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   43871   clinical trials with a EudraCT protocol, of which   7290   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:
    A phase 3, multicenter, randomized, double-blind, active control study to evaluate the safety and efficacy of IV pro-netupitant/palonosetron (260 mg/0.25 mg) combination for the prevention of chemotherapy-induced nausea and vomiting in repeated chemotherapy cycles in patients receiving highly emetogenic chemotherapy

    Summary
    EudraCT number
    		 2015-001800-74
    Trial protocol
    		 AT   DE   CZ   ES   PL   HR  
    Global end of trial date
    02 Aug 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 Dec 2017
    First version publication date
    02 Dec 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    NEPA-15-18
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02517021
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Helsinn Healthcare SA
    Sponsor organisation address
    Via Pian Scairolo 9, Lugano, Switzerland, 6912
    Public contact
    Clinical Operation, Helsinn Healthcare SA, +41 91 985 21 21, daniel.voisin@helsinn.com
    Scientific contact
    Clinical Operation, Helsinn Healthcare SA, +41 91 985 21 21, daniel.voisin@helsinn.com
    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
    02 Aug 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    02 Aug 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Aug 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective is to assess the safety and tolerability of a single dose of intravenous fosnetupitant/palonosetron (260 mg/0.25 mg) fixed-dose combination (IV NEPA FDC) infused over 30 minutes (min), with Oral dexamethasone, in initial and repeated cycles of highly emetogenic chemotherapy (HEC).
    Protection of trial subjects
    This study was in compliance with the ethical principles founded in the Declaration of Helsinki, the International Conference on Harmonisation (ICH) guidelines regarding Good Clinical Practices and the European Union Directives on Clinical Trials. The appropriateness of the clinical trial protocol as well as the risks and benefits to study participants were approved by the relevant IECs/IRBs. In addition, an independent Data Safety Monitoring Board (DSMB) was convened for the evaluation of safety data during the study in order to perform a qualitative safety assessment.
    Background therapy
    		 Oral dexamethasone
    Evidence for comparator
    		 -
    Actual start date of recruitment
    17 Nov 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Israel: 2
    Country: Number of subjects enrolled
    Italy: 18
    Country: Number of subjects enrolled
    Serbia: 55
    Country: Number of subjects enrolled
    Ukraine: 162
    Country: Number of subjects enrolled
    United States: 12
    Country: Number of subjects enrolled
    Poland: 113
    Country: Number of subjects enrolled
    Spain: 8
    Country: Number of subjects enrolled
    Croatia: 23
    Country: Number of subjects enrolled
    Austria: 1
    Country: Number of subjects enrolled
    Czech Republic: 6
    Country: Number of subjects enrolled
    Germany: 5
    Worldwide total number of subjects
    405
    EEA total number of subjects
    174
    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)
    262
    From 65 to 84 years
    143
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Adult chemotherapy-naïve (at study entry) male or female patients with a diagnosis of malignant solid tumor requiring treatment with one of the reference HEC regimens on Day 1 of each cycle. Patients were enrolled in 56 study centers in 11 countries.

    Pre-assignment
    Screening details
    		 A total of 400 patients (200 per treatment group) were planned to be randomized in the study. A total of 405 patients who met the inclusion criteria were eventually randomized. Of the 405 patients randomized, only one randomized patient in the Oral NEPA FDC group did not receive active study drug and reference HEC and was excluded from all analysis

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Monitor, Data analyst, Carer, Assessor, Subject, Investigator
    Blinding implementation details
    The blinding of the study drugs was guaranteed by the use of identical placebos to the respective active drugs (double-dummy technique). When Oral NEPA FDC capsule was administered to subjects of the control group, a placebo capsule was administered to subjects of the test group. When IV NEPA FDC infusion was administered to subjects of the test group, an IV infusion of placebo was administered to subjects of the control group.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 IV NEPA FDC
    Arm description
    		 IV fosnetupitant/palonosetron (260 mg/0.25 mg) FDC (IV NEPA FDC) was to be administered as a 30-min infusion of a 50-mL solution on Day 1 of each cycle. The 30-min (±5 min) IV NEPA FDC infusion was to be started 30 min prior to the start of the reference chemotherapy administration. The 30-min IV infusion was to be completed before starting chemotherapy administration.
    Arm type
    		 Experimental

    Investigational medicinal product name
    IV fosnetupitant/palonosetron fixed-dose combination for infusion (IV NEPA FDC)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    IV infusion of 30 min duration to begin 30 min prior to the start of reference chemotherapy administration.

    Arm title
    		 Oral NEPA FDC
    Arm description
    		 Oral netupitant/palonosetron (300 mg/0.50 mg) FDC (Oral NEPA FDC) was to be administered on Day 1 of each cycle. Oral NEPA FDC capsule was to be administered 60 min prior to the start of the reference chemotherapy administration.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Oral netupitant/palonosetron fixed-dose combination (Oral NEPA FDC)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    300 mg netupitant/0.50 mg palonosetron. To be administered 60 min prior to the start of reference chemotherapy administration

    Number of subjects in period 1
    		IV NEPA FDC Oral NEPA FDC
    Started
    203
    202
    Completed
    120
    117
    Not completed
    83
    85
         Consent withdrawn by subject
    8
    7
         Physician decision
    8
    12
         Adverse event, non-fatal
    16
    18
         Death
    10
    15
         I/E criteria not met for a repeated cycle
    10
    5
         Overall study closure
    24
    19
         Other reasons
    5
    6
         Lost to follow-up
    2
    3

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    IV NEPA FDC
    Reporting group description
    		 IV fosnetupitant/palonosetron (260 mg/0.25 mg) FDC (IV NEPA FDC) was to be administered as a 30-min infusion of a 50-mL solution on Day 1 of each cycle. The 30-min (±5 min) IV NEPA FDC infusion was to be started 30 min prior to the start of the reference chemotherapy administration. The 30-min IV infusion was to be completed before starting chemotherapy administration.

    Reporting group title
    Oral NEPA FDC
    Reporting group description
    		 Oral netupitant/palonosetron (300 mg/0.50 mg) FDC (Oral NEPA FDC) was to be administered on Day 1 of each cycle. Oral NEPA FDC capsule was to be administered 60 min prior to the start of the reference chemotherapy administration.

    Reporting group values
    		 IV NEPA FDC Oral NEPA FDC Total
    Number of subjects
    		 203 202 405
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 129 133 262
        From 65-84 years
    		 74 69 143
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 60 ( 9.7 ) 58.9 ( 10.6 ) -
    Gender categorical
    Units: Subjects
        Female
    		 96 94 190
        Male
    		 107 108 215

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    IV NEPA FDC
    Reporting group description
    		 IV fosnetupitant/palonosetron (260 mg/0.25 mg) FDC (IV NEPA FDC) was to be administered as a 30-min infusion of a 50-mL solution on Day 1 of each cycle. The 30-min (±5 min) IV NEPA FDC infusion was to be started 30 min prior to the start of the reference chemotherapy administration. The 30-min IV infusion was to be completed before starting chemotherapy administration.

    Reporting group title
    Oral NEPA FDC
    Reporting group description
    		 Oral netupitant/palonosetron (300 mg/0.50 mg) FDC (Oral NEPA FDC) was to be administered on Day 1 of each cycle. Oral NEPA FDC capsule was to be administered 60 min prior to the start of the reference chemotherapy administration.

    Subject analysis set title
    Full Analysis Set: IV NEPA FDC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Included all randomized patients who received the HEC regimen and active study drug (including partial infusion). Following the intent-to-treat principle, patients were assigned to the treatment group to which they were randomized.

    Subject analysis set title
    Safety population: IV NEPA FDC
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Included all patients who received at least one dose of active study drug (including partial infusion). Patients were assigned to treatment groups according to the actual treatment received.

    Subject analysis set title
    Full Analysis Set: Oral NEPA FDC
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Included all randomized patients who received the HEC regimen and active study drug (including partial infusion). Following the intent-to-treat principle, patients were assigned to the treatment group to which they were randomized.

    Subject analysis set title
    Safety Population: Oral NEPA FDC
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Included all patients who received at least one dose of active study drug (including partial infusion). Patients were assigned to treatment groups according to the actual treatment received.

    Primary: Complete Response in acute phase: Cycle 1

    		 Close Top of page
    End point title
    		 Complete Response in acute phase: Cycle 1
    End point description
    Complete response in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-24 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Primary
    End point timeframe
    Acute phase (0-24 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    203
    201
    Units: Proportion
        number (confidence interval 95%)
    92.6 (88.2 to 95.5)
    90.5 (85.7 to 93.9)
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: Oral NEPA FDC v Full Analysis Set: IV NEPA FDC
    Number of subjects included in analysis
    404
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    2.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.7
         upper limit
    		 7.2
    Notes
    [1] - No formal test was planned for this endpoint.

    Primary: Complete Response in delayed phase: Cycle 1

    		 Close Top of page
    End point title
    		 Complete Response in delayed phase: Cycle 1
    End point description
    Complete response in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting >24-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Primary
    End point timeframe
    Delayed phase (>24-120 h)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    203
    201
    Units: Proportion
        number (confidence interval 95%)
    78.3 (72.2 to 83.4)
    87.6 (82.3 to 91.4)
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    404
    Analysis specification
    Pre-specified
    Analysis type
    		 other [2]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.8
         upper limit
    		 -2.2
    Notes
    [2] - No formal test was planned for this endpoint.

    Primary: Complete Response in overall phase: Cycle 1

    		 Close Top of page
    End point title
    		 Complete Response in overall phase: Cycle 1
    End point description
    Complete response in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Primary
    End point timeframe
    Overall phase (0-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    203
    201
    Units: Proportion
        number (confidence interval 95%)
    76.8 (70.6 to 82.1)
    84.1 (78.4 to 88.5)
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    404
    Analysis specification
    Pre-specified
    Analysis type
    		 other [3]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -7.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.2
         upper limit
    		 -0.1
    Notes
    [3] - No formal test was planned for this endpoint.

    Secondary: Complete Response in acute phase: Cycle 2

    		 Close Top of page
    End point title
    		 Complete Response in acute phase: Cycle 2
    End point description
    Complete response in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-24 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Acute phase (0-24 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    179 [4]
    176 [5]
    Units: Proportion
        number (confidence interval 95%)
    89.9 (84.7 to 93.5)
    90.3 (85.1 to 93.9)
    Notes
    [4] - Discontinuation after cycle 1
    [5] - Discontinuation after cycle 1
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    355
    Analysis specification
    Pre-specified
    Analysis type
    		 other [6]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.4
         upper limit
    		 6.3
    Notes
    [6] - No formal test was planned for this endpoint.

    Secondary: Complete Response in delayed phase: Cycle 2

    		 Close Top of page
    End point title
    		 Complete Response in delayed phase: Cycle 2
    End point description
    Complete response in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting >24-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Delayed phase (>24-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    179 [7]
    176 [8]
    Units: Proportion
        number (confidence interval 95%)
    82.1 (75.9 to 87)
    89.2 (83.8 to 93)
    Notes
    [7] - Discontinuation after cycle 1
    [8] - Discontinuation after cycle 1
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    355
    Analysis specification
    Pre-specified
    Analysis type
    		 other [9]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -6.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.1
         upper limit
    		 0.4
    Notes
    [9] - No formal test was planned for this endpoint.

    Secondary: Complete Response in overall phase: Cycle 2

    		 Close Top of page
    End point title
    		 Complete Response in overall phase: Cycle 2
    End point description
    Complete response in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Overall phase (0-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    179 [10]
    176 [11]
    Units: Proportion
        number (confidence interval 95%)
    79.9 (73.4 to 85.1)
    85.8 (79.9 to 90.2)
    Notes
    [10] - Discontinuation after cycle 1
    [11] - Discontinuation after cycle 1
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    355
    Analysis specification
    Pre-specified
    Analysis type
    		 other [12]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -5.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.7
         upper limit
    		 2
    Notes
    [12] - No formal test was planned for this endpoint.

    Secondary: Complete Response in acute phase: Cycle 3

    		 Close Top of page
    End point title
    		 Complete Response in acute phase: Cycle 3
    End point description
    Complete response in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-24 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Acute phase (0-24 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    163 [13]
    150 [14]
    Units: Proportion
        number (confidence interval 95%)
    92.6 (87.6 to 95.7)
    96 (91.5 to 98.2)
    Notes
    [13] - Discontinuation after previous cycle
    [14] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    		 other [15]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -2.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.3
         upper limit
    		 2.4
    Notes
    [15] - No formal test was planned for this endpoint.

    Secondary: Complete Response in delayed phase: Cycle 3

    		 Close Top of page
    End point title
    		 Complete Response in delayed phase: Cycle 3
    End point description
    Complete response in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting >24-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Delayed phase (>24-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    163 [16]
    150 [17]
    Units: Proportion
        number (confidence interval 95%)
    85.9 (79.7 to 90.4)
    90 (84.2 to 93.8)
    Notes
    [16] - Discontinuation after previous cycle
    [17] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    		 other [18]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.5
         upper limit
    		 4
    Notes
    [18] - No formal test was planned for this endpoint.

    Secondary: Complete Response in overall phase: Cycle 3

    		 Close Top of page
    End point title
    		 Complete Response in overall phase: Cycle 3
    End point description
    Complete response in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Overall phase (0-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    163 [19]
    150 [20]
    Units: Proportion
        number (confidence interval 95%)
    84 (77.7 to 88.9)
    88.7 (82.6 to 92.8)
    Notes
    [19] - Discontinuation after previous cycle
    [20] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    		 other [21]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -2.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.1
         upper limit
    		 4.2
    Notes
    [21] - No formal test was planned for this endpoint.

    Secondary: Complete Response in acute phase: Cycle 4

    		 Close Top of page
    End point title
    		 Complete Response in acute phase: Cycle 4
    End point description
    Complete response in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-24 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Acute phase (0-24 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    122 [22]
    117 [23]
    Units: Proportion
        number (confidence interval 95%)
    90.2 (83.6 to 94.3)
    99.1 (95.3 to 99.8)
    Notes
    [22] - Discontinuation after previous cycle
    [23] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    239
    Analysis specification
    Pre-specified
    Analysis type
    		 other [24]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.9
         upper limit
    		 -2.2
    Notes
    [24] - No formal test was planned for this endpoint.

    Secondary: Complete Response in delayed phase: Cycle 4

    		 Close Top of page
    End point title
    		 Complete Response in delayed phase: Cycle 4
    End point description
    Complete response in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting >24-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Delayed phase (>24-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    122 [25]
    117 [26]
    Units: Proportion
        number (confidence interval 95%)
    86.1 (78.8 to 91.1)
    98.3 (94 to 99.5)
    Notes
    [25] - Discontinuation after previous cycle
    [26] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    239
    Analysis specification
    Pre-specified
    Analysis type
    		 other [27]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -9.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.4
         upper limit
    		 -3.8
    Notes
    [27] - No formal test was planned for this endpoint.

    Secondary: Complete Response in overall phase: Cycle 4

    		 Close Top of page
    End point title
    		 Complete Response in overall phase: Cycle 4
    End point description
    Complete response in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Overall phase (0-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    122 [28]
    117 [29]
    Units: Proportion
        number (confidence interval 95%)
    83.6 (76 to 89.1)
    97.4 (92.7 to 99.1)
    Notes
    [28] - Discontinuation after previous cycle
    [29] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    239
    Analysis specification
    Pre-specified
    Analysis type
    		 other [30]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -11.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.6
         upper limit
    		 -4.6
    Notes
    [30] - No formal test was planned for this endpoint.

    Secondary: Absence of Emetic Episodes in acute phase: Cycle 1

    		 Close Top of page
    End point title
    		 Absence of Emetic Episodes in acute phase: Cycle 1
    End point description
    Absence of Emetic Episodes in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-24 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Acute phase (0-24 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    203
    201
    Units: Proportion
        number (confidence interval 95%)
    95.1 (91.2 to 97.3)
    93 (88.6 to 95.8)
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    404
    Analysis specification
    Pre-specified
    Analysis type
    		 other [31]
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    2.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.8
         upper limit
    		 6.5
    Notes
    [31] - No formal test was planned for this endpoint.

    Secondary: Absence of Emetic Episodes in delayed phase: Cycle 1

    		 Close Top of page
    End point title
    		 Absence of Emetic Episodes in delayed phase: Cycle 1
    End point description
    Absence of Emetic Episodes in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting >24-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Delayed phase (>24-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    203
    201
    Units: Proportion
        number (confidence interval 95%)
    85.2 (79.7 to 89.4)
    91.5 (86.9 to 94.7)
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    404
    Analysis specification
    Pre-specified
    Analysis type
    		 other [32]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -6.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12
         upper limit
    		 -0.4
    Notes
    [32] - No formal test was planned for this endpoint.

    Secondary: Absence of Emetic Episodes in overall phase: Cycle 1

    		 Close Top of page
    End point title
    		 Absence of Emetic Episodes in overall phase: Cycle 1
    End point description
    Absence of Emetic Episodes in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Overall phase (0-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    203
    201
    Units: Proportion
        number (confidence interval 95%)
    84.2 (78.6 to 88.6)
    88.6 (83.4 to 92.3)
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    404
    Analysis specification
    Pre-specified
    Analysis type
    		 other [33]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -4.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.4
         upper limit
    		 1.8
    Notes
    [33] - No formal test was planned for this endpoint.

    Secondary: Absence of Emetic Episodes in acute phase: Cycle 2

    		 Close Top of page
    End point title
    		 Absence of Emetic Episodes in acute phase: Cycle 2
    End point description
    Absence of Emetic Episodes in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-24 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Acute phase (0-24 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    179 [34]
    176 [35]
    Units: Proportion
        number (confidence interval 95%)
    91.6 (86.6 to 94.9)
    93.8 (89.2 to 96.5)
    Notes
    [34] - Discontinuation after cycle 1
    [35] - Discontinuation after cycle 1
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    355
    Analysis specification
    Pre-specified
    Analysis type
    		 other [36]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -1.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7
         upper limit
    		 3.2
    Notes
    [36] - No formal test was planned for this endpoint.

    Secondary: Absence of Emetic Episodes in delayed phase: Cycle 2

    		 Close Top of page
    End point title
    		 Absence of Emetic Episodes in delayed phase: Cycle 2
    End point description
    Absence of Emetic Episodes in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting >24-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Delayed phase (>24-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    179 [37]
    176 [38]
    Units: Proportion
        number (confidence interval 95%)
    87.2 (81.5 to 91.3)
    94.9 (90.6 to 97.3)
    Notes
    [37] - Discontinuation after cycle 1
    [38] - Discontinuation after cycle 1
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    355
    Analysis specification
    Pre-specified
    Analysis type
    		 other [39]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -7.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.2
         upper limit
    		 -2
    Notes
    [39] - No formal test was planned for this endpoint.

    Secondary: Absence of Emetic Episodes in overall phase: Cycle 2

    		 Close Top of page
    End point title
    		 Absence of Emetic Episodes in overall phase: Cycle 2
    End point description
    Absence of Emetic Episodes in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Overall phase (0-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    179 [40]
    176 [41]
    Units: Proportion
        number (confidence interval 95%)
    85.5 (79.6 to 89.9)
    93.2 (88.5 to 96.1)
    Notes
    [40] - Discontinuation after cycle 1
    [41] - Discontinuation after cycle 1
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    355
    Analysis specification
    Pre-specified
    Analysis type
    		 other [42]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -7.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.8
         upper limit
    		 -1.7
    Notes
    [42] - No formal test was planned for this endpoint.

    Secondary: Absence of Emetic Episodes in acute phase: Cycle 3

    		 Close Top of page
    End point title
    		 Absence of Emetic Episodes in acute phase: Cycle 3
    End point description
    Absence of Emetic Episodes in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-24 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Acute phase (0-24 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    163 [43]
    150 [44]
    Units: Proportion
        number (confidence interval 95%)
    94.5 (89.8 to 97.1)
    96.7 (92.4 to 98.6)
    Notes
    [43] - Discontinuation after previous cycle
    [44] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    		 other [45]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.7
         upper limit
    		 3
    Notes
    [45] - No formal test was planned for this endpoint.

    Secondary: Absence of Emetic Episodes in delayed phase: Cycle 3

    		 Close Top of page
    End point title
    		 Absence of Emetic Episodes in delayed phase: Cycle 3
    End point description
    Absence of Emetic Episodes in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting >24-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Delayed phase (>24-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    163 [46]
    150 [47]
    Units: Proportion
        number (confidence interval 95%)
    92 (86.8 to 95.3)
    93.3 (88.2 to 96.3)
    Notes
    [46] - Discontinuation after previous cycle
    [47] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    		 other [48]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.4
         upper limit
    		 4.8
    Notes
    [48] - No formal test was planned for this endpoint.

    Secondary: Absence of Emetic Episodes in overall phase: Cycle 3

    		 Close Top of page
    End point title
    		 Absence of Emetic Episodes in overall phase: Cycle 3
    End point description
    Absence of Emetic Episodes in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Overall phase (0-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    163 [49]
    150 [50]
    Units: Proportion
        number (confidence interval 95%)
    90.2 (84.7 to 93.9)
    92.7 (87.3 to 95.9)
    Notes
    [49] - Discontinuation after previous cycle
    [50] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    		 other [51]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.7
         upper limit
    		 4.4
    Notes
    [51] - No formal test was planned for this endpoint.

    Secondary: Absence of Emetic Episodes in acute phase: Cycle 4

    		 Close Top of page
    End point title
    		 Absence of Emetic Episodes in acute phase: Cycle 4
    End point description
    Absence of Emetic Episodes in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-24 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Acute phase (0-24 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    122 [52]
    117 [53]
    Units: Proportion
        number (confidence interval 95%)
    92.6 (86.6 to 96.1)
    100 (96.8 to 100)
    Notes
    [52] - Discontinuation after previous cycle
    [53] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    239
    Analysis specification
    Pre-specified
    Analysis type
    		 other [54]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -6.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.6
         upper limit
    		 -2.3
    Notes
    [54] - No formal test was planned for this endpoint.

    Secondary: Absence of Emetic Episodes in delayed phase: Cycle 4

    		 Close Top of page
    End point title
    		 Absence of Emetic Episodes in delayed phase: Cycle 4
    End point description
    Absence of Emetic Episodes in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting >24-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Delayed phase (>24-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    122 [55]
    117 [56]
    Units: Proportion
        number (confidence interval 95%)
    90.2 (83.6 to 94.3)
    99.1 (95.3 to 99.8)
    Notes
    [55] - Discontinuation after previous cycle
    [56] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    239
    Analysis specification
    Pre-specified
    Analysis type
    		 other [57]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -7.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.7
         upper limit
    		 -2.4
    Notes
    [57] - No formal test was planned for this endpoint.

    Secondary: Absence of Emetic Episodes in overall phase: Cycle 4

    		 Close Top of page
    End point title
    		 Absence of Emetic Episodes in overall phase: Cycle 4
    End point description
    Absence of Emetic Episodes in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Overall phase (0-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    122 [58]
    117 [59]
    Units: Proportion
        number (confidence interval 95%)
    88.5 (81.7 to 93)
    99.1 (95.3 to 99.8)
    Notes
    [58] - Discontinuation after previous cycle
    [59] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    239
    Analysis specification
    Pre-specified
    Analysis type
    		 other [60]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -9.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.7
         upper limit
    		 -3.7
    Notes
    [60] - No formal test was planned for this endpoint.

    Secondary: Absence of Rescue Medication in acute phase: Cycle 1

    		 Close Top of page
    End point title
    		 Absence of Rescue Medication in acute phase: Cycle 1
    End point description
    Absence of Rescue Medication in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-24 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Acute phase (0-24 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    203
    201
    Units: Proportion
        number (confidence interval 95%)
    96.1 (92.4 to 98)
    93 (88.6 to 95.8)
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    404
    Analysis specification
    Pre-specified
    Analysis type
    		 other [61]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    3.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 7.3
    Notes
    [61] - No formal test was planned for this endpoint.

    Secondary: Absence of Rescue Medication in delayed phase: Cycle 1

    		 Close Top of page
    End point title
    		 Absence of Rescue Medication in delayed phase: Cycle 1
    End point description
    Absence of Rescue Medication in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting >24-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Delayed phase (>24-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    203
    201
    Units: Proportion
        number (confidence interval 95%)
    84.7 (79.1 to 89)
    91.5 (86.9 to 94.7)
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    404
    Analysis specification
    Pre-specified
    Analysis type
    		 other [62]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -6.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.9
         upper limit
    		 -1
    Notes
    [62] - No formal test was planned for this endpoint.

    Secondary: Absence of Rescue Medication in overall phase: Cycle 1

    		 Close Top of page
    End point title
    		 Absence of Rescue Medication in overall phase: Cycle 1
    End point description
    Absence of Rescue Medication in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Overall phase (0-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    203
    201
    Units: Proportion
        number (confidence interval 95%)
    82.8 (77 to 87.3)
    89.1 (84 to 92.7)
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    404
    Analysis specification
    Pre-specified
    Analysis type
    		 other [63]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.3
         upper limit
    		 0.2
    Notes
    [63] - No formal test was planned for this endpoint.

    Secondary: Absence of Rescue Medication in acute phase: Cycle 2

    		 Close Top of page
    End point title
    		 Absence of Rescue Medication in acute phase: Cycle 2
    End point description
    Absence of Rescue Medication in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-24 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Acute phase (0-24 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    179 [64]
    176 [65]
    Units: Proportion
        number (confidence interval 95%)
    94.4 (90 to 96.9)
    91.5 (86.4 to 94.8)
    Notes
    [64] - Discontinuation after cycle 1
    [65] - Discontinuation after cycle 1
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    355
    Analysis specification
    Pre-specified
    Analysis type
    		 other [66]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    3.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 8.9
    Notes
    [66] - No formal test was planned for this endpoint.

    Secondary: Absence of Rescue Medication in delayed phase: Cycle 2

    		 Close Top of page
    End point title
    		 Absence of Rescue Medication in delayed phase: Cycle 2
    End point description
    Absence of Rescue Medication in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting >24-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Delayed phase (>24-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    179 [67]
    176 [68]
    Units: Proportion
        number (confidence interval 95%)
    87.2 (81.5 to 91.3)
    89.8 (84.4 to 93.4)
    Notes
    [67] - Discontinuation after cycle 1
    [68] - Discontinuation after cycle 1
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    355
    Analysis specification
    Pre-specified
    Analysis type
    		 other [69]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.4
         upper limit
    		 4
    Notes
    [69] - No formal test was planned for this endpoint.

    Secondary: Absence of Rescue Medication in overall phase: Cycle 2

    		 Close Top of page
    End point title
    		 Absence of Rescue Medication in overall phase: Cycle 2
    End point description
    Absence of Rescue Medication in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Overall phase (0-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    179 [70]
    176 [71]
    Units: Proportion
        number (confidence interval 95%)
    85.5 (79.6 to 89.9)
    86.9 (81.2 to 91.1)
    Notes
    [70] - Discontinuation after cycle
    [71] - Discontinuation after cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    355
    Analysis specification
    Pre-specified
    Analysis type
    		 other [72]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.4
         upper limit
    		 6.1
    Notes
    [72] - No formal test was planned for this endpoint.

    Secondary: Absence of Rescue Medication in acute phase: Cycle 3

    		 Close Top of page
    End point title
    		 Absence of Rescue Medication in acute phase: Cycle 3
    End point description
    Absence of Rescue Medication in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-24 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Acute phase (0-24 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    163 [73]
    150 [74]
    Units: Proportion
        number (confidence interval 95%)
    95.7 (91.4 to 97.9)
    96.7 (92.4 to 98.6)
    Notes
    [73] - Discontinuation after previous cycle
    [74] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    		 other [75]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.7
         upper limit
    		 3.5
    Notes
    [75] - No formal test was planned for this endpoint.

    Secondary: Absence of Rescue Medication in delayed phase: Cycle 3

    		 Close Top of page
    End point title
    		 Absence of Rescue Medication in delayed phase: Cycle 3
    End point description
    Absence of Rescue Medication in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting >24-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Delayed phase (>24-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    163 [76]
    150 [77]
    Units: Proportion
        number (confidence interval 95%)
    90.8 (85.4 to 94.3)
    90.7 (84.9 to 94.4)
    Notes
    [76] - Discontinuation after previous cycle
    [77] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    		 other [78]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.4
         upper limit
    		 6.9
    Notes
    [78] - No formal test was planned for this endpoint.

    Secondary: Absence of Rescue Medication in overall phase: Cycle 3

    		 Close Top of page
    End point title
    		 Absence of Rescue Medication in overall phase: Cycle 3
    End point description
    Absence of Rescue Medication in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Overall phase (0-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    163 [79]
    150 [80]
    Units: Proportion
        number (confidence interval 95%)
    89.6 (83.9 to 93.4)
    90 (84.2 to 93.8)
    Notes
    [79] - Discontinuation after previous cycle
    [80] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    		 other [81]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.8
         upper limit
    		 6.9
    Notes
    [81] - No formal test was planned for this endpoint.

    Secondary: Absence of Rescue Medication in acute phase: Cycle 4

    		 Close Top of page
    End point title
    		 Absence of Rescue Medication in acute phase: Cycle 4
    End point description
    Absence of Rescue Medication in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-24 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Acute phase (0-24 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    122 [82]
    117 [83]
    Units: Proportion
        number (confidence interval 95%)
    93.4 (87.6 to 96.6)
    99.1 (95.3 to 99.8)
    Notes
    [82] - Discontinuation after previous cycle
    [83] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    239
    Analysis specification
    Pre-specified
    Analysis type
    		 other [84]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -4.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.6
         upper limit
    		 -0.4
    Notes
    [84] - No formal test was planned for this endpoint.

    Secondary: Absence of Rescue Medication in delayed phase: Cycle 4

    		 Close Top of page
    End point title
    		 Absence of Rescue Medication in delayed phase: Cycle 4
    End point description
    Absence of Rescue Medication in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting >24-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Delayed phase (>24-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    122 [85]
    117 [86]
    Units: Proportion
        number (confidence interval 95%)
    90.2 (83.6 to 94.3)
    98.3 (94 to 99.5)
    Notes
    [85] - Discontinuation after previous cycle
    [86] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    239
    Analysis specification
    Pre-specified
    Analysis type
    		 other [87]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.8
         upper limit
    		 -1.1
    Notes
    [87] - No formal test was planned for this endpoint.

    Secondary: Absence of Rescue Medication in overall phase: Cycle 4

    		 Close Top of page
    End point title
    		 Absence of Rescue Medication in overall phase: Cycle 4
    End point description
    Absence of Rescue Medication in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Overall phase (0-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    122 [88]
    117 [89]
    Units: Proportion
        number (confidence interval 95%)
    88.5 (81.7 to 93)
    97.4 (92.7 to 99.1)
    Notes
    [88] - Discontinuation after previous cycle
    [89] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    239
    Analysis specification
    Pre-specified
    Analysis type
    		 other [90]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -6.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.3
         upper limit
    		 -1.1
    Notes
    [90] - No formal test was planned for this endpoint.

    Secondary: Absence of Significant Nausea in acute phase: Cycle 1

    		 Close Top of page
    End point title
    		 Absence of Significant Nausea in acute phase: Cycle 1
    End point description
    Absence of Significant Nausea in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-24 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Acute phase (0-24 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    203
    201
    Units: Proportion
        number (confidence interval 95%)
    90.1 (85.3 to 93.5)
    93 (88.6 to 95.8)
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    404
    Analysis specification
    Pre-specified
    Analysis type
    		 other [91]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -2.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.6
         upper limit
    		 2.3
    Notes
    [91] - No formal test was planned for this endpoint.

    Secondary: Absence of Significant Nausea in delayed phase: Cycle 1

    		 Close Top of page
    End point title
    		 Absence of Significant Nausea in delayed phase: Cycle 1
    End point description
    Absence of Significant Nausea in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting >24-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Delayed phase (>24-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    203
    201
    Units: Proportion
        number (confidence interval 95%)
    81.3 (75.4 to 86)
    89.1 (84 to 92.7)
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    404
    Analysis specification
    Pre-specified
    Analysis type
    		 other [92]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -7.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.7
         upper limit
    		 -0.8
    Notes
    [92] - No formal test was planned for this endpoint.

    Secondary: Absence of Significant Nausea in overall phase: Cycle 1

    		 Close Top of page
    End point title
    		 Absence of Significant Nausea in overall phase: Cycle 1
    End point description
    Absence of Significant Nausea in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Overall phase (0-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    203
    201
    Units: Proportion
        number (confidence interval 95%)
    79.3 (73.2 to 84.3)
    86.6 (81.2 to 90.6)
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    404
    Analysis specification
    Pre-specified
    Analysis type
    		 other [93]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.8
         upper limit
    		 -0.2
    Notes
    [93] - No formal test was planned for this endpoint.

    Secondary: Absence of Significant Nausea in acute phase: Cycle 2

    		 Close Top of page
    End point title
    		 Absence of Significant Nausea in acute phase: Cycle 2
    End point description
    Absence of Significant Nausea in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-24 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Acute phase (0-24 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    179 [94]
    176 [95]
    Units: Proportion
        number (confidence interval 95%)
    91.1 (86 to 94.4)
    93.8 (89.2 to 96.5)
    Notes
    [94] - Discontinuation after cycle 1
    [95] - Discontinuation after cycle 1
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    355
    Analysis specification
    Pre-specified
    Analysis type
    		 other [96]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7
         upper limit
    		 3.4
    Notes
    [96] - No formal test was planned for this endpoint.

    Secondary: Absence of Significant Nausea in delayed phase: Cycle 2

    		 Close Top of page
    End point title
    		 Absence of Significant Nausea in delayed phase: Cycle 2
    End point description
    Absence of Significant Nausea in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting >24-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Delayed phase (>24-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    179 [97]
    176 [98]
    Units: Proportion
        number (confidence interval 95%)
    81 (74.6 to 86.1)
    89.2 (83.8 to 93)
    Notes
    [97] - Discontinuation after cycle 1
    [98] - Discontinuation after cycle 1
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    355
    Analysis specification
    Pre-specified
    Analysis type
    		 other [99]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -8.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.1
         upper limit
    		 -1.7
    Notes
    [99] - No formal test was planned for this endpoint.

    Secondary: Absence of Significant Nausea in overall phase: Cycle 2

    		 Close Top of page
    End point title
    		 Absence of Significant Nausea in overall phase: Cycle 2
    End point description
    Absence of Significant Nausea in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Overall phase (0-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    179 [100]
    176 [101]
    Units: Proportion
        number (confidence interval 95%)
    79.9 (73.4 to 85.1)
    86.9 (81.2 to 91.1)
    Notes
    [100] - Discontinuation after cycle 1
    [101] - Discontinuation after cycle 1
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    355
    Analysis specification
    Pre-specified
    Analysis type
    		 other [102]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -7.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.4
         upper limit
    		 -0.3
    Notes
    [102] - No formal test was planned for this endpoint.

    Secondary: Absence of Significant Nausea in acute phase: Cycle 3

    		 Close Top of page
    End point title
    		 Absence of Significant Nausea in acute phase: Cycle 3
    End point description
    Absence of Significant Nausea in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-24 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Acute phase (0-24 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    163 [103]
    150 [104]
    Units: Proportion
        number (confidence interval 95%)
    92.6 (87.6 to 95.7)
    95.3 (90.7 to 97.7)
    Notes
    [103] - Discontinuation after previous cycle
    [104] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    		 other [105]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.3
         upper limit
    		 3.2
    Notes
    [105] - No formal test was planned for this endpoint.

    Secondary: Absence of Significant Nausea in delayed phase: Cycle 3

    		 Close Top of page
    End point title
    		 Absence of Significant Nausea in delayed phase: Cycle 3
    End point description
    Absence of Significant Nausea in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting >24-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Delayed phase (>24-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    163 [106]
    150 [107]
    Units: Proportion
        number (confidence interval 95%)
    86.5 (80.4 to 90.9)
    90 (84.2 to 93.8)
    Notes
    [106] - Discontinuation after previous cycle
    [107] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    		 other [108]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.5
         upper limit
    		 4.2
    Notes
    [108] - No formal test was planned for this endpoint.

    Secondary: Absence of Significant Nausea in overall phase: Cycle 3

    		 Close Top of page
    End point title
    		 Absence of Significant Nausea in overall phase: Cycle 3
    End point description
    Absence of Significant Nausea in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Overall phase (0-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    163 [109]
    150 [110]
    Units: Proportion
        number (confidence interval 95%)
    84 (77.7 to 88.9)
    90 (84.2 to 93.8)
    Notes
    [109] - Discontinuation after previous cycle
    [110] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    		 other [111]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -4.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.8
         upper limit
    		 2.3
    Notes
    [111] - No formal test was planned for this endpoint.

    Secondary: Absence of Significant Nausea in acute phase: Cycle 4

    		 Close Top of page
    End point title
    		 Absence of Significant Nausea in acute phase: Cycle 4
    End point description
    Absence of Significant Nausea in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-24 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Acute phase (0-24 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    122 [112]
    117 [113]
    Units: Proportion
        number (confidence interval 95%)
    90.2 (83.6 to 94.3)
    94.9 (89.3 to 97.6)
    Notes
    [112] - Discontinuation after previous cycle
    [113] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    239
    Analysis specification
    Pre-specified
    Analysis type
    		 other [114]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.2
         upper limit
    		 3.3
    Notes
    [114] - No formal test was planned for this endpoint.

    Secondary: Absence of Significant Nausea in delayed phase: Cycle 4

    		 Close Top of page
    End point title
    		 Absence of Significant Nausea in delayed phase: Cycle 4
    End point description
    Absence of Significant Nausea in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting >24-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Delayed phase (>24-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    122 [115]
    117 [116]
    Units: Proportion
        number (confidence interval 95%)
    87.7 (80.7 to 92.4)
    94.9 (89.3 to 97.6)
    Notes
    [115] - Discontinuation after previous cycle
    [116] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    239
    Analysis specification
    Pre-specified
    Analysis type
    		 other [117]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -5.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.5
         upper limit
    		 1.1
    Notes
    [117] - No formal test was planned for this endpoint.

    Secondary: Absence of Significant Nausea in overall phase: Cycle 4

    		 Close Top of page
    End point title
    		 Absence of Significant Nausea in overall phase: Cycle 4
    End point description
    Absence of Significant Nausea in the acute phase which is defined as the absence of chemotherapy induced nausea or vomiting 0-120 hour after start of reference highly emetogenic chemotherapy [HEC]. Confidence interval of proportions are obtained by using the Newcombe-Wilson method.
    End point type
    Secondary
    End point timeframe
    Overall phase (0-120 hour)
    End point values
    		 Full Analysis Set: IV NEPA FDC Full Analysis Set: Oral NEPA FDC
    Number of subjects analysed
    122 [118]
    117 [119]
    Units: Proportion
        number (confidence interval 95%)
    84.4 (77 to 89.8)
    94 (88.2 to 97.1)
    Notes
    [118] - Discontinuation after previous cycle
    [119] - Discontinuation after previous cycle
    Statistical analysis title
    		 Statistical analysis (FAS)
    Statistical analysis description
    The Cochran-Mantel-Haenszel test stratified by gender and country was used to compare both treatment with a 2-sided 95% confidence interval.
    Comparison groups
    Full Analysis Set: IV NEPA FDC v Full Analysis Set: Oral NEPA FDC
    Number of subjects included in analysis
    239
    Analysis specification
    Pre-specified
    Analysis type
    		 other [120]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14
         upper limit
    		 0.1
    Notes
    [120] - No formal test was planned for this endpoint.

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse Events were collected from Informed consent signature or day 1 of each cycle up to the follow-up visit contact which is a maximum of 35 days for each cycle. The study contains four (4) cycles with a 21 day interval between consecutive cycles.
    Adverse event reporting additional description
    Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship wit h this treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18
    Reporting groups
    Reporting group title
    Oral NEPA FDC
    Reporting group description
    		 Oral netupitant/palonosetron (300 mg/0.50 mg) FDC (Oral NEPA FDC) was to be administered on Day 1 of each cycle. Oral NEPA FDC capsule was to be administered 60 min prior to the start of the reference chemotherapy administration.

    Reporting group title
    IV NEPA FDC
    Reporting group description
    		 IV fosnetupitant/palonosetron (260 mg/0.25 mg) FDC (IV NEPA FDC) was to be administered as a 30-min infusion of a 50-mL solution on Day 1 of each cycle. The 30-min (±5 min) IV NEPA FDC infusion was to be started 30 min prior to the start of the reference chemotherapy administration. The 30-min IV infusion was to be completed before starting chemotherapy administration.

    Serious adverse events
    		 Oral NEPA FDC IV NEPA FDC
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 201 (0.00%)
    0 / 203 (0.00%)
         number of deaths (all causes)
    14
    10
         number of deaths resulting from adverse events
    0
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Oral NEPA FDC IV NEPA FDC
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    170 / 201 (84.58%)
    161 / 203 (79.31%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    24 / 201 (11.94%)
    15 / 203 (7.39%)
         occurrences all number
    43
    25
    Aspartate aminotransferase increased
         subjects affected / exposed
    19 / 201 (9.45%)
    12 / 203 (5.91%)
         occurrences all number
    30
    17
    Blood creatinine increased
         subjects affected / exposed
    6 / 201 (2.99%)
    11 / 203 (5.42%)
         occurrences all number
    10
    15
    Vascular disorders
    Hypertension
         subjects affected / exposed
    13 / 201 (6.47%)
    8 / 203 (3.94%)
         occurrences all number
    16
    12
    Nervous system disorders
    Headache
         subjects affected / exposed
    9 / 201 (4.48%)
    11 / 203 (5.42%)
         occurrences all number
    21
    19
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    34 / 201 (16.92%)
    33 / 203 (16.26%)
         occurrences all number
    52
    54
    Leukopenia
         subjects affected / exposed
    21 / 201 (10.45%)
    21 / 203 (10.34%)
         occurrences all number
    35
    28
    Neutropenia
         subjects affected / exposed
    52 / 201 (25.87%)
    57 / 203 (28.08%)
         occurrences all number
    81
    89
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    17 / 201 (8.46%)
    13 / 203 (6.40%)
         occurrences all number
    26
    16
    Fatigue
         subjects affected / exposed
    17 / 201 (8.46%)
    17 / 203 (8.37%)
         occurrences all number
    32
    30
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    26 / 201 (12.94%)
    21 / 203 (10.34%)
         occurrences all number
    30
    29
    Nausea
         subjects affected / exposed
    14 / 201 (6.97%)
    20 / 203 (9.85%)
         occurrences all number
    20
    28
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    29 / 201 (14.43%)
    32 / 203 (15.76%)
         occurrences all number
    31
    35
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    11 / 201 (5.47%)
    7 / 203 (3.45%)
         occurrences all number
    14
    7

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Jul 2015
    The following change to the study protocol is implemented to comply with a request from the US Food and Drug Administration: - During the conduct of the study, a Data Safety Monitoring Board (DSMB) will periodically review safety data.

    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-Mon May 06 02:46:10 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA