Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 1b/2, Open-Label, Multi-Center, Dose Escalation Study of Binimetinib In Combination with Panitumumab in Adult Patients with Mutant RAS or Wild-Type RAS Metastatic Colorectal Cancer

    Summary
    EudraCT number
    		 2013-001986-18
    Trial protocol
    		 ES   BE   IT   NL   DE   FR  
    Global end of trial date
    25 Jan 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    25 Nov 2017
    First version publication date
    25 Nov 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CMEK162X2116
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Array BioPharma Inc.
    Sponsor organisation address
    3200 Walnut Street, Boulder, United States, 80301 Colorado
    Public contact
    Victor Sandor, MD Chief Medical Officer , Array BioPharma Inc., +34 900353036, info@arraybiopharma.com
    Scientific contact
    Victor Sandor, MD Chief Medical Officer, Array BioPharma Inc., +34 900353036, info@arraybiopharma.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
    11 Aug 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    25 Jan 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Jan 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Phase Ib: To estimate the MTD and/or RP2D of MEK162 in combination with panitumumab Phase II: To assess clinical efficacy of the MEK162 and panitumumab combination
    Protection of trial subjects
    In both study phases, doses of study drug were adjusted or interrupted as appropriate based on protocol-defined treatment modifications. If an infusion reaction occurred while panitumumab was being administered, the infusion was stopped immediately, and the patient was closely monitored and treated according to institutional standards.
    Background therapy
    		 Patients who took concomitant medication chronically were advised to maintain the same dose and dose schedule throughout the study period, as medically feasible
    Evidence for comparator
    		 -
    Actual start date of recruitment
    19 Nov 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 10
    Country: Number of subjects enrolled
    Spain: 7
    Country: Number of subjects enrolled
    Belgium: 3
    Country: Number of subjects enrolled
    France: 2
    Country: Number of subjects enrolled
    Italy: 7
    Country: Number of subjects enrolled
    Canada: 8
    Country: Number of subjects enrolled
    United States: 16
    Worldwide total number of subjects
    53
    EEA total number of subjects
    29
    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)
    40
    From 65 to 84 years
    13
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This study was conducted at a total of 8 sites: 2 sites in the United States, and 1 site each in Belgium, Canada, France, Italy, The Netherlands, and Spain. The patient population consisted of adult patients with mutant RAS or WT RAS mCRC. A total of 10 patients were enrolled in Phase 1b and 43 patients were enrolled in Phase 2.

    Pre-assignment
    Screening details
    		 Four patients were screened but not enrolled in Phase 1b and 35 patients were screened but not enrolled in Phase 2. Patients were male or female, at least 18 years of age with a histological or cytological confirmation of mCRC, with evidence of measurable disease as determined by RECIST v1.1.

    Period 1
    Period 1 title
    Dose-escalation Phase (Phase 1b)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    Not applicable, this clinical trial was open-label.

    Arms
    Arm title
    		 Binimetinib (MEK162) plus Panitumumab
    Arm description
    		 Phase 1b was conducted in 10 adult patients with mutant RAS or WT RAS mCRC who had progressed while on standard therapy or following standard therapy, or for whom there was no standard therapy available. During the Phase 1b, the starting dose for the study drug combination was 45 mg twice daily (BID) for binimetinib and 6 mg/kg once every second week (Q2W) of panitumumab based on available data from Array’s first-in-human study [ARRAY-162-111] and the recommended panitumumab dose for mCRC in combination with other anticancer agents according to the panitumumab label, respectively.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Binimetinib
    Investigational medicinal product code
    MEK162
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The tablets were yellow to dark yellow and supplied in dosage strengths of 15 mg. Binimetinib tablets were to be taken orally BID, 12 ± 2 hours apart at approximately the same time each day, 2 hours before and 1 hour after food intake.

    Investigational medicinal product name
    Panitumumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Panitumumab was dosed based on patient body weight and the starting dose selected for Panitumumab was 6 mg/kg Q2W. Each dose of panitumumab dose was administered intravenously at the study site Q2W on Days 1 and 15 of every 28-day cycle according to institutional standards. The panitumumab dose was calculated based on the patient’s actual body weight at baseline and was recalculated for subsequent doses per institutional guidelines.

    Number of subjects in period 1
    		Binimetinib (MEK162) plus Panitumumab
    Started
    10
    Completed
    53
    Joined
    43
         Late recruitment
         Late recruitment reason:
    43
             based on Mutant / WT RAS and anti-EGFRi/- Naive
    Period 2
    Period 2 title
    Efficacy Phase (Phase 2)
    Is this the baseline period?
    		 Yes [1]
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    Not applicable, this study was open-label.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Binimetinib (MEK162) plus Panitumumab Mutant RAS EGFRi-Naïve
    Arm description
    		 Phase 1b was conducted in 10 adult patients with mutant RAS or WT RAS mCRC who had progressed while on standard therapy or following standard therapy, or for whom there was no standard therapy available. During the Phase 1b, the starting dose for the study drug combination was 45 mg twice daily (BID) for binimetinib and 6 mg/kg once every second week (Q2W) of panitumumab based on available data from Array’s first-in-human study [ARRAY-162-111] and the recommended panitumumab dose for mCRC in combination with other anticancer agents according to the panitumumab label, respectively.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Binimetinib
    Investigational medicinal product code
    MEK162
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The tablets were yellow to dark yellow and supplied in dosage strengths of 15 mg. Binimetinib tablets were to be taken orally BID, 12 ± 2 hours apart at approximately the same time each day, 2 hours before and 1 hour after food intake.

    Investigational medicinal product name
    Panitumumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Panitumumab was dosed based on patient body weight and the starting dose selected for panitumumab was 6 mg/kg Q2W. Each dose of panitumumab dose was administered intravenously at the study site Q2W on Days 1 and 15 of every 28-day cycle according to institutional standards. The panitumumab dose was calculated based on the patient’s actual body weight at baseline and was recalculated for subsequent doses per institutional guidelines.

    Arm title
    		 Binimetinib (MEK162) plus Panitumumab WT RAS Anti-EGFRi
    Arm description
    		 Phase 1b was conducted in 10 adult patients with mutant RAS or WT RAS mCRC who had progressed while on standard therapy or following standard therapy, or for whom there was no standard therapy available. During the Phase 1b, the starting dose for the study drug combination was 45 mg twice daily (BID) for binimetinib and 6 mg/kg once every second week (Q2W) of panitumumab based on available data from Array’s first-in-human study [ARRAY-162-111] and the recommended panitumumab dose for mCRC in combination with other anticancer agents according to the panitumumab label, respectively.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Binimetinib
    Investigational medicinal product code
    MEK162
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The tablets were yellow to dark yellow and supplied in dosage strengths of 15 mg. Binimetinib tablets were to be taken orally BID, 12 ± 2 hours apart at approximately the same time each day, 2 hours before and 1 hour after food intake.

    Investigational medicinal product name
    Panitumumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Panitumumab was dosed based on patient body weight and the starting dose selected for panitumumab was 6 mg/kg Q2W. Each dose of panitumumab dose was administered intravenously at the study site Q2W on Days 1 and 15 of every 28-day cycle according to institutional standards. The panitumumab dose was calculated based on the patient’s actual body weight at baseline and was recalculated for subsequent doses per institutional guidelines.

    Arm title
    		 Binimetinib (MEK162) plus Panitumumab WT RAS EGFRi-Naïve
    Arm description
    		 Phase 1b was conducted in 10 adult patients with mutant RAS or WT RAS mCRC who had progressed while on standard therapy or following standard therapy, or for whom there was no standard therapy available. During the Phase 1b, the starting dose for the study drug combination was 45 mg twice daily (BID) for binimetinib and 6 mg/kg once every second week (Q2W) of panitumumab based on available data from Array’s first-in-human study [ARRAY-162-111] and the recommended panitumumab dose for mCRC in combination with other anticancer agents according to the panitumumab label, respectively.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Binimetinib
    Investigational medicinal product code
    MEK162
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The tablets were yellow to dark yellow and supplied in dosage strengths of 15 mg. Binimetinib tablets were to be taken orally BID, 12 ± 2 hours apart at approximately the same time each day, 2 hours before and 1 hour after food intake.

    Investigational medicinal product name
    Panitumumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Panitumumab was dosed based on patient body weight and the starting dose selected for panitumumab was 6 mg/kg Q2W. Each dose of panitumumab dose was administered intravenously at the study site Q2W on Days 1 and 15 of every 28-day cycle according to institutional standards. The panitumumab dose was calculated based on the patient’s actual body weight at baseline and was recalculated for subsequent doses per institutional guidelines.

    Arm title
    		 Binimetinib (MEK162) plus Panitumumab WT RAS EGFRi-Naïve
    Arm description
    		 Phase 1b was conducted in 10 adult patients with mutant RAS or WT RAS mCRC who had progressed while on standard therapy or following standard therapy, or for whom there was no standard therapy available. During the Phase 1b, the starting dose for the study drug combination was 45 mg twice daily (BID) for binimetinib and 6 mg/kg once every second week (Q2W) of panitumumab based on available data from Array’s first-in-human study [ARRAY-162-111] and the recommended panitumumab dose for mCRC in combination with other anticancer agents according to the panitumumab label, respectively.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Binimetinib
    Investigational medicinal product code
    MEK162
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The tablets were yellow to dark yellow and supplied in dosage strengths of 15 mg. Binimetinib tablets were to be taken orally BID, 12 ± 2 hours apart at approximately the same time each day, 2 hours before and 1 hour after food intake.

    Investigational medicinal product name
    Panitumumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Panitumumab was dosed based on patient body weight and the starting dose selected for panitumumab was 6 mg/kg Q2W. Each dose of panitumumab dose was administered intravenously at the study site Q2W on Days 1 and 15 of every 28-day cycle according to institutional standards. The panitumumab dose was calculated based on the patient’s actual body weight at baseline and was recalculated for subsequent doses per institutional guidelines.

    Notes
    [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
    Justification: Period 1 is dose escalation part only (10 patients enrolled) to estimate the maximum tolerated dose (MTD) and/or RP2D of binimetinib in combination with panitumumab. Phase 2 began after the declaration of the MTD/RP2D. For this phase of the study, additional patients were enrolled, based on previous anti-EGFR monoclonal antibody therapy and RAS mutational status, into 1 of 4 different Phase 2 patient groups.
    Number of subjects in period 2 [2] [3]
    		Binimetinib (MEK162) plus Panitumumab Mutant RAS EGFRi-Naïve Binimetinib (MEK162) plus Panitumumab WT RAS Anti-EGFRi Binimetinib (MEK162) plus Panitumumab WT RAS EGFRi-Naïve Binimetinib (MEK162) plus Panitumumab WT RAS EGFRi-Naïve
    Started
    15
    5
    15
    8
    Completed
    15
    5
    15
    8
    Notes
    [2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: This study was a multi-center, open-label, dose-finding escalation study comprising 2 parts: Phase 1b was the dose escalation part, and it was followed by a Phase 2 clinical efficacy evaluation. In the first part 10 patients have been enrolled and subsequently 43 patients in the second part have been enrolled to a total of 53 patients globally included.
    [3] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: This study was a multi-center, open-label, dose-finding escalation study comprising 2 parts: Phase 1b was the dose escalation part, and it was followed by a Phase 2 clinical efficacy evaluation. In the first part 10 patients have been enrolled and subsequently 43 patients in the second part have been enrolled to a total of 53 patients globally included.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Binimetinib (MEK162) plus Panitumumab Mutant RAS EGFRi-Naïve
    Reporting group description
    		 Phase 1b was conducted in 10 adult patients with mutant RAS or WT RAS mCRC who had progressed while on standard therapy or following standard therapy, or for whom there was no standard therapy available. During the Phase 1b, the starting dose for the study drug combination was 45 mg twice daily (BID) for binimetinib and 6 mg/kg once every second week (Q2W) of panitumumab based on available data from Array’s first-in-human study [ARRAY-162-111] and the recommended panitumumab dose for mCRC in combination with other anticancer agents according to the panitumumab label, respectively.

    Reporting group title
    Binimetinib (MEK162) plus Panitumumab WT RAS Anti-EGFRi
    Reporting group description
    		 Phase 1b was conducted in 10 adult patients with mutant RAS or WT RAS mCRC who had progressed while on standard therapy or following standard therapy, or for whom there was no standard therapy available. During the Phase 1b, the starting dose for the study drug combination was 45 mg twice daily (BID) for binimetinib and 6 mg/kg once every second week (Q2W) of panitumumab based on available data from Array’s first-in-human study [ARRAY-162-111] and the recommended panitumumab dose for mCRC in combination with other anticancer agents according to the panitumumab label, respectively.

    Reporting group title
    Binimetinib (MEK162) plus Panitumumab WT RAS EGFRi-Naïve
    Reporting group description
    		 Phase 1b was conducted in 10 adult patients with mutant RAS or WT RAS mCRC who had progressed while on standard therapy or following standard therapy, or for whom there was no standard therapy available. During the Phase 1b, the starting dose for the study drug combination was 45 mg twice daily (BID) for binimetinib and 6 mg/kg once every second week (Q2W) of panitumumab based on available data from Array’s first-in-human study [ARRAY-162-111] and the recommended panitumumab dose for mCRC in combination with other anticancer agents according to the panitumumab label, respectively.

    Reporting group title
    Binimetinib (MEK162) plus Panitumumab WT RAS EGFRi-Naïve
    Reporting group description
    		 Phase 1b was conducted in 10 adult patients with mutant RAS or WT RAS mCRC who had progressed while on standard therapy or following standard therapy, or for whom there was no standard therapy available. During the Phase 1b, the starting dose for the study drug combination was 45 mg twice daily (BID) for binimetinib and 6 mg/kg once every second week (Q2W) of panitumumab based on available data from Array’s first-in-human study [ARRAY-162-111] and the recommended panitumumab dose for mCRC in combination with other anticancer agents according to the panitumumab label, respectively.

    Reporting group values
    		 Binimetinib (MEK162) plus Panitumumab Mutant RAS EGFRi-Naïve Binimetinib (MEK162) plus Panitumumab WT RAS Anti-EGFRi Binimetinib (MEK162) plus Panitumumab WT RAS EGFRi-Naïve Binimetinib (MEK162) plus Panitumumab WT RAS EGFRi-Naïve Total
    Number of subjects
    		 15 5 15 8 43
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 13 3 10 6 32
        From 65-84 years
    		 2 2 5 2 11
    Age continuous
    Units: years
        median (full range (min-max))
    		 56 (36 to 71) 55 (49 to 75) 58 (30 to 79) 55 (30 to 79) -
    Gender categorical
    Units: Subjects
        Female
    		 9 4 9 5 27
        Male
    		 6 1 6 3 16
    Subject analysis sets

    Subject analysis set title
    Full analysis set (FAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All 53 patients were included in the full analysis set (FAS). The FAS included all patients who received at least 1 full or partial dose of binimetinib or panitumumab.

    Subject analysis sets values
    		 Full analysis set (FAS)
    Number of subjects
    53
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    40
        From 65-84 years
    13
    Age continuous
    Units: years
        median (full range (min-max))
    55 (30 to 79)
    Gender categorical
    Units: Subjects
        Female
    31
        Male
    22

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Binimetinib (MEK162) plus Panitumumab
    Reporting group description
    		 Phase 1b was conducted in 10 adult patients with mutant RAS or WT RAS mCRC who had progressed while on standard therapy or following standard therapy, or for whom there was no standard therapy available. During the Phase 1b, the starting dose for the study drug combination was 45 mg twice daily (BID) for binimetinib and 6 mg/kg once every second week (Q2W) of panitumumab based on available data from Array’s first-in-human study [ARRAY-162-111] and the recommended panitumumab dose for mCRC in combination with other anticancer agents according to the panitumumab label, respectively.
    Reporting group title
    Binimetinib (MEK162) plus Panitumumab Mutant RAS EGFRi-Naïve
    Reporting group description
    		 Phase 1b was conducted in 10 adult patients with mutant RAS or WT RAS mCRC who had progressed while on standard therapy or following standard therapy, or for whom there was no standard therapy available. During the Phase 1b, the starting dose for the study drug combination was 45 mg twice daily (BID) for binimetinib and 6 mg/kg once every second week (Q2W) of panitumumab based on available data from Array’s first-in-human study [ARRAY-162-111] and the recommended panitumumab dose for mCRC in combination with other anticancer agents according to the panitumumab label, respectively.

    Reporting group title
    Binimetinib (MEK162) plus Panitumumab WT RAS Anti-EGFRi
    Reporting group description
    		 Phase 1b was conducted in 10 adult patients with mutant RAS or WT RAS mCRC who had progressed while on standard therapy or following standard therapy, or for whom there was no standard therapy available. During the Phase 1b, the starting dose for the study drug combination was 45 mg twice daily (BID) for binimetinib and 6 mg/kg once every second week (Q2W) of panitumumab based on available data from Array’s first-in-human study [ARRAY-162-111] and the recommended panitumumab dose for mCRC in combination with other anticancer agents according to the panitumumab label, respectively.

    Reporting group title
    Binimetinib (MEK162) plus Panitumumab WT RAS EGFRi-Naïve
    Reporting group description
    		 Phase 1b was conducted in 10 adult patients with mutant RAS or WT RAS mCRC who had progressed while on standard therapy or following standard therapy, or for whom there was no standard therapy available. During the Phase 1b, the starting dose for the study drug combination was 45 mg twice daily (BID) for binimetinib and 6 mg/kg once every second week (Q2W) of panitumumab based on available data from Array’s first-in-human study [ARRAY-162-111] and the recommended panitumumab dose for mCRC in combination with other anticancer agents according to the panitumumab label, respectively.

    Reporting group title
    Binimetinib (MEK162) plus Panitumumab WT RAS EGFRi-Naïve
    Reporting group description
    		 Phase 1b was conducted in 10 adult patients with mutant RAS or WT RAS mCRC who had progressed while on standard therapy or following standard therapy, or for whom there was no standard therapy available. During the Phase 1b, the starting dose for the study drug combination was 45 mg twice daily (BID) for binimetinib and 6 mg/kg once every second week (Q2W) of panitumumab based on available data from Array’s first-in-human study [ARRAY-162-111] and the recommended panitumumab dose for mCRC in combination with other anticancer agents according to the panitumumab label, respectively.

    Subject analysis set title
    Full analysis set (FAS)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All 53 patients were included in the full analysis set (FAS). The FAS included all patients who received at least 1 full or partial dose of binimetinib or panitumumab.

    Primary: Overall Response Rate (ORR) as per RECIST version 1.1

    		 Close Top of page
    End point title
    		 Overall Response Rate (ORR) as per RECIST version 1.1
    End point description
    Overall response rate is the sum of patients with complete response and partial response. The best overall response (BOR) was recorded from the start of the treatment until disease progression.
    End point type
    Primary
    End point timeframe
    All patients considered for enrollment in Phase 2. Patients continued treatment with the combination therapy of binimetinib and panitumumab until progression of disease, development of unacceptable toxicity.
    End point values
    		 Binimetinib (MEK162) plus Panitumumab Mutant RAS EGFRi-Naïve Binimetinib (MEK162) plus Panitumumab WT RAS Anti-EGFRi Binimetinib (MEK162) plus Panitumumab WT RAS EGFRi-Naïve Binimetinib (MEK162) plus Panitumumab WT RAS EGFRi-Naïve Full analysis set (FAS)
    Number of subjects analysed
    15
    5
    15
    8
    53
    Units: number of patiens
        complete response (confirmed)
    0
    0
    0
    0
    0
        partial response (confirmed)
    0
    0
    1
    0
    1
    Statistical analysis title
    		 Statistical Analysis version 9.2
    Statistical analysis description
    The clinical study data were analyzed by Array BioPharma Inc. and/or a designated contract research organization. For Bayesian modeling, programs were compiled using R (version 2.13.2) and WinBUGS (version 1.4.3) available in the production environment from MODESIM.
    Comparison groups
    Binimetinib (MEK162) plus Panitumumab WT RAS Anti-EGFRi v Binimetinib (MEK162) plus Panitumumab WT RAS EGFRi-Naïve v Binimetinib (MEK162) plus Panitumumab WT RAS EGFRi-Naïve v Binimetinib (MEK162) plus Panitumumab Mutant RAS EGFRi-Naïve
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    2.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.1
         upper limit
    		 12.3
    Variability estimate
    Standard deviation
    Notes
    [1] - Clopper-Pearson method

    Primary: Incidence of dose-limiting toxicities (DLTs) in Cycle 1

    		 Close Top of page
    End point title
    		 Incidence of dose-limiting toxicities (DLTs) in Cycle 1 [2]
    End point description
    At least 21 out of the 28 planned daily doses of binimetinib [BID] and both doses of panitumumab [Q2W] in the first 28 days of dosing. A DLT was defined as an AE or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first 28 days of treatment with binimetinib and panitumumab and met the specified criteria for the type of toxicity.
    End point type
    Primary
    End point timeframe
    Patients had been observed for ≥ 28 days following the first dose.
    Notes
    [2] - 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: An adaptive Bayesian logistic regression model (BLRM) guided by the escalation with overdose control principle was used to guide the dose escalation of the combination treatment to its maximum tolerated dose/recommended Phase 2 dose.
    End point values
    		 Full analysis set (FAS)
    Number of subjects analysed
    53
    Units: number of patients with DLT
        Dose Limiting Toxicity (all)
    5
        DLTs leading to discontinuation
    1
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Overall Survival (OS)
    End point description
    Kaplan-Meier Estimates of Overall Survival Rate – % [95% CI]. Analysis of OS was performed if at least 50% of the patients died.
    End point type
    Secondary
    End point timeframe
    Overall survival is defined as the time from the start of treatment to the date of death due to any cause. If it was not known whether a patient had died, survival was censored at the date of last contact.
    End point values
    		 Binimetinib (MEK162) plus Panitumumab Mutant RAS EGFRi-Naïve Binimetinib (MEK162) plus Panitumumab WT RAS Anti-EGFRi Binimetinib (MEK162) plus Panitumumab WT RAS EGFRi-Naïve Binimetinib (MEK162) plus Panitumumab WT RAS EGFRi-Naïve Full analysis set (FAS)
    Number of subjects analysed
    15
    5
    15
    8
    53
    Units: months
    median (confidence interval 95%)
        50th Percentile Events
    3.5 (2.1 to 8)
    5.5 (3.9 to 9.6)
    5.8 (3.1 to 8)
    11.2 (2.1 to 13.3)
    5.5 (3.9 to 8)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Information related to AEs (including concomitant medication taken for ongoing AEs) and ongoing antineoplastic treatments was to be collected for 30 days after the last dose of study treatment.
    Adverse event reporting additional description
    Progression of malignancy (including fatal outcomes), if documented by use of appropriate method (RECIST version 1.1 criteria), were not to be reported as a SAE. Adverse events separate from the progression of malignancy were reported as per the usual guidelines used for such events.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    All Phase 2 Patients
    Reporting group description
    		 All Phase 2 Patients (N=43) inlcuded

    Reporting group title
    Phase 1b
    Reporting group description
    		 Phase 1b (N=10) patients

    Reporting group title
    All Patients (Phase 1b and Phase 2)
    Reporting group description
    		 All Patients (N=53) included in both Phase 1b and 2 phases

    Serious adverse events
    		 All Phase 2 Patients Phase 1b All Patients (Phase 1b and Phase 2)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    22 / 43 (51.16%)
    3 / 10 (30.00%)
    25 / 53 (47.17%)
         number of deaths (all causes)
    5
    2
    7
         number of deaths resulting from adverse events
    0
    0
    0
    Investigations
    Blood CPK increased
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypovolaemic shock
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Hypoxia
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Sinus tachycardia
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Troponin T increased
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Transient ischaemic attack
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Abdominal distension
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Septic shock
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    4 / 43 (9.30%)
    0 / 10 (0.00%)
    4 / 53 (7.55%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    2 / 43 (4.65%)
    1 / 10 (10.00%)
    3 / 53 (5.66%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    2 / 43 (4.65%)
    1 / 10 (10.00%)
    3 / 53 (5.66%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 10 (10.00%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 10 (10.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumonia
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 10 (10.00%)
    2 / 53 (3.77%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumomediastinum
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 10 (10.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 10 (10.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash maculo-papular
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 10 (10.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 10 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 All Phase 2 Patients Phase 1b All Patients (Phase 1b and Phase 2)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    43 / 43 (100.00%)
    10 / 10 (100.00%)
    53 / 53 (100.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 43 (6.98%)
    2 / 10 (20.00%)
    5 / 53 (9.43%)
         occurrences all number
    3
    2
    5
    Hypotension
         subjects affected / exposed
    2 / 43 (4.65%)
    1 / 10 (10.00%)
    3 / 53 (5.66%)
         occurrences all number
    2
    1
    3
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    16 / 43 (37.21%)
    9 / 10 (90.00%)
    25 / 53 (47.17%)
         occurrences all number
    16
    9
    25
    Chills
         subjects affected / exposed
    7 / 43 (16.28%)
    3 / 10 (30.00%)
    10 / 53 (18.87%)
         occurrences all number
    7
    3
    10
    Oedema Peripheral
         subjects affected / exposed
    8 / 43 (18.60%)
    2 / 10 (20.00%)
    10 / 53 (18.87%)
         occurrences all number
    8
    2
    10
    Pyrexia
         subjects affected / exposed
    8 / 43 (18.60%)
    2 / 10 (20.00%)
    10 / 53 (18.87%)
         occurrences all number
    8
    2
    10
    Asthenia
         subjects affected / exposed
    8 / 43 (18.60%)
    0 / 10 (0.00%)
    8 / 53 (15.09%)
         occurrences all number
    8
    0
    8
    Feeling Cold
         subjects affected / exposed
    0 / 43 (0.00%)
    3 / 10 (30.00%)
    3 / 53 (5.66%)
         occurrences all number
    0
    3
    3
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    3 / 43 (6.98%)
    1 / 10 (10.00%)
    4 / 53 (7.55%)
         occurrences all number
    3
    1
    4
    Cough
         subjects affected / exposed
    2 / 43 (4.65%)
    1 / 10 (10.00%)
    3 / 53 (5.66%)
         occurrences all number
    2
    1
    3
    Dysphonia
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 10 (20.00%)
    3 / 53 (5.66%)
         occurrences all number
    1
    2
    3
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    1 / 43 (2.33%)
    3 / 10 (30.00%)
    4 / 53 (7.55%)
         occurrences all number
    1
    3
    4
    Anxiety
         subjects affected / exposed
    3 / 43 (6.98%)
    0 / 10 (0.00%)
    3 / 53 (5.66%)
         occurrences all number
    3
    0
    3
    Investigations
    Blood Creatine Phosphokinase Increased
         subjects affected / exposed
    12 / 43 (27.91%)
    5 / 10 (50.00%)
    17 / 53 (32.08%)
         occurrences all number
    12
    5
    17
    Aspartate Aminotransferase Increased
         subjects affected / exposed
    8 / 43 (18.60%)
    0 / 10 (0.00%)
    8 / 53 (15.09%)
         occurrences all number
    8
    0
    8
    Ejection Fraction Decreased
         subjects affected / exposed
    6 / 43 (13.95%)
    1 / 10 (10.00%)
    7 / 53 (13.21%)
         occurrences all number
    6
    1
    7
    Blood Creatinine Increased
         subjects affected / exposed
    6 / 43 (13.95%)
    0 / 10 (0.00%)
    6 / 53 (11.32%)
         occurrences all number
    6
    0
    6
    Lipase Increased
         subjects affected / exposed
    5 / 43 (11.63%)
    1 / 10 (10.00%)
    6 / 53 (11.32%)
         occurrences all number
    5
    1
    6
    Alanine Aminotransferase Increased
         subjects affected / exposed
    5 / 43 (11.63%)
    0 / 10 (0.00%)
    5 / 53 (9.43%)
         occurrences all number
    5
    0
    5
    Blood Bilirubin Increased
         subjects affected / exposed
    4 / 43 (9.30%)
    0 / 10 (0.00%)
    4 / 53 (7.55%)
         occurrences all number
    4
    0
    4
    Weight Decreased
         subjects affected / exposed
    1 / 43 (2.33%)
    3 / 10 (30.00%)
    4 / 53 (7.55%)
         occurrences all number
    1
    3
    4
    Blood Alkaline Phosphatase Increased
         subjects affected / exposed
    3 / 43 (6.98%)
    0 / 10 (0.00%)
    3 / 53 (5.66%)
         occurrences all number
    3
    0
    3
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    3 / 43 (6.98%)
    3 / 10 (30.00%)
    6 / 53 (11.32%)
         occurrences all number
    3
    3
    6
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    9 / 43 (20.93%)
    0 / 10 (0.00%)
    9 / 53 (16.98%)
         occurrences all number
    9
    0
    9
    Leukocytosis
         subjects affected / exposed
    4 / 43 (9.30%)
    0 / 10 (0.00%)
    4 / 53 (7.55%)
         occurrences all number
    4
    0
    4
    Eye disorders
    Vision Blurred
         subjects affected / exposed
    5 / 43 (11.63%)
    2 / 10 (20.00%)
    7 / 53 (13.21%)
         occurrences all number
    5
    2
    7
    Chorioretinopathy
         subjects affected / exposed
    4 / 43 (9.30%)
    2 / 10 (20.00%)
    6 / 53 (11.32%)
         occurrences all number
    4
    2
    6
    Retinal Detachment
         subjects affected / exposed
    4 / 43 (9.30%)
    1 / 10 (10.00%)
    5 / 53 (9.43%)
         occurrences all number
    4
    1
    5
    Retinopathy
         subjects affected / exposed
    3 / 43 (6.98%)
    2 / 10 (20.00%)
    5 / 53 (9.43%)
         occurrences all number
    3
    2
    5
    Periorbital Oedema
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 10 (20.00%)
    3 / 53 (5.66%)
         occurrences all number
    1
    2
    3
    Vitreous Floaters
         subjects affected / exposed
    2 / 43 (4.65%)
    1 / 10 (10.00%)
    3 / 53 (5.66%)
         occurrences all number
    2
    1
    3
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    31 / 43 (72.09%)
    7 / 10 (70.00%)
    38 / 53 (71.70%)
         occurrences all number
    31
    7
    38
    Vomiting
         subjects affected / exposed
    24 / 43 (55.81%)
    4 / 10 (40.00%)
    28 / 53 (52.83%)
         occurrences all number
    24
    4
    28
    Nausea
         subjects affected / exposed
    22 / 43 (51.16%)
    5 / 10 (50.00%)
    27 / 53 (50.94%)
         occurrences all number
    22
    5
    27
    Abdominal Pain
         subjects affected / exposed
    13 / 43 (30.23%)
    1 / 10 (10.00%)
    14 / 53 (26.42%)
         occurrences all number
    13
    1
    14
    Stomatitis
         subjects affected / exposed
    10 / 43 (23.26%)
    3 / 10 (30.00%)
    13 / 53 (24.53%)
         occurrences all number
    10
    3
    13
    Constipation
         subjects affected / exposed
    10 / 43 (23.26%)
    2 / 10 (20.00%)
    12 / 53 (22.64%)
         occurrences all number
    10
    2
    12
    Dry Mouth
         subjects affected / exposed
    5 / 43 (11.63%)
    1 / 10 (10.00%)
    6 / 53 (11.32%)
         occurrences all number
    5
    1
    6
    Dyspepsia
         subjects affected / exposed
    4 / 43 (9.30%)
    2 / 10 (20.00%)
    6 / 53 (11.32%)
         occurrences all number
    4
    2
    6
    Abdominal Pain Upper
         subjects affected / exposed
    4 / 43 (9.30%)
    0 / 10 (0.00%)
    4 / 53 (7.55%)
         occurrences all number
    4
    0
    4
    Oral Pain
         subjects affected / exposed
    4 / 43 (9.30%)
    0 / 10 (0.00%)
    4 / 53 (7.55%)
         occurrences all number
    4
    0
    4
    Gastrooesophageal Reflux Disease
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 10 (20.00%)
    3 / 53 (5.66%)
         occurrences all number
    1
    2
    3
    Glossodynia
         subjects affected / exposed
    3 / 43 (6.98%)
    0 / 10 (0.00%)
    3 / 53 (5.66%)
         occurrences all number
    3
    0
    3
    Skin and subcutaneous tissue disorders
    Dermatitis Acneiform
         subjects affected / exposed
    15 / 43 (34.88%)
    8 / 10 (80.00%)
    23 / 53 (43.40%)
         occurrences all number
    15
    8
    23
    Rash
         subjects affected / exposed
    20 / 43 (46.51%)
    2 / 10 (20.00%)
    22 / 53 (41.51%)
         occurrences all number
    20
    2
    22
    Dry Skin
         subjects affected / exposed
    11 / 43 (25.58%)
    6 / 10 (60.00%)
    17 / 53 (32.08%)
         occurrences all number
    11
    6
    17
    Rash Maculo-Papular
         subjects affected / exposed
    7 / 43 (16.28%)
    5 / 10 (50.00%)
    12 / 53 (22.64%)
         occurrences all number
    7
    5
    12
    Skin Fissures
         subjects affected / exposed
    5 / 43 (11.63%)
    3 / 10 (30.00%)
    8 / 53 (15.09%)
         occurrences all number
    5
    3
    8
    Pruritus
         subjects affected / exposed
    3 / 43 (6.98%)
    1 / 10 (10.00%)
    4 / 53 (7.55%)
         occurrences all number
    3
    1
    4
    Erythema
         subjects affected / exposed
    2 / 43 (4.65%)
    1 / 10 (10.00%)
    3 / 53 (5.66%)
         occurrences all number
    2
    1
    3
    Musculoskeletal and connective tissue disorders
    Back Pain
         subjects affected / exposed
    5 / 43 (11.63%)
    3 / 10 (30.00%)
    8 / 53 (15.09%)
         occurrences all number
    5
    3
    8
    Arthralgia
         subjects affected / exposed
    2 / 43 (4.65%)
    3 / 10 (30.00%)
    5 / 53 (9.43%)
         occurrences all number
    2
    3
    5
    Pain In Extremity
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 10 (20.00%)
    3 / 53 (5.66%)
         occurrences all number
    1
    2
    3
    Infections and infestations
    Paronychia
         subjects affected / exposed
    5 / 43 (11.63%)
    3 / 10 (30.00%)
    8 / 53 (15.09%)
         occurrences all number
    5
    3
    8
    Folliculitis
         subjects affected / exposed
    5 / 43 (11.63%)
    3 / 10 (30.00%)
    8 / 53 (15.09%)
         occurrences all number
    5
    3
    8
    Conjunctivitis
         subjects affected / exposed
    3 / 43 (6.98%)
    1 / 10 (10.00%)
    4 / 53 (7.55%)
         occurrences all number
    3
    1
    4
    Sepsis
         subjects affected / exposed
    3 / 43 (6.98%)
    0 / 10 (0.00%)
    3 / 53 (5.66%)
         occurrences all number
    3
    0
    3
    Urinary Tract Infection
         subjects affected / exposed
    2 / 43 (4.65%)
    1 / 10 (10.00%)
    3 / 53 (5.66%)
         occurrences all number
    2
    1
    3
    Metabolism and nutrition disorders
    Hypomagnesaemia
         subjects affected / exposed
    6 / 43 (13.95%)
    6 / 10 (60.00%)
    12 / 53 (22.64%)
         occurrences all number
    6
    6
    12
    Decreased Appetite
         subjects affected / exposed
    6 / 43 (13.95%)
    5 / 10 (50.00%)
    11 / 53 (20.75%)
         occurrences all number
    6
    5
    11
    Hypokalaemia
         subjects affected / exposed
    9 / 43 (20.93%)
    0 / 10 (0.00%)
    9 / 53 (16.98%)
         occurrences all number
    9
    0
    9
    Dehydration
         subjects affected / exposed
    5 / 43 (11.63%)
    2 / 10 (20.00%)
    7 / 53 (13.21%)
         occurrences all number
    5
    2
    7
    Hyponatraemia
         subjects affected / exposed
    4 / 43 (9.30%)
    1 / 10 (10.00%)
    5 / 53 (9.43%)
         occurrences all number
    4
    1
    5
    Hypophosphataemia
         subjects affected / exposed
    3 / 43 (6.98%)
    2 / 10 (20.00%)
    5 / 53 (9.43%)
         occurrences all number
    3
    2
    5
    Hypoalbuminaemia
         subjects affected / exposed
    3 / 43 (6.98%)
    0 / 10 (0.00%)
    3 / 53 (5.66%)
         occurrences all number
    3
    0
    3
    Hypocalcaemia
         subjects affected / exposed
    3 / 43 (6.98%)
    0 / 10 (0.00%)
    3 / 53 (5.66%)
         occurrences all number
    3
    0
    3

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Apr 2014
    Protocol Version 01, dated 02 April 2014
    18 Sep 2015
    Protocol Version 02, dated 18 September 2015

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

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

    European Medicines Agency © 1995-Sat Apr 27 04:06:44 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA