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    Clinical Trial Results:
    A randomized, double-blind placebo-controlled, Phase 3 study of Debio 1143 in combination with platinum-based chemotherapy and standard fractionation intensity-modulated radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck, suitable for definitive chemoradiotherapy (TrilynX)

    Summary
    EudraCT number
    		 2020-000377-25
    Trial protocol
    		 FR   DE   HU   PT   AT   BE   CZ   GR   IT  
    Global end of trial date
    18 Sep 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    23 Oct 2025
    First version publication date
    23 Oct 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MS202359_0006
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04459715
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany
    Sponsor organisation address
    Frankfurter Strasse 250, Darmstadt, Germany,
    Public contact
    Communication Center, Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany, +49 6151725200, service@emdgroup.com
    Scientific contact
    Communication Center, Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany, +49 6151725200, service@emdgroup.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
    18 Sep 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Sep 2024
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to demonstrate superior efficacy of Xevinapant (Debio 1143) vs placebo when added to chemoradiotherapy (CRT) in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN).
    Protection of trial subjects
    Subject protection was ensured by following high medical and ethical standards in accordance with the principles laid down in the Declaration of Helsinki, and that are consistent with Good Clinical Practice and applicable regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    07 Aug 2020
    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
    China: 49
    Country: Number of subjects enrolled
    Japan: 38
    Country: Number of subjects enrolled
    Korea, Republic of: 10
    Country: Number of subjects enrolled
    Taiwan: 21
    Country: Number of subjects enrolled
    Australia: 5
    Country: Number of subjects enrolled
    Czechia: 1
    Country: Number of subjects enrolled
    Georgia: 45
    Country: Number of subjects enrolled
    Hungary: 15
    Country: Number of subjects enrolled
    Poland: 39
    Country: Number of subjects enrolled
    Russian Federation: 9
    Country: Number of subjects enrolled
    Ukraine: 2
    Country: Number of subjects enrolled
    Israel: 9
    Country: Number of subjects enrolled
    Canada: 7
    Country: Number of subjects enrolled
    Argentina: 22
    Country: Number of subjects enrolled
    Brazil: 55
    Country: Number of subjects enrolled
    Austria: 7
    Country: Number of subjects enrolled
    Belgium: 31
    Country: Number of subjects enrolled
    France: 149
    Country: Number of subjects enrolled
    Germany: 20
    Country: Number of subjects enrolled
    Greece: 16
    Country: Number of subjects enrolled
    Italy: 22
    Country: Number of subjects enrolled
    Portugal: 26
    Country: Number of subjects enrolled
    Spain: 58
    Country: Number of subjects enrolled
    Switzerland: 11
    Country: Number of subjects enrolled
    United Kingdom: 22
    Country: Number of subjects enrolled
    United States: 41
    Worldwide total number of subjects
    730
    EEA total number of subjects
    384
    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)
    496
    From 65 to 84 years
    234
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 1237 subjects were screened out of which only 730 received a study intervention.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Sequence 1: Debio 1143 + CRT
    Arm description
    		 Subjects received a combination of Debio 1143 along with Chemoradiotherapy (CRT): Radiotherapy +Cisplatin + Xevinapant (Debio 1143). Subjects received 6 cycles of oral solution of Xevinapant at a dose of 200 milligrams per day (mg/day) once daily from Day 1 to 14, per 3-week cycle in combination with 70 Gray (Gy) of intensity modulated radiation therapy (IMRT) in 35 fractions, 2 Gy/fraction, over 7 weeks, and High-dose cisplatin (100 Milligram per square meter (mg/m2) on Day 2 of a 3-week cycle per 3 cycles (combination therapy period). If high-dose cisplatin 100 mg/m2 was not tolerated after the first dose, subjects could be switched to carboplatin (10 Milligrams per milliliter [mg/mL], intravenous [iv] infusion), followed by 3 cycles of monotherapy of Xevinapant at a dose of 200 mg/day from Day 1 to 14, per 3-week cycle (monotherapy period).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cisplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cisplatin administered as an IV infusion every 3 weeks (Q3W).

    Investigational medicinal product name
    Xevinapant
    Investigational medicinal product code
    Other name
    Debio 1143
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Xevinapant (Debio 1143) administrated as oral solution from Day 1 to 14, every 21-day cycle.

    Arm title
    		 Sequence 2: Placebo + CRT
    Arm description
    		 Subjects received a combination of placebo matched to Debio 1143 along with Chemoradiotherapy(CRT): Radiotherapy +Cisplatin+ placebo matched to Xevinapant (Debio 1143). Subjects received 6 cycles of oral solution of placebo matched to Xevinapant once daily from Day 1 to 14, per 3-week cycle in combination with 70 Gray (Gy) of intensity modulated radiation therapy (IMRT) in 35 fractions, 2 Gy/fraction, over 7 weeks, and High-dose cisplatin (100 mg/m2) on Day 2 of a 3-week cycle per 3 cycles(combination therapy period).If high-dose cisplatin 100 mg/m2 was not tolerated after the first dose, subjects could be switched to carboplatin (10mg/mL, iv infusion), followed by 3 cycles of monotherapy of placebo matched to Xevinapant from Day 1 to 14, per 3-week cycle (monotherapy period).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Matched placebo administrated as oral solution from Day 1 to 14, every 21-day cycle.

    Investigational medicinal product name
    Cisplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cisplatin administered as an IV infusion every 3 weeks (Q3W).

    Number of subjects in period 1
    		Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Started
    364
    366
    Completed
    0
    0
    Not completed
    364
    366
         Adverse event, serious fatal
    111
    93
         Consent withdrawn by subject
    22
    22
         Adverse event, non-fatal
    3
    3
         RANDOMIZED BY MISTAKE
    -
    1
         STUDY TERMINATED BY SPONSOR
    214
    232
         Lost to follow-up
    10
    9
         PROTOCOL DEVIATION
    4
    5

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Sequence 1: Debio 1143 + CRT
    Reporting group description
    		 Subjects received a combination of Debio 1143 along with Chemoradiotherapy (CRT): Radiotherapy +Cisplatin + Xevinapant (Debio 1143). Subjects received 6 cycles of oral solution of Xevinapant at a dose of 200 milligrams per day (mg/day) once daily from Day 1 to 14, per 3-week cycle in combination with 70 Gray (Gy) of intensity modulated radiation therapy (IMRT) in 35 fractions, 2 Gy/fraction, over 7 weeks, and High-dose cisplatin (100 Milligram per square meter (mg/m2) on Day 2 of a 3-week cycle per 3 cycles (combination therapy period). If high-dose cisplatin 100 mg/m2 was not tolerated after the first dose, subjects could be switched to carboplatin (10 Milligrams per milliliter [mg/mL], intravenous [iv] infusion), followed by 3 cycles of monotherapy of Xevinapant at a dose of 200 mg/day from Day 1 to 14, per 3-week cycle (monotherapy period).

    Reporting group title
    Sequence 2: Placebo + CRT
    Reporting group description
    		 Subjects received a combination of placebo matched to Debio 1143 along with Chemoradiotherapy(CRT): Radiotherapy +Cisplatin+ placebo matched to Xevinapant (Debio 1143). Subjects received 6 cycles of oral solution of placebo matched to Xevinapant once daily from Day 1 to 14, per 3-week cycle in combination with 70 Gray (Gy) of intensity modulated radiation therapy (IMRT) in 35 fractions, 2 Gy/fraction, over 7 weeks, and High-dose cisplatin (100 mg/m2) on Day 2 of a 3-week cycle per 3 cycles(combination therapy period).If high-dose cisplatin 100 mg/m2 was not tolerated after the first dose, subjects could be switched to carboplatin (10mg/mL, iv infusion), followed by 3 cycles of monotherapy of placebo matched to Xevinapant from Day 1 to 14, per 3-week cycle (monotherapy period).

    Reporting group values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT Total
    Number of subjects
    		 364 366 730
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 243 253 496
        From 65-84 years
    		 121 113 234
        85 years and over
    		 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 60 ( 8.01 ) 60 ( 8.53 ) -
    Sex: Female, Male
    Units: subjects
        Female
    		 64 57 121
        Male
    		 300 309 609
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 41 46 87
        Not Hispanic or Latino
    		 264 273 537
        Missing
    		 59 47 106
    Race
    Units: Subjects
        Asian
    		 59 60 119
        American Indian or Alaska Native
    		 0 0 0
        Black or African American
    		 5 6 11
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        White
    		 253 256 509
        Other
    		 5 9 14
        Missing
    		 42 35 77

    End points

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    End points reporting groups
    Reporting group title
    Sequence 1: Debio 1143 + CRT
    Reporting group description
    		 Subjects received a combination of Debio 1143 along with Chemoradiotherapy (CRT): Radiotherapy +Cisplatin + Xevinapant (Debio 1143). Subjects received 6 cycles of oral solution of Xevinapant at a dose of 200 milligrams per day (mg/day) once daily from Day 1 to 14, per 3-week cycle in combination with 70 Gray (Gy) of intensity modulated radiation therapy (IMRT) in 35 fractions, 2 Gy/fraction, over 7 weeks, and High-dose cisplatin (100 Milligram per square meter (mg/m2) on Day 2 of a 3-week cycle per 3 cycles (combination therapy period). If high-dose cisplatin 100 mg/m2 was not tolerated after the first dose, subjects could be switched to carboplatin (10 Milligrams per milliliter [mg/mL], intravenous [iv] infusion), followed by 3 cycles of monotherapy of Xevinapant at a dose of 200 mg/day from Day 1 to 14, per 3-week cycle (monotherapy period).

    Reporting group title
    Sequence 2: Placebo + CRT
    Reporting group description
    		 Subjects received a combination of placebo matched to Debio 1143 along with Chemoradiotherapy(CRT): Radiotherapy +Cisplatin+ placebo matched to Xevinapant (Debio 1143). Subjects received 6 cycles of oral solution of placebo matched to Xevinapant once daily from Day 1 to 14, per 3-week cycle in combination with 70 Gray (Gy) of intensity modulated radiation therapy (IMRT) in 35 fractions, 2 Gy/fraction, over 7 weeks, and High-dose cisplatin (100 mg/m2) on Day 2 of a 3-week cycle per 3 cycles(combination therapy period).If high-dose cisplatin 100 mg/m2 was not tolerated after the first dose, subjects could be switched to carboplatin (10mg/mL, iv infusion), followed by 3 cycles of monotherapy of placebo matched to Xevinapant from Day 1 to 14, per 3-week cycle (monotherapy period).

    Primary: Event-Free Survival (EFS) as assessed by Blinded Independent Review Committee (BIRC)

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    End point title
    		 Event-Free Survival (EFS) as assessed by Blinded Independent Review Committee (BIRC) [1]
    End point description
    Event-Free Survival (EFS) as assessed by BIRC is the time from randomization to the first of: (1) Death from any cause; (2) Progression: either radiological (per RECIST v1.1) or clinical (with/without radiologic proof, assessed endoscopically); (3) Primary treatment failure prior to complete response (CR): requirement for radical salvage surgery at primary tumor site with viable tumor confirmed histologically, even without RECIST progression; (4) Relapse after CR (locoregional): including radical salvage surgery or elective neck dissection/biopsy more than equal to (>=) 22 weeks post-randomization showing viable tumor cells regardless of radiologic status; (5) Second cancers, unless histology excludes squamous origin. Calculated via Kaplan Meier method. The Intention To Treat (ITT) set included all randomized subjects.
    End point type
    Primary
    End point timeframe
    From randomization to the earliest between any EFS event or End of Study (EOS) (up to 188 weeks and 5 days)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical and comparison analysis were performed in single arm for this endpoint.
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364 [2]
    366 [3]
    Units: months
        median (confidence interval 95%)
    19.4 (14.46 to 99999)
    33.1 (20.99 to 99999)
    Notes
    [2] - 99999 = no data; 95% CI upper limit for median not estimable due to few events.
    [3] - 99999 = no data; 95% CI upper limit for median not estimable due to few events.
    No statistical analyses for this end point

    Secondary: Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Assessed by Blinded Independent Review Committee (BIRC)

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    End point title
    		 Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Assessed by Blinded Independent Review Committee (BIRC)
    End point description
    PFS according to RECIST v1.1 defined as the time from randomization to the first occurrence of progression (radiological or clinical, as assessed by the BIRC) or death from any cause. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of >5 millimeter (mm) in the SOD, or the appearance of new lesions. Calculated via Kaplan Meier method. The ITT set included all randomized subjects. Subjects were analyzed according to the randomized treatment (assigned arm) assignment following the intention-to-treat principle.
    End point type
    Secondary
    End point timeframe
    From randomization to the first occurrence of progression (radiological or clinical, as assessed by the BIRC) or death from any cause or EOS (up to 188 weeks and 5 days )
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364 [4]
    366 [5]
    Units: months
        median (confidence interval 95%)
    26.8 (15.93 to 99999)
    33.1 (22.83 to 99999)
    Notes
    [4] - 9.9999 = no observation; median not derived due to limited number of events.
    [5] - 9.9999 = no observation; median not derived due to limited number of events.
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    Overall survival is defined as the time from randomization to the date of death. Calculated via Kaplan Meier method. The ITT set included all randomized subjects. Subjects were analyzed according to the randomized treatment (assigned arm) assignment following the intention-to-treat principle.
    End point type
    Secondary
    End point timeframe
    From randomization to the earliest between death or EOS (up to 188 weeks and 5 days)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364 [6]
    366 [7]
    Units: months
        median (full range (min-max))
    9.9999 (0.0 to 37.6)
    9.9999 (0.0 to 39.4)
    Notes
    [6] - 9.9999 = no observation; median not derived due to limited number of events.
    [7] - 9.9999 = no observation; median not derived due to limited number of events.
    No statistical analyses for this end point

    Secondary: Locoregional control (LRC) Time

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    End point title
    		 Locoregional control (LRC) Time
    End point description
    LRC time is defined as the time from randomization to the first occurrence of progression at the site of the primary tumor or the locoregional lymph nodes, either according to RECIST v1.1 or based on clinical assessment (radiological or clinical, as assessed by the Investigator). According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of >5 millimeter (mm) in the SOD, or the appearance of new lesions. Calculated via Kaplan Meier method. The ITT set included all randomized subjects. Subjects were analyzed according to the randomized treatment (assigned arm) assignment following the intention-to-treat principle.
    End point type
    Secondary
    End point timeframe
    From randomization to the first occurrence of progression at the site of the primary tumor or the locoregional lymph nodes or End Of Study (EOS) (188 weeks and 5 days)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364 [8]
    366 [9]
    Units: months
        median (full range (min-max))
    9.9999 (0.0 to 37.0)
    9.9999 (0.0 to 38.2)
    Notes
    [8] - 9.9999 = no observation; median not derived due to limited number of events.
    [9] - 9.9999 = no observation; median not derived due to limited number of events.
    No statistical analyses for this end point

    Secondary: Objective Response Rate (ORR) as Assessed by BIRC

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    End point title
    		 Objective Response Rate (ORR) as Assessed by BIRC
    End point description
    Objective response rate was defined as percentage of subjects with either a confirmed complete response (CR) or partial response (PR). CR: Disappearance of all target and non-target lesions. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of their diameters, and no unequivocal progression of non-target lesions. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, or unequivocal progression of non-target lesions, or appearance of any new lesion. The ITT set included all randomized subjects. Subjects were analyzed according to the randomized treatment (assigned arm) assignment following the intention-to-treat principle.
    End point type
    Secondary
    End point timeframe
    At 9 and 12 months post randomization
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    366
    Units: percentage of subjects
    number (not applicable)
        9 Months Post Randomization
    73.4
    77.3
        12 Months Post Randomization
    73.6
    77.9
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR)

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    End point title
    		 Duration of Response (DOR)
    End point description
    Duration of response (DoR) defined as the time from the first evidence of response (partial or complete, as assessed by the BIRC according to RECIST v1.1) to the first occurrence of progression (radiological or clinical, as assessed by the BIRC) or death from any cause. Kaplan Meier method was used for calculation. The ITT set included all randomized subjects. Subjects were analyzed according to the randomized treatment (assigned arm) assignment following the intention-to-treat principle. "Number of subjects analyzed" signifies subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Time from first evidence of response to the first occurrence of progression or death from any cause, assessed up to 24 months
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    269 [10]
    287 [11]
    Units: months
        median (full range (min-max))
    9.9999 (0.0 to 33.5)
    9.9999 (0.0 to 33.7)
    Notes
    [10] - 9.9999 = no observation; median not derived due to limited number of events.
    [11] - 9.9999 = no observation; median not derived due to limited number of events.
    No statistical analyses for this end point

    Secondary: Number of Subjects with Radical Salvage Surgery

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    End point title
    		 Number of Subjects with Radical Salvage Surgery
    End point description
    Number of subjects with Radical Salvage Surgery (excluding elective neck dissection without anatomopathological evidence of residual malignant cells) was reported. The ITT set included all randomized subjects. Subjects were analyzed according to the randomized treatment (assigned arm) assignment following the intention-to-treat principle.
    End point type
    Secondary
    End point timeframe
    At 9, 12, 24 and 36 months post randomization
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    366
    Units: subjects
        Month 9
    10
    3
        Month 12
    19
    5
        Month 24
    23
    9
        Month 36
    23
    9
    No statistical analyses for this end point

    Secondary: Complete Response Rate (CRR)

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    End point title
    		 Complete Response Rate (CRR)
    End point description
    CRR defined as the number of subjects with Complete Response by RECIST v1.1, as assessed by the BIRC. Complete response is defined as disappearance of all target and non-target lesions. The ITT set included all randomized subjects. Subjects were analyzed according to the randomized treatment (assigned arm) assignment following the intention-to-treat principle.
    End point type
    Secondary
    End point timeframe
    At 9 and 12 months post randomization
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    366
    Units: subjects
        9 Months Post Randomization
    187
    212
        12 Months Post Randomization
    194
    222
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events (AEs) of Special Interest

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    End point title
    		 Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events (AEs) of Special Interest
    End point description
    An AE is any unfavorable/unintended sign symptom or disease temporally linked to study drug, whether or not related. A serious AE leads to death, is life-threatening, causes significant/persistent disability, hospitalization, congenital anomaly, or is medically important. TEAEs include both serious and non-serious AEs after treatment. AESIs are events of clinical interest needing close monitoring. The safety analysis set (SAF set) included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT).
    End point type
    Secondary
    End point timeframe
    From signed informed consent to EOS (up to 188 weeks and 5 days)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    356
    Units: subjects
        TEAEs
    362
    351
        Serious TEAEs
    194
    129
        AESI
    357
    342
    No statistical analyses for this end point

    Secondary: Time to Subsequent Systemic Cancer Treatments

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    End point title
    		 Time to Subsequent Systemic Cancer Treatments
    End point description
    Time to new subsequent systemic cancer treatment (in months) was derived as (date of event/censoring – randomization date +1) / 30.4375. Calculated via kaplan meier method. The ITT set included all randomized subjects. Subjects were analyzed according to the randomized treatment (assigned arm) assignment following the intention-to-treat principle.
    End point type
    Secondary
    End point timeframe
    Up to 188 weeks and 5 days post randomization
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364 [12]
    366 [13]
    Units: months
        median (confidence interval 95%)
    9.9999 (9.9999 to 9.9999)
    9.9999 (9.9999 to 9.9999)
    Notes
    [12] - 9.9999 = no observation; median not derived due to limited number of events.
    [13] - 9.9999 = no observation; median not derived due to limited number of events.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Severity of Grade Greater or Equal to 3 TEAEs

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    End point title
    		 Number of Subjects With Severity of Grade Greater or Equal to 3 TEAEs
    End point description
    Severity of TEAEs were evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version. The grade are as follows: grade 1 : mild grade 2 : moderate grade 3 : severe or medically significant but not immediately life-threatening grade 4 : life threatening or disabling grade 5 : death related to AE. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT).
    End point type
    Secondary
    End point timeframe
    From signed informed consent to EOS (up to 188 weeks and 5 days)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    356
    Units: subjects
    320
    286
    No statistical analyses for this end point

    Secondary: Change from Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets

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    End point title
    		 Change from Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets
    End point description
    Change from Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets was reported. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "overall number of subjects analyzed signified" subjects who were evaluable for this outcome measure and "number analyzed" or "n" signifies subjects who were evaluable at specified timepoints. Please note Sequence 1= S1, Sequence 2= S2, Basophils = BP, Leukocytes= Leuko, Lymphocyte = Lympho, Monocyte = mono, Neutrophils = Neutro, Platelets = Plt and Maximum on treatment change = max change.
    End point type
    Secondary
    End point timeframe
    At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    363
    352
    Units: 10^9 cells per liter
    arithmetic mean (standard deviation)
        Basophils: Baseline
    0.052 ( 0.0343 )
    0.054 ( 0.0367 )
        Baso: C3D1 (n= S1-283, S2-288)
    -0.032 ( 0.0367 )
    -0.041 ( 0.0362 )
        Baso: EOT (n= S1-280, S2-287)
    -0.021 ( 0.0367 )
    -0.023 ( 0.0312 )
        Baso: Max change (n= S1-357, S2-345)
    -0.022 ( 0.0673 )
    -0.031 ( 0.0618 )
        Leukos: Baseline (n= S1-363, S2-352)
    8.175 ( 2.9656 )
    8.105 ( 2.6725 )
        Leuko: C3D1 (n= S1-288, S2-290)
    -4.065 ( 3.1244 )
    -4.597 ( 2.9352 )
        Leuko: EOT (n=S1-282, S2-287)
    -2.129 ( 3.2074 )
    -2.354 ( 2.4137 )
        Leuko: Max change (n= S1-357, S2-345)
    -3.045 ( 7.5455 )
    -3.444 ( 6.7059 )
        Lympho: Baseline (n= S1-363,S2-352)
    1.753 ( 0.5734 )
    1.753 ( 0.6367 )
        Lympho: C3D1 (283, 288)
    -1.168 ( 0.5804 )
    -1.251 ( 0.5742 )
        Lympho: EOT (n= S1-280, S2-287)
    -0.884 ( 0.5485 )
    -0.901 ( 0.5536 )
        Lympho: Max change (n=S1-357, S2-345)
    -1.382 ( 0.6359 )
    -1.356 ( 0.6150 )
        Mono: Baseline (n= S1-363, S2- 352)
    0.518 ( 0.2156 )
    0.506 ( 0.2072 )
        Mono: C3D1 (n= S1-283, S2-288)
    -0.139 ( 0.2389 )
    -0.169 ( 0.2063 )
        Mono: EOT (n= S1-280, S2-287)
    -0.114 ( 0.1991 )
    -0.100 ( 0.1683 )
        Mono: Max change (n= S1-357, S2-345)
    -0.175 ( 0.4050 )
    -0.152 ( 0.3870 )
        Neutro: Baseline (n= S1-363, S2-352)
    5.669 ( 2.6589 )
    5.610 ( 2.3663 )
        Neutro: C3D1 (n= S1-283, S2-288)
    -2.646 ( 2.8532 )
    -3.018 ( 2.6744 )
        Neutro: EOT (n= S1-280, S2-287)
    -1.081 ( 2.9287 )
    -1.275 ( 2.2696 )
        Neutro: Max change (n= S1-357, S2-345)
    -0.528 ( 7.2775 )
    -1.095 ( 6.3143 )
        Plt: Baseline (n= S1-362, S2-351)
    292.6 ( 104.86 )
    287.7 ( 107.38 )
        Plt: C3D1 (n= S1-282, S2-277)
    -48.2 ( 112.13 )
    -56.5 ( 109.52 )
        Plt: EOT (n= S1-278, S2-284)
    -24.8 ( 94.59 )
    -38.6 ( 87.16 )
        Plt: Max change (n=S1-356, S2-344)
    -63.2 ( 203.40 )
    -88.7 ( 171.61 )
    No statistical analyses for this end point

    Secondary: Percent Change from Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes

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    End point title
    		 Percent Change from Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes
    End point description
    Percent change from Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes was reported. Here "overall number of subjects analyzed signified" subjects who were evaluable for this outcome measure and "number analyzed" or "n" signifies subjects who were evaluable at specified timepoints. Please note Sequence 1= S1, Sequence 2= S2, Basophils = BP, Leukocytes= Leuko, Lymphocyte = Lympho, Monocyte = mono, Neutrophils = Neutro and Maximum on treatment change = max change.
    End point type
    Secondary
    End point timeframe
    At Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    363
    352
    Units: percent change
    arithmetic mean (standard deviation)
        C3D1: Baso/Leuko (n= S1-283, S2-288)
    -0.21 ( 0.551 )
    -0.29 ( 0.527 )
        EOT: Baso/Leuko (n=S1-280,S2-287)
    -0.14 ( 0.502 )
    -0.13 ( 0.483 )
        Max change: Baso/Leuko (n=S1-357,S2-345)
    0.03 ( 0.985 )
    0.00 ( 1.032 )
        C3D1: Eosino/Leuko (n=S1-283,S2-288)
    -0.04 ( 2.874 )
    -0.39 ( 2.147 )
        EOT: Eosino/Leuko (n=S1-280,S2-287)
    0.60 ( 3.435 )
    0.07 ( 1.878 )
        Max change: Eosino/Leuko (n=S1-357,S2-345)
    1.32 ( 5.005 )
    0.04 ( 3.308 )
        C3D1: Lympho/Leuko (n=S1-283,S2-288)
    -6.89 ( 10.604 )
    -5.80 ( 10.086 )
        EOT:Lympho/Leuko (n=S1-280,S2-287)
    -6.85 ( 8.855 )
    -6.91 ( 7.850 )
        Max change: Lympho/Leuko (n=S1-357,S2-345)
    -11.39 ( 15.553 )
    -10.07 ( 15.985 )
        C3D1: Mono/Leuko (n=S1-283,S2-288)
    3.65 ( 4.502 )
    3.90 ( 3.840 )
        EOT: Mono/Leuko (n=S1-280,S2-287)
    0.64 ( 2.666 )
    0.89 ( 2.454 )
        Max change: Mono/Leuko (n=S1-280,S2-287)
    5.87 ( 6.060 )
    6.26 ( 5.631 )
        C3D1: Neutro/Leuko (n=S1-283,S2-288)
    2.67 ( 14.064 )
    2.33 ( 12.467 )
        EOT: Neutro/Leuko (n=S1-280,S2-287)
    5.75 ( 10.651 )
    6.08 ( 9.086 )
        Max change: Neutro/Leuko (n=S1-357,S2-345)
    6.80 ( 24.388 )
    7.45 ( 21.764 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Laboratory Parameters: Erythrocytes

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    End point title
    		 Change from Baseline in Laboratory Parameters: Erythrocytes
    End point description
    Change from Baseline in Laboratory Parameters: Erythrocytes was reported. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "number analyzed" or "n" signifies subjects who were evaluable at specified timepoints. Please note S1- Sequence 1, S2- Sequence 2 and Max on treatment change - Max change.
    End point type
    Secondary
    End point timeframe
    At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    363
    352
    Units: 10^12 cells per liter
    arithmetic mean (standard deviation)
        Baseline
    4.27 ( 0.507 )
    4.37 ( 0.477 )
        C3D1 (n=S1- 288, S2-290)
    -0.81 ( 0.456 )
    -0.82 ( 0.433 )
        EOT (n=S1- 282, S2-287)
    -0.70 ( 0.575 )
    -0.59 ( 0.464 )
        Max change (n=S1- 357, S2-345)
    -1.14 ( 0.636 )
    -1.19 ( 0.605 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein

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    End point title
    		 Change from Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein
    End point description
    Change from Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein was reported. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "overall number of subjects analyzed signified" subjects who were evaluable for this outcome measure and "number analyzed" or "n" signifies subjects who were evaluable at specified timepoints. Please note Sequence 1= S1, Sequence 2= S2, hemoglobin - Hb, Albumin- Alb, Protein - Prt and Maximum on treatment change = max change.
    End point type
    Secondary
    End point timeframe
    At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    356
    Units: grams per liters (g/L)
    arithmetic mean (standard deviation)
        Hb: Baseline(n= S1- 363,S2-352)
    132.9 ( 15.08 )
    135.4 ( 14.34 )
        Hb: C3D1(n= S1- 288,S2-290)
    -25.7 ( 14.24 )
    -25.2 ( 13.75 )
        Hb: EOT(n= S1- 282,S2-287)
    -19.1 ( 17.73 )
    -14.4 ( 14.44 )
        Hb: Max change(n= S1- 357,S2-345)
    -34.8 ( 19.83 )
    -35.8 ( 18.82 )
        Alb: Baseline(n= S1- 364,S2-352)
    43.2 ( 3.95 )
    43.6 ( 3.55 )
        Alb: C3D1(n= S1- 304,S2-314)
    -4.0 ( 4.33 )
    -2.6 ( 3.61 )
        Alb: EOT (n= S1- 309,S2-314)
    -1.1 ( 4.43 )
    0.4 ( 4.02 )
        Alb: Max change (n= S1- 351,S2-343)
    -4.8 ( 6.38 )
    -2.6 ( 5.90 )
        Prt: Baseline(n= S1- 363,S2-356)
    70.1 ( 5.11 )
    70.5 ( 4.78 )
        Prt: C3D1(n= S1- 300,S2-313)
    -4.5 ( 5.73 )
    -4.3 ( 5.24 )
        Prt: EOT(n= S1- 306,S2-312)
    -0.3 ( 6.10 )
    -0.7 ( 5.32 )
        Prt: Max change (n= S1- 350,S2-343)
    -4.7 ( 9.12 )
    -5.0 ( 8.03 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase

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    End point title
    		 Change from Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase
    End point description
    Change from Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase was reported. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "overall number of subjects analyzed signified" subjects who were evaluable for this outcome measure and "number analyzed" or "n" signifies subjects who were evaluable at specified timepoints. Please note Sequence 1= S1, Sequence 2= S2, Alanine aminotransferase - ALT, Alkaline Phosphatase- ALP, Aspartate Aminotransferase-AST and Maximum on treatment change = max change.
    End point type
    Secondary
    End point timeframe
    At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    356
    Units: microgram per liter (mcg/L)
    arithmetic mean (standard deviation)
        ALT: Baseline (n= S1-363, S2-353)
    18.9 ( 12.10 )
    19.4 ( 12.66 )
        ALT: C3D1 (n= S1-295, S2-300)
    0.5 ( 16.77 )
    -4.6 ( 13.53 )
        ALT: EOT (n= S1-297, S2-297)
    -2.0 ( 18.25 )
    -3.4 ( 15.87 )
        ALT: Max change (n= S1-356, S2-346)
    55.8 ( 70.73 )
    26.5 ( 45.39 )
        ALP: Baseline (n= S1-363, S2-356)
    79.3 ( 24.48 )
    78.0 ( 23.20 )
        ALP: C3D1 (n= S1-301, S2-312)
    -0.8 ( 19.94 )
    -1.0 ( 21.89 )
        ALP: EOT (n= S1-305, S2-311)
    -2.2 ( 28.14 )
    -5.6 ( 18.79 )
        ALP: Max change (n= S1-364, S2-356)
    12.7 ( 47.38 )
    5.6 ( 49.27 )
        Amylase: Baseline (n= S1-, S2-)
    70.0 ( 42.81 )
    67.8 ( 61.61 )
        Amylase: C3D1 (n= S1-304, S2-310)
    -14.0 ( 38.07 )
    -14.0 ( 32.85 )
        Amylase: EOT (n= S1-308, S2-313)
    -13.5 ( 40.51 )
    -13.5 ( 33.79 )
        Amylase: Max change (n= S1-359, S2-350)
    125.8 ( 205.22 )
    60.4 ( 119.29 )
        AST: Baseline (n= S1-363, S2-356)
    19.8 ( 11.10 )
    19.8 ( 8.31 )
        AST: C3D1 (n= S1-302, S2-311)
    -2.4 ( 12.30 )
    -3.5 ( 8.63 )
        AST: EOT (n= S1-304, S2-312)
    0.4 ( 19.01 )
    0.9 ( 18.80 )
        AST: Max change (n= S1-356, S2-350)
    20.0 ( 37.35 )
    9.7 ( 25.02 )
        Lipase: Baseline (n= S1-364, S2-356)
    35.4 ( 48.01 )
    29.8 ( 19.37 )
        Lipase: C3D1 (n= S1-305, S2-309)
    -4.0 ( 39.69 )
    -4.0 ( 23.64 )
        Lipase: EOT (n= S1-308, S2-314)
    -1.8 ( 47.38 )
    -1.0 ( 21.69 )
        Lipase: Max change (n= S1-359, S2-350)
    87.3 ( 196.87 )
    25.0 ( 60.54 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate

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    End point title
    		 Change from Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate
    End point description
    Change from Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate was reported. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "overall number of subjects analyzed signified" subjects who were evaluable for this outcome measure and "number analyzed" or "n" signifies subjects who were evaluable at specified timepoints. Please note Bilirubin - Bil, Creatine- Creat, Direct Bilirubin-DB, Sequence 1-S1, Sequence 2-S2 and Max on treatment change - max change
    End point type
    Secondary
    End point timeframe
    At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364 [14]
    356 [15]
    Units: micromole per liter (mcmol/L)
    arithmetic mean (standard deviation)
        Bil: Baseline(n= S1-364,S2-355)
    7.4 ( 4.03 )
    7.8 ( 4.06 )
        Bil: C3D1(n= S1-304,S2-312)
    -1.8 ( 3.74 )
    -1.5 ( 3.68 )
        Bil: EOT(n= S1-309,S2-314)
    -2.0 ( 3.85 )
    -1.3 ( 3.52 )
        Bil: Max change(n= S1-359,S2-349)
    1.1 ( 7.49 )
    0.1 ( 6.83 )
        Creat: Baseline(n= S1-363,S2-356)
    67.884 ( 15.1427 )
    70.612 ( 15.3405 )
        Creat: C3D1(n= S1-301,S2-312)
    11.771 ( 27.4012 )
    11.740 ( 26.2545 )
        Creat: EOT(n= S1-306,S2-313)
    17.660 ( 49.3934 )
    16.243 ( 32.1216 )
        Creat: Max change(n= S1-358,S2-350)
    292.808 ( 4199.9623 )
    360.521 ( 5664.5213 )
        DB: Baseline(n= S1-6,S2-9)
    4.8 ( 0.75 )
    5.6 ( 1.33 )
        DB: C3D1(n= S1-0,S2-1)
    99999 ( 99999 )
    3.0 ( 99999 )
        DB: EOT(n= S1-0,S2-2)
    99999 ( 99999 )
    0.0 ( 1.41 )
        DB: Max change(n= S1-2,S2-8)
    2.5 ( 2.12 )
    1.0 ( 2.14 )
        Urate: Baseline(n= S1-363,S2-356)
    303.1 ( 79.62 )
    305.9 ( 82.79 )
        Urate: C3D1(n= S1-301,S2-313)
    -25.4 ( 90.93 )
    -21.5 ( 91.07 )
        Urate: EOT(n= S1-306,S2-313)
    25.9 ( 85.01 )
    33.1 ( 80.07 )
        Urate: Max change(n= S1-350,S2-343)
    1.2 ( 140.44 )
    12.7 ( 137.74 )
    Notes
    [14] - 99999 denotes no observation.no participants were analyzed and no data was collected
    [15] - 99999 denotes no observation.no participants were analyzed and no data was collected
    No statistical analyses for this end point

    Secondary: Change from Baseline in Laboratory Parameters: C Reactive Protein

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    End point title
    		 Change from Baseline in Laboratory Parameters: C Reactive Protein
    End point description
    Change from Baseline in Laboratory Parameters: C Reactive Protein was reported. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "number analyzed" or "n" signifies subjects who were evaluable at specified timepoints. Please note Maximum on-treatment change - max change, Sequence 1 - S1 and Sequence 2- S2)
    End point type
    Secondary
    End point timeframe
    At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    356
    Units: milligrams per liter (mg/L)
    arithmetic mean (standard deviation)
        Baseline
    15.80 ( 24.655 )
    13.78 ( 21.780 )
        C3D1 (n=S1-304, S2-307)
    25.30 ( 50.259 )
    11.66 ( 36.791 )
        EOT (n=S1-306, S2-314)
    1.26 ( 31.784 )
    1.22 ( 27.720 )
        Max change (n=S1-351, S2-343)
    43.91 ( 66.024 )
    27.90 ( 56.262 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea

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    End point title
    		 Change from Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea
    End point description
    Change from Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea was reported. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "overall number of subjects analyzed signified" subjects who were evaluable for this outcome measure and "number analyzed" or "n" signifies subjects who were evaluable at specified timepoints. Please note Sequence 1- S1, Sequence 2-S2, Calcium - Ca, Magnesium - Mg, Potassium - K, Sodium - Na and maximum on treatment change - max change.
    End point type
    Secondary
    End point timeframe
    At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    356
    Units: millimoles per liter (mmol/L)
    arithmetic mean (standard deviation)
        Ca: Baseline(n=S1-364,S2-356)
    2.4065 ( 0.14050 )
    2.4043 ( 0.11777 )
        Ca: C3D1(n=S1-304,S2-314)
    -0.1054 ( 0.16830 )
    -0.0574 ( 0.12989 )
        Ca: EOT(n=S1-309,S2-314)
    0.0006 ( 0.15586 )
    0.0136 ( 0.12258 )
        Ca: Max change(n=S1-351,S2-346)
    -0.1182 ( 0.64226 )
    -0.0575 ( 0.63941 )
        Mg: Baseline(n=S1-363,S2-356)
    0.8731 ( 0.08816 )
    0.8718 ( 0.08800 )
        Mg: C3D1(n=S1-301,S2-313)
    -0.0871 ( 0.11743 )
    -0.0719 ( 0.11889 )
        Mg: EOT(n=S1-306,S2-313)
    -0.0588 ( 0.10612 )
    -0.0372 ( 0.08725 )
        Mg: Max change(n=S1-350,S2-345)
    -0.1231 ( 0.21711 )
    -0.0860 ( 0.21948 )
        K: Baseline(n=S1-363,S2-356)
    4.4270 ( 0.41610 )
    4.4534 ( 0.44584 )
        K: C3D1(n=S1-301,S2-309)
    -0.1226 ( 0.60007 )
    -0.0877 ( 0.58424 )
        K: EOT(n=S1-302,S2-311)
    -0.0374 ( 0.52898 )
    0.0170 ( 0.58221 )
        K: Max change(n=S1-356,S2-350)
    -0.2845 ( 1.13356 )
    -0.2551 ( 1.14282 )
        Na: Baseline(n=S1-363,S2-356)
    139.3333 ( 2.72935 )
    139.1798 ( 3.19705 )
        Na: C3D1(n=S1-302,S2-313)
    -2.0828 ( 3.96368 )
    -1.5527 ( 3.73110 )
        Na: EOT(n=S1-306,S2-313)
    -0.9510 ( 3.53728 )
    -0.9521 ( 3.71944 )
        Na: Max change(n=S1-358,S2-350)
    -4.7482 ( 9.86512 )
    -4.6627 ( 14.14911 )
        Urea: Baseline(n=S1-363,S2-356)
    5.22 ( 1.885 )
    5.23 ( 2.068 )
        Urea: C3D1(n=S1-302,S2-312)
    1.89 ( 3.302 )
    1.87 ( 3.961 )
        Urea: EOT(n=S1-306,S2-313)
    1.73 ( 3.266 )
    1.40 ( 2.922 )
        Urea: Max change (n=S1-358,S2-350)
    8.51 ( 7.226 )
    6.18 ( 6.110 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Estimated Glomerular Filtration Rate

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    End point title
    		 Change from Baseline in Estimated Glomerular Filtration Rate
    End point description
    Change from baseline in biochemistry parameter eGFR was reported. The Glomerular Filtration Rate was measured as milliliter per minute per 1.73 square meter (mL/min/1.73m^2). The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "number analyzed" or "n" signifies subjects who were evaluable at specified timepoints. Please note Sequence 1- S1, Sequence 2-S2, Max on treatment change - max change.
    End point type
    Secondary
    End point timeframe
    At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    361
    356
    Units: mL/min/1.73m*2
    arithmetic mean (standard deviation)
        Baseline
    96.956 ( 14.2212 )
    95.244 ( 14.1290 )
        C3D1(n=S1-299, S2-312)
    -8.799 ( 19.0295 )
    -9.205 ( 18.5178 )
        EOT(n=S1-304, S2-313)
    -11.385 ( 20.6015 )
    -12.594 ( 18.0053 )
        Max change(n=S1-348, S2-346)
    -19.439 ( 27.3672 )
    -19.528 ( 25.7099 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Activated partial thromboplastin time (PTT)/ Standard and Prothrombin Time

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    End point title
    		 Change from Baseline in Activated partial thromboplastin time (PTT)/ Standard and Prothrombin Time
    End point description
    Change from Baseline in coagulation parameter activated PTT/standard and prothrombin Time was reported. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "overall number of subjects analyzed signified" subjects who were evaluable for this outcome measure and "number analyzed" or "n" signifies subjects who were evaluable at specified timepoints. Please note Sequence 1 - S1, Sequence 2- S2, Activated PTT/Standard - APTT/S, Prothrombin Time- PT and Maximum on treatment change - Max change.
    End point type
    Secondary
    End point timeframe
    At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    349
    344
    Units: seconds (Sec)
    arithmetic mean (standard deviation)
        APTT/S: Baseline
    26.15 ( 2.349 )
    26.25 ( 2.540 )
        APTT/S: C3D1(n=S1-269,S2-273)
    -0.80 ( 3.132 )
    -0.91 ( 2.324 )
        APTT/S: EOT(n=S1-260,S2-268)
    -0.29 ( 2.812 )
    -0.09 ( 2.419 )
        APTT/S: Max change(n=S1-331,S2-322)
    -1.01 ( 4.165 )
    -0.87 ( 3.509 )
        PT: Baseline(n=S1-349,S2-344)
    10.50 ( 0.730 )
    10.73 ( 1.696 )
        PT: C3D1(n=S1-274,S2-284)
    0.11 ( 1.730 )
    -0.17 ( 1.543 )
        PT: EOT(n=S1-266,S2-283)
    0.17 ( 1.757 )
    -0.04 ( 1.697 )
        PT: Max change(n=S1-334,S2-329)
    0.35 ( 2.364 )
    -0.01 ( 1.838 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Fibrinogen

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    End point title
    		 Change from Baseline in Fibrinogen
    End point description
    Change from Baseline in coagulation parameter fibrinogen was reported. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "number of subjects analyzed signified" participants who were evaluable for this outcome measure and "n=number analyzed" signifies participants who were evaluable at specified timepoints. Please note Sequence 1-S1, Sequence 2-S2, Maximum on treatment change - Max change.
    End point type
    Secondary
    End point timeframe
    At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    348
    343
    Units: milligrams per deciliter (mg/dl)
    arithmetic mean (standard deviation)
        Baseline
    486.9 ( 140.35 )
    467.7 ( 119.14 )
        C3D1 (n=S1-273,S2-282)
    121.3 ( 164.05 )
    109.8 ( 157.03 )
        EOT (n=S1-265,S2-283)
    17.8 ( 150.78 )
    1.0 ( 138.69 )
        Max change (n=S1-333,S2-328)
    112.6 ( 212.46 )
    122.4 ( 207.11 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Prothrombin International Normalized Ratio

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    End point title
    		 Change from Baseline in Prothrombin International Normalized Ratio
    End point description
    Change from baseline in coagulation parameters prothrombin international normalized ratio was reported. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Please note Sequence 1-S1, Sequence 2-S2, Maximum on treatment change - Max change.
    End point type
    Secondary
    End point timeframe
    At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    349
    344
    Units: ratio
    arithmetic mean (standard deviation)
        Baseline
    0.96 ( 0.090 )
    0.99 ( 0.188 )
        C3D1 (n=S1-274,S2-284)
    0.01 ( 0.195 )
    -0.02 ( 0.175 )
        EOT (n=S1-266,S2-283)
    0.02 ( 0.197 )
    0.00 ( 0.195 )
        Max change (n=S1-334,S2-329)
    0.04 ( 0.265 )
    0.00 ( 0.212 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure

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    End point title
    		 Change from Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure
    End point description
    Change from Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure was reported. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "overall number of subjects analyzed signified" subjects who were evaluable for this outcome measure and "number analyzed" signifies subjects who were evaluable at specified timepoints. Please note Sequence 1-S1, Sequence 2-S2, Maximum on treatment change - Max change, Systolic Blood Pressure - SBP and Diastolic Blood Pressure - DBP.
    End point type
    Secondary
    End point timeframe
    At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment increase & decrease)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    356
    Units: millimeters of mercury (mmHg)
    arithmetic mean (standard deviation)
        SBP: Baseline(n= S1-364 , S2-356)
    128.0 ( 18.08 )
    128.2 ( 16.96 )
        SBP: C3D1 (n= S1-320, S2-326)
    -10.1 ( 19.36 )
    -7.9 ( 17.53 )
        SBP: EOT (n= S1-320, S2-323)
    -5.8 ( 20.47 )
    -3.4 ( 20.03 )
        SBP: Max increase(n= S1-249 , S2-274 )
    15.6 ( 12.89 )
    16.5 ( 12.43 )
        SBP: Max decrease(n= S1-328, S2-323)
    -24.7 ( 15.85 )
    -21.9 ( 14.48 )
        DBP: Baseline(n= S1- , S2- )
    77.4 ( 10.60 )
    77.5 ( 9.75 )
        DBP: C3D1(n= S1-320, S2-326 )
    -5.6 ( 12.04 )
    -4.0 ( 10.65 )
        DBP: EOT(n= S1-320, S2-323 )
    -1.8 ( 12.02 )
    -1.2 ( 11.55 )
        DBP: Max increase(n= S1-241, S2-250)
    11.1 ( 7.54 )
    11.2 ( 8.09 )
        DBP: Max decrease(n= S1-323, S2-319)
    -15.2 ( 9.43 )
    -13.2 ( 8.42 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Vital Signs: Heart Rate

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    End point title
    		 Change from Baseline in Vital Signs: Heart Rate
    End point description
    Change from Baseline in Vital Signs: Heart Rate was reported. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "number analyzed" signifies subjects who were evaluable at specified timepoints. Please note Sequence 1-S1, Sequence 2-S2, Maximum on treatment change - Max change and Heart Rate - HR.
    End point type
    Secondary
    End point timeframe
    At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment increase & decrease)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    356
    Units: beats/minute
    arithmetic mean (standard deviation)
        HR: Baseline(n=S1-364,S2-356)
    77.6 ( 12.35 )
    76.1 ( 12.60 )
        HR: C3D1(n=S1-320,S2-326)
    5.2 ( 13.71 )
    3.4 ( 13.92 )
        HR: EOT(n=S1-318,S2-323)
    2.8 ( 14.33 )
    2.2 ( 13.51 )
        HR: Max increase(n=S1-316,S2-304)
    17.8 ( 12.30 )
    16.7 ( 10.97 )
        HR: Max decrease(n=S1-274,S2-280)
    -11.7 ( 9.00 )
    -12.2 ( 9.13 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Vital Signs: Respiratory Rate

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    End point title
    		 Change from Baseline in Vital Signs: Respiratory Rate
    End point description
    Change from Baseline in Vital Signs: Respiratory Rate was reported. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "number analyzed" signifies subjects who were evaluable at specified timepoints. Please note Sequence 1-S1, Sequence 2-S2, Maximum on treatment change - Max change and Respiratory Rate - RR.
    End point type
    Secondary
    End point timeframe
    At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment increase & decrease)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    359
    355
    Units: breaths/minute
    arithmetic mean (standard deviation)
        RR: Baseline(n=S1-359,S2-355)
    16.8 ( 2.38 )
    16.7 ( 2.98 )
        RR: C3D1(n=S1-304,S2-319)
    -0.1 ( 2.65 )
    0.0 ( 2.76 )
        RR: EOT(n=S1-308,S2-317)
    -0.1 ( 2.83 )
    -0.1 ( 3.01 )
        RR: Max increase(n=S1-208,S2-316)
    3.2 ( 2.66 )
    2.7 ( 2.13 )
        RR: Max decrease(n=S1-208,S2-216)
    -3.1 ( 2.52 )
    -2.7 ( 2.88 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Vital Signs: Body Temperature

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    End point title
    		 Change from Baseline in Vital Signs: Body Temperature
    End point description
    Change from Baseline in Vital Signs: Body Temperature was reported. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "number analyzed" signifies subjects who were evaluable at specified timepoints. Please note Sequence 1-S1, Sequence 2-S2, Maximum on treatment change - Max channge.
    End point type
    Secondary
    End point timeframe
    At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment increase)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    355
    Units: degree Celsius
    arithmetic mean (standard deviation)
        Baseline(n=S1-364,s2-355)
    36.44 ( 0.443 )
    36.41 ( 0.432 )
        C3D1(n=S1-318,s2-325)
    0.10 ( 36.49 )
    0.07 ( 0.476 )
        EOT(n=S1-317,s2-320)
    0.00 ( 0.463 )
    0.00 ( 0.453 )
        Max increase(n=S1-292,s2-295)
    0.57 ( 0.445 )
    0.51 ( 0.413 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Vital Signs: Body Weight

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    End point title
    		 Change from Baseline in Vital Signs: Body Weight
    End point description
    Change from Baseline in Vital Signs: Body Weight was reported. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "number analyzed" signifies subjects who were evaluable at specified timepoints. Please note Sequence 1-S1, Sequence 2-S2, Maximum on treatment change - Max change.
    End point type
    Secondary
    End point timeframe
    At Baseline, C3D1 (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment increase & decrease)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    356
    Units: kilograms (kg)
    arithmetic mean (standard deviation)
        Baseline(n=S1-364,S2-356)
    69.552 ( 16.8493 )
    70.261 ( 15.2793 )
        C3D1(n=S1-321,S2-327)
    -4.762 ( 3.9129 )
    -4.331 ( 3.6001 )
        EOT(n=S1-319,S2-328)
    -6.282 ( 6.1160 )
    -4.819 ( 5.9718 )
        Max increase(n=S1-86,S2-104)
    2.497 ( 2.1157 )
    2.549 ( 2.7503 )
        Max decrease(n=S1-340,S2-331)
    -8.182 ( 5.1605 )
    -7.379 ( 4.8001 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in ECG Parameters

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    End point title
    		 Change from Baseline in ECG Parameters
    End point description
    The 12-lead ECGs were recorded after the subjects have rested for at least 5 minutes in supine position. The parameters included Respiratory Rate (RR), Pulse Rate (PR), QRS, QT and QTcF calculated by the Bazett formula. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "number analyzed" signifies subjects who were evaluable for each specific category. Please note Sequence 1-S1, Sequence 2-S2, Maximum on treatment change - Max change, PR Interval - PRI, QRS Duration - QRSD, QT Interval - QRI, RR Interval - RRI, QTcF Interval - QRcFI.
    End point type
    Secondary
    End point timeframe
    At Baseline, and upto event free survival (EFS) follow up Month 18 after EOT (max on treatment increase)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    356
    Units: millisecond
    arithmetic mean (standard deviation)
        PRI: Baseline(n=S1-361,S2-353)
    154.6 ( 28.05 )
    159.2 ( 29.85 )
        PRI: Max increase(n=S1-273,S2-247)
    15.2 ( 16.48 )
    15.8 ( 19.90 )
        QRSD: Baseline(n=S1-364,S2-355)
    90.4 ( 14.78 )
    91.9 ( 14.48 )
        QRSD: Max increase(n=S1-267,S2-268)
    9.8 ( 9.87 )
    9.8 ( 21.97 )
        QTI: Baseline(n=S1-364,S2-356)
    381.9 ( 30.29 )
    385.7 ( 33.47 )
        QTI: Max increase(n=S1-307,S2-278)
    33.3 ( 26.91 )
    26.9 ( 21.78 )
        RRI: Baseline(n=S1-359,S2-349)
    824.5 ( 163.43 )
    858.0 ( 153.30 )
        RRI: Max increase(n=S1-291,S2-266)
    139.5 ( 125.19 )
    117.2 ( 87.11 )
        QTcFI: Baseline(n=S1-364,S2-356)
    406.3 ( 22.78 )
    406.6 ( 25.06 )
        QTcFI: Max increase(n=S1-305,S2-279)
    24.9 ( 21.27 )
    19.7 ( 19.17 )
    No statistical analyses for this end point

    Secondary: Number of Subjects who Completed Cycle 1, 2, 3, 4, 5 and 6

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    End point title
    		 Number of Subjects who Completed Cycle 1, 2, 3, 4, 5 and 6
    End point description
    Number of subjects who completed cycle 1, 2, 3, 4, 5 or 6 of xevinapant/matched placebo were reported. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT).
    End point type
    Secondary
    End point timeframe
    Cycle 1, 2, 3, 4, 5 and 6 (each cycle is of 3 weeks)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    356
    Units: count of subjects
        Cycle 1
    363
    355
        Cycle 2
    325
    335
        Cycle 3
    290
    314
        Cycle 4
    266
    210
        Cycle 5
    263
    307
        Cycle 6
    246
    297
    No statistical analyses for this end point

    Secondary: Treatment Duration

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    End point title
    		 Treatment Duration
    End point description
    Treatment duration is calculated by study treatment component as (last dose date minus first dose date plus x)/7, where x=8 for xevinapant/matched placebo, x=21 for cisplatin/carboplatin, x=3 for IMRT.The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "number analyzed" signifies subjects who were evaluable for each specific category.
    End point type
    Secondary
    End point timeframe
    Up to end of study (up to 188weeks and 5 days)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    356
    Units: weeks
    median (full range (min-max))
        Xevinapant/matched placebo
    18.00 (10.71 to 18.14)
    18.00 (18.00 to 18.29)
        Cisplatin(n=S1-360,S2-351)
    8.86 (6.00 to 9.00)
    9.00 (6.00 to 9.00)
        Carboplatin(n=S1-55,s2-60)
    3.00 (3.00 to 6.00)
    3.00 (3.00 to 6.00)
        IMRT(n=S1-364,S2-355)
    7.43 (7.21 to 7.86)
    7.43 (7.29 to 7.71)
    No statistical analyses for this end point

    Secondary: Total Cumulative Dose of Cisplatin

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    End point title
    		 Total Cumulative Dose of Cisplatin
    End point description
    Total cumulative dose of cisplatin was reported. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here” overall number of subjects analyzed signified” subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Up to end of treatment (Day 134)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    360
    351
    Units: milligrams per square meter (mg/m^2)
        arithmetic mean (standard deviation)
    223.3 ( 76.26 )
    236.3 ( 73.14 )
    No statistical analyses for this end point

    Secondary: Total Cumulative Dose of Carboplatin

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    End point title
    		 Total Cumulative Dose of Carboplatin
    End point description
    Total cumulative dose of carboplatin was reported as mean and standard deviation. The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "overall number of subjects analyzed signified” subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Up to end of treatment (Day 134)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    54
    60
    Units: Area under curve (AUC)
        arithmetic mean (standard deviation)
    6.9 ( 2.37 )
    6.6 ( 2.26 )
    No statistical analyses for this end point

    Secondary: Total Cumulative Dose of Xevinapant/ Matched Placebo

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    End point title
    		 Total Cumulative Dose of Xevinapant/ Matched Placebo
    End point description
    Total cumulative dose of Xevinapant/ Matched Placebo was reported in form of mean and standard deviation. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "overall number of subjects analyzed signified" subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Up to end of treatment (Day 134)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    355
    Units: milligrams (mg)
        arithmetic mean (standard deviation)
    12383.6 ( 5375.66 )
    14417.0 ( 4288.55 )
    No statistical analyses for this end point

    Secondary: Overall Dose intensity of Cisplatin

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    End point title
    		 Overall Dose intensity of Cisplatin
    End point description
    Overall dose intensity of Cisplatin is calculated as the mean of the dose intensities of the individual cycles. This was reported with the unit of measure milligrams per meter square per week (mg/m2/week). The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "overall number of participants analyzed signified” subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Cycle 1, 2, 3, 4 5, 6 (each cycle is of 3 weeks) or End of Treatment (Day 134)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    360
    351
    Units: mg/m2/week
        arithmetic mean (standard deviation)
    32.33 ( 3.053 )
    32.55 ( 2.301 )
    No statistical analyses for this end point

    Secondary: Overall Dose Intensity of Xevinapant/Matched Placebo

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    End point title
    		 Overall Dose Intensity of Xevinapant/Matched Placebo
    End point description
    Overall dose intensity of Xevinapant/ matched placebo is calculated as the mean of the dose intensities of the individual cycles. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT).Here "overall number of subjects analyzed signified” subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Cycle 1, 2, 3, 4 5, 6 (each cycle is of 3 weeks) or End of Treatment (Day 134)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    355
    Units: milligrams per day (mg/day)
        arithmetic mean (standard deviation)
    122.72 ( 18.274 )
    126.56 ( 16.495 )
    No statistical analyses for this end point

    Secondary: Total Cumulative Dose of Intensity-Modulated Radiation Therapy (IMRT)

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    End point title
    		 Total Cumulative Dose of Intensity-Modulated Radiation Therapy (IMRT)
    End point description
    Total cumulative dose of IMRT were reported in form of mean and standard deviation. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here” overall number of subjects analyzed signified” subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Up to end of treatment (Day 134)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    355
    Units: Gray (Gy)
        arithmetic mean (standard deviation)
    66.4 ( 12.32 )
    67.9 ( 9.74 )
    No statistical analyses for this end point

    Secondary: Overall Dose intensity of Carboplatin

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    End point title
    		 Overall Dose intensity of Carboplatin
    End point description
    Overall dose intensity of Carboplatin is calculated as the mean of the dose intensities of the individual cycles. This was reported with unit of measure Milligrams per minute per milliliter per week (mg min/mL/week). The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT).Here "overall number of subjects analyzed signified” subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Cycle 1, 2, 3, 4 5, 6 (each cycle is of 3 weeks) or End of Treatment (Day 134)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    54
    60
    Units: mg min/mL/week
        arithmetic mean (standard deviation)
    1.59 ( 0.136 )
    1.60 ( 0.123 )
    No statistical analyses for this end point

    Secondary: Relative Dose Intensity

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    End point title
    		 Relative Dose Intensity
    End point description
    Relative dose intensity (RDI) represents the percentage of the amount of a drug actually delivered [actual dose intensity (DI)] to the amount planned (planned DI). The purpose of calculating RDI is to evaluate whether the planned DI of an anti-cancer treatment was actually achieved which may suggest the feasibility of planned treatment regimen. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "number analyzed" signifies subjects who were evaluable for each specific category.
    End point type
    Secondary
    End point timeframe
    Up to 50 months
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    363
    355
    Units: percentage (%) of dose intensity
    arithmetic mean (standard deviation)
        Xevinapant/matched placebo
    92.04 ( 13.706 )
    94.92 ( 12.372 )
        Cisplatin
    96.98 ( 9.159 )
    97.65 ( 6.904 )
        Carboplatin
    95.19 ( 8.182 )
    96.17 ( 7.386 )
    No statistical analyses for this end point

    Secondary: Number of Subjects with Treatment Interruption, Treatment Reduction and Treatment Discontinuation for Xevinapant/ Matched Placebo

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    End point title
    		 Number of Subjects with Treatment Interruption, Treatment Reduction and Treatment Discontinuation for Xevinapant/ Matched Placebo
    End point description
    Number of subjects with Treatment Interruption, Treatment Reduction and Treatment Discontinuation was reported. The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here "number analyzed" signifies subjects who were evaluable for each specific category.
    End point type
    Secondary
    End point timeframe
    Up to end of treatment (Day 134)
    End point values
    		 Sequence 1: Debio 1143 + CRT Sequence 2: Placebo + CRT
    Number of subjects analysed
    364
    356
    Units: subjects
        Treatment Interruption-xevinapant/Placebo
    206
    147
        Treatment Reduction-xevinapant/placebo
    34
    17
        Treatment Discontinuation-xevinapant/placebo
    71
    30
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All AEs were be collected from the time of Informed Consent Form signature until the End Of Treatment(EOT)visit (Day134).From the EOT visit until the End Of Study visit(Up to 44 months),only SAEs and late onset AEs of Special Interest were collected
    Adverse event reporting additional description
    The SAF set included all subjects who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT).
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    Sequence 2: Placebo + CRT
    Reporting group description
    		 Subjects received a combination of placebo matched to Debio 1143 along with Chemoradiotherapy(CRT): Radiotherapy +Cisplatin+ placebo matched to Xevinapant (Debio 1143). Subjects received 6 cycles of oral solution of placebo matched to Xevinapant once daily from Day 1 to 14, per 3-week cycle in combination with 70 Gray (Gy) of intensity modulated radiation therapy (IMRT) in 35 fractions, 2 Gy/fraction, over 7 weeks, and High-dose cisplatin (100 mg/m2) on Day 2 of a 3-week cycle per 3 cycles(combination therapy period).If high-dose cisplatin 100 mg/m2 was not tolerated after the first dose, subjects could be switched to carboplatin (10mg/mL, iv infusion), followed by 3 cycles of monotherapy of placebo matched to Xevinapant from Day 1 to 14, per 3-week cycle (monotherapy period).

    Reporting group title
    Sequence 1: Debio 1143 + CRT
    Reporting group description
    		 Subjects received a combination of Debio 1143 along with Chemoradiotherapy (CRT): Radiotherapy +Cisplatin + Xevinapant (Debio 1143). Subjects received 6 cycles of oral solution of Xevinapant at a dose of 200 milligrams per day (mg/day) once daily from Day 1 to 14, per 3-week cycle in combination with 70 Gray (Gy) of intensity modulated radiation therapy (IMRT) in 35 fractions, 2 Gy/fraction, over 7 weeks, and High-dose cisplatin (100 mg/m2) on Day 2 of a 3-week cycle per 3 cycles (combination therapy period). If high-dose cisplatin 100 mg/m2 was not tolerated after the first dose, subjects could be switched to carboplatin (10mg/mL, iv infusion), followed by 3 cycles of monotherapy of Xevinapant at a dose of 200 mg/day from Day 1 to 14, per 3-week cycle (monotherapy period).

    Serious adverse events
    		 Sequence 2: Placebo + CRT Sequence 1: Debio 1143 + CRT
    Total subjects affected by serious adverse events
         subjects affected / exposed
    129 / 356 (36.24%)
    194 / 364 (53.30%)
         number of deaths (all causes)
    93
    111
         number of deaths resulting from adverse events
    13
    22
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour haemorrhage
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    6 / 356 (1.69%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    3 / 7
    0 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Tumour rupture
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Vascular disorders
    Peripheral vein thrombus extension
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic aneurysm
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic thrombosis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neurogenic shock
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Shock
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Malaise
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    2 / 356 (0.56%)
    8 / 364 (2.20%)
         occurrences causally related to treatment / all
    0 / 2
    6 / 8
         deaths causally related to treatment / all
    0 / 0
    1 / 2
    Fatigue
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disease progression
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    2 / 356 (0.56%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Death
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    2 / 356 (0.56%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    1 / 2
    1 / 2
    Multiple organ dysfunction syndrome
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Asthenia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    2 / 356 (0.56%)
    5 / 364 (1.37%)
         occurrences causally related to treatment / all
    2 / 2
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pyrexia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    2 / 356 (0.56%)
    5 / 364 (1.37%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Prostatitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory distress syndrome
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal oedema
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    3 / 356 (0.84%)
    3 / 364 (0.82%)
         occurrences causally related to treatment / all
    2 / 4
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspiration
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal haemorrhage
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asphyxia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lung disorder
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oropharyngeal pain
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngeal haemorrhage
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngeal inflammation
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pulmonary oedema
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    2 / 356 (0.56%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Respiratory distress
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Stridor
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    2 / 356 (0.56%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    2 / 356 (0.56%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicidal ideation
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device dislocation
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device malfunction
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Amylase increased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    2 / 356 (0.56%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatinine increased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    5 / 356 (1.40%)
    12 / 364 (3.30%)
         occurrences causally related to treatment / all
    5 / 5
    11 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood potassium decreased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrocardiogram QT prolonged
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    4 / 364 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Glomerular filtration rate decreased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lipase increased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    3 / 356 (0.84%)
    4 / 364 (1.10%)
         occurrences causally related to treatment / all
    2 / 3
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight increased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count decreased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Gastrostomy tube site complication
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrostomy failure
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stoma site discharge
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    3 / 364 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Unintentional medical device removal
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Bradycardia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Atrial fibrillation
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular dysfunction
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ischaemic cardiomyopathy
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Cardio-respiratory arrest
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Nervous system disorders
    Bell's palsy
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coma
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diplegia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Guillain-Barre syndrome
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle spasticity
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peroneal nerve palsy
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal cord compression
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vocal cord paralysis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    7 / 356 (1.97%)
    7 / 364 (1.92%)
         occurrences causally related to treatment / all
    7 / 7
    6 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile bone marrow aplasia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Agranulocytosis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    4 / 356 (1.12%)
    8 / 364 (2.20%)
         occurrences causally related to treatment / all
    4 / 4
    8 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphopenia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    3 / 356 (0.84%)
    7 / 364 (1.92%)
         occurrences causally related to treatment / all
    3 / 3
    7 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    3 / 356 (0.84%)
    7 / 364 (1.92%)
         occurrences causally related to treatment / all
    2 / 3
    7 / 7
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Leukopenia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Ototoxicity
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoacusis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Constipation
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Odynophagia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    5 / 364 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    8 / 356 (2.25%)
    5 / 364 (1.37%)
         occurrences causally related to treatment / all
    8 / 9
    4 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mouth haemorrhage
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ischaemia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric perforation
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    9 / 356 (2.53%)
    21 / 364 (5.77%)
         occurrences causally related to treatment / all
    8 / 9
    20 / 21
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    4 / 356 (1.12%)
    6 / 364 (1.65%)
         occurrences causally related to treatment / all
    4 / 5
    5 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Upper gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tongue ulceration
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomatitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    6 / 356 (1.69%)
    15 / 364 (4.12%)
         occurrences causally related to treatment / all
    6 / 6
    15 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumoperitoneum
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic failure
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Skin and subcutaneous tissue disorders
    Dermatitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angioedema
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermatitis acneiform
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermatitis exfoliative generalised
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erythema multiforme
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash macular
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash maculo-papular
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    3 / 364 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin exfoliation
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin ulcer
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    19 / 356 (5.34%)
    25 / 364 (6.87%)
         occurrences causally related to treatment / all
    19 / 20
    24 / 31
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal injury
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephropathy toxic
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prerenal failure
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    6 / 356 (1.69%)
    10 / 364 (2.75%)
         occurrences causally related to treatment / all
    5 / 7
    8 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic kidney disease
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcapsular renal haematoma
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    2 / 356 (0.56%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Central hypothyroidism
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adrenal insufficiency
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in jaw
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Device related infection
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis perforated
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis bacterial
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    3 / 356 (0.84%)
    4 / 364 (1.10%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess jaw
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oral infection
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    2 / 356 (0.56%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epiglottic abscess
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocarditis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parotitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia necrotising
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia legionella
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia escherichia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia bacterial
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    4 / 356 (1.12%)
    8 / 364 (2.20%)
         occurrences causally related to treatment / all
    2 / 4
    4 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    14 / 356 (3.93%)
    23 / 364 (6.32%)
         occurrences causally related to treatment / all
    7 / 14
    11 / 24
         deaths causally related to treatment / all
    0 / 1
    3 / 6
    Peritonitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary sepsis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    3 / 364 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    3 / 356 (0.84%)
    8 / 364 (2.20%)
         occurrences causally related to treatment / all
    1 / 3
    5 / 8
         deaths causally related to treatment / all
    1 / 2
    1 / 2
    Stoma site infection
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    5 / 364 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular device infection
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    2 / 356 (0.56%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tracheitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    5 / 364 (1.37%)
         occurrences causally related to treatment / all
    1 / 1
    4 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    3 / 356 (0.84%)
    7 / 364 (1.92%)
         occurrences causally related to treatment / all
    2 / 3
    5 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrolyte imbalance
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemic hyperosmolar nonketotic syndrome
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    4 / 356 (1.12%)
    7 / 364 (1.92%)
         occurrences causally related to treatment / all
    3 / 5
    6 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypomagnesaemia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    3 / 356 (0.84%)
    7 / 364 (1.92%)
         occurrences causally related to treatment / all
    2 / 4
    3 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypophagia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 356 (0.28%)
    0 / 364 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    2 / 356 (0.56%)
    2 / 364 (0.55%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypernatraemia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 356 (0.00%)
    1 / 364 (0.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Sequence 2: Placebo + CRT Sequence 1: Debio 1143 + CRT
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    350 / 356 (98.31%)
    360 / 364 (98.90%)
    Vascular disorders
    Hypertension
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    20 / 356 (5.62%)
    14 / 364 (3.85%)
         occurrences all number
    26
    15
    General disorders and administration site conditions
    Pyrexia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    35 / 356 (9.83%)
    58 / 364 (15.93%)
         occurrences all number
    42
    72
    Asthenia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    68 / 356 (19.10%)
    98 / 364 (26.92%)
         occurrences all number
    88
    108
    Fatigue
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    66 / 356 (18.54%)
    58 / 364 (15.93%)
         occurrences all number
    75
    71
    Respiratory, thoracic and mediastinal disorders
    Dysphonia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    42 / 356 (11.80%)
    36 / 364 (9.89%)
         occurrences all number
    45
    38
    Cough
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    45 / 356 (12.64%)
    36 / 364 (9.89%)
         occurrences all number
    48
    38
    Dyspnoea
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    18 / 356 (5.06%)
    19 / 364 (5.22%)
         occurrences all number
    20
    22
    Hiccups
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    28 / 356 (7.87%)
    21 / 364 (5.77%)
         occurrences all number
    33
    24
    Oropharyngeal pain
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    62 / 356 (17.42%)
    56 / 364 (15.38%)
         occurrences all number
    65
    60
    Pharyngeal inflammation
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    13 / 356 (3.65%)
    21 / 364 (5.77%)
         occurrences all number
    13
    23
    Productive cough
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    23 / 356 (6.46%)
    23 / 364 (6.32%)
         occurrences all number
    23
    23
    Psychiatric disorders
    Insomnia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    26 / 356 (7.30%)
    37 / 364 (10.16%)
         occurrences all number
    27
    37
    Investigations
    Amylase increased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    44 / 356 (12.36%)
    84 / 364 (23.08%)
         occurrences all number
    50
    110
    Alanine aminotransferase increased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    40 / 356 (11.24%)
    78 / 364 (21.43%)
         occurrences all number
    54
    115
    C-reactive protein increased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    17 / 356 (4.78%)
    24 / 364 (6.59%)
         occurrences all number
    21
    26
    Blood urea increased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    17 / 356 (4.78%)
    20 / 364 (5.49%)
         occurrences all number
    28
    27
    Blood creatinine increased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    81 / 356 (22.75%)
    87 / 364 (23.90%)
         occurrences all number
    106
    119
    Aspartate aminotransferase increased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    30 / 356 (8.43%)
    47 / 364 (12.91%)
         occurrences all number
    43
    56
    Electrocardiogram QT prolonged
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    14 / 356 (3.93%)
    26 / 364 (7.14%)
         occurrences all number
    14
    29
    White blood cell count decreased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    65 / 356 (18.26%)
    63 / 364 (17.31%)
         occurrences all number
    127
    113
    Weight decreased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    157 / 356 (44.10%)
    187 / 364 (51.37%)
         occurrences all number
    171
    201
    Platelet count decreased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    46 / 356 (12.92%)
    57 / 364 (15.66%)
         occurrences all number
    71
    82
    Neutrophil count decreased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    76 / 356 (21.35%)
    78 / 364 (21.43%)
         occurrences all number
    122
    118
    Lymphocyte count decreased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    30 / 356 (8.43%)
    45 / 364 (12.36%)
         occurrences all number
    39
    63
    Lipase increased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    23 / 356 (6.46%)
    56 / 364 (15.38%)
         occurrences all number
    32
    76
    Gamma-glutamyltransferase increased
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    19 / 356 (5.34%)
    23 / 364 (6.32%)
         occurrences all number
    22
    26
    Injury, poisoning and procedural complications
    Radiation skin injury
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    160 / 356 (44.94%)
    165 / 364 (45.33%)
         occurrences all number
    166
    175
    Radiation mucositis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    23 / 356 (6.46%)
    20 / 364 (5.49%)
         occurrences all number
    23
    20
    Nervous system disorders
    Headache
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    22 / 356 (6.18%)
    23 / 364 (6.32%)
         occurrences all number
    24
    24
    Dysgeusia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    111 / 356 (31.18%)
    106 / 364 (29.12%)
         occurrences all number
    117
    109
    Dizziness
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    18 / 356 (5.06%)
    20 / 364 (5.49%)
         occurrences all number
    19
    22
    Blood and lymphatic system disorders
    Neutropenia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    100 / 356 (28.09%)
    110 / 364 (30.22%)
         occurrences all number
    136
    141
    Lymphopenia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    42 / 356 (11.80%)
    39 / 364 (10.71%)
         occurrences all number
    46
    48
    Thrombocytopenia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    45 / 356 (12.64%)
    63 / 364 (17.31%)
         occurrences all number
    61
    79
    Anaemia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    180 / 356 (50.56%)
    199 / 364 (54.67%)
         occurrences all number
    212
    244
    Leukopenia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    44 / 356 (12.36%)
    57 / 364 (15.66%)
         occurrences all number
    69
    79
    Ear and labyrinth disorders
    Tinnitus
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    65 / 356 (18.26%)
    59 / 364 (16.21%)
         occurrences all number
    70
    67
    Hypoacusis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    30 / 356 (8.43%)
    21 / 364 (5.77%)
         occurrences all number
    33
    21
    Deafness
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    18 / 356 (5.06%)
    19 / 364 (5.22%)
         occurrences all number
    18
    19
    Gastrointestinal disorders
    Odynophagia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    77 / 356 (21.63%)
    66 / 364 (18.13%)
         occurrences all number
    84
    69
    Nausea
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    162 / 356 (45.51%)
    144 / 364 (39.56%)
         occurrences all number
    238
    188
    Dysphagia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    97 / 356 (27.25%)
    138 / 364 (37.91%)
         occurrences all number
    103
    154
    Dry mouth
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    124 / 356 (34.83%)
    138 / 364 (37.91%)
         occurrences all number
    131
    143
    Diarrhoea
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    46 / 356 (12.92%)
    40 / 364 (10.99%)
         occurrences all number
    51
    44
    Constipation
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    125 / 356 (35.11%)
    126 / 364 (34.62%)
         occurrences all number
    146
    144
    Vomiting
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    84 / 356 (23.60%)
    66 / 364 (18.13%)
         occurrences all number
    112
    85
    Stomatitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    160 / 356 (44.94%)
    193 / 364 (53.02%)
         occurrences all number
    173
    224
    Salivary hypersecretion
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    12 / 356 (3.37%)
    20 / 364 (5.49%)
         occurrences all number
    13
    20
    Skin and subcutaneous tissue disorders
    Rash
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    13 / 356 (3.65%)
    40 / 364 (10.99%)
         occurrences all number
    15
    49
    Dermatitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    54 / 356 (15.17%)
    57 / 364 (15.66%)
         occurrences all number
    58
    60
    Musculoskeletal and connective tissue disorders
    Neck pain
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    21 / 356 (5.90%)
    20 / 364 (5.49%)
         occurrences all number
    21
    23
    Infections and infestations
    Oral candidiasis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    20 / 356 (5.62%)
    18 / 364 (4.95%)
         occurrences all number
    26
    19
    COVID-19
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    22 / 356 (6.18%)
    27 / 364 (7.42%)
         occurrences all number
    22
    27
    Metabolism and nutrition disorders
    Decreased appetite
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    97 / 356 (27.25%)
    65 / 364 (17.86%)
         occurrences all number
    115
    76
    Dehydration
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    17 / 356 (4.78%)
    19 / 364 (5.22%)
         occurrences all number
    22
    20
    Hyperkalaemia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    17 / 356 (4.78%)
    25 / 364 (6.87%)
         occurrences all number
    21
    34
    Hypoalbuminaemia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    22 / 356 (6.18%)
    31 / 364 (8.52%)
         occurrences all number
    30
    40
    Hypocalcaemia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    12 / 356 (3.37%)
    26 / 364 (7.14%)
         occurrences all number
    14
    36
    Hypokalaemia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    63 / 356 (17.70%)
    71 / 364 (19.51%)
         occurrences all number
    83
    103
    Hypomagnesaemia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    43 / 356 (12.08%)
    54 / 364 (14.84%)
         occurrences all number
    52
    64
    Hyponatraemia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    42 / 356 (11.80%)
    64 / 364 (17.58%)
         occurrences all number
    49
    97

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 May 2020
    The protocol for study Debio 1143-SCCHN-301 was amended to correct a typo in the gender specific QTcF values mentioned in the exclusion criterion.
    02 Jul 2020
    The protocol for study Debio 1143-SCCHN-301 was amended to 1. To add a recommendation on cryoconservation of sperm prior to treatment because of the possibility of infertility due to therapy with cisplatin, carboplatin or Debio 1143. 2. The addition of an ECG examination 3. The addition in the prohibited medication list of live-attenuated vaccinations 4. Two modifications in the management of grade 4 anemia and grade 3/4 thrombocytopenia potentially related to study treatment 5. A clarification of the assumptions used for the sample size calculation 6. A clarification of dynamic allocation 7. Correction regarding laboratory assessments.
    06 Dec 2020
    The following modifications were made to the protocol: • Exclusion of patients with hypersensitivity to the active substances or other compounds containing platinum. • Additional information on the management and dose modification of the Investigational Medicinal Products in case of hemolytic uremic syndrome. • Additional information on the management and dose modification of the Investigational Medicinal Products in case of allergic reactions. • Addition of an optional audiogram before each new cycle of cisplatin throughout the study, as required per the cisplatin prescribing information. • Additional information on the prohibited medications and medications to be used with caution in combination with cisplatin and carboplatin, following the prescribing information of these products. These modifications are considered substantial because an exclusion criterion and some clinical follow-up instructions have been modified.
    28 Jun 2021
    The protocol for study Debio 1143-SCCHN-301 version 7.0 dated 28 June 2021 was amended to reflect the following changes: 1. Modification of inclusion criterion number 2. Granulocyte-Colony Stimulating Factors (G-CSF) use 3. Abnormal QTcF prolongation and ECG changes
    08 Nov 2021
    Version 8.0 dated 08 November 2021 has been amended to include a modified hierarchical testing procedure of secondary endpoints and to update EOS definition taking into account an event driven OS analysis. In addition, clear guidance on close monitoring of renal function was added by including additional local laboratory assessment timepoints.
    31 Jan 2022
    Version 8 .0 dated 8 November 2021 was amended (for China only ) to include an additional, China-specific extension cohort to increase the sample size of the overall Chinese population analysis to approximately 15 % (106 subjects ) of the global ITT population in order to adequately represent the Chinese population. Statistical evaluations of the global ITT population will remain unchanged; a separate analysis of the overall Chinese population included in the study will be performed as described in this amendment.

    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
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