Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    An open-labeled, randomized, two-dose, parallel group trial of ofatumumab, a fully human monoclonal anti-CD20 antibody, in combination with CHOP, in patients with previously untreated Follicular Lymphoma

    Summary
    EudraCT number
    		 2007-000244-27
    Trial protocol
    		 DE   DK   SE   CZ  
    Global end of trial date
    09 Jan 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 May 2016
    First version publication date
    14 Mar 2015
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    Hx-CD20-409
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    07 Feb 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Jan 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To investigate the efficacy in two dose regimens of ofatumumab in combination with CHOP in previously untreated patients with FL.
    Protection of trial subjects
    Not Applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    20 Jun 2007
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 60 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 59
    Worldwide total number of subjects
    59
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    49
    From 65 to 84 years
    10
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants (par.) were randomized to one of two ofatumumab dose treatment groups as soon as the participant was evaluated and considered eligible for the study. A total of 59 par. were randomized and 58 par. entered the treatment period. The 58 par. are represented in the Subject disposition and Baseline characteristics sections of this summary.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 500 mg Ofatumumab + CHOP
    Arm description
    		 Ofatumumab was given on Day 1 and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) on Day 3 of each 21-day cycle, with 300 milligrams (mg) in Cycle 1 and 500 mg in Cycles 2 to 6. Participants were followed up for 15 weeks during the Treatment period; then every 3 months for 24 months in the Follow-up period; then every 6 months until Month 60 or withdrawal from the study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ofatumumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    During the treatment period each patient will receive a total of 6 infusions of ofatumumab in combination with CHOP every 3 weeks. The first infusion in both arms will be 300 mg, followed by 5 infusions of 500 or 1000 mg.

    Investigational medicinal product name
    cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    750 mg/m2 iv x 1 for one day 24-48 hrs post-ofatumumab infusion started

    Investigational medicinal product name
    doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    50 mg/m2 iv x 1 for one day 24-48 hrs post-ofatumumab infusion started

    Investigational medicinal product name
    vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1.4 mg/m2 iv (to a maximum of 2mg) x 1 for one day 24-48 hrs post-ofatumumab infusion started

    Investigational medicinal product name
    prednisolone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg p.o. x 1 daily for 5 days 24-48 hrs post-ofatumumab infusion started

    Arm title
    		 1000 mg Ofatumumab + CHOP
    Arm description
    		 Ofatumumab was given on Day 1 and CHOP on Day 3 of each 21-day cycle, with 300 mg in Cycle 1 and 1000 mg in Cycles 2 to 6. Participants were followed up for 15 weeks during the Treatment period; then every 3 months for 24 months in the Follow-up period; then every 6 months until Month 60 or withdrawal from the study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ofatumumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    During the treatment period each patient will receive a total of 6 infusions of ofatumumab in combination with CHOP every 3 weeks. The first infusion in both arms will be 300 mg, followed by 5 infusions of 500 or 1000 mg.

    Investigational medicinal product name
    cyclophosphamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    750 mg/m2 iv x 1 for one day 24-48 hrs post-ofatumumab infusion started

    Investigational medicinal product name
    doxorubicin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    50 mg/m2 iv x 1 for one day 24-48 hrs post-ofatumumab infusion started

    Investigational medicinal product name
    vincristine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1.4 mg/m2 iv (to a maximum of 2mg) x 1 for one day 24-48 hrs post-ofatumumab infusion started

    Investigational medicinal product name
    prednisolone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg p.o. x 1 daily for 5 days 24-48 hrs post-ofatumumab infusion started

    Number of subjects in period 1 [1]
    		500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP
    Started
    29
    29
    Completed
    18
    17
    Not completed
    11
    12
         Progression of Study Disease
    7
    8
         Insurance Issues
    -
    1
         Adverse event, non-fatal
    1
    -
         Residual Tumour Mass
    -
    1
         Non-compliance
    1
    -
         New Treatment
    2
    2
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Baseline characteristics were collected in the Full Analysis Set (FAS), comprised of all participants who were exposed to trial drug irrespective of their compliance to the planned course of treatment. One participant was enrolled and randomized to receive 1000 mg Ofatumumab + CHOP, but withdrew prior to initiation of therapy.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    500 mg Ofatumumab + CHOP
    Reporting group description
    		 Ofatumumab was given on Day 1 and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) on Day 3 of each 21-day cycle, with 300 milligrams (mg) in Cycle 1 and 500 mg in Cycles 2 to 6. Participants were followed up for 15 weeks during the Treatment period; then every 3 months for 24 months in the Follow-up period; then every 6 months until Month 60 or withdrawal from the study.

    Reporting group title
    1000 mg Ofatumumab + CHOP
    Reporting group description
    		 Ofatumumab was given on Day 1 and CHOP on Day 3 of each 21-day cycle, with 300 mg in Cycle 1 and 1000 mg in Cycles 2 to 6. Participants were followed up for 15 weeks during the Treatment period; then every 3 months for 24 months in the Follow-up period; then every 6 months until Month 60 or withdrawal from the study.

    Reporting group values
    		 500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP Total
    Number of subjects
    		 29 29 58
    Age categorical
    Units: Subjects
    Age continuous
    Baseline characteristics were collected in the Full Analysis Set (FAS), comprised of all participants who were exposed to trial drug irrespective of their compliance to the planned course of treatment. One participant was enrolled and randomized to receive 1000 mg Ofatumumab + CHOP, but withdrew prior to initiation of therapy. The age was recorded as missing for 1 participant; therefore, this participant is not included in the "Subjects enrolled per age group" section.
    Units: years
        arithmetic mean (standard deviation)
    		 54.1 ( 11.4 ) 53.7 ( 9.14 ) -
    Gender categorical
    Units: Subjects
        Female
    		 14 21 35
        Male
    		 15 8 23
    Race
    Units: Subjects
        White
    		 29 27 56
        Hispanic or Latino
    		 0 2 2

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    500 mg Ofatumumab + CHOP
    Reporting group description
    		 Ofatumumab was given on Day 1 and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) on Day 3 of each 21-day cycle, with 300 milligrams (mg) in Cycle 1 and 500 mg in Cycles 2 to 6. Participants were followed up for 15 weeks during the Treatment period; then every 3 months for 24 months in the Follow-up period; then every 6 months until Month 60 or withdrawal from the study.

    Reporting group title
    1000 mg Ofatumumab + CHOP
    Reporting group description
    		 Ofatumumab was given on Day 1 and CHOP on Day 3 of each 21-day cycle, with 300 mg in Cycle 1 and 1000 mg in Cycles 2 to 6. Participants were followed up for 15 weeks during the Treatment period; then every 3 months for 24 months in the Follow-up period; then every 6 months until Month 60 or withdrawal from the study.

    Primary: Number of participants with the indicated overall best response (OBR) at Visit 26 (3 months after the last infusion of Ofatumumab)

    		 Close Top of page
    End point title
    		 Number of participants with the indicated overall best response (OBR) at Visit 26 (3 months after the last infusion of Ofatumumab) [1]
    End point description
    Based on standardized response criteria for NHL, responders included participants with CR (complete disappearance of all detectable clinical and radiographic evidence of disease), CRu (more than a 75% decrease in LN size compared to baseline), and PR (>=50% decrease in LN size and evidence of new lesions). Non-responders included participants with stable disease (SD; <50% decrease in LN size from baseline) and progressive disease (PD; >=50% increase in LN size and evidence of new lesions).
    End point type
    Primary
    End point timeframe
    Maximum of 23 months after the start of treatment
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis is not available for this primary endpoint.
    End point values
    		 500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP
    Number of subjects analysed
    29 [2]
    29 [3]
    Units: Participants
        Responder, CR
    6
    9
        Responder, CRu
    10
    7
        Responder, PR
    10
    13
        Non-Responder, SD
    2
    0
        Non-Responder, PD
    1
    0
    Notes
    [2] - FAS
    [3] - FAS
    No statistical analyses for this end point

    Secondary: Number of participants with complete remission (CR) at Visit 26

    		 Close Top of page
    End point title
    		 Number of participants with complete remission (CR) at Visit 26
    End point description
    Participants were evaluated for response by an Independent Endpoint Review Committee in accordance with the standardized response criteria for NHL. Participants with CR were defined as those with the complete disappearance of all detectable clinical and radiographic evidence of disease.
    End point type
    Secondary
    End point timeframe
    Maximum of 23 months after the start of treatment
    End point values
    		 500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP
    Number of subjects analysed
    29 [4]
    29 [5]
    Units: Participants
    6
    9
    Notes
    [4] - FAS
    [5] - FAS
    No statistical analyses for this end point

    Secondary: Median percent change from Visit 1 (Screening, Week -2) in tumor size at Visit 33 (24 months after the last infusion of Ofatumumab)

    		 Close Top of page
    End point title
    		 Median percent change from Visit 1 (Screening, Week -2) in tumor size at Visit 33 (24 months after the last infusion of Ofatumumab)
    End point description
    The tumor size for a participant was computed as the sum of product of diameters (SPD) for the indicator lesions. Reduction in tumor size was calculated as percent change from Visit 1 until Visit 33, separately by radiologist 1 and radiologist 2. Percent change from Visit 1 (Screening, Week -2) = (value at Visit 33 minus value at Visit 1 divided by value at Visit 1) * 100.
    End point type
    Secondary
    End point timeframe
    Maximum of 24 months after the last infusion of Ofatumumab (Visit 33; median of 33.8 months)
    End point values
    		 500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP
    Number of subjects analysed
    17 [6]
    16 [7]
    Units: Percent change in tumor size
    median (full range (min-max))
        Radiologist 1
    -100 (-100 to 17)
    -100 (-100 to -80)
        Radiologist 2
    -100 (-100 to -25)
    -100 (-100 to -79)
    Notes
    [6] - FAS. Participants were withdrawn from the study between Visits 1 and 33.
    [7] - FAS. Participants were withdrawn from the study between Visits 1 and 33.
    No statistical analyses for this end point

    Secondary: Duration of response

    		 Close Top of page
    End point title
    		 Duration of response
    End point description
    The duration of response is defined as the time from the initial response (the first visit at which response was observed) to progression or death. There were too few events for the upper limit of the CI to be estimated (system value of 99999 = NA for upper limit of the 95% CI).
    End point type
    Secondary
    End point timeframe
    Followed up to 5 years
    End point values
    		 500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP
    Number of subjects analysed
    26 [8]
    29 [9]
    Units: months
        median (confidence interval 95%)
    21 (13.3 to 26.2)
    25 (13.7 to 99999)
    Notes
    [8] - FAS. Only those participants with a response were analyzed.
    [9] - FAS. Only those participants with a response were analyzed.
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (PFS)

    		 Close Top of page
    End point title
    		 Progression-Free Survival (PFS)
    End point description
    PFS is defined as the time from randomization until progression or death. There were too few events for the median and upper limit of the CI to be estimated (system value of 99999 = NA for the median and the upper limit of the 95% CI).
    End point type
    Secondary
    End point timeframe
    Followed up to 5 years
    End point values
    		 500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP
    Number of subjects analysed
    29 [10]
    29 [11]
    Units: months
        median (confidence interval 95%)
    27.6 (15.1 to 28.3)
    99999 (21.3 to 99999)
    Notes
    [10] - FAS
    [11] - FAS
    No statistical analyses for this end point

    Secondary: Time to new anti-follicular lymphoma (FL) therapy

    		 Close Top of page
    End point title
    		 Time to new anti-follicular lymphoma (FL) therapy
    End point description
    Time to new FL therapy is defined as the time from randomization until the time of first administration of the new FL therapy other than ofatumumab. Time to new FL therapy will be censored if participants are lost to follow-up. The censoring date in such cases will be the date of the last attended visit at which the endpoint was assessed. There were too few participants; therefore, the upper limit of the CI could not be estimated for the 500 mg Ofatumumab + CHOP treatment and because there were too few participants the median and the upper limit of the CI could not be estimated for the 1000 mg Ofatumumab + CHOP treatment (system value of 99999 = NA).
    End point type
    Secondary
    End point timeframe
    Followed up to 5 years
    End point values
    		 500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP
    Number of subjects analysed
    29 [12]
    29 [13]
    Units: months
        median (confidence interval 95%)
    47.2 (30.4 to 99999)
    99999 (32.2 to 99999)
    Notes
    [12] - FAS
    [13] - FAS
    No statistical analyses for this end point

    Secondary: Percent change from Visit 1 (Screening) in peripheral CD19+ and CD20+ cell counts at Visit 33 (24 months after the last infusion of Ofatumumab)

    		 Close Top of page
    End point title
    		 Percent change from Visit 1 (Screening) in peripheral CD19+ and CD20+ cell counts at Visit 33 (24 months after the last infusion of Ofatumumab)
    End point description
    The peripheral blood for each participant was collected and analyzed for CD19+ and CD20+ cell counts. CD19+ and CD20+ are B-cell types which are used as an index of a participant's response to treatment.
    End point type
    Secondary
    End point timeframe
    Maximum of 24 months after the last infusion of Ofatumumab (Visit 33; median of 33.8 months)
    End point values
    		 500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP
    Number of subjects analysed
    17 [14]
    16 [15]
    Units: Percent change in cell counts
    median (full range (min-max))
        CD19+
    154.1 (-95 to 748)
    307.9 (-51 to 1767)
        CD20+
    154.1 (-95 to 520)
    307.9 (-51 to 1767)
    Notes
    [14] - FAS. Only those participants who provided samples at Visit 33 were analyzed.
    [15] - FAS. Only those participants who provided samples at Visit 33 were analyzed.
    No statistical analyses for this end point

    Secondary: Number of participants who experienced any adverse event (AEs) from first treatment to Visit 33 (24 months after last infusion)

    		 Close Top of page
    End point title
    		 Number of participants who experienced any adverse event (AEs) from first treatment to Visit 33 (24 months after last infusion)
    End point description
    An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with the treatment. A list of AEs experienced in the study with a frequency threshold of 5% can be found in the AE section.
    End point type
    Secondary
    End point timeframe
    Up to 22 months after study start
    End point values
    		 500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP
    Number of subjects analysed
    29 [16]
    29 [17]
    Units: Participants
    29
    29
    Notes
    [16] - FAS
    [17] - FAS
    No statistical analyses for this end point

    Secondary: Number of participants with positive human anti-human antibodies (HAHA) at Visits 1, 28, and 33

    		 Close Top of page
    End point title
    		 Number of participants with positive human anti-human antibodies (HAHA) at Visits 1, 28, and 33
    End point description
    HAHA are indicators of immunogenicity to ofatumumab. Blood samples were drawn from participants at Visits 1, 28, and 33 for analysis of HAHA.
    End point type
    Secondary
    End point timeframe
    Visits 1 (Screening), 28 (9 months after last dose), and 33 (24 months after last dose)
    End point values
    		 500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP
    Number of subjects analysed
    29 [18]
    29 [19]
    Units: Participants
        Visit 1, n=29, 29
    0
    0
        Visit 28, n=18, 21
    0
    0
        Visit 33, n=16, 16
    0
    0
    Notes
    [18] - FAS. Particiapants dropped out of the study as the study progressed.
    [19] - FAS. Particiapants dropped out of the study as the study progressed.
    No statistical analyses for this end point

    Secondary: Median percent change from Visit 1 (Screening) in serum complement (CH50) levels at Visit 22

    		 Close Top of page
    End point title
    		 Median percent change from Visit 1 (Screening) in serum complement (CH50) levels at Visit 22
    End point description
    The peripheral blood for each participant was collected and analyzed for serum complement CH50 levels. Cluster of Differentiation index 50 (CD50) is a human gene which is used as an index of immune response. CD50Percent change from Visit 1 (Screening, Week -2) = (value at Visit 22 minus value at Visit 1 divided by value at Visit 1) * 100.
    End point type
    Secondary
    End point timeframe
    Visit 1 (Screening, Week -2) and Visit 22 (Week 15)
    End point values
    		 500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP
    Number of subjects analysed
    24 [20]
    28 [21]
    Units: Percent change in serum complement CH50
        median (full range (min-max))
    42 (-36 to 450)
    23.2 (-55 to 620)
    Notes
    [20] - FAS. Only those participants who remained in the study at Visit 22 were analyzed.
    [21] - FAS. Only those participants who remained in the study at Visit 22 were analyzed.
    No statistical analyses for this end point

    Secondary: Cmax and Ctrough at the sixth infusion (Week 15, Visit 22)

    		 Close Top of page
    End point title
    		 Cmax and Ctrough at the sixth infusion (Week 15, Visit 22)
    End point description
    Cmax is defined as the maximum concentration of drug in plasma samples. Ctrough is defined as the trough plasma concentration (measured concentration at the end of a dosing interval [taken directly before next administration]).
    End point type
    Secondary
    End point timeframe
    Week 15 (Visit 22)
    End point values
    		 500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP
    Number of subjects analysed
    26 [22]
    29 [23]
    Units: milligrams per liter (mg/L)
    geometric mean (geometric coefficient of variation)
        Cmax
    232 ( 0.25 )
    497 ( 0.26 )
        Ctrough
    78.5 ( 0.5 )
    188 ( 0.47 )
    Notes
    [22] - FAS. Data were provided for the number of participants who had a value.
    [23] - FAS. Data were provided for the number of participants who had a value.
    No statistical analyses for this end point

    Secondary: AUC(0-inf) and AUC(0-504) after the sixth infusion (Week 15, Visit 22)

    		 Close Top of page
    End point title
    		 AUC(0-inf) and AUC(0-504) after the sixth infusion (Week 15, Visit 22)
    End point description
    AUC is defined as the area under the ofatumumab concentration-time curve as a measure of drug exposure. AUC(0-504) is AUC from the start of infusion to 504 hours after the start of the infusion; AUC(0-inf) is AUC from the start of infusion extrapolated to infinity.
    End point type
    Secondary
    End point timeframe
    Week 15 (Visit 22)
    End point values
    		 500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP
    Number of subjects analysed
    25 [24]
    29 [25]
    Units: Milligrams * hours/liter (mg.h/L)
    geometric mean (geometric coefficient of variation)
        AUC(0-inf), n=20, 28
    177133 ( 0.41 )
    399676 ( 0.47 )
        AUC(0-504), n=24, 28
    79500 ( 0.26 )
    168866 ( 0.33 )
    Notes
    [24] - FAS. Data were provided for the number of participants for whom the parameter could be calculated.
    [25] - FAS. Data were provided for the number of participants for whom the parameter could be calculated.
    No statistical analyses for this end point

    Secondary: Half life (t1/2) of ofatumumab at the sixth infusion (Week 15, Visit 22)

    		 Close Top of page
    End point title
    		 Half life (t1/2) of ofatumumab at the sixth infusion (Week 15, Visit 22)
    End point description
    Half life is defined as the period of time required for the amount of drug in the body to be reduced by half.
    End point type
    Secondary
    End point timeframe
    Week 15 (Visit 22)
    End point values
    		 500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP
    Number of subjects analysed
    23 [26]
    29 [27]
    Units: Hours
        geometric mean (geometric coefficient of variation)
    652 ( 0.57 )
    644 ( 0.32 )
    Notes
    [26] - FAS. Data provided for participants attending each visit for whom the parameter could be calculated.
    [27] - FAS. Data provided for participants attending each visit for whom the parameter could be calculated.
    No statistical analyses for this end point

    Secondary: CL after the sixth infusion (Week 15, Visit 22)

    		 Close Top of page
    End point title
    		 CL after the sixth infusion (Week 15, Visit 22)
    End point description
    CL is the clearance of drug from plasma, which is defined as the volume of plasma from which the drug is cleared per unit time.
    End point type
    Secondary
    End point timeframe
    Week 15 (Visit 22)
    End point values
    		 500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP
    Number of subjects analysed
    26 [28]
    29 [29]
    Units: Milliliters per hour (mL/h)
        geometric mean (geometric coefficient of variation)
    6.29 ( 0.26 )
    5.92 ( 0.33 )
    Notes
    [28] - FAS. Data provided for participants attending each visit for whom the parameter could be calculated.
    [29] - FAS. Data provided for participants attending each visit for whom the parameter could be calculated.
    No statistical analyses for this end point

    Secondary: Vss at the sixth infusion (Week 15, Visit 22)

    		 Close Top of page
    End point title
    		 Vss at the sixth infusion (Week 15, Visit 22)
    End point description
    Vss is defined as the volume of distribution at steady state of ofatumumab.
    End point type
    Secondary
    End point timeframe
    Week 15 (Visit 22)
    End point values
    		 500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP
    Number of subjects analysed
    23 [30]
    29 [31]
    Units: Liters
        geometric mean (geometric coefficient of variation)
    5.15 ( 0.34 )
    5.32 ( 0.38 )
    Notes
    [30] - FAS. Data provided for participants attending each visit for whom the parameter could be calculated.
    [31] - FAS. Data provided for participants attending each visit for whom the parameter could be calculated.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Non-serious adverse events (AEs) were collected from the start of study medication until Follow-up (up to 24 months after last treatment). Serious AEs were collected from the start of study medication until study completion (up to 60 months).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    15.1
    Reporting groups
    Reporting group title
    500 mg Ofatumumab + CHOP
    Reporting group description
    		 Ofatumumab was given on Day 1 and CHOP on Day 3 of each 21-day cycle, with 300 mg in Cycle 1 and 500 mg in Cycles 2 to 6. Participants were followed up for 15 weeks during the Treatment period; then every 3 months for 24 months in the Follow-up period; then every 6 months until Month 60 or withdrawal from the study.

    Reporting group title
    1000 mg Ofatumumab + CHOP
    Reporting group description
    		 Ofatumumab was given on Day 1 and CHOP on Day 3 of each 21-day cycle, with 300 mg in Cycle 1 and 1000 mg in Cycles 2 to 6. Participants were followed up for 15 weeks during the Treatment period; then every 3 months for 24 months in the Follow-up period; then every 6 months until Month 60 or withdrawal from the study.

    Reporting group title
    500 mg Ofatumumab + CHOP: Extended Follow-up
    Reporting group description
    		 Ofatumumab was given on Day 1 and CHOP on Day 3 of each 21-day cycle, with 300 mg in Cycle 1 and 500 mg in Cycles 2 to 6. Participants were followed up for 15 weeks during the Treatment period; then every 3 months for 24 months in the Follow-up period; then every 6 months until Month 60 or withdrawal from the study.

    Reporting group title
    1000 mg Ofatumumab + CHOP: Extended Follow-up
    Reporting group description
    		 Ofatumumab was given on Day 1 and CHOP on Day 3 of each 21-day cycle, with 300 mg in Cycle 1 and 1000 mg in Cycles 2 to 6. Participants were followed up for 15 weeks during the Treatment period; then every 3 months for 24 months in the Follow-up period; then every 6 months until Month 60 or withdrawal from the study.

    Serious adverse events
    		 500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP 500 mg Ofatumumab + CHOP: Extended Follow-up 1000 mg Ofatumumab + CHOP: Extended Follow-up
    Total subjects affected by serious adverse events
         subjects affected / exposed
    13 / 29 (44.83%)
    11 / 29 (37.93%)
    1 / 29 (3.45%)
    6 / 29 (20.69%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cancer
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vulval cancer
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Infarction (CNS)
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Ileostomy
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injection site extravasation
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 29 (3.45%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytokine release syndrome
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Weight decreased
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fibula fracture
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Migraine
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    5 / 29 (17.24%)
    3 / 29 (10.34%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    4 / 29 (13.79%)
    3 / 29 (10.34%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    2 / 11
    1 / 5
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    2 / 29 (6.90%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Ascites
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal perforation
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abnorminal hernia
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    2 / 29 (6.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Precancerous skin lesion
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rosacea
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Periostitis
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Candidiasis
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    0 / 29 (0.00%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 500 mg Ofatumumab + CHOP 1000 mg Ofatumumab + CHOP 500 mg Ofatumumab + CHOP: Extended Follow-up 1000 mg Ofatumumab + CHOP: Extended Follow-up
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    29 / 29 (100.00%)
    28 / 29 (96.55%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lipoma
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Vascular disorders
    Flushing
         subjects affected / exposed
    1 / 29 (3.45%)
    6 / 29 (20.69%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    6
    0
    0
    Hot flush
         subjects affected / exposed
    2 / 29 (6.90%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Hypertension
         subjects affected / exposed
    0 / 29 (0.00%)
    3 / 29 (10.34%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Haematoma
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Phlebitis
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    13 / 29 (44.83%)
    13 / 29 (44.83%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    23
    17
    0
    0
    Infusion related reaction
         subjects affected / exposed
    7 / 29 (24.14%)
    8 / 29 (27.59%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    13
    10
    0
    0
    Oedema peripheral
         subjects affected / exposed
    7 / 29 (24.14%)
    6 / 29 (20.69%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    8
    10
    0
    0
    Pyrexia
         subjects affected / exposed
    5 / 29 (17.24%)
    8 / 29 (27.59%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    6
    10
    0
    0
    Oedema
         subjects affected / exposed
    3 / 29 (10.34%)
    5 / 29 (17.24%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    5
    5
    0
    0
    Chills
         subjects affected / exposed
    3 / 29 (10.34%)
    3 / 29 (10.34%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    4
    3
    0
    0
    Asthenia
         subjects affected / exposed
    2 / 29 (6.90%)
    3 / 29 (10.34%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    3
    0
    0
    Pain
         subjects affected / exposed
    2 / 29 (6.90%)
    3 / 29 (10.34%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    3
    0
    0
    Mucosal inflammation
         subjects affected / exposed
    2 / 29 (6.90%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    2
    0
    0
    Chest Pain
         subjects affected / exposed
    1 / 29 (3.45%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Abdominal distension
         subjects affected / exposed
    3 / 29 (10.34%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    2
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    6 / 29 (20.69%)
    7 / 29 (24.14%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    6
    9
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    8 / 29 (27.59%)
    5 / 29 (17.24%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    14
    6
    0
    0
    Nasal congestion
         subjects affected / exposed
    2 / 29 (6.90%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    3
    0
    0
    Nasal disorder
         subjects affected / exposed
    2 / 29 (6.90%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    4
    2
    0
    0
    Throat irritation
         subjects affected / exposed
    1 / 29 (3.45%)
    3 / 29 (10.34%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    4
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Dyspnea
         subjects affected / exposed
    9 / 29 (31.03%)
    8 / 29 (27.59%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    16
    11
    0
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    4 / 29 (13.79%)
    3 / 29 (10.34%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    5
    3
    0
    0
    Depression
         subjects affected / exposed
    2 / 29 (6.90%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    3
    0
    0
    Depressed mood
         subjects affected / exposed
    1 / 29 (3.45%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Sleep disorder
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Investigations
    Weight increased
         subjects affected / exposed
    2 / 29 (6.90%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    1
    0
    0
    White blood cell count decreased
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Injury, poisoning and procedural complications
    Fungal skin infection
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    1 / 29 (3.45%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Arrhythmia
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Nervous system disorders
    Polyneuropathy
         subjects affected / exposed
    8 / 29 (27.59%)
    8 / 29 (27.59%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    9
    11
    0
    0
    Headache
         subjects affected / exposed
    6 / 29 (20.69%)
    7 / 29 (24.14%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    8
    12
    0
    0
    Dizziness
         subjects affected / exposed
    4 / 29 (13.79%)
    6 / 29 (20.69%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    4
    6
    0
    0
    Dysgeusia
         subjects affected / exposed
    2 / 29 (6.90%)
    8 / 29 (27.59%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    8
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    3 / 29 (10.34%)
    4 / 29 (13.79%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    4
    0
    0
    Paraesthesia
         subjects affected / exposed
    4 / 29 (13.79%)
    3 / 29 (10.34%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    4
    3
    0
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    4 / 29 (13.79%)
    3 / 29 (10.34%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    4
    5
    0
    0
    Tremor
         subjects affected / exposed
    1 / 29 (3.45%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Hypoaesthesia
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Presyncope
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    9 / 29 (31.03%)
    9 / 29 (31.03%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    32
    25
    0
    0
    Neutropenia
         subjects affected / exposed
    7 / 29 (24.14%)
    7 / 29 (24.14%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    17
    9
    0
    0
    Anaemia
         subjects affected / exposed
    3 / 29 (10.34%)
    4 / 29 (13.79%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    7
    0
    0
    Lymphopenia
         subjects affected / exposed
    2 / 29 (6.90%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    2
    0
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    4 / 29 (13.79%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    5
    2
    0
    0
    Tinnitus
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Eye disorders
    Vision blurred
         subjects affected / exposed
    3 / 29 (10.34%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    2
    0
    0
    Keratoconjunctivitis sicca
         subjects affected / exposed
    2 / 29 (6.90%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Ocular surface disease
         subjects affected / exposed
    0 / 29 (0.00%)
    3 / 29 (10.34%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Eye irritation
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    11 / 29 (37.93%)
    12 / 29 (41.38%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    22
    24
    0
    0
    Constipation
         subjects affected / exposed
    9 / 29 (31.03%)
    12 / 29 (41.38%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    10
    15
    0
    0
    Diarrhoea
         subjects affected / exposed
    8 / 29 (27.59%)
    10 / 29 (34.48%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    9
    15
    0
    0
    Dyspepsia
         subjects affected / exposed
    6 / 29 (20.69%)
    6 / 29 (20.69%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    7
    7
    0
    0
    Vomiting
         subjects affected / exposed
    5 / 29 (17.24%)
    6 / 29 (20.69%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    7
    15
    0
    0
    Gingivitis
         subjects affected / exposed
    5 / 29 (17.24%)
    3 / 29 (10.34%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    7
    3
    0
    0
    Abdominal pain
         subjects affected / exposed
    2 / 29 (6.90%)
    4 / 29 (13.79%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    5
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 29 (3.45%)
    5 / 29 (17.24%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    6
    0
    0
    Dry mouth
         subjects affected / exposed
    2 / 29 (6.90%)
    3 / 29 (10.34%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    3
    0
    0
    Haemorrhoids
         subjects affected / exposed
    1 / 29 (3.45%)
    4 / 29 (13.79%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    6
    0
    0
    Aphthous stomatitis
         subjects affected / exposed
    1 / 29 (3.45%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Flatulence
         subjects affected / exposed
    1 / 29 (3.45%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Glossodynia
         subjects affected / exposed
    2 / 29 (6.90%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Dysphagia
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Gingival bleeding
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    17 / 29 (58.62%)
    11 / 29 (37.93%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    17
    11
    0
    0
    Urticaria
         subjects affected / exposed
    11 / 29 (37.93%)
    9 / 29 (31.03%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    19
    11
    0
    0
    Rash
         subjects affected / exposed
    11 / 29 (37.93%)
    8 / 29 (27.59%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    11
    12
    0
    0
    Pruritus
         subjects affected / exposed
    4 / 29 (13.79%)
    8 / 29 (27.59%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    4
    8
    0
    0
    Erythema
         subjects affected / exposed
    5 / 29 (17.24%)
    3 / 29 (10.34%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    6
    3
    0
    0
    Hyperhidrosis
         subjects affected / exposed
    3 / 29 (10.34%)
    5 / 29 (17.24%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    4
    5
    0
    0
    Dry skin
         subjects affected / exposed
    2 / 29 (6.90%)
    3 / 29 (10.34%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    4
    0
    0
    Skin lesion
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Renal and urinary disorders
    Urinary incontinence
         subjects affected / exposed
    0 / 29 (0.00%)
    3 / 29 (10.34%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    4
    0
    0
    Dysuria
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Incontinence
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    3 / 29 (10.34%)
    10 / 29 (34.48%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    10
    0
    0
    Arthralgia
         subjects affected / exposed
    6 / 29 (20.69%)
    4 / 29 (13.79%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    9
    6
    0
    0
    Bone pain
         subjects affected / exposed
    1 / 29 (3.45%)
    5 / 29 (17.24%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    8
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 29 (3.45%)
    5 / 29 (17.24%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    5
    0
    0
    Intervertebral disc protrusion
         subjects affected / exposed
    3 / 29 (10.34%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    1
    0
    0
    Pain in extremity
         subjects affected / exposed
    4 / 29 (13.79%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    5
    0
    0
    0
    Joint stiffness
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Musculoskeletal discomfort
         subjects affected / exposed
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    4 / 29 (13.79%)
    7 / 29 (24.14%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    4
    10
    0
    0
    Cystitis
         subjects affected / exposed
    3 / 29 (10.34%)
    4 / 29 (13.79%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    4
    0
    0
    Bronchitis
         subjects affected / exposed
    3 / 29 (10.34%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    5
    2
    0
    0
    Herpes zoster
         subjects affected / exposed
    3 / 29 (10.34%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    2
    0
    0
    Oral herpes
         subjects affected / exposed
    3 / 29 (10.34%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    4
    3
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 29 (6.90%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    3
    0
    0
    Pharyngitis
         subjects affected / exposed
    2 / 29 (6.90%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Rhinitis
         subjects affected / exposed
    0 / 29 (0.00%)
    3 / 29 (10.34%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    4
    0
    0
    Sinusitis
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    6
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    5 / 29 (17.24%)
    3 / 29 (10.34%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    8
    3
    0
    0
    Hypokalaemia
         subjects affected / exposed
    2 / 29 (6.90%)
    1 / 29 (3.45%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    5
    1
    0
    0
    Diabetes mellitus
         subjects affected / exposed
    0 / 29 (0.00%)
    2 / 29 (6.90%)
    0 / 29 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Mar 2010
    Amendment No.: 01 Addition of primary efficacy endpoint data and updated safety data
    03 Aug 2010
    Amendment No.: 02 Pharmacokinetic data were removed as re-analysis is ongoing

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun May 04 14:51:46 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA