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    Clinical Trial Results:
    A phase I open-label multicentre dose-escalation study of subcutaneous ALM201 in patients with advanced ovarian cancer and other solid tumours.

    Summary
    EudraCT number
    		 2014-001175-31
    Trial protocol
    		 GB  
    Global end of trial date
    13 Mar 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 Mar 2018
    First version publication date
    02 Mar 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    ALM201/0001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03427073
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Almac Discovery
    Sponsor organisation address
    Centre for Precision, Therapeutics, Health Sciences Building, 97 Lisburn Road, Belfast, United Kingdom, BT9 7AE
    Public contact
    Professor Richard Kennedy, Medical Director, Almac Discovery, r.kennedy@qub.ac.uk
    Scientific contact
    Professor Richard Kennedy, Medical Director, Almac Discovery, r.kennedy@qub.ac.uk
    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
    10 Oct 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    13 Mar 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Mar 2017
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective was to characterise the safety and tolerability of ALM201 (Part 1 and Part 2) and to identify a recommended phase 2 dose (RP2D) and schedule of ALM201 (Part 2 only)
    Protection of trial subjects
    This trial was conducted in compliance with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines for conducting, recording, and reporting trials, as well as for archiving essential documents. No trial procedures were performed on trial participants until written consent had been obtained from them. The informed consent form (ICF), protocol, and amendments for this trial were submitted to and approved by the Ethics committee. Routine monitoring was performed to verify that rights and well being of patients were protected. Also, any medication considered necessary for the patient’s safety and well-being was given at the discretion of the Investigator.
    Background therapy
    		 For treatment of DLT or any other clinically significant events, any available standard therapy was to be used as required. In the case of anaemia, transfusions with packed red blood cells (pRBC) were to be administered if required. Local irritation at the injection site could be treated according to local treatment guidelines.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Apr 2015
    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
    United Kingdom: 20
    Worldwide total number of subjects
    20
    EEA total number of subjects
    20
    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)
    14
    From 65 to 84 years
    6
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Recruitment was carried out in three study sites in Belfast, Manchester and Newcastle, UK starting on 27 April 2015.

    Pre-assignment
    Screening details
    		 Part 1 enrolled adult patients with advanced solid tumours in whom treatment with an anti-angiogenic agent was appropriate. Participants had screening evaluations between Day -1 and -28 before entering the first 21-day treatment cycle.

    Period 1
    Period 1 title
    overall study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    This was an open label study.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1 - ALM201
    Arm description
    		 One patient received 10 mg IMP from cycle 1 through cycle 6.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ALM201
    Investigational medicinal product code
    ALM201
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Parenteral use
    Dosage and administration details
    One vial contains 1.2 mL solution for injection containing 100mg/mL ALM201, 80 mM sodium carbonate, 20 mM Tris and 25 mM sodium chloride. Route of administration: subcutaneous (SC) The starting dose of ALM201 for cohort 1 was 10 mg per dose given on Days 1-5, 8-12 and 15-19 of a 21-day treatment cycle. In case of no DLT, the ALM201 dose was to be escalated for future cohorts in recommended increments according to the protocol.

    Arm title
    		 Cohort 2 - ALM201
    Arm description
    		 One patient received 20 mg IMP in cycle 1 and cycle 2.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ALM201
    Investigational medicinal product code
    ALM201
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Parenteral use
    Dosage and administration details
    One vial contains 1.2 mL solution for injection containing 100mg/mL ALM201, 80 mM sodium carbonate, 20 mM Tris and 25 mM sodium chloride. Route of administration: subcutaneous (SC) The patient was given 20 mg per dose on Days 1-5, 8-12 and 15-19 of a 21-day treatment cycle.

    Arm title
    		 Cohort 3 - ALM201
    Arm description
    		 One patient received 40 mg IMP from cycle 1 through cycle 3.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ALM201
    Investigational medicinal product code
    ALM201
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Parenteral use
    Dosage and administration details
    One vial contains 1.2 mL solution for injection containing 100mg/mL ALM201, 80 mM sodium carbonate, 20 mM Tris and 25 mM sodium chloride. Route of administration: subcutaneous (SC) The patient received 40 mg per dose on Days 1-5, 8-12 and 15-19 of a 21-day treatment cycle.

    Arm title
    		 Cohort 4 - ALM201
    Arm description
    		 Three patients received 80 mg IMP (3 patients during cycle 1, 2 patients in cycle 1 and cycle 2).
    Arm type
    		 Experimental

    Investigational medicinal product name
    ALM201
    Investigational medicinal product code
    ALM201
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Parenteral use
    Dosage and administration details
    One vial contains 1.2 mL solution for injection containing 100mg/mL ALM201, 80 mM sodium carbonate, 20 mM Tris and 25 mM sodium chloride. Route of administration: subcutaneous (SC) Three patients received 80 mg per dose given on Days 1-5, 8-12 and 15-19 of a 21-day treatment cycle.

    Arm title
    		 Cohort 5 - ALM201
    Arm description
    		 Three patients received 160 mg of IMP in cycles 1 and 2.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ALM201
    Investigational medicinal product code
    ALM201
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Parenteral use
    Dosage and administration details
    One vial contains 1.2 mL solution for injection containing 100mg/mL ALM201, 80 mM sodium carbonate, 20 mM Tris and 25 mM sodium chloride. Route of administration: subcutaneous (SC) 3 patients were given a dose of 160 mg on Days 1-5, 8-12 and 15-19 of a 21-day treatment cycle.

    Arm title
    		 Cohort 6 - ALM201
    Arm description
    		 Four patients received 200 mg IMP in cycle 1; 3 patients in cycle 1 and 2, 2 patients in cycle 1 through 4 and one patient in cycle 1 through 5.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ALM201
    Investigational medicinal product code
    ALM201
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Parenteral use
    Dosage and administration details
    One vial contains 1.2 mL solution for injection containing 100mg/mL ALM201, 80 mM sodium carbonate, 20 mM Tris and 25 mM sodium chloride. Route of administration: subcutaneous (SC) Cohort 6 was given 200 mg on Days 1-5, 8-12 and 15-19 of a 21-day treatment cycle.

    Arm title
    		 Cohort 7 - ALM201
    Arm description
    		 Three patients received 300 mg IMP in cycle 1 and 2; one of them received the IMP in cycle 1 through cycle 6.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ALM201
    Investigational medicinal product code
    ALM201
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Parenteral use
    Dosage and administration details
    One vial contains 1.2 mL solution for injection containing 100mg/mL ALM201, 80 mM sodium carbonate, 20 mM Tris and 25 mM sodium chloride. Route of administration: subcutaneous (SC) Cohort 7 was given 300 mg IMP on Days 1-5, 8-12 and 15-19 of a 21-day treatment cycle.

    Arm title
    		 Cohort 8 - ALM201
    Arm description
    		 Four patients received 100 mg IMP in cycle 1; two of them completed cycle 2.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ALM201
    Investigational medicinal product code
    ALM201
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Parenteral use
    Dosage and administration details
    One vial contains 1.2 mL solution for injection containing 100mg/mL ALM201, 80 mM sodium carbonate, 20 mM Tris and 25 mM sodium chloride. Route of administration: subcutaneous (SC) Cohort 8 was given 100 mg per dose on Days 1-5, 8-12 and 15-19 of a 21-day treatment cycle.

    Number of subjects in period 1
    		Cohort 1 - ALM201 Cohort 2 - ALM201 Cohort 3 - ALM201 Cohort 4 - ALM201 Cohort 5 - ALM201 Cohort 6 - ALM201 Cohort 7 - ALM201 Cohort 8 - ALM201
    Started
    1
    1
    1
    3
    3
    4
    3
    4
    Completed
    0
    0
    0
    0
    0
    0
    0
    0
    Not completed
    1
    1
    1
    3
    3
    4
    3
    4
         Physician decision
    -
    -
    -
    -
    -
    -
    1
    1
         disease progression
    1
    1
    1
    3
    3
    4
    2
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    overall study
    Reporting group description
    		 -

    Reporting group values
    		 overall study Total
    Number of subjects
    		 20 20
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 14 14
        From 65-84 years
    		 6 6
        85 years and over
    		 0 0
    Gender categorical
    Units: Subjects
        Female
    		 12 12
        Male
    		 8 8
    Ethnic origin
    Units: Subjects
        white
    		 20 20

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1 - ALM201
    Reporting group description
    		 One patient received 10 mg IMP from cycle 1 through cycle 6.

    Reporting group title
    Cohort 2 - ALM201
    Reporting group description
    		 One patient received 20 mg IMP in cycle 1 and cycle 2.

    Reporting group title
    Cohort 3 - ALM201
    Reporting group description
    		 One patient received 40 mg IMP from cycle 1 through cycle 3.

    Reporting group title
    Cohort 4 - ALM201
    Reporting group description
    		 Three patients received 80 mg IMP (3 patients during cycle 1, 2 patients in cycle 1 and cycle 2).

    Reporting group title
    Cohort 5 - ALM201
    Reporting group description
    		 Three patients received 160 mg of IMP in cycles 1 and 2.

    Reporting group title
    Cohort 6 - ALM201
    Reporting group description
    		 Four patients received 200 mg IMP in cycle 1; 3 patients in cycle 1 and 2, 2 patients in cycle 1 through 4 and one patient in cycle 1 through 5.

    Reporting group title
    Cohort 7 - ALM201
    Reporting group description
    		 Three patients received 300 mg IMP in cycle 1 and 2; one of them received the IMP in cycle 1 through cycle 6.

    Reporting group title
    Cohort 8 - ALM201
    Reporting group description
    		 Four patients received 100 mg IMP in cycle 1; two of them completed cycle 2.

    Primary: Safety and tolerability - evaluation of AEs and DLT

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    End point title
    		 Safety and tolerability - evaluation of AEs and DLT [1]
    End point description
    All events and suspected dose limiting toxicities (DLTs) were graded according to the CTCAE, version 4.03. A DLT was defined as a Grade 3 or 4 AE that, in the opinion of the CRC, was likely to be related to ALM201 and represented a clinically significant hazard to the patient. Qualifying DLT events were considered to be clinically relevant; e.g. in duration, apparent reversibility, required management, and upon consideration of the patient’s medical history and/or concomitant medications. DLT events were also evaluated in terms of what was considered to be an appropriate next escalation step: In the case where the CRC agreed that an escalation step of approximately 33% or lower was merited; the toxicity of concern could be declared a DLT. In order to be evaluable for DLT assessment, a patient had to receive at least 80% of their scheduled doses (e.g. 12 of the 15), unless this lack of compliance was due to ALM201-related toxicity.
    End point type
    Primary
    End point timeframe
    Adverse event evaluation was done during treatment and follow-up. DLT evaluation was done during cycle 1.
    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 inferential statistical analysis was performed for this primary endpoint.
    End point values
    		 Cohort 1 - ALM201 Cohort 2 - ALM201 Cohort 3 - ALM201 Cohort 4 - ALM201 Cohort 5 - ALM201 Cohort 6 - ALM201 Cohort 7 - ALM201 Cohort 8 - ALM201
    Number of subjects analysed
    1
    1
    1
    3
    3
    4
    3
    4
    Units: Number of patients
        TEAE
    1
    0
    1
    3
    3
    4
    3
    4
        treatment related TEAE
    1
    0
    1
    1
    3
    4
    3
    2
        DLT
    0
    0
    0
    0
    0
    0
    0
    0
        SAE
    1
    0
    0
    1
    1
    2
    0
    1
        treatment related SAE
    0
    0
    0
    0
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Tumour response assessment

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    End point title
    		 Tumour response assessment
    End point description
    As this was a Phase 1 study, the extent of efficacy data was expected to be limited. A summary of clinical benefit, by RECIST Version 1.1 from patients with evaluable disease was generated.
    End point type
    Secondary
    End point timeframe
    Response assessments were done to assess clinical benefit in the efficacy population overall and at the end of cycles 2, 4 and 6, as applicable
    End point values
    		 Cohort 1 - ALM201 Cohort 2 - ALM201 Cohort 3 - ALM201 Cohort 4 - ALM201 Cohort 5 - ALM201 Cohort 6 - ALM201 Cohort 7 - ALM201 Cohort 8 - ALM201
    Number of subjects analysed
    1
    1
    1
    3
    3
    4
    3
    4
    Units: number of patients
        Complete Response (CR)
    0
    0
    0
    0
    0
    0
    0
    0
        Partial Response (PR)
    0
    0
    0
    0
    0
    0
    0
    0
        Overall Response Rate (CR+PR)
    0
    0
    0
    0
    0
    0
    0
    0
        Stable Disease (SD)
    1
    0
    1
    0
    0
    2
    2
    1
        Disease Control Rate (CR+PR+SD)
    1
    0
    1
    0
    0
    2
    2
    1
        Progressive Disease
    0
    1
    0
    3
    3
    1
    1
    3
        Not Evaluable (NE+NA)
    0
    0
    0
    0
    0
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Pharmacokinetics

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    End point title
    		 Pharmacokinetics
    End point description
    Only data from cycles 1 and 2 are presented, since data for cycles 4 and 6 are not available for all cohorts.
    End point type
    Secondary
    End point timeframe
    Tmax was determined in cycles 1, 2, 4 and 6 of treatment.
    End point values
    		 Cohort 1 - ALM201 Cohort 2 - ALM201 Cohort 3 - ALM201 Cohort 4 - ALM201 Cohort 5 - ALM201 Cohort 6 - ALM201 Cohort 7 - ALM201 Cohort 8 - ALM201
    Number of subjects analysed
    1
    1
    1
    3 [2]
    3 [3]
    4 [4]
    3
    4 [5]
    Units: Tmax (h)
    median (full range (min-max))
        Cycle 1 - Day 1
    1.45 (1.45 to 1.45)
    1.50 (1.50 to 1.50)
    1.63 (1.63 to 1.63)
    1.53 (0.75 to 2.0)
    1.52 (0.80 to 3.07)
    2.50 (1.50 to 3.08)
    2.00 (0.75 to 4.00)
    1.50 (1.30 to 1.50)
        Cycle 1 - Day 3
    0.50 (0.50 to 0.50)
    1.00 (1.00 to 1.00)
    1.50 (1.50 to 1.50)
    1.50 (1.05 to 2.0)
    1.52 (1.52 to 2.05)
    2.00 (1.48 to 2.00)
    1.02 (1.00 to 2.00)
    1.61 (0.50 to 2.02)
        Cycle 1 - Day 18
    1.58 (1.58 to 1.58)
    1.02 (1.02 to 1.02)
    1.00 (1.00 to 1.00)
    1.23 (0.47 to 2.0)
    1.50 (0.50 to 2.00)
    2.03 (1.00 to 3.50)
    1.50 (1.00 to 2.07)
    1.90 (1.45 to 2.35)
        Cycle 2 - Day 18
    2.00 (2.00 to 2.00)
    1.00 (1.00 to 1.00)
    1.03 (1.03 to 1.03)
    3.50 (3.50 to 3.50)
    2.00 (2.00 to 2.00)
    1.54 (1.50 to 1.58)
    2.00 (1.48 to 2.13)
    1.02 (1.02 to 1.02)
    Notes
    [2] - 2 patients on Cycle 1 - Day 18; 1 patient on Cycle 2 - Day 18
    [3] - 1 patient on Cycle 2 - Day 18
    [4] - 3 patients on Cycle 1 - Day 18; 2 patients on Cycle 2 - Day 18
    [5] - 2 patients on Cycle 1 - Day 18; 1 patient on Cycle 2 - Day 18
    No statistical analyses for this end point

    Secondary: Pharmacokinetics

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    End point title
    		 Pharmacokinetics
    End point description
    Only data from cycles 1 and 2 are presented, since data for cycles 4 and 6 are not available for all cohorts.
    End point type
    Secondary
    End point timeframe
    AUC 0-t was determined in cycles 1, 2, 4 and 6 of treatment.
    End point values
    		 Cohort 1 - ALM201 Cohort 2 - ALM201 Cohort 3 - ALM201 Cohort 4 - ALM201 Cohort 5 - ALM201 Cohort 6 - ALM201 Cohort 7 - ALM201 Cohort 8 - ALM201
    Number of subjects analysed
    1
    1
    1
    3 [6]
    3 [7]
    4 [8]
    3
    4 [9]
    Units: AUC0-t (ng.h/mL)
    geometric mean (full range (min-max))
        Cycle 1 - Day 1
    485 (485 to 485)
    1040 (1040 to 1040)
    1920 (1920 to 1920)
    3380 (3100 to 3790)
    6510 (5600 to 7560)
    5860 (3460 to 10200)
    11900 (9470 to 15100)
    6280 (1140 to 14800)
        Cycle 1 - Day 3
    868 (868 to 868)
    1160 (1160 to 1160)
    898 (898 to 898)
    2970 (2660 to 3430)
    5100 (4970 to 5280)
    6630 (4460 to 11900)
    12500 (10500 to 14700)
    8870 (5380 to 12800)
        Cycle 1 - Day 18
    817 (817 to 817)
    718 (718 to 718)
    1840 (1840 to 1840)
    3500 (3440 to 3570)
    4930 (4400 to 5400)
    5570 (3900 to 10000)
    12100 (11400 to 12900)
    8100 (7000 to 9370)
        Cycle 2 - Day 18
    702 (702 to 702)
    1020 (1020 to 1020)
    1950 (1950 to 1950)
    3230 (3230 to 3230)
    5710 (5710 to 5710)
    5680 (3810 to 8480)
    10400 (7290 to 16700)
    5930 (5930 to 5930)
    Notes
    [6] - 2 patients on Cycle 1 - Day 18; 1 patient on Cycle 2 - Day 18
    [7] - 1 patient on Cycle 2 - Day 18
    [8] - 3 patients on Cycle 1 - Day 18; 2 patients on Cycle 2 - Day 18
    [9] - 2 patients on Cycle 1 - Day 18; 1 patient on Cycle 2 - Day 18
    No statistical analyses for this end point

    Secondary: Pharmacokinetics

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    End point title
    		 Pharmacokinetics
    End point description
    Only data from cycles 1 and 2 are presented, since data for cycles 4 and 6 are not available for all cohorts.
    End point type
    Secondary
    End point timeframe
    Cmax of ALM201 following subcutaneous (SC) administration of ALM201 was determined in cycles 1, 2, 4 and 6 of treatment.
    End point values
    		 Cohort 1 - ALM201 Cohort 2 - ALM201 Cohort 3 - ALM201 Cohort 4 - ALM201 Cohort 5 - ALM201 Cohort 6 - ALM201 Cohort 7 - ALM201 Cohort 8 - ALM201
    Number of subjects analysed
    1
    1
    1
    3 [10]
    3 [11]
    4 [12]
    3
    4 [13]
    Units: Cmax (ng/mL)
    geometric mean (full range (min-max))
        Cycle 1 - Day 1
    200 (200 to 200)
    542 (542 to 542)
    592 (592 to 592)
    835 (749 to 892)
    1990 (1730 to 2190)
    1490 (890 to 2690)
    2550 (2100 to 3650)
    1810 (465 to 4600)
        Cycle 1 - Day 3
    406 (406 to 406)
    614 (614 to 614)
    759 (759 to 759)
    861 (762 to 1090)
    1490 (1390 to 1660)
    1620 (1160 to 3100)
    2690 (2300 to 3260)
    2750 (1450 to 4280)
        Cycle 1 - Day 18
    352 (352 to 352)
    319 (319 to 319)
    405 (405 to 405)
    1090 (1090 to 1100)
    1350 (1240 to 1420)
    1670 (1230 to 2880)
    2880 (2420 to 3450)
    2330 (2140 to 2530)
        Cycle 2 - Day 18
    288 (288 to 288)
    394 (394 to 394)
    583 (583 to 583)
    849 (849 to 849)
    1870 (1870 to 1870)
    1890 (1280 to 2790)
    2780 (2110 to 4310)
    1790 (1790 to 1790)
    Notes
    [10] - 2 patients on Cycle 1 - Day 18; 1 patient on Cycle 2 - Day 18
    [11] - 1 patient on Cycle 2 - Day 18
    [12] - 3 patients on Cycle 1 - Day 18; 2 patients on Cycle 2 - Day 18
    [13] - 2 patients on Cycle 1 - Day 18; 1 patient on Cycle 2 - Day 18
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Ongoing during treatment and follow-up
    Adverse event reporting additional description
    During the study, AEs were spontaneously reported or elicited during open-ended questioning, examination, or evaluation of a patient.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Cohort 1 - ALM201
    Reporting group description
    		 One patient received 10 mg IMP from cycle 1 through cycle 6.

    Reporting group title
    Cohort 2 - ALM201
    Reporting group description
    		 One patient received 20 mg IMP in cycle 1 and cycle 2.

    Reporting group title
    Cohort 3 - ALM201
    Reporting group description
    		 One patient received 40 mg IMP from cycle 1 through cycle 3.

    Reporting group title
    Cohort 4 - ALM201
    Reporting group description
    		 Three patients received 80 mg IMP (3 patients during cycle 1, 2 patients in cycle 1 and cycle 2).

    Reporting group title
    Cohort 6 - ALM201
    Reporting group description
    		 Four patients received 200 mg IMP in cycle 1; 3 patients in cycle 1 and 2, 2 patients in cycle 1 through 4 and one patient in cycle 1 through 5.

    Reporting group title
    Cohort 7 - ALM201
    Reporting group description
    		 Three patients received 300 mg IMP in cycle 1 and 2; one of them received the IMP in cycle 1 through cycle 6.

    Reporting group title
    Cohort 8 - ALM201
    Reporting group description
    		 Four patients received 100 mg IMP in cycle 1; two of them completed cycle 2.

    Reporting group title
    Cohort 5 - ALM201
    Reporting group description
    		 Three patients received 160 mg of IMP in cycles 1 and 2.

    Serious adverse events
    		 Cohort 1 - ALM201 Cohort 2 - ALM201 Cohort 3 - ALM201 Cohort 4 - ALM201 Cohort 6 - ALM201 Cohort 7 - ALM201 Cohort 8 - ALM201 Cohort 5 - ALM201
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    General disorders and administration site conditions
    Device occlusion
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Large intestinal obstruction
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal vein thrombosis
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0.05%
    Non-serious adverse events
    		 Cohort 1 - ALM201 Cohort 2 - ALM201 Cohort 3 - ALM201 Cohort 4 - ALM201 Cohort 6 - ALM201 Cohort 7 - ALM201 Cohort 8 - ALM201 Cohort 5 - ALM201
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    1 / 1 (100.00%)
    3 / 3 (100.00%)
    4 / 4 (100.00%)
    3 / 3 (100.00%)
    4 / 4 (100.00%)
    3 / 3 (100.00%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Thrombosis
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    General disorders and administration site conditions
    Chest discomfort
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Device occlusion
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Fatigue
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    2 / 3 (66.67%)
    2 / 4 (50.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    0
    1
    0
    2
    2
    2
    1
    Injection site bruising
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    2 / 4 (50.00%)
    2 / 3 (66.67%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    2
    2
    1
    1
    Injection site erythema
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    Injection site pain
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Injection site pruritus
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Injection site rash
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Injection site reaction
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    2 / 3 (66.67%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    2
    0
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    2
    0
    2
    0
    Pyrexia
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    1
    Reproductive system and breast disorders
    Scrotal swelling
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    1
    Dyspnoea
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 1 (100.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    1
    1
    Pulmonary embolism
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Wheezing
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Depressed mood
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Depression
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Insomnia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Blood creatinine increased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Urine output decreased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Injury, poisoning and procedural complications
    Catheter site pain
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Contusion
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    Excoriation
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Fall
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    Procedural pain
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Cardiac disorders
    Conduction disorder
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Tachycardia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Nervous system disorders
    Aphasia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Dizziness
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    Dysgeusia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Headache
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    2 / 3 (66.67%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    2
    Memory impairment
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Neuralgia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    1
    1
    Eye disorders
    Vision blurred
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    Ascites
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Constipation
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 1 (100.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    1
    Diarrhoea
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    0
    0
    1
    2
    0
    0
    1
    Dyspepsia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    Flatulence
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Large intestinal obstruction
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Lip swelling
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    2 / 3 (66.67%)
         occurrences all number
    1
    0
    0
    0
    1
    1
    0
    2
    Rectal haemorrhage
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Stomatitis
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Vomiting
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Dry skin
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Erythema
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Rash erythematous
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Rash macular
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Renal and urinary disorders
    Renal failure acute
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Renal vein thrombosis
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Urinary retention
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    0
    0
    Flank pain
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Muscle spasms
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 1 (100.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    Neck pain
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Back pain
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    2 / 3 (66.67%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    1
    1
    Infections and infestations
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    2
    0
    Oral candidiasis
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Oral fungal infection
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Skin infection
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    1 / 3 (33.33%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    1
    0
    Urinary tract infection enterococcal
         subjects affected / exposed
    1 / 1 (100.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Viral infection
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    1 / 1 (100.00%)
    0 / 3 (0.00%)
    2 / 4 (50.00%)
    1 / 3 (33.33%)
    2 / 4 (50.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    1
    0
    2
    1
    2
    0
    Hypophosphataemia
         subjects affected / exposed
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 1 (0.00%)
    0 / 3 (0.00%)
    0 / 4 (0.00%)
    0 / 3 (0.00%)
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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.
    It was decided not to proceed with Part 2 of the study as several preclinical studies running in parallel did not support the hypothesis around the biomarker strategy for the selection of patients for Part 2.

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/19097774
    http://www.ncbi.nlm.nih.gov/pubmed/21270624
    http://www.ncbi.nlm.nih.gov/pubmed/21364036
    http://www.ncbi.nlm.nih.gov/pubmed/17396134
    http://www.ncbi.nlm.nih.gov/pubmed/20980167
    http://www.ncbi.nlm.nih.gov/pubmed/21593862
    http://www.ncbi.nlm.nih.gov/pubmed/15701823
    http://www.ncbi.nlm.nih.gov/pubmed/7059456
    http://www.ncbi.nlm.nih.gov/pubmed/1244564
    http://www.ncbi.nlm.nih.gov/pubmed/9262252
    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.

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