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GP2013 in the Treatment of Patients With Previously Untreated, Advanced Stage Follicular Lymphoma (ASSIST_FL)

Sponsor
Sandoz (Industry)
Overall Status
Completed
CT.gov ID
NCT01419665
Collaborator
Novartis Pharmaceuticals (Industry)
629
Enrollment
153
Locations
2
Arms
73.7
Actual Duration (Months)
4.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to demonstrate comparability of the ORR in patients with previously untreated, advanced stage FL who receive GP2013-treatment to patients who receive MabThera-treatment.

Condition or Disease Intervention/Treatment Phase
  • Biological: GP2013
  • Biological: rituximab
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
629 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
A subset of patients is switched from GP2013 to MabThera or continued with MabThera during the maintenance phase, for these patients the treatment is finished as an open labeled parallel arm study. The original treatment assignment is kept blinded.A subset of patients is switched from GP2013 to MabThera or continued with MabThera during the maintenance phase, for these patients the treatment is finished as an open labeled parallel arm study. The original treatment assignment is kept blinded.
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Controlled, Double-Blind Phase III Trial to Compare the Efficacy, Safety and Pharmacokinetics of GP2013 vs. MabThera® in Patients With Previously Untreated, Advanced Stage Follicular Lymphoma
Actual Study Start Date :
Dec 1, 2011
Actual Primary Completion Date :
Jul 10, 2015
Actual Study Completion Date :
Jan 22, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: GP2013

Type: Biological/Vaccine

Biological: GP2013
Type: Biological/Vaccine
Other Names:
  • no brand name available

    		•
    Active Comparator: rituximab

    Type: Biological/Vaccine

    Biological: rituximab
    Type: Biological/Vaccine
    Other Names:
  • MabThera(R)

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate (ORR) [24 weeks]

      ORR is defined as the proportion of patients whose best overall disease response was either CR or PR during the combination treatment period based on blinded independent central radiology review.

    Secondary Outcome Measures

    1. To Evaluate the Complete Response (CR) Rate During the Combination Treatment Period [24 weeks]

    2. To Evaluate the Partial Response (PR) Rate During the Combination Treatment Period [24 weeks]

    3. To Evaluate the Progression Free Survival (PFS) With up to 3 Years of Follow-up Post Randomization [3 years]

      Number of participants with progression free survival events

    4. To Evaluate the Overall Survival (OS) With up to 3 Years of Follow-up Post Randomization, as Assessed by the Number of Deaths [3 years]

      OS was defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died, OS was censored at the date of last contact including survival follow-up.

    5. To Evaluate the Incidence of Immunogenicity (ADA Formation) Against GP2013 and MabThera (Rituximab) [24 weeks, 3 years]

      number of participants with confirmed positive ADA

    6. To Evaluate a PK Marker Following the Treatment With GP2013-Chemotherapy and MabThera-Chemotherapy (C Max) [day 63]

      C max For descriptive purposes only, no hypothesis testing

    7. To Evaluate a PK Marker Following the Treatment With GP2013-Chemotherapy and MabThera-Chemotherapy (C Trough) [day 63]

      C through For descriptive purposes only, no hypothesis testing

    8. To Evaluate a PD Marker (Peripheral CD19+ B-cell Counts) Following the Treatment With GP2013 + Chemotherapy Amd MabThera- Chemotherapy [21 days]

      AUEC (0-21d) For descriptive purposes only, no hypothesis testing

    Eligibility Criteria

    Criteria

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

    • Patient with previously untreated advanced stage, CD20-positive FL

    • Patient with ECOG performance status 0, 1 or 2.

    Exclusion Criteria:

    • Patient with Grade 3b (aggressive) FL or any histology other than FL grade 1, 2 or 3a

    • Patient who has previously received any prior therapy for lymphoma

    • Patient with evidence of any uncontrolled, active infection (viral, bacterial or fungal).

    • Patient with any malignancy within 5 years prior to date of randomization, with the exception of adequately treated in situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer.

    Other protocol-defined inclusion/exclusion criteria may apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Investigative site La Plata Argentina
    2 Investigative site Rosario Argentina
    3 Investigative site San Miguel de Tucuman Argentina
    4 Investigative site Adelaide Australia
    5 Investigative site Ballarat Australia
    6 Investigative site Epping Australia
    7 Investigative site Footscray Australia
    8 Investigative site Wodonga Australia
    9 Investigative site Graz Austria
    10 Investigative site Wien Austria
    11 Investigative site Barretos Brazil
    12 Investigator site Barretos Brazil
    13 Investigative site Botucatu Brazil
    14 Investigative site Campinas Brazil
    15 Investigative site Curitiba Brazil
    16 Investigative site Florianopolis Brazil
    17 Investigative site Fortaleza Brazil
    18 Investigative site Goiania Brazil
    19 Investigative site Jau Brazil
    20 Investigative site Passo Fundo Brazil
    21 Investigative site Porto Alegre Brazil
    22 Investigative Site Rio de Janeiro Brazil
    23 Investigative site Santo Andre Brazil
    24 Investigative site Sao Paulo Brazil
    25 Investigative site Sorocaba Brazil
    26 Investigative site Pleven Bulgaria
    27 Investigative site Plovdiv Bulgaria
    28 Investigative site Ruse Bulgaria
    29 Investigative site Sofia Bulgaria
    30 Investigative site Varna Bulgaria
    31 Investigative site Medellin Colombia
    32 Investigative site Monteria Colombia
    33 Investigative site Colmar France
    34 Investigative site Nimes France
    35 Investigative site Strasbourg France
    36 Investigative site Bad Saarow Germany
    37 Investigative site Koblenz Germany
    38 Investigative site Athens Greece
    39 Investigative site Ioannina Greece
    40 Investigative site Larissa Greece
    41 Investigative site Patras Greece
    42 Investigative site Györ Hungary
    43 Investigative site Kaposvar Hungary
    44 Investigative site Ahmedabad India
    45 India Amritsar India
    46 Investigative site Aurangabad India
    47 Investigative site Bangalore India
    48 Investigative site Chennai India
    49 Investigative site Hyderabad India
    50 Investigative site Kolkata India
    51 Investigtive site Kolkata India
    52 Investigative site Madurai India
    53 Investigative site Mumbai India
    54 Investigative site Nashik India
    55 Investigative site New Delhi India
    56 Investigative site Pune India
    57 Investigative site Surat India
    58 Investigative site Trivandrum India
    59 Investigative site Vellore India
    60 Investigative site Dublin Ireland
    61 Investigative site Limerick Ireland
    62 Investigative site Waterford Ireland
    63 Investigative site Ashkelon Israel
    64 Investigative site Nahariya Israel
    65 Investigative site Bari Italy
    66 Investigative site Firenze Italy
    67 Investigative site Meldola Italy
    68 Investigative site Milano Italy
    69 Investigative site Palermo Italy
    70 Investigative site Pavia Italy
    71 Investigative site Pescara Italy
    72 Investigative site Piacenza Italy
    73 Investigative site Ravenna Italy
    74 Investigative site Reggio Calabria Italy
    75 Investigative site Varese Italy
    76 Investigative site Aomori Japan
    77 Investigative site Fukuoka Japan
    78 Investigative site Gifu Japan
    79 Investigative site Kagoshima Japan
    80 Investigative site Kitakyushu Japan
    81 Investigative site Kobe Japan
    82 Investigative site Komaki Japan
    83 Investigative site Matsuyama Japan
    84 Investigative site Ogaki Japan
    85 Investigative site Okayama Japan
    86 Invstigative site Omura Japan
    87 Investigative site Saga Japan
    88 Investigative site Tachikawa Japan
    89 Investigative site Ōtake Japan
    90 Investigative site Alor Setar Malaysia
    91 Investigative site Ampang Malaysia
    92 Investigative site George Town Malaysia
    93 Investigative site Ipoh Malaysia
    94 Investigative site Johor Bahru Malaysia
    95 Investigative site Klang Malaysia
    96 Investigative site Kuala Lumpur Malaysia
    97 Investigative site Kuching Malaysia
    98 Investigative site Melaka Malaysia
    99 Investigative site Pulau Pinang Malaysia
    100 Investigative site Subang Jaya Malaysia
    101 Investigative site Amsterdam Netherlands
    102 Investigative site Delft Netherlands
    103 Investigative site Gouda Netherlands
    104 Investigative site Heerlen Netherlands
    105 Investigative site Rotterdam Netherlands
    106 Investigative site Schiedam Netherlands
    107 Investigative site Sittard Netherlands
    108 Investigative site Zwolle Netherlands
    109 Investigative site Lima Peru
    110 Investigative site Brzozow Poland
    111 Investigative site Bydgoszcz Poland
    112 Investigative site Chorzow Poland
    113 Investigative site Krakow Poland
    114 Investigative site Lublin Poland
    115 Investigative site Warszawa Poland
    116 Investigative site Braga Portugal
    117 Investigative site Coimbra Portugal
    118 Investigative site Lisboa Portugal
    119 Investigative site Porto Portugal
    120 Investigative site Brasov Romania
    121 Investigative site Bucharest Romania
    122 Investigative site Cluj-Napoca Romania
    123 Investigative site Iasi Romania
    124 Investigative site Timisoara Romania
    125 Investigative site Arkhangelsk Russian Federation
    126 Investigative site Chelyabinsk Russian Federation
    127 Investigative site Krasnodar Russian Federation
    128 Investigative site Kursk Russian Federation
    129 Investigative site Moscow Russian Federation
    130 Investigative site Nizhniy Novgorod Russian Federation
    131 Investigative site Rostov-on -Don Russian Federation
    132 Investigative site St. Petersburg Russian Federation
    133 Investigative site Cape Town South Africa
    134 Investigative site George South Africa
    135 Investigative site Johannesburg South Africa
    136 Investigative site Port Elizabeth South Africa
    137 Investigative site Pretoria South Africa
    138 Investigative site Barcelona Spain
    139 Investigative site Madrid Spain
    140 Investigative site Oviedo Spain
    141 Investigative site San Sebastian Spain
    142 Investigative site Sevilla Spain
    143 Investigative site Zaragoza Spain
    144 Investigative site Cherkasy Ukraine
    145 Investigative site Dnipropetrovsk Ukraine
    146 Investigative site Donetsk Ukraine
    147 Investigative site Ivano-Frankivsk Ukraine
    148 Investigative site Kharkiv Ukraine
    149 Investigative site Kyiv Ukraine
    150 Investigative site Lviv Ukraine
    151 Investigative site Eastbourne United Kingdom
    152 Investigative site London United Kingdom
    153 Investigative site Worthing United Kingdom

    Sponsors and Collaborators

    • Sandoz
    • Novartis Pharmaceuticals

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sandoz
    ClinicalTrials.gov Identifier:
    NCT01419665
    Other Study ID Numbers:
    • GP13-301
    • 2010-019522-13
    • NCT03814785
    First Posted:
    Aug 18, 2011
    Last Update Posted:
    May 14, 2021
    Last Verified:
    Apr 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Keywords provided by Sandoz
    Follicular Lymphoma
    Biosimilar
    GP13-301
    rituximab
    Antibodies
    CD20
    Additional relevant MeSH terms:
    Lymphoma
    Lymphoma, Follicular
    Rituximab

    Study Results

    Participant Flow

    Recruitment Details A total of 629 patients were randomized at 159 centers in 26 countries, 314 patients to GP2013 (312 patients treated) and 315 to MabThera. Of those 314 patients in the GP2013 group, 2 patients were randomized by error and discontinued before any treatment with GP2013. The number of patients in both treatment groups remained similar.
    Pre-assignment Detail full analysis set participants : GP2013 312 MabThera 315 safety set participants : GP2013 312 MabThera 315 per protocol set participants: GP2013 310 MabThera 312 pharmacokinetic analysis set 1 : GP2013 119 MabThera 120 immunogenicity analysis set: GP2013 275 MabThera 287 pharmacodynamic analysis set : GP2013 24 MabThera 24
    Arm/Group Title GP2013 Rituximab
    Arm/Group Description Experimental Type: Biological/Vaccine Comparator Type: Biological/Vaccine
    Period Title: Combination Treatment
    STARTED 312 315
    COMPLETED 274 274
    NOT COMPLETED 38 41
    Period Title: Combination Treatment
    STARTED 254 252
    COMPLETED 132 150
    NOT COMPLETED 122 102
    Period Title: Combination Treatment
    STARTED 44 39
    COMPLETED 43 38
    NOT COMPLETED 1 1

    Baseline Characteristics

    Arm/Group Title GP2013 Rituximab Total
    Arm/Group Description Experimental Type: Biological/Vaccine Comparator Type: Biological/Vaccine Total of all reporting groups
    Overall Participants 312 315 627
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    57.5
    (11.86)
    56.4
    (11.72)
    56.9
    (11.79)
    Sex: Female, Male (Count of Participants)
    Female
    181
    58%
    169
    53.7%
    350
    55.8%
    Male
    131
    42%
    146
    46.3%
    277
    44.2%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    71
    22.8%
    85
    27%
    156
    24.9%
    Black
    6
    1.9%
    3
    1%
    9
    1.4%
    Caucasian
    214
    68.6%
    207
    65.7%
    421
    67.1%
    Native American
    2
    0.6%
    5
    1.6%
    7
    1.1%
    Other
    19
    6.1%
    15
    4.8%
    34
    5.4%
    Race/Ethnicity, Customized (Count of Participants)
    Chinese
    5
    1.6%
    6
    1.9%
    11
    1.8%
    Hispanic / Latino
    59
    18.9%
    68
    21.6%
    127
    20.3%
    Indian (Indian Subcontinent)
    40
    12.8%
    54
    17.1%
    94
    15%
    Mixed Ethnicity
    8
    2.6%
    3
    1%
    11
    1.8%
    Other
    183
    58.7%
    170
    54%
    353
    56.3%
    Unknown / missing
    1
    0.3%
    0
    0%
    1
    0.2%
    Japanese
    16
    5.1%
    14
    4.4%
    30
    4.8%

    Outcome Measures

    1. Primary Outcome
    Title Overall Response Rate (ORR)
    Description ORR is defined as the proportion of patients whose best overall disease response was either CR or PR during the combination treatment period based on blinded independent central radiology review.
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    per protocol set, participants with measure
    Arm/Group Title GP2013 Rituximab
    Arm/Group Description Experimental Type: Biological/Vaccine Comparator Type: Biological/Vaccine
    Measure Participants 311 313
    Number (90% Confidence Interval) [percentage]
    87.1
    87.5
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection GP2013, Rituximab
    Comments
    Type of Statistical Test Equivalence
    Comments The equivalence margin of + or - 12% was determined considering the variability of the point estimate of the add-on effect by taking a value lower than the lower boundary of the 95% CI for Rituximab+chemotherapy versus chemotherapy obtained from historical data.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter difference in overall response rate
    Estimated Value -0.40
    Confidence Interval (2-Sided) 95%
    -5.94 to 5.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title To Evaluate the Complete Response (CR) Rate During the Combination Treatment Period
    Description
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    per protocol set, participants with measure
    Arm/Group Title GP2013 Rituximab
    Arm/Group Description Experimental Type: Biological/Vaccine Comparator Type: Biological/Vaccine
    Measure Participants 311 313
    Count of Participants [Participants]
    46
    14.7%
    42
    13.3%
    3. Secondary Outcome
    Title To Evaluate the Partial Response (PR) Rate During the Combination Treatment Period
    Description
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    per protocol set, participants with measure
    Arm/Group Title GP2013 Rituximab
    Arm/Group Description Experimental Type: Biological/Vaccine Comparator Type: Biological/Vaccine
    Measure Participants 311 313
    Count of Participants [Participants]
    225
    72.1%
    232
    73.7%
    4. Secondary Outcome
    Title To Evaluate the Progression Free Survival (PFS) With up to 3 Years of Follow-up Post Randomization
    Description Number of participants with progression free survival events
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    per protocol set, participants with measure
    Arm/Group Title GP2013 Rituximab
    Arm/Group Description Experimental Type: Biological/Vaccine Comparator Type: Biological/Vaccine
    Measure Participants 312 315
    Count of Participants [Participants]
    97
    31.1%
    78
    24.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection GP2013, Rituximab
    Comments
    Type of Statistical Test Other
    Comments descriptive purposes, not powered for hypothesis testing
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.30
    Confidence Interval (2-Sided) 95%
    0.97 to 1.76
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title To Evaluate the Overall Survival (OS) With up to 3 Years of Follow-up Post Randomization, as Assessed by the Number of Deaths
    Description OS was defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died, OS was censored at the date of last contact including survival follow-up.
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    per protocol set, participants with measure
    Arm/Group Title GP2013 Rituximab
    Arm/Group Description Experimental Type: Biological/Vaccine Comparator Type: Biological/Vaccine
    Measure Participants 312 315
    Count of Participants [Participants]
    29
    9.3%
    31
    9.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection GP2013, Rituximab
    Comments
    Type of Statistical Test Other
    Comments descriptive purposes, not powered for hypothesis testing
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.92
    Confidence Interval (2-Sided) 95%
    0.55 to 1.52
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title To Evaluate the Incidence of Immunogenicity (ADA Formation) Against GP2013 and MabThera (Rituximab)
    Description number of participants with confirmed positive ADA
    Time Frame 24 weeks, 3 years

    Outcome Measure Data

    Analysis Population Description
    immunogenicity set, participants with measure
    Arm/Group Title GP2013 Rituximab
    Arm/Group Description Experimental Type: Biological/Vaccine Comparator Type: Biological/Vaccine
    Measure Participants 275 287
    end of treatment combination phase (24 weeks)
    1
    0.3%
    2
    0.6%
    end of treatment manintenance phase (3 years)
    1
    0.3%
    0
    0%
    7. Secondary Outcome
    Title To Evaluate a PK Marker Following the Treatment With GP2013-Chemotherapy and MabThera-Chemotherapy (C Max)
    Description C max For descriptive purposes only, no hypothesis testing
    Time Frame day 63

    Outcome Measure Data

    Analysis Population Description
    pharmacokinetic analysis set 1, participants with measure
    Arm/Group Title GP2013 Rituximab
    Arm/Group Description Experimental Type: Biological/Vaccine Comparator Type: Biological/Vaccine
    Measure Participants 119 120
    Geometric Mean (Geometric Coefficient of Variation) [microg/mL]
    333.59
    (41.09)
    331.93
    (35.32)
    8. Secondary Outcome
    Title To Evaluate a PK Marker Following the Treatment With GP2013-Chemotherapy and MabThera-Chemotherapy (C Trough)
    Description C through For descriptive purposes only, no hypothesis testing
    Time Frame day 63

    Outcome Measure Data

    Analysis Population Description
    pharmacokinetic analysis set 1, participants with measure
    Arm/Group Title GP2013 Rituximab
    Arm/Group Description Experimental Type: Biological/Vaccine Comparator Type: Biological/Vaccine
    Measure Participants 119 120
    Mean (Standard Deviation) [microg/mL]
    66.42
    (47.593)
    82.13
    (61.526)
    9. Secondary Outcome
    Title To Evaluate a PD Marker (Peripheral CD19+ B-cell Counts) Following the Treatment With GP2013 + Chemotherapy Amd MabThera- Chemotherapy
    Description AUEC (0-21d) For descriptive purposes only, no hypothesis testing
    Time Frame 21 days

    Outcome Measure Data

    Analysis Population Description
    Pharmnacodynamic analysis set, participants with measure
    Arm/Group Title GP2013 Rituximab
    Arm/Group Description Experimental Type: Biological/Vaccine Comparator Type: Biological/Vaccine
    Measure Participants 24 24
    Geometric Mean (Geometric Coefficient of Variation) [%*day]
    1790
    (23.5)
    1910
    (13.3)
    10. Post-Hoc Outcome
    Title All Collected Deaths
    Description On treatment deaths were collected from the start of treatment up to 30 days after study drug discontinuation, for a maximum duration of 30 months (treatment duration ranged from 90 to 782 days) Deaths post treatment survival follow up were collected after the on- treatment period, up to 3 years.
    Time Frame 30 months, 3 years

    Outcome Measure Data

    Analysis Population Description
    clinical data base population - treated patients
    Arm/Group Title GP2013 Rituximab
    Arm/Group Description Experimental Type: Biological/Vaccine Comparator Type: Biological/Vaccine
    Measure Participants 312 315
    on treatment death
    4
    1.3%
    5
    1.6%
    on treatment deaths maintenance
    2
    0.6%
    2
    0.6%
    all deaths
    29
    9.3%
    31
    9.8%

    Adverse Events

    Time Frame On treatment AE, SAE and deaths were collected from the start of treatment up to 30/90 days after study drug discontinuation (30 days for combination phase and 90 for maintenance/open label phase), for a maximum duration of 30 months (treatment duration ranged from 90 to 782 days)
    Adverse Event Reporting Description Safety follow-up (treatment emergent AE/SAEs): after discontinuation of study treatment, all subjects were followed for safety for 30 days for combination phase and 90 for maintenance/open label phase.
    Arm/Group Title Combination GP2013+CVP Combination MabThera+CVP Maintenance GP2013 Maintenance MabThera
    Arm/Group Description Combination GP2013+CVP Combination MabThera+CVP Maintenance GP2013 Maintenance MabThera
    All Cause Mortality
    Combination GP2013+CVP Combination MabThera+CVP Maintenance GP2013 Maintenance MabThera
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/312 (1.3%) 5/315 (1.6%) 2/254 (0.8%) 2/252 (0.8%)
    Serious Adverse Events
    Combination GP2013+CVP Combination MabThera+CVP Maintenance GP2013 Maintenance MabThera
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 71/312 (22.8%) 63/315 (20%) 24/254 (9.4%) 21/252 (8.3%)
    Blood and lymphatic system disorders
    Anaemia 0/312 (0%) 2/315 (0.6%) 0/254 (0%) 0/252 (0%)
    Febrile neutropenia 15/312 (4.8%) 9/315 (2.9%) 0/254 (0%) 2/252 (0.8%)
    Leukocytosis 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Leukopenia 2/312 (0.6%) 2/315 (0.6%) 0/254 (0%) 0/252 (0%)
    Lymphadenopathy 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Microcytic anaemia 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Neutropenia 4/312 (1.3%) 5/315 (1.6%) 0/254 (0%) 0/252 (0%)
    Pancytopenia 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Thrombocytopenia 2/312 (0.6%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Cardiac disorders
    Acute coronary syndrome 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Angina pectoris 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Atrial fibrillation 1/312 (0.3%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Atrial flutter 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Cardiac arrest 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Cardiac failure 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Cardio-respiratory arrest 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Extrasystoles 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Palpitations 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Prinzmetal angina 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Tachycardia 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Congenital, familial and genetic disorders
    Congenital cystic kidney disease 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Hydrocele 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Polycystic liver disease 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Endocrine disorders
    Inappropriate antidiuretic hormone secretion 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Eye disorders
    Cataract 0/312 (0%) 1/315 (0.3%) 1/254 (0.4%) 0/252 (0%)
    Gastrointestinal disorders
    Abdominal distension 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Abdominal pain 4/312 (1.3%) 6/315 (1.9%) 0/254 (0%) 0/252 (0%)
    Abdominal pain lower 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Abdominal pain upper 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Acute abdomen 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Ascites 1/312 (0.3%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Colitis 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Colitis microscopic 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Constipation 3/312 (1%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Diarrhoea 1/312 (0.3%) 3/315 (1%) 1/254 (0.4%) 1/252 (0.4%)
    Dysphagia 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Erosive duodenitis 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Gastritis 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Gastrointestinal hypomotility 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Haemorrhoidal haemorrhage 0/312 (0%) 0/315 (0%) 1/254 (0.4%) 0/252 (0%)
    Ileus paralytic 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Intestinal obstruction 0/312 (0%) 3/315 (1%) 0/254 (0%) 0/252 (0%)
    Mouth ulceration 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Nausea 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Pancreatitis acute 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Small intestinal obstruction 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Vomiting 0/312 (0%) 2/315 (0.6%) 1/254 (0.4%) 0/252 (0%)
    General disorders
    Asthenia 1/312 (0.3%) 0/315 (0%) 1/254 (0.4%) 0/252 (0%)
    Chills 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Fatigue 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Hypothermia 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Malaise 0/312 (0%) 2/315 (0.6%) 0/254 (0%) 1/252 (0.4%)
    Multiple organ dysfunction syndrome 1/312 (0.3%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Non-cardiac chest pain 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Oedema peripheral 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Pain 1/312 (0.3%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Pyrexia 4/312 (1.3%) 7/315 (2.2%) 1/254 (0.4%) 0/252 (0%)
    Sudden death 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Hepatobiliary disorders
    Cholelithiasis 1/312 (0.3%) 2/315 (0.6%) 0/254 (0%) 0/252 (0%)
    Hepatic cirrhosis 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Hepatic failure 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Immune system disorders
    Anaphylactic reaction 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Cytokine release syndrome 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Drug hypersensitivity 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Hypersensitivity 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Infections and infestations
    Abscess limb 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Anal abscess 0/312 (0%) 0/315 (0%) 0/254 (0%) 2/252 (0.8%)
    Appendicitis 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Bronchitis 2/312 (0.6%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Cholecystitis infective 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Cystitis 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Diverticulitis 0/312 (0%) 0/315 (0%) 1/254 (0.4%) 1/252 (0.4%)
    Endometritis 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Erysipelas 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Escherichia bacteraemia 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Escherichia infection 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Escherichia sepsis 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Gastroenteritis 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 1/252 (0.4%)
    Gastroenteritis viral 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Genital herpes 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Helicobacter infection 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Hepatitis B 0/312 (0%) 0/315 (0%) 1/254 (0.4%) 0/252 (0%)
    Herpes zoster 1/312 (0.3%) 1/315 (0.3%) 1/254 (0.4%) 1/252 (0.4%)
    Infectious pleural effusion 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Influenza 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Malaria 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Oral candidiasis 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Peritonitis 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Peritonsillar abscess 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Pneumonia 3/312 (1%) 4/315 (1.3%) 3/254 (1.2%) 1/252 (0.4%)
    Pneumonia pseudomonal 0/312 (0%) 0/315 (0%) 1/254 (0.4%) 0/252 (0%)
    Pyelonephritis 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Respiratory tract infection 1/312 (0.3%) 0/315 (0%) 2/254 (0.8%) 0/252 (0%)
    Sepsis 2/312 (0.6%) 5/315 (1.6%) 1/254 (0.4%) 0/252 (0%)
    Septic shock 3/312 (1%) 1/315 (0.3%) 1/254 (0.4%) 0/252 (0%)
    Tooth infection 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Upper respiratory tract infection 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Urinary tract infection 3/312 (1%) 1/315 (0.3%) 0/254 (0%) 2/252 (0.8%)
    Viral infection 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Injury, poisoning and procedural complications
    Head injury 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Humerus fracture 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Infusion related reaction 3/312 (1%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Multiple fractures 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Patella fracture 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Procedural pain 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Pubis fracture 0/312 (0%) 0/315 (0%) 1/254 (0.4%) 0/252 (0%)
    Toxicity to various agents 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Upper limb fracture 0/312 (0%) 0/315 (0%) 1/254 (0.4%) 0/252 (0%)
    Investigations
    Alanine aminotransferase increased 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Aspartate aminotransferase increased 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Coagulation test abnormal 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Gamma-glutamyltransferase increased 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Lipase increased 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Weight decreased 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Metabolism and nutrition disorders
    Decreased appetite 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Diabetes mellitus inadequate control 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Hyperglycaemia 1/312 (0.3%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Hyperkalaemia 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Hyperuricaemia 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Hypervolaemia 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Hypocalcaemia 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Hypoglycaemia 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Hyponatraemia 2/312 (0.6%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Metabolic acidosis 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/312 (0%) 2/315 (0.6%) 0/254 (0%) 0/252 (0%)
    Flank pain 0/312 (0%) 0/315 (0%) 1/254 (0.4%) 0/252 (0%)
    Intervertebral disc disorder 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Spinal osteoarthritis 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Spinal pain 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colon cancer 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Invasive ductal breast carcinoma 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Lung neoplasm malignant 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Nervous system disorders
    Cerebrovascular accident 1/312 (0.3%) 0/315 (0%) 1/254 (0.4%) 0/252 (0%)
    Cervical cord compression 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Dementia 0/312 (0%) 0/315 (0%) 1/254 (0.4%) 0/252 (0%)
    Dizziness 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Headache 1/312 (0.3%) 0/315 (0%) 1/254 (0.4%) 0/252 (0%)
    Hemiparesis 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Ischaemic stroke 0/312 (0%) 0/315 (0%) 2/254 (0.8%) 0/252 (0%)
    Meningeal disorder 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Occipital neuralgia 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Peripheral sensory neuropathy 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Syncope 2/312 (0.6%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Vascular dementia 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Psychiatric disorders
    Confusional state 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Delirium 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Depression 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Mental disorder 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Suicide attempt 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Renal and urinary disorders
    Acute kidney injury 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 1/252 (0.4%)
    Anuria 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Haematuria 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Hydronephrosis 0/312 (0%) 0/315 (0%) 1/254 (0.4%) 0/252 (0%)
    Nephrolithiasis 0/312 (0%) 0/315 (0%) 2/254 (0.8%) 1/252 (0.4%)
    Oliguria 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Pollakiuria 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Renal colic 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Renal failure 2/312 (0.6%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Renal impairment 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 1/252 (0.4%)
    Reproductive system and breast disorders
    Endometrial hyperplasia 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Prostatism 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Scrotal swelling 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Uterine haemorrhage 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Vaginal haemorrhage 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Acute respiratory distress syndrome 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Acute respiratory failure 1/312 (0.3%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Asthma 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Asthmatic crisis 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Bronchitis chronic 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Cough 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Dyspnoea 0/312 (0%) 6/315 (1.9%) 0/254 (0%) 0/252 (0%)
    Interstitial lung disease 1/312 (0.3%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Laryngeal pain 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Non-cardiogenic pulmonary oedema 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Pleural effusion 0/312 (0%) 3/315 (1%) 0/254 (0%) 0/252 (0%)
    Pneumonia aspiration 0/312 (0%) 0/315 (0%) 1/254 (0.4%) 0/252 (0%)
    Pulmonary arterial hypertension 0/312 (0%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Pulmonary embolism 1/312 (0.3%) 3/315 (1%) 0/254 (0%) 0/252 (0%)
    Pulmonary mass 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Pulmonary oedema 0/312 (0%) 0/315 (0%) 1/254 (0.4%) 0/252 (0%)
    Respiratory failure 1/312 (0.3%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Skin and subcutaneous tissue disorders
    Drug eruption 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Toxic skin eruption 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Vascular disorders
    Circulatory collapse 0/312 (0%) 0/315 (0%) 0/254 (0%) 1/252 (0.4%)
    Deep vein thrombosis 1/312 (0.3%) 0/315 (0%) 0/254 (0%) 0/252 (0%)
    Hypotension 1/312 (0.3%) 1/315 (0.3%) 0/254 (0%) 0/252 (0%)
    Peripheral artery stenosis 0/312 (0%) 0/315 (0%) 1/254 (0.4%) 0/252 (0%)
    Other (Not Including Serious) Adverse Events
    Combination GP2013+CVP Combination MabThera+CVP Maintenance GP2013 Maintenance MabThera
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 262/312 (84%) 255/315 (81%) 141/254 (55.5%) 144/252 (57.1%)
    Blood and lymphatic system disorders
    Anaemia 25/312 (8%) 28/315 (8.9%) 2/254 (0.8%) 5/252 (2%)
    Leukopenia 23/312 (7.4%) 25/315 (7.9%) 11/254 (4.3%) 5/252 (2%)
    Neutropenia 78/312 (25%) 91/315 (28.9%) 32/254 (12.6%) 16/252 (6.3%)
    Gastrointestinal disorders
    Abdominal pain 28/312 (9%) 35/315 (11.1%) 6/254 (2.4%) 7/252 (2.8%)
    Abdominal pain upper 20/312 (6.4%) 16/315 (5.1%) 4/254 (1.6%) 7/252 (2.8%)
    Constipation 69/312 (22.1%) 64/315 (20.3%) 8/254 (3.1%) 10/252 (4%)
    Diarrhoea 39/312 (12.5%) 33/315 (10.5%) 11/254 (4.3%) 18/252 (7.1%)
    Nausea 51/312 (16.3%) 42/315 (13.3%) 11/254 (4.3%) 8/252 (3.2%)
    Vomiting 22/312 (7.1%) 26/315 (8.3%) 6/254 (2.4%) 12/252 (4.8%)
    General disorders
    Asthenia 30/312 (9.6%) 31/315 (9.8%) 12/254 (4.7%) 11/252 (4.4%)
    Fatigue 35/312 (11.2%) 31/315 (9.8%) 6/254 (2.4%) 10/252 (4%)
    Oedema peripheral 13/312 (4.2%) 24/315 (7.6%) 4/254 (1.6%) 11/252 (4.4%)
    Pyrexia 27/312 (8.7%) 32/315 (10.2%) 12/254 (4.7%) 13/252 (5.2%)
    Infections and infestations
    Influenza 16/312 (5.1%) 7/315 (2.2%) 7/254 (2.8%) 8/252 (3.2%)
    Upper respiratory tract infection 22/312 (7.1%) 22/315 (7%) 12/254 (4.7%) 17/252 (6.7%)
    Urinary tract infection 27/312 (8.7%) 22/315 (7%) 14/254 (5.5%) 25/252 (9.9%)
    Viral upper respiratory tract infection 8/312 (2.6%) 10/315 (3.2%) 5/254 (2%) 15/252 (6%)
    Injury, poisoning and procedural complications
    Infusion related reaction 41/312 (13.1%) 37/315 (11.7%) 5/254 (2%) 4/252 (1.6%)
    Metabolism and nutrition disorders
    Decreased appetite 17/312 (5.4%) 21/315 (6.7%) 3/254 (1.2%) 4/252 (1.6%)
    Hyperglycaemia 17/312 (5.4%) 22/315 (7%) 4/254 (1.6%) 9/252 (3.6%)
    Hyperuricaemia 8/312 (2.6%) 18/315 (5.7%) 5/254 (2%) 10/252 (4%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 19/312 (6.1%) 21/315 (6.7%) 9/254 (3.5%) 21/252 (8.3%)
    Back pain 26/312 (8.3%) 30/315 (9.5%) 14/254 (5.5%) 14/252 (5.6%)
    Myalgia 17/312 (5.4%) 20/315 (6.3%) 4/254 (1.6%) 3/252 (1.2%)
    Pain in extremity 19/312 (6.1%) 24/315 (7.6%) 7/254 (2.8%) 14/252 (5.6%)
    Nervous system disorders
    Dizziness 18/312 (5.8%) 12/315 (3.8%) 5/254 (2%) 2/252 (0.8%)
    Headache 29/312 (9.3%) 34/315 (10.8%) 12/254 (4.7%) 14/252 (5.6%)
    Neuropathy peripheral 49/312 (15.7%) 30/315 (9.5%) 8/254 (3.1%) 2/252 (0.8%)
    Paraesthesia 24/312 (7.7%) 44/315 (14%) 7/254 (2.8%) 4/252 (1.6%)
    Peripheral sensory neuropathy 26/312 (8.3%) 23/315 (7.3%) 6/254 (2.4%) 5/252 (2%)
    Psychiatric disorders
    Insomnia 15/312 (4.8%) 19/315 (6%) 3/254 (1.2%) 4/252 (1.6%)
    Respiratory, thoracic and mediastinal disorders
    Cough 32/312 (10.3%) 37/315 (11.7%) 33/254 (13%) 23/252 (9.1%)
    Dyspnoea 16/312 (5.1%) 17/315 (5.4%) 5/254 (2%) 4/252 (1.6%)
    Skin and subcutaneous tissue disorders
    Alopecia 31/312 (9.9%) 26/315 (8.3%) 1/254 (0.4%) 1/252 (0.4%)
    Vascular disorders
    Hypertension 22/312 (7.1%) 15/315 (4.8%) 12/254 (4.7%) 12/252 (4.8%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

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

    Results Point of Contact

    Name/Title Study Director
    Organization Hexal AG / Novartis Pharmaceuticals
    Phone +41613241111
    Email novartis.email@novartis.com
    Responsible Party:
    Sandoz
    ClinicalTrials.gov Identifier:
    NCT01419665
    Other Study ID Numbers:
    • GP13-301
    • 2010-019522-13
    • NCT03814785
    First Posted:
    Aug 18, 2011
    Last Update Posted:
    May 14, 2021
    Last Verified:
    Apr 1, 2021