina Bucuresti Romania 020125
310 Hiperdia Ritmului Bucuresti Romania 021675
311 Affidea Fundeni Bucuresti Romania 022328
312 Affidea Romania SRL Bucuresti Romania 022328
313 Spitalul Clinic Coltea, Clinica de Hematologie Bucuresti Romania 030171
314 Institutul Oncologic Prof. Dr. Ion Chiricuta, Laborator Radiologie si Imagistica Medicala Cluj-Napoca Romania 400015
315 Institutul Oncologic Prof. Dr. Ion Chiricuta, Sectia Oncologie Medicala Cluj-Napoca Romania 400015
316 Clinica de Hematologie-Institutul Oncologic, Prof. Dr. Ion Chiricuta Cluj-Napoca Romania 400124
317 CT Clinic S.R.L. Cluj-Napoca Romania 400489
318 A.Tsyb Medical Radiological Research Centre - Obninsk Kaluga Region Russian Federation 249036
319 State Healthcare Institution Republican Oncology Dispensary Saransk Mordovian Republic Russian Federation 430032
320 "SBHI of NNR ""Nizhniy Novgorod Regional Clinical Hospital n.a. N.A. Semashko""" Nizhniy Novgorod Nizhniy Novgorod Region Russian Federation 603126
321 LLC MC "MRT-Diagnostika" Nizhniy Novgorod Nizhniy Novgorod Region Russian Federation 603126
322 FSBI "Russian Research Centre of Radiology and Surgical Technologies" of MoH of RF Saint-Petersburg Pesochniy TOWN Russian Federation 197758
323 FSBI "Russian Research Centre of Radiology and Surgical Technologies" Saint-Petersburg Pesochniy TOWN Russian Federation 197758
324 FSBI "Russian Research Centre of Radiology and Surgical Technologies Saint-Petersburg Pesochniy TOWN Russian Federation 197758
325 FSBI 'Russian Research Centre of Radiology and Surgical Technologies Saint-Petersburg Pesochniy TOWN Russian Federation 197758
326 FSBI "Russian Research Centre of Radiology and Surgical Technologies n.a. A.M. Granov" of MoH of RF Saint-Petersburg Pesochniy Russian Federation 197758
327 FSBI "Russian Research Centre of Radiology and Surgical Technologies named after academician Saint-Petersburg Pesochniy Russian Federation 197758
328 FSBI "Russian Research Centre of Radiology and Surgical Technologies Saint-Petersburg Pesochniy Russian Federation 197758
329 FSBI 'National Medical Oncology Research Centre n.a. N.N.Petrov' Saint-Petersburg Pos.pesochny Russian Federation 197758
330 Branch office of LLC 'PET-Technology' at Ufa city Ufa Republic Bashkortostan Russian Federation 450054
331 State Budgetary Healthcare Institution "Republican Clinical Oncology Dispensary of the Ministry Ufa Republic Bashkortostan Russian Federation 450054
332 Private medical institution "Euromedservice" Pushkin Saint Petersburg Russian Federation 196603
333 FSBI "Russian Research Centre of Radiology and Surgical Technologies" of MoH of RF Pesochniy Town Saint-petersburg Russian Federation 197758
334 Federal State-Financed Institution 'North-Caucasian Research and Clinical Center' Lermontov Stavropol Region Russian Federation 357340
335 SBHI of Stavropol Region "Pyatigorsk Interdistrict Oncology Dispensary Pyatigorsk Stavropol Region Russian Federation 357502
336 "State Budget Healthcare Institution ""Chelyabinsk Regional Clinical Center of Oncology Chelyabinsk Russian Federation 454087
337 FSBSI 'N.N.Blokhin Russian Cancer Research Center' of MoH of RF Moscow Russian Federation 115478
338 Russian Cancer Research Centre them N.N. Blokhin Moscow Russian Federation 115478
339 LLC "VitaMed" Moscow Russian Federation 121309
340 SBHI of Moscow City Clinical Hospital n.a. S.P.Botkin of Healthcare Department of Moscow Moscow Russian Federation 125284
341 Ramsay Diagnostics Moscow Russian Federation 127473
342 State Budgetary Institution of Healthcare "Leningrad Regional Clinical Hospital" Saint Petersburg Russian Federation 194291
343 Dr. Berezin Medical Institute Saint-Petersburg Russian Federation 194214
344 N.P. Bechtereva Institute of Human Brain of the Russian Academy of Sciences Saint-Petersburg Russian Federation 197376
345 N.P. Bechtereva Institute of the Human Brain of the Russian Academy of Sciences Saint-Petersburg Russian Federation 197376
346 Non-state healthcare institution "Road Clinical Hospital of Joint Stock Company "Russian Railways" Saint-Petersurg Russian Federation 195271
347 Yaroslavl State Medical Academy Yaroslavl Russian Federation 150010
348 GBUZ of Yaroslavl Region "Regional Clinical Hospital" Yaroslavl Russian Federation 150062
349 NIKSCH & PARTNERS t/a CAPITAL RADIOLOGY Groenkloof Gauteng South Africa 0181
350 The Medical Oncology Centre of Rosebank Johannesburg Gauteng South Africa 2196
351 Department of Medical Oncology, University of Pretoria, Steve Biko Academic Hospitals Complex Pretoria Gauteng South Africa 0002
352 Albert Alberts Stem Cell Transplant Centre Pretoria Gauteng South Africa 0044
353 Dr JN De Jong and Partners t/a East Rad Pretoria Gauteng South Africa 0044
354 NIKSCH & PARTNERS t/a CAPITAL RADIOLOGY Pretoria Gauteng South Africa 0181
355 Drs Sulman & Partners Specialist Radiologists Rosebank Gauteng South Africa 2196
356 Drs Bloch & Partners Incorporated Sandton Gauteng South Africa 2191
357 Hospital Parc Tauli Sabadell Barcelona Spain 08208
358 Onkologikoa San Sebastian Guipuzcoa Spain 20014
359 Hospital Universitario Sanitas La Zarzuela Aravaca Madrid Spain 28023
360 Hospital Rey Juan Carlos Mostoles Madrid Spain 28933
361 Hospital Clinico Universitario Virgen de la Arrixaca El Palmar Murcia Spain 30120
362 Hospital Clínico Universitario Virgen de la Arrixaca El Palmar Murcia Spain 30120
363 Hospital do Meixoeiro Complejo Hospitalario Universitario de Vigo Vigo Pontevedra Spain 36200
364 Complejo Hospitalario Universitario A Coruna A Coruna Spain 15006
365 Hospital Modelo A Coruna Spain 15011
366 Hospital Del Mar Barcelona Spain 08003
367 Hospital Quiron de Barcelona, IEC Barcelona Spain 08012
368 CETIR, Centre Medic Barcelona Spain 08029
369 Radiodiagnostic CETIR - Clinica del Pilar Barcelona Spain 08029
370 Hospital Universitario Puerta del Mar Cadiz Spain 11009
371 Hospital Universitario Fundacion Jimenez Diaz Madrid Spain 28040
372 Hospital Universitario Sanitas La Moraleja Madrid Spain 28050
373 Centro CIMES Malaga Spain 29010
374 Hospital universitario Virgen de la Victoria Malaga Spain 29010
375 Centro Mario Gallegos Malaga Spain 29016
376 Complejo Hospitalario de Ourense. Hematología Ourense Spain 32005
377 Hospital Universitario Virgen del Rocio Sevilla Spain 41013
378 H. Quiron Zaragoza Zaragoza Spain 50006
379 Hospital de Dia Quiron Zaragoza Zaragoza Spain 50012
380 Universitatsspital Basel Basel Switzerland 4031
381 Inselspital Bern Bern Switzerland 3010
382 Apotheke, Spital STS AG Thun Switzerland 3600
383 Onkologiezentrum Thun-Berner Oberland Spital Sts Ag Thun Switzerland 3600
384 Kantonsapotheke Zuerich Zuerich Switzerland 8006
385 UniversitaetsSpital Zuerich Zuerich Switzerland 8091
386 Cardiology Unit,Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Bangkok Thailand 10400
387 Department of Radiology, Ramathibodi Hospital Bangkok Thailand 10400
388 National Cancer Institute Bangkok Thailand 10400
389 Hacettepe Universitesi Tip Fakultesi Onkoloji Hastanesi Ankara Turkey 06100
390 Dr. Abdurrahman Yurtaslan Ankara Onkoloji Eg. ve Aras. Ankara Turkey 06200
391 Ultramar Tibbi Gorunteleme Merkezi Ankara Turkey 06420
392 Ultramar Tibbi Goruntuleme Merkezi Ankara Turkey 06420
393 Integra Gurses Teshis Tedavi ve Saglik Hizmetleri A.S. Ankara Turkey 06540
394 Adnan Menderes University Medical Faculty Aydin Turkey 09010
395 Gaziantep Universitesi Sahinbey Arastirma ve Uygulama Hastanesi Gaziantep Turkey 27310
396 Gaziantep Universitesi Sahinbey Arastirma ve Uygulama Gaziantep Turkey 27310
397 Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi Istanbul Turkey 34093
398 Ege Universitesi Tip Fakultesi Ic Hastaliklari Anabilim Dali Izmir Turkey 35040
399 EGE-RAD Bilgisayarli Tomografi Ozel Saglik Hizmetleri ve Malzemeleri Tic.Ltd.Sti. Izmir Turkey 35040
400 Erciyes Universitesi Tip Fakultesi Nukleer Tip Laboratuvari Kayseri Turkey 38100
401 Erciyes Universitesi Tip Fakultesi Radyoloji Laboratuvari Kayseri Turkey 38100
402 Erciyes Universitesi Tip Fakultesi Kayseri Turkey 38100
403 Inonu Universitesi Tip Fakultesi Turgut Ozal Tip Merkezi Malatya Turkey 44280
404 Celal Bayar University Medical Faculty Manisa Turkey 45000
405 Ondokuz Mayis Universitesi Tip Fakultesi Samsun Turkey 55139
406 "Mediks-rey International Group" LLC Obukhiv District KYIV Region Ukraine 08720
407 "MedX-rey International Group" LLC Obukhiv District KYIV Region Ukraine 08720
408 "MedX-Ray International Group" LLC Obukhiv KYIV Region Ukraine 08720
409 "Municipal Institution ""Chernivtsi Regional Clinical Oncology Center"", Chernivtsi Ukraine 58013
410 MI 'City Dnipropetrovsk Multi-field Clin. Hospital #4 of DRC', Dnipropetrovsk Ukraine 49102
411 Municipal Non-Profit Enterprise "Regional Oncology Centre" Kharkiv Ukraine 61070
412 National Cancer Institute Kyiv Ukraine 03022
413 "Central City Clinical Hospital, City Oncology Center, SHEI ""Uzhhorod National University"", Chair Uzhhorod Ukraine 88017
414 Podilskyy Regional Oncology Center, Chemotherapy Department Vinnytsia Ukraine 21029
415 Municipal Establishment 'Zaporizhzhia Regional Clinical Oncology Dispensary' Zaporizhzhia Ukraine 69040
416 LLC "Diaservis" Zaporizhzhia Ukraine 69076
417 Southend University Hospital NHS Foundation Trust Westcliff-On-Sea Essex United Kingdom SS0 0RY
418 Cobalt Diagnostic Imaging Cheltenham Glos. United Kingdom GL53 7AS
419 Royal United Hospitals Bath NHS Foundation Trust Bath United Kingdom BA1 3NG
420 Barts Health NHS Trust London United Kingdom EC1A 7BE
421 Positron Emission Tomography (PET) Centre Newcastle upon Tyne United Kingdom NE4 6BE
422 City Hospitals Sunderland NHS Foundation Trust-Sunderland Royal Hospital Sunderland United Kingdom SR4 7TP
423 Diagnostic Imaging Sunderland United Kingdom SR4 7TP

Sponsors and Collaborators

  • Pfizer

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02213263
Other Study ID Numbers:
  • B3281006
  • 2014-000132-41
  • REFLECTIONS
First Posted:
Aug 11, 2014
Last Update Posted:
Jun 20, 2019
Last Verified:
Jun 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Pfizer
rituximab
follicular lymphoma
Non-Hodgkin lymphoma
Non-Hodgkin's lymphoma
Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Rituximab

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail A total of 394 participants were enrolled and randomized in 1:1 ratio to 1 of the 2 study treatment arms: PF-05280586 (Rituximab-Pfizer) and Rituximab-EU (MabThera®).
Arm/Group Title Rituximab-EU PF-05280586
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Period Title: Overall Study
STARTED 198 196
Treated 197 196
COMPLETED 170 170
NOT COMPLETED 28 26

Baseline Characteristics

Arm/Group Title Rituximab-EU PF-05280586 Total
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Total of all reporting groups
Overall Participants 198 196 394
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
58.3
(12.8)
58.7
(12.1)
58.5
(12.4)
Sex: Female, Male (Count of Participants)
Female
106
53.5%
110
56.1%
216
54.8%
Male
92
46.5%
86
43.9%
178
45.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
26
13.1%
31
15.8%
57
14.5%
Not Hispanic or Latino
172
86.9%
165
84.2%
337
85.5%
Unknown or Not Reported
0
0%
0
0%
0
0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
44
22.2%
30
15.3%
74
18.8%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
0
0%
1
0.5%
1
0.3%
White
146
73.7%
158
80.6%
304
77.2%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
8
4%
7
3.6%
15
3.8%

Outcome Measures

1. Primary Outcome
Title Overall Response Rate (ORR): Percentage of Participants With Overall Response (OR) at Week 26
Description ORR was defined as the percentage of participants who achieved complete response (CR) or partial response (PR) in accordance with the revised response criteria for malignant lymphoma (Cheson 2007). CR was defined as disappearance of all evidence of disease. PR was defined as regression of measureable disease and no new sites.
Time Frame Week 26

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Rituximab-EU PF-05280586
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Measure Participants 198 196
Number (95% Confidence Interval) [percentage of participants]
70.7
35.7%
75.5
38.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab-EU, PF-05280586
Comments Difference in ORR between PF-05280586 and rituximab-EU was computed using the stratified Mantel-Haenszel method. The 95% confidence interval for the difference was calculated using the asymptotic stratified method proposed by Miettinen and Nurminen.
Type of Statistical Test Equivalence
Comments Equivalence was tested within the pre-specified margins of (-16%, 16%) 95% confidence interval.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference in ORR
Estimated Value 4.66
Confidence Interval (2-Sided) 95%
-4.16 to 13.47
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description An AE was any untoward medical occurrence in participants who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious.
Time Frame Baseline up to Week 52

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title Rituximab-EU PF-05280586
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Measure Participants 197 196
AEs
145
73.2%
156
79.6%
SAEs
15
7.6%
17
8.7%
3. Secondary Outcome
Title Number of Participants With Treatment Related Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state. Relatedness to treatment was assessed by investigator. AEs included both serious and non-serious AEs.
Time Frame Baseline up to Week 52

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title Rituximab-EU PF-05280586
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Measure Participants 197 196
AEs
94
47.5%
86
43.9%
SAEs
2
1%
2
1%
4. Secondary Outcome
Title Number of Participants With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03
Description An AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Grade 1=Mild, asymptomatic or mild symptoms, Grade 2=Moderate; minimal, local or noninvasive intervention indicated, Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life threatening) events caused participant to be in imminent danger of death. Grade 5 = death. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state.
Time Frame Baseline up to Week 52

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title Rituximab-EU PF-05280586
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Measure Participants 197 196
Count of Participants [Participants]
26
13.1%
28
14.3%
5. Secondary Outcome
Title Number of Participants With Grade 3 or Higher Treatment-Related Treatment-Emergent Adverse Events (AEs) as Graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03
Description Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Grade 1=Mild, asymptomatic or mild symptoms, Grade 2=Moderate; minimal, local or noninvasive intervention indicated; Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. Grade 5 = death. Treatment-emergent were events after first dose of study drug that were absent before treatment or that worsened relative to pretreatment state.
Time Frame Baseline up to Week 52

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received at least 1 dose of any study drug.
Arm/Group Title Rituximab-EU PF-05280586
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Measure Participants 197 196
Count of Participants [Participants]
8
4%
9
4.6%
6. Secondary Outcome
Title Number of Participants With Clinically Significant Laboratory Abnormalities
Description Criteria for clinically significant laboratory abnormalities included total bilirubin (TB) less than (<) 2*upper limit of normal (ULN), alanine aminotransferase (ALT)<3*ULN; TB<2*ULN, ALT more than (>) 3 equal to (=) *ULN; TB<2*ULN, aspartate aminotransferase (AST)<3*ULN; TB<2*ULN, AST>=3*ULN. Data for only those categories are reported for which at least one participant had clinically significant laboratory abnormality.
Time Frame Baseline up to Week 52

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received at least 1 dose of any study drug. Here, 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
Arm/Group Title Rituximab-EU PF-05280586
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Measure Participants 197 195
TB<2*ULN, ALT<3*ULN
194
98%
192
98%
TB<2*ULN, ALT>=3*ULN
3
1.5%
3
1.5%
TB<2*ULN, AST<3*ULN
196
99%
195
99.5%
TB<2*ULN, AST>=3*ULN
1
0.5%
0
0%
7. Secondary Outcome
Title Time to Treatment Failure (TTF)
Description TTF was defined as the time (in months) from date of randomization to first progression of disease based on central review, death due to any cause, or permanent discontinuation from treatment, or discontinuation from study for any reason, whichever came first. Progression was defined as any new lesion or increase by greater than or equal to (>=) 50% of previously involved sites from nadir. TTF was calculated using Kaplan-Meier method.
Time Frame From randomization until disease progression, death or permanent discontinuation from treatment/study due to any reason, or up to Week 52

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized. Here. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
Arm/Group Title Rituximab-EU PF-05280586
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Measure Participants 48 54
Median (95% Confidence Interval) [months]
18.9
NA
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab-EU, PF-05280586
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.450
Comments A log-rank test stratified by follicular lymphoma international prognostic index 2 (FLIPI2) risk was used to compare the treatment groups with respect to TTF at a 2-sided alpha level of 0.05.
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.163
Confidence Interval (2-Sided) 95%
0.786 to 1.720
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio and its confidence intervals (CIs) were estimated from Cox Proportional hazards model stratified by FLIPI2 risk categorization.
8. Secondary Outcome
Title Progression-Free Survival (PFS)
Description PFS was defined as the time (in months) from date of randomization to first progression of disease (PD) based on central review or death due to any cause in the absence of documented PD. PD was defined as any new lesion or increase by >=50% of previously involved sites from nadir. PFS was calculated using Kaplan-Meier method.
Time Frame From randomization until disease progression or death due to any cause or up to Week 52

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized. Here. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
Arm/Group Title Rituximab-EU PF-05280586
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Measure Participants 28 37
Median (95% Confidence Interval) [months]
18.9
NA
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab-EU, PF-05280586
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.189
Comments
Method Log Rank
Comments A log-rank test stratified by FLIPI2 risk was used to compare the treatment groups with respect to PFS at a 2-sided alpha level of 0.05.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.393
Confidence Interval (2-Sided) 95%
0.847 to 2.291
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio and its CIs were estimated from Cox Proportional hazards model stratified by FLIPI2 risk categorization.
9. Secondary Outcome
Title Percentage of Participants With Complete Remission (CR) at Week 26
Description Complete Remission (CR) was defined as disappearance of all evidence of disease. CR was assessed by central review based on scans done at Week 26.
Time Frame Week 26

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Rituximab-EU PF-05280586
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Measure Participants 198 196
Number (95% Confidence Interval) [percentage of participants]
28.3
14.3%
26.0
13.3%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab-EU, PF-05280586
Comments Difference in CR between PF-05280586 and rituximab-EU was computed using the stratified Mantel-Haenszel method. The 95% confidence interval for the difference was calculated using the asymptotic stratified method proposed by Miettinen and Nurminen.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.31
Confidence Interval (2-Sided) 95%
-11.09 to 6.50
Parameter Dispersion Type:
Value:
Estimation Comments
10. Secondary Outcome
Title Duration of Response (DOR)
Description DOR was defined as the time (in months) from date of the first documentation of overall response (CR or PR) to the first documentation of progressive disease (PD) based on central review or to death due to any cause in the absence of documented PD. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measureable disease and no new sites. PD was defined as any new lesion or increase by >=50% of previously involved sites from nadir. DOR was calculated using Kaplan-Meier method.
Time Frame From date of first documentation of overall response to first documentation of PD or to death due to any cause in absence of PD or up to Week 52

Outcome Measure Data

Analysis Population Description
The response-evaluable population was defined as all randomized participants who received at least 1 dose of study drug, had adequate disease assessment at baseline, and at least 1 post baseline response assessment. Here. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
Arm/Group Title Rituximab-EU PF-05280586
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Measure Participants 19 28
Median (95% Confidence Interval) [months]
15.4
NA
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab-EU, PF-05280586
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.185
Comments A log-rank test stratified by FLIPI2 risk was used to compare the treatment groups with respect to DOR at a 2-sided alpha level of 0.05.
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.492
Confidence Interval (2-Sided) 95%
0.823 to 2.704
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio and its CIs were estimated from Cox Proportional hazards model stratified by FLIPI2 risk categorization.
11. Secondary Outcome
Title Overall Survival
Description Overall survival was defined as the time (in months) from date of randomization to death due to any cause. For participants who were alive, overall survival was censored at the last contact. Overall survival was calculated using Kaplan-Meier method.
Time Frame From randomization until death due to any cause or up to Week 52

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Rituximab-EU PF-05280586
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Measure Participants 198 196
Median (95% Confidence Interval) [months]
18.9
NA
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rituximab-EU, PF-05280586
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.319
Comments A log-rank test stratified by FLIPI2 risk was used to compare the treatment groups with respect to overall survival at a 2-sided alpha level of 0.05.
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.94
Confidence Interval (2-Sided) 95%
0.000 to
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio and its CIs were estimated from Cox Proportional hazards model stratified by FLIPI2 risk categorization.
12. Secondary Outcome
Title Maximum Observed Serum Concentration (Cmax) of PF-05280586 and Rituximab-EU
Description
Time Frame Predose (within 4 hours prior to start of infusion) on Days 1, 8, 15 and 22; within 15 minutes prior to end of infusion on Days 1 and 22

Outcome Measure Data

Analysis Population Description
The pharmacokinetic analysis set (PKAS) included participants who received at least 1 dose of any study drug and who provided at least one post-dose pharmacokinetic concentration. Here, 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
Arm/Group Title Rituximab-EU PF-05280586
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Measure Participants 132 138
Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter (ng/mL)]
334848.88
(33)
337708.05
(36)
13. Secondary Outcome
Title Minimum Observed (Trough) Serum Concentration (Ctrough) of PF-05280586 and Rituximab-EU
Description
Time Frame Predose (within 4 hours prior to the start of dosing) on Day 1, 8, 15, and 22

Outcome Measure Data

Analysis Population Description
The pharmacokinetic analysis set (PKAS) included participants who received at least 1 dose of any study drug and who provided at least one post-dose pharmacokinetic concentration. Here 'Number analyzed' signifies number of participants evaluable for this outcome measure at specified time points.
Arm/Group Title Rituximab-EU PF-05280586
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Measure Participants 197 196
Day 1
0.01
(577)
0.01
(1320)
Day 8
62311.74
(47)
66669.15
(45)
Day 15
109619.73
(43)
119026.91
(29)
Day 22
144650.79
(68)
158294.91
(32)
14. Secondary Outcome
Title Cluster of Differentiation (CD) 19-Positive B-Cell Counts
Description
Time Frame Baseline, Week 2, 3, 4, 5, 13, 26, 39, 52

Outcome Measure Data

Analysis Population Description
The modified ITT (mITT) Population included all participants who were randomized and received at least 1 dose of any study drug. Here 'Number analyzed' signifies number of participants evaluable for this outcome measure at specified time points.
Arm/Group Title Rituximab-EU PF-05280586
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Measure Participants 197 196
Baseline
114.2
119.9
Week 2
1.0
0.8
Week 3
0.6
0.6
Week 4
0.5
0.4
Week 5
0.5
0.4
Week 13
0.5
0.5
Week 26
1.2
0.9
Week 39
21.7
10.7
Week 52
60.8
51.6
15. Secondary Outcome
Title Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs)
Description Human serum ADA samples were analyzed for the presence or absence of anti-rituximab antibodies or anti-PF-05280586 antibodies using the validated drug-specific assay with a tiered approach using screening, confirmation and titer/quantitation. Human NAb serum samples testing ADA positive were analyzed for the presence or absence of neutralizing anti-rituximab antibody and neutralizing anti-PF-05280586 antibody using the validated drug-specific assay with a tiered approach using screening, confirmation and titer/quantitation. Participants with their ADA titer >= 1.88 were considered to be ADA positive. Only participants with a positive ADA result were further tested for NAb.
Time Frame Baseline up to Week 52

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received at least 1 dose of any study drug. Here, 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
Arm/Group Title Rituximab-EU PF-05280586
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Measure Participants 197 195
ADA Positive
39
19.7%
43
21.9%
NAB Positive
0
0%
0
0%
16. Secondary Outcome
Title Number of Participants Reporting Immune-Based Adverse Effects
Description Immune-based adverse effects included infusion related reaction (IRR), adverse events which fulfill Sampson's criteria, and adverse events which belong to the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) anaphylaxis or hypersensitivity reactions. Potential allergic and anaphylactic reactions were identified programmatically based on the criteria of Sampson et al, (2006).
Time Frame Baseline up to Week 52

Outcome Measure Data

Analysis Population Description
The Safety analysis population include all participants who received at least 1 dose of any study treatment.
Arm/Group Title Rituximab-EU PF-05280586
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
Measure Participants 197 196
IRR reported
59
29.8%
49
25%
AE based on Sampson's criteria
17
8.6%
17
8.7%
Anaphylaxis/Hypersensitivity (SMQ)
48
24.2%
39
19.9%

Adverse Events

Time Frame Baseline up to end of study (up to 52 weeks)
Adverse Event Reporting Description Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis was performed on safety population.
Arm/Group Title Rituximab-EU PF-05280586
Arm/Group Description Participants received Rituximab-EU intravenous (IV) infusion at a dose of 375 milligrams per meter square (mg/m^2) on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg. Participants received PF-05280586 IV infusion at a dose of 375 mg/m^2 on Day 1, 8, 15, and 22. The maximum dose that could be infused in 1 day was 1125 mg.
All Cause Mortality
Rituximab-EU PF-05280586
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/197 (0.5%) 1/196 (0.5%)
Serious Adverse Events
Rituximab-EU PF-05280586
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 15/197 (7.6%) 17/196 (8.7%)
Cardiac disorders
Angina unstable 1/197 (0.5%) 0/196 (0%)
Atrial fibrillation 0/197 (0%) 1/196 (0.5%)
Intracardiac thrombus 1/197 (0.5%) 0/196 (0%)
Gastrointestinal disorders
Abdominal pain 0/197 (0%) 1/196 (0.5%)
Mesenteric artery stenosis 0/197 (0%) 1/196 (0.5%)
Ileus 0/197 (0%) 1/196 (0.5%)
Inguinal hernia 1/197 (0.5%) 0/196 (0%)
General disorders
Disease progression 1/197 (0.5%) 1/196 (0.5%)
Non-cardiac chest pain 1/197 (0.5%) 0/196 (0%)
Pyrexia 0/197 (0%) 1/196 (0.5%)
Hepatobiliary disorders
Cholelithiasis 1/197 (0.5%) 0/196 (0%)
Immune system disorders
Serum sickness 1/197 (0.5%) 0/196 (0%)
Infections and infestations
Appendicitis 0/197 (0%) 1/196 (0.5%)
Clostridium difficile infection 0/197 (0%) 1/196 (0.5%)
Diverticulitis 0/197 (0%) 1/196 (0.5%)
Escherichia sepsis 1/197 (0.5%) 0/196 (0%)
Hepatitis B 1/197 (0.5%) 0/196 (0%)
Kidney infection 1/197 (0.5%) 0/196 (0%)
Peritonitis 0/197 (0%) 1/196 (0.5%)
Urinary tract infection 0/197 (0%) 1/196 (0.5%)
Viral sinusitis 1/197 (0.5%) 0/196 (0%)
Injury, poisoning and procedural complications
Contusion 0/197 (0%) 1/196 (0.5%)
Infusion related reaction 1/197 (0.5%) 0/196 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder 0/197 (0%) 1/196 (0.5%)
Polyarthritis 1/197 (0.5%) 0/196 (0%)
Spinal column stenosis 1/197 (0.5%) 0/196 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer 1/197 (0.5%) 0/196 (0%)
Lung adenocarcinoma stage I 0/197 (0%) 1/196 (0.5%)
Prostate cancer 0/197 (0%) 1/196 (0.5%)
Squamous cell carcinoma of lung 1/197 (0.5%) 0/196 (0%)
Uterine cancer 0/197 (0%) 1/196 (0.5%)
Colon adenoma 0/197 (0%) 1/196 (0.5%)
Nervous system disorders
Paraesthesia 0/197 (0%) 1/196 (0.5%)
Transient ischaemic attack 0/197 (0%) 1/196 (0.5%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea 1/197 (0.5%) 0/196 (0%)
Pulmonary embolism 1/197 (0.5%) 0/196 (0%)
Other (Not Including Serious) Adverse Events
Rituximab-EU PF-05280586
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 143/197 (72.6%) 153/196 (78.1%)
Blood and lymphatic system disorders
Anaemia 1/197 (0.5%) 1/196 (0.5%)
Lymph node pain 0/197 (0%) 1/196 (0.5%)
Lymphopenia 1/197 (0.5%) 1/196 (0.5%)
Neutropenia 3/197 (1.5%) 1/196 (0.5%)
Thrombocytopenia 1/197 (0.5%) 0/196 (0%)
Cardiac disorders
Angina pectoris 1/197 (0.5%) 0/196 (0%)
Angina unstable 1/197 (0.5%) 0/196 (0%)
Atrial fibrillation 0/197 (0%) 2/196 (1%)
Bradycardia 1/197 (0.5%) 0/196 (0%)
Cardiac failure congestive 0/197 (0%) 1/196 (0.5%)
Palpitations 2/197 (1%) 5/196 (2.6%)
Sinus bradycardia 1/197 (0.5%) 0/196 (0%)
Tachycardia 2/197 (1%) 0/196 (0%)
Ear and labyrinth disorders
Ear discomfort 0/197 (0%) 2/196 (1%)
Ear disorder 0/197 (0%) 1/196 (0.5%)
Ear pain 1/197 (0.5%) 1/196 (0.5%)
Ear pruritus 2/197 (1%) 3/196 (1.5%)
Hypoacusis 2/197 (1%) 2/196 (1%)
Tinnitus 1/197 (0.5%) 1/196 (0.5%)
Vertigo 3/197 (1.5%) 2/196 (1%)
Vertigo positional 1/197 (0.5%) 0/196 (0%)
Endocrine disorders
Hyperthyroidism 1/197 (0.5%) 0/196 (0%)
Hypothyroidism 2/197 (1%) 0/196 (0%)
Thyroid cyst 0/197 (0%) 1/196 (0.5%)
Eye disorders
Accommodation disorder 0/197 (0%) 1/196 (0.5%)
Cataract 1/197 (0.5%) 2/196 (1%)
Conjunctival disorder 1/197 (0.5%) 0/196 (0%)
Diplopia 1/197 (0.5%) 0/196 (0%)
Dry eye 2/197 (1%) 0/196 (0%)
Erythema of eyelid 0/197 (0%) 1/196 (0.5%)
Eye pruritus 3/197 (1.5%) 0/196 (0%)
Lacrimation increased 1/197 (0.5%) 0/196 (0%)
Meibomianitis 1/197 (0.5%) 0/196 (0%)
Ocular hyperaemia 1/197 (0.5%) 0/196 (0%)
Entropion 0/197 (0%) 1/196 (0.5%)
Visual impairment 0/197 (0%) 1/196 (0.5%)
Gastrointestinal disorders
Abdominal discomfort 1/197 (0.5%) 1/196 (0.5%)
Abdominal pain 3/197 (1.5%) 7/196 (3.6%)
Abdominal pain lower 0/197 (0%) 1/196 (0.5%)
Abdominal pain upper 5/197 (2.5%) 9/196 (4.6%)
Cheilitis 0/197 (0%) 1/196 (0.5%)
Chronic gastritis 0/197 (0%) 1/196 (0.5%)
Colitis 0/197 (0%) 1/196 (0.5%)
Constipation 8/197 (4.1%) 8/196 (4.1%)
Dental caries 0/197 (0%) 2/196 (1%)
Diarrhoea 12/197 (6.1%) 14/196 (7.1%)
Diverticulum intestinal 1/197 (0.5%) 0/196 (0%)
Dry mouth 1/197 (0.5%) 0/196 (0%)
Dyspepsia 2/197 (1%) 5/196 (2.6%)
Dysphagia 1/197 (0.5%) 0/196 (0%)
Enterocolitis 0/197 (0%) 1/196 (0.5%)
Faeces soft 1/197 (0.5%) 0/196 (0%)
Flatulence 0/197 (0%) 1/196 (0.5%)
Functional gastrointestinal disorder 1/197 (0.5%) 0/196 (0%)
Gastritis 0/197 (0%) 1/196 (0.5%)
Gastrointestinal disorder 0/197 (0%) 3/196 (1.5%)
Gastrooesophageal reflux disease 0/197 (0%) 1/196 (0.5%)
Gingival pain 1/197 (0.5%) 0/196 (0%)
Gingival swelling 0/197 (0%) 1/196 (0.5%)
Haematochezia 1/197 (0.5%) 0/196 (0%)
Haemorrhoids 2/197 (1%) 0/196 (0%)
Inguinal hernia 1/197 (0.5%) 0/196 (0%)
Lip oedema 1/197 (0.5%) 0/196 (0%)
Mouth swelling 0/197 (0%) 1/196 (0.5%)
Nausea 17/197 (8.6%) 15/196 (7.7%)
Odynophagia 1/197 (0.5%) 1/196 (0.5%)
Oral discomfort 0/197 (0%) 1/196 (0.5%)
Oral mucosal erythema 0/197 (0%) 1/196 (0.5%)
Paraesthesia oral 1/197 (0.5%) 0/196 (0%)
Periodontal disease 1/197 (0.5%) 0/196 (0%)
Rectal haemorrhage 0/197 (0%) 1/196 (0.5%)
Salivary gland pain 0/197 (0%) 1/196 (0.5%)
Stomatitis 3/197 (1.5%) 0/196 (0%)
Swollen tongue 0/197 (0%) 1/196 (0.5%)
Tooth disorder 0/197 (0%) 1/196 (0.5%)
Toothache 2/197 (1%) 2/196 (1%)
Vomiting 7/197 (3.6%) 3/196 (1.5%)
General disorders
Asthenia 13/197 (6.6%) 9/196 (4.6%)
Axillary pain 1/197 (0.5%) 0/196 (0%)
Catheter site pain 1/197 (0.5%) 0/196 (0%)
Catheter site related reaction 1/197 (0.5%) 0/196 (0%)
Chest discomfort 1/197 (0.5%) 2/196 (1%)
Chest pain 3/197 (1.5%) 2/196 (1%)
Chills 3/197 (1.5%) 3/196 (1.5%)
Discomfort 1/197 (0.5%) 0/196 (0%)
Face oedema 0/197 (0%) 1/196 (0.5%)
Facial pain 1/197 (0.5%) 0/196 (0%)
Fatigue 13/197 (6.6%) 12/196 (6.1%)
Feeling abnormal 1/197 (0.5%) 0/196 (0%)
Feeling cold 0/197 (0%) 1/196 (0.5%)
Feeling hot 2/197 (1%) 2/196 (1%)
Generalised oedema 0/197 (0%) 2/196 (1%)
Influenza like illness 4/197 (2%) 2/196 (1%)
Infusion site bruising 1/197 (0.5%) 0/196 (0%)
General physical health deterioration 1/197 (0.5%) 0/196 (0%)
Infusion site erythema 1/197 (0.5%) 0/196 (0%)
Infusion site extravasation 1/197 (0.5%) 0/196 (0%)
Infusion site pain 0/197 (0%) 1/196 (0.5%)
Malaise 0/197 (0%) 3/196 (1.5%)
Non-cardiac chest pain 1/197 (0.5%) 1/196 (0.5%)
Oedema 1/197 (0.5%) 2/196 (1%)
Oedema peripheral 7/197 (3.6%) 2/196 (1%)
Pain 3/197 (1.5%) 3/196 (1.5%)
Peripheral swelling 1/197 (0.5%) 0/196 (0%)
Pyrexia 11/197 (5.6%) 11/196 (5.6%)
Suprapubic pain 1/197 (0.5%) 0/196 (0%)
Swelling 0/197 (0%) 1/196 (0.5%)
Hepatobiliary disorders
Hepatic steatosis 1/197 (0.5%) 0/196 (0%)
Hepatocellular injury 0/197 (0%) 1/196 (0.5%)
Immune system disorders
Contrast media allergy 1/197 (0.5%) 2/196 (1%)
Cytokine release syndrome 0/197 (0%) 1/196 (0.5%)
Drug hypersensitivity 0/197 (0%) 1/196 (0.5%)
Hypersensitivity 1/197 (0.5%) 0/196 (0%)
Hypogammaglobulinaemia 1/197 (0.5%) 0/196 (0%)
Infections and infestations
Acarodermatitis 0/197 (0%) 1/196 (0.5%)
Acute sinusitis 1/197 (0.5%) 1/196 (0.5%)
Atypical mycobacterial infection 1/197 (0.5%) 0/196 (0%)
Bronchitis 7/197 (3.6%) 3/196 (1.5%)
Cellulitis 0/197 (0%) 1/196 (0.5%)
Conjunctivitis 3/197 (1.5%) 0/196 (0%)
Cystitis 3/197 (1.5%) 1/196 (0.5%)
Cystitis bacterial 1/197 (0.5%) 0/196 (0%)
Diverticulitis 0/197 (0%) 1/196 (0.5%)
Enteritis infectious 1/197 (0.5%) 0/196 (0%)
Folliculitis 1/197 (0.5%) 0/196 (0%)
Gastroenteritis 3/197 (1.5%) 2/196 (1%)
Genital herpes 0/197 (0%) 1/196 (0.5%)
Gingivitis 1/197 (0.5%) 0/196 (0%)
Herpes zoster 3/197 (1.5%) 1/196 (0.5%)
Infected bite 1/197 (0.5%) 0/196 (0%)
Influenza 6/197 (3%) 4/196 (2%)
Laryngitis 1/197 (0.5%) 0/196 (0%)
Nasopharyngitis 9/197 (4.6%) 5/196 (2.6%)
Oral herpes 2/197 (1%) 3/196 (1.5%)
Otitis externa fungal 1/197 (0.5%) 0/196 (0%)
Paronychia 0/197 (0%) 1/196 (0.5%)
Pertussis 1/197 (0.5%) 0/196 (0%)
Pharyngitis 4/197 (2%) 4/196 (2%)
Pneumonia 0/197 (0%) 1/196 (0.5%)
Purulence 0/197 (0%) 1/196 (0.5%)
Respiratory tract infection 1/197 (0.5%) 3/196 (1.5%)
Rhinitis 3/197 (1.5%) 1/196 (0.5%)
Sinusitis 2/197 (1%) 5/196 (2.6%)
Skin infection 2/197 (1%) 0/196 (0%)
Sycosis barbae 1/197 (0.5%) 0/196 (0%)
Systemic infection 1/197 (0.5%) 0/196 (0%)
Tracheitis 0/197 (0%) 1/196 (0.5%)
Trichophytosis 1/197 (0.5%) 0/196 (0%)
Upper respiratory tract infection 5/197 (2.5%) 9/196 (4.6%)
Urinary tract infection 5/197 (2.5%) 4/196 (2%)
Viral infection 0/197 (0%) 1/196 (0.5%)
Viral pharyngitis 2/197 (1%) 0/196 (0%)
Viral upper respiratory tract infection 1/197 (0.5%) 0/196 (0%)
Injury, poisoning and procedural complications
Bone contusion 0/197 (0%) 1/196 (0.5%)
Chest injury 1/197 (0.5%) 1/196 (0.5%)
Contusion 1/197 (0.5%) 2/196 (1%)
Fall 2/197 (1%) 5/196 (2.6%)
Hand fracture 1/197 (0.5%) 0/196 (0%)
Head injury 2/197 (1%) 0/196 (0%)
Humerus fracture 1/197 (0.5%) 0/196 (0%)
Infusion related reaction 58/197 (29.4%) 49/196 (25%)
Laceration 2/197 (1%) 0/196 (0%)
Limb injury 0/197 (0%) 2/196 (1%)
Neck injury 1/197 (0.5%) 0/196 (0%)
Post procedural haemorrhage 0/197 (0%) 1/196 (0.5%)
Road traffic accident 1/197 (0.5%) 0/196 (0%)
Skin abrasion 0/197 (0%) 1/196 (0.5%)
Suture related complication 1/197 (0.5%) 0/196 (0%)
Suture rupture 1/197 (0.5%) 0/196 (0%)
Tendon rupture 1/197 (0.5%) 0/196 (0%)
Thermal burn 1/197 (0.5%) 1/196 (0.5%)
Upper limb fracture 0/197 (0%) 1/196 (0.5%)
Wound complication 2/197 (1%) 0/196 (0%)
Wrist fracture 0/197 (0%) 1/196 (0.5%)
Incision site pain 1/197 (0.5%) 0/196 (0%)
Procedural pain 0/197 (0%) 1/196 (0.5%)
Investigations
Alanine aminotransferase increased 3/197 (1.5%) 0/196 (0%)
Aspartate aminotransferase increased 1/197 (0.5%) 1/196 (0.5%)
Blood bilirubin increased 1/197 (0.5%) 0/196 (0%)
Blood creatinine increased 0/197 (0%) 1/196 (0.5%)
Blood glucose increased 0/197 (0%) 1/196 (0.5%)
Blood lactate dehydrogenase increased 1/197 (0.5%) 3/196 (1.5%)
Blood potassium increased 1/197 (0.5%) 0/196 (0%)
Blood pressure decreased 2/197 (1%) 0/196 (0%)
Blood pressure increased 1/197 (0.5%) 1/196 (0.5%)
Blood thyroid stimulating hormone increased 0/197 (0%) 1/196 (0.5%)
Blood urine present 1/197 (0.5%) 0/196 (0%)
C-reactive protein increased 1/197 (0.5%) 0/196 (0%)
Gamma-glutamyltransferase increased 1/197 (0.5%) 1/196 (0.5%)
Lymphocyte count decreased 1/197 (0.5%) 1/196 (0.5%)
Neutrophil count decreased 0/197 (0%) 5/196 (2.6%)
Neutrophil count increased 1/197 (0.5%) 0/196 (0%)
Serum ferritin decreased 0/197 (0%) 1/196 (0.5%)
Weight decreased 1/197 (0.5%) 0/196 (0%)
White blood cell count decreased 1/197 (0.5%) 4/196 (2%)
Breath sounds abnormal 1/197 (0.5%) 1/196 (0.5%)
Metabolism and nutrition disorders
Decreased appetite 1/197 (0.5%) 2/196 (1%)
Dehydration 0/197 (0%) 2/196 (1%)
Diabetes mellitus 0/197 (0%) 2/196 (1%)
Dyslipidaemia 0/197 (0%) 1/196 (0.5%)
Fluid retention 1/197 (0.5%) 0/196 (0%)
Hypercholesterolaemia 1/197 (0.5%) 1/196 (0.5%)
Hyperglycaemia 4/197 (2%) 1/196 (0.5%)
Hypertriglyceridaemia 1/197 (0.5%) 3/196 (1.5%)
Hyperuricaemia 2/197 (1%) 0/196 (0%)
Hypoglycaemia 1/197 (0.5%) 0/196 (0%)
Hypokalaemia 1/197 (0.5%) 0/196 (0%)
Type 2 diabetes mellitus 1/197 (0.5%) 1/196 (0.5%)
Vitamin D deficiency 1/197 (0.5%) 1/196 (0.5%)
Musculoskeletal and connective tissue disorders
Arthralgia 6/197 (3%) 7/196 (3.6%)
Back pain 10/197 (5.1%) 8/196 (4.1%)
Bone loss 0/197 (0%) 1/196 (0.5%)
Bone pain 3/197 (1.5%) 0/196 (0%)
Costochondritis 1/197 (0.5%) 0/196 (0%)
Flank pain 2/197 (1%) 1/196 (0.5%)
Groin pain 2/197 (1%) 3/196 (1.5%)
Haemarthrosis 1/197 (0.5%) 0/196 (0%)
Intervertebral disc protrusion 1/197 (0.5%) 0/196 (0%)
Joint effusion 1/197 (0.5%) 0/196 (0%)
Joint stiffness 1/197 (0.5%) 1/196 (0.5%)
Joint swelling 1/197 (0.5%) 1/196 (0.5%)
Muscle contracture 0/197 (0%) 1/196 (0.5%)
Muscle spasms 1/197 (0.5%) 0/196 (0%)
Muscle twitching 0/197 (0%) 1/196 (0.5%)
Muscular weakness 2/197 (1%) 1/196 (0.5%)
Musculoskeletal chest pain 1/197 (0.5%) 0/196 (0%)
Musculoskeletal discomfort 0/197 (0%) 2/196 (1%)
Musculoskeletal pain 2/197 (1%) 1/196 (0.5%)
Musculoskeletal stiffness 2/197 (1%) 2/196 (1%)
Myalgia 5/197 (2.5%) 9/196 (4.6%)
Neck pain 3/197 (1.5%) 2/196 (1%)
Osteoarthritis 1/197 (0.5%) 0/196 (0%)
Pain in extremity 4/197 (2%) 7/196 (3.6%)
Posture abnormal 1/197 (0.5%) 0/196 (0%)
Pubic pain 1/197 (0.5%) 0/196 (0%)
Spinal osteoarthritis 1/197 (0.5%) 0/196 (0%)
Spinal pain 2/197 (1%) 2/196 (1%)
Spondylolisthesis 1/197 (0.5%) 0/196 (0%)
Tendon calcification 0/197 (0%) 1/196 (0.5%)
Tendonitis 1/197 (0.5%) 1/196 (0.5%)
Periarthritis 1/197 (0.5%) 0/196 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma 2/197 (1%) 1/196 (0.5%)
Infected neoplasm 1/197 (0.5%) 0/196 (0%)
Lung adenocarcinoma stage I 0/197 (0%) 1/196 (0.5%)
Meningioma 0/197 (0%) 1/196 (0.5%)
Non-Hodgkin's lymphoma 0/197 (0%) 1/196 (0.5%)
Nervous system disorders
Burning sensation 1/197 (0.5%) 1/196 (0.5%)
Dizziness 6/197 (3%) 2/196 (1%)
Dysgeusia 1/197 (0.5%) 0/196 (0%)
Head discomfort 0/197 (0%) 1/196 (0.5%)
Headache 19/197 (9.6%) 16/196 (8.2%)
Hypoaesthesia 1/197 (0.5%) 1/196 (0.5%)
Hypotonia 0/197 (0%) 1/196 (0.5%)
Intercostal neuralgia 0/197 (0%) 1/196 (0.5%)
Lethargy 0/197 (0%) 1/196 (0.5%)
Migraine 0/197 (0%) 1/196 (0.5%)
Nerve compression 0/197 (0%) 1/196 (0.5%)
Neuralgia 1/197 (0.5%) 0/196 (0%)
Neuropathy peripheral 1/197 (0.5%) 1/196 (0.5%)
Paraesthesia 3/197 (1.5%) 2/196 (1%)
Polyneuropathy 0/197 (0%) 1/196 (0.5%)
Presyncope 1/197 (0.5%) 0/196 (0%)
Restless legs syndrome 1/197 (0.5%) 3/196 (1.5%)
Somnolence 3/197 (1.5%) 2/196 (1%)
Speech disorder 1/197 (0.5%) 0/196 (0%)
Syncope 0/197 (0%) 1/196 (0.5%)
Tension headache 1/197 (0.5%) 0/196 (0%)
Psychiatric disorders
Affect lability 0/197 (0%) 1/196 (0.5%)
Agitation 1/197 (0.5%) 0/196 (0%)
Anxiety 7/197 (3.6%) 6/196 (3.1%)
Confusional state 1/197 (0.5%) 0/196 (0%)
Depression 2/197 (1%) 3/196 (1.5%)
Gastrointestinal somatic symptom disorder 0/197 (0%) 1/196 (0.5%)
Insomnia 8/197 (4.1%) 5/196 (2.6%)
Irritability 1/197 (0.5%) 1/196 (0.5%)
Panic attack 0/197 (0%) 1/196 (0.5%)
Restlessness 1/197 (0.5%) 0/196 (0%)
Renal and urinary disorders
Bladder spasm 0/197 (0%) 1/196 (0.5%)
Calculus bladder 1/197 (0.5%) 0/196 (0%)
Dysuria 1/197 (0.5%) 2/196 (1%)
Nocturia 0/197 (0%) 1/196 (0.5%)
Pollakiuria 1/197 (0.5%) 0/196 (0%)
Renal pain 1/197 (0.5%) 0/196 (0%)
Strangury 1/197 (0.5%) 0/196 (0%)
Urinary retention 1/197 (0.5%) 0/196 (0%)
Urinary tract pain 0/197 (0%) 1/196 (0.5%)
Reproductive system and breast disorders
Benign prostatic hyperplasia 1/197 (0.5%) 0/196 (0%)
Breast pain 1/197 (0.5%) 0/196 (0%)
Breast tenderness 0/197 (0%) 1/196 (0.5%)
Genital burning sensation 0/197 (0%) 1/196 (0.5%)
Menorrhagia 1/197 (0.5%) 1/196 (0.5%)
Metrorrhagia 1/197 (0.5%) 0/196 (0%)
Ovarian cyst 1/197 (0.5%) 0/196 (0%)
Pelvic pain 1/197 (0.5%) 1/196 (0.5%)
Prostatitis 1/197 (0.5%) 0/196 (0%)
Scrotal pain 0/197 (0%) 1/196 (0.5%)
Testicular pain 0/197 (0%) 1/196 (0.5%)
Vaginal haemorrhage 0/197 (0%) 3/196 (1.5%)
Vulvovaginal inflammation 0/197 (0%) 1/196 (0.5%)
Vulvovaginal pain 0/197 (0%) 1/196 (0.5%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm 1/197 (0.5%) 0/196 (0%)
Cough 11/197 (5.6%) 11/196 (5.6%)
Dry throat 1/197 (0.5%) 2/196 (1%)
Dysphonia 2/197 (1%) 0/196 (0%)
Dyspnoea 8/197 (4.1%) 6/196 (3.1%)
Dyspnoea exertional 1/197 (0.5%) 0/196 (0%)
Emphysema 1/197 (0.5%) 0/196 (0%)
Epistaxis 1/197 (0.5%) 1/196 (0.5%)
Hiccups 0/197 (0%) 1/196 (0.5%)
Hyperventilation 0/197 (0%) 1/196 (0.5%)
Laryngeal discomfort 1/197 (0.5%) 0/196 (0%)
Laryngeal inflammation 1/197 (0.5%) 0/196 (0%)
Laryngeal oedema 2/197 (1%) 0/196 (0%)
Laryngeal pain 1/197 (0.5%) 0/196 (0%)
Lung disorder 1/197 (0.5%) 0/196 (0%)
Nasal congestion 1/197 (0.5%) 2/196 (1%)
Nasal discomfort 1/197 (0.5%) 1/196 (0.5%)
Nasal pruritus 1/197 (0.5%) 0/196 (0%)
Oropharyngeal discomfort 1/197 (0.5%) 4/196 (2%)
Oropharyngeal pain 10/197 (5.1%) 2/196 (1%)
Paranasal sinus mucosal hypertrophy 1/197 (0.5%) 1/196 (0.5%)
Pharyngeal erythema 0/197 (0%) 2/196 (1%)
Pharyngeal inflammation 0/197 (0%) 1/196 (0.5%)
Pharyngeal oedema 1/197 (0.5%) 1/196 (0.5%)
Pharyngeal paraesthesia 1/197 (0.5%) 2/196 (1%)
Productive cough 1/197 (0.5%) 2/196 (1%)
Pulmonary embolism 1/197 (0.5%) 1/196 (0.5%)
Respiratory disorder 1/197 (0.5%) 1/196 (0.5%)
Rhinalgia 1/197 (0.5%) 0/196 (0%)
Rhinitis allergic 0/197 (0%) 1/196 (0.5%)
Rhinorrhoea 1/197 (0.5%) 0/196 (0%)
Sleep apnoea syndrome 1/197 (0.5%) 0/196 (0%)
Suffocation feeling 1/197 (0.5%) 0/196 (0%)
Throat tightness 1/197 (0.5%) 0/196 (0%)
Tonsillar disorder 1/197 (0.5%) 0/196 (0%)
Tonsillar erythema 0/197 (0%) 1/196 (0.5%)
Tonsillar hypertrophy 1/197 (0.5%) 0/196 (0%)
Upper respiratory tract inflammation 3/197 (1.5%) 1/196 (0.5%)
Upper-airway cough syndrome 0/197 (0%) 1/196 (0.5%)
Sinus disorder 0/197 (0%) 1/196 (0.5%)
Sneezing 0/197 (0%) 1/196 (0.5%)
Throat irritation 10/197 (5.1%) 14/196 (7.1%)
Skin and subcutaneous tissue disorders
Acne 0/197 (0%) 1/196 (0.5%)
Angioedema 0/197 (0%) 1/196 (0.5%)
Asteatosis 1/197 (0.5%) 0/196 (0%)
Blister 1/197 (0.5%) 0/196 (0%)
Dermatitis 0/197 (0%) 1/196 (0.5%)
Dermatitis allergic 1/197 (0.5%) 0/196 (0%)
Dermatitis contact 1/197 (0.5%) 1/196 (0.5%)
Drug eruption 1/197 (0.5%) 0/196 (0%)
Dry skin 0/197 (0%) 1/196 (0.5%)
Eczema 3/197 (1.5%) 1/196 (0.5%)
Erythema 2/197 (1%) 7/196 (3.6%)
Hyperhidrosis 3/197 (1.5%) 2/196 (1%)
Hyperkeratosis 0/197 (0%) 1/196 (0.5%)
Intertrigo 0/197 (0%) 1/196 (0.5%)
Nail disorder 0/197 (0%) 1/196 (0.5%)
Neurodermatitis 1/197 (0.5%) 0/196 (0%)
Night sweats 1/197 (0.5%) 0/196 (0%)
Pruritus allergic 0/197 (0%) 1/196 (0.5%)
Rash 8/197 (4.1%) 10/196 (5.1%)
Rash erythematous 0/197 (0%) 1/196 (0.5%)
Rash maculo-papular 0/197 (0%) 1/196 (0.5%)
Rash pruritic 0/197 (0%) 2/196 (1%)
Scab 0/197 (0%) 1/196 (0.5%)
Seborrhoeic dermatitis 1/197 (0.5%) 0/196 (0%)
Skin burning sensation 1/197 (0.5%) 0/196 (0%)
Skin lesion 2/197 (1%) 1/196 (0.5%)
Swelling face 1/197 (0.5%) 0/196 (0%)
Urticaria 6/197 (3%) 3/196 (1.5%)
Pruritus 22/197 (11.2%) 13/196 (6.6%)
Pruritus generalised 0/197 (0%) 1/196 (0.5%)
Scar pain 1/197 (0.5%) 0/196 (0%)
Social circumstances
Menopause 0/106 (0%) 1/110 (0.9%)
Vascular disorders
Deep vein thrombosis 2/197 (1%) 0/196 (0%)
Flushing 4/197 (2%) 1/196 (0.5%)
Hot flush 2/197 (1%) 1/196 (0.5%)
Hypertension 7/197 (3.6%) 5/196 (2.6%)
Hypotension 1/197 (0.5%) 2/196 (1%)
Lymphoedema 0/197 (0%) 1/196 (0.5%)
Haematoma 0/197 (0%) 1/196 (0.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact

Name/Title Pfizer ClinicalTrials.gov Call Center
Organization Pfizer Inc.
Phone 1-800-718-1021
Email ClinicalTrials.gov_Inquiries@pfizer.com
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02213263
Other Study ID Numbers:
  • B3281006
  • 2014-000132-41
  • REFLECTIONS
First Posted:
Aug 11, 2014
Last Update Posted:
Jun 20, 2019
Last Verified:
Jun 1, 2019