Document:

exv4w72

 

    Exhibit 4.72

 

    Change
    Order Number 4

 

			
	
    DATED 		
    the
    18th January
    2007
	 
	
    BETWEEN 		
    Amarin Neuroscience Limited of Magdalen Centre North, Oxford
    Science Park, Oxford OX4 4GA UK (‘Amarin’)
	 
	
    AND 		
    ICON Clinical Research Limited of South County Business Park,
    Leopardstown, Dublin 18 (‘ICON’)
	 
	
    WHEREAS: 		

	 
	
    A. 		
    The parties entered into an Agreement for Services on
    30th June
    2005, concerning Study known as Protocol
    AN01.01.0012 — A Multi-centre, double-blind,
    randomized, parallel group, placebo-controlled trial of
    ethyl-epa (Ethyl-Icosapent) in patients with Huntington’s
    Disease. This is a Europe only study as amended by Change
    Order #2 dated
    8th of
    June 2006 and Change Order #3 dated
    30th of
    November 2006.
	 
	
    B. 		
    The parties have agreed to certain change to the services to be
    provided and the associated cost as set out herein.

 

    IT IS
    AGREED BY THE PARTIES AS FOLLOWS:

 

    1. The parties agree to amend the Agreement to reflect
    changes set out in the Appendix 1 which is attached hereto
    and incorporated hereby.

 

    2. Save as otherwise provided in this Change Order, all the
    terms and conditions of the Agreement dated the
    30th June
    2005 and subsequent change orders shall remain in full force and
    effect.

 

    3. The value of this Change Order shall be £573,158
    in direct fees and £364,500 in pass through
    costs. The payment schedule has been revised and attached herein
    as Appendix 2.

 

    IN WITNESS WHEREOF, the parties hereto have executed this
    Change Order by their duly authorised representatives on the
    date(s) written below.

 

	 	 	 
	

    Amarin Neuroscience Limited

	
 
	

    ICON Clinical Research Limited

	 

	

    NAME Alan Cooke
    

	
 
	
    Mr. Sean Leech
    

	

    TITLE CFO, Director
    

	
 
	
    TITLE: Executive VP
    Commercial &

    Organisational Development.
    

	

    DATE 15 February 2007
    

	
 
	
    DATE 29 January 2007
    

	

    SIGNED Alan Cooke
    

	
 
	
    SIGNED Sean Leech
    

 

    Appendix 1

 

		
	
    1.  
	
    Introduction

 

    The main changes to the project specifications are the following:

 

			
	 	    • 
	
    Management of the one year Open Label
    Follow-Up
    trial to the Phase III study entitled “A multi-centre,
    double-blind, randomized, parallel group, placebo-controlled
    trial of Miraxion (ethyl-EPA) in patients with mild to moderate
    Huntington’s Disease in Europe” (AN01.01.0012).

	 
	 	    • 
	
    Study Timelines:  The overall study timelines
    have been assumed in line with the revised milestone dates as
    outlined in Table 1 below.

	 
	 	    • 
	
    It is assumed that 261 patients will roll over into this
    study extension. It is assumed that all 27 sites participating
    in the double-blind study will participate in the open label
    study also. The total number of patients to roll over into the
    extension study is based on 90% of the number of patients
    randomized in the main study. It is assumed that final site
    distribution will be as detailed in Table 2 below.

	 
	 	    • 
	
    Staff Allocation:  This is in line with the
    study extension timelines and the assumed number of monitoring
    visits to be undertaken per site. The clinical team proposed by
    ICON to conduct this study is illustrated in Table 3 below. This
    allocation is based on the participation of 27 sites in the
    project. During the double blind phase only the monitoring of
    Informed Consent forms for patients entering the extension study
    will be undertaken. A total of 4 monitoring visits (including
    the close-out visit) will be performed at each site. The first
    monitoring visit will occur in March/April, follow up visits
    will be scheduled at the 4 month safety
    follow-up
    and the second at the end of 12 months. The maximum
    allocation of each member to the extension study, in terms of a
    full-time equivalent (FTE) and main task required for each
    period are detailed in Table 3 below:

	 
	 	    • 
	
    Source document verification is restricted to Informed Consent,
    SAEs/AEs and 20% of patients full check of CRF data versus
    source.

	 
	 	    • 
	
    The official Close-Out visits for the overall study (core and
    extension phase) will now be performed as part of the Open Label
    extension study as agreed with Amarin.

	 
	 	    • 
	
    Data Management:  The Data Management
    specifications have been proposed for the study extension and
    are presented in Section 3 below.

 

		
	
    2.  
	
    Clinical
    Research Management

 

		
	
    2.1  
	
    Clinical
    Research Specifications

 

    The revised study timelines are presented below:

 

	 	 	 
	

    Milestones for Study Extension

	
 
	

    Timelines — Open Label Study

	 

	

    ICON involvement begin
    

	
 
	
    15 July 2006
    

	

    First patient in
    

	
 
	
    September 2006
    

	

    Last patient in
    

	
 
	
    End January 2007
    

	

    Last patient off treatment
    

	
 
	
    31 January 2008
    

	

    Last patient out
    

	
 
	
    28 February 2008
    

	

    Data Base Lock
    

	
 
	
    Mid Apr 2008
    

	

    Open Label Study completed
    

	
 
	
    Jun 2008
    

 

    Table
    1

 

 

	 	 	 	 	 	 	 	 	 
	
 
	
 
	
 
	
 
	
 
	
    Number of

    
	
 

	

    Country

	
 
	
    Sites
	
 
	
 
	
    Patients
	
 

	 

	

    Austria
    

	
 
	
 
	
    2
	
 
	
 
	
 
	
    25
	
 

	

    Germany
    

	
 
	
 
	
    9
	
 
	
 
	
 
	
    77
	
 

	

    Italy
    

	
 
	
 
	
    3
	
 
	
 
	
 
	
    52
	
 

	

    Portugal
    

	
 
	
 
	
    1
	
 
	
 
	
 
	
    5
	
 

	

    Spain
    

	
 
	
 
	
    4
	
 
	
 
	
 
	
    26
	
 

	

    UK
    

	
 
	
 
	
    8
	
 
	
 
	
 
	
    76
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Total

	
 
	
 
	
    27
	
 
	
 
	
 
	
    261
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

 

    Table
    2

 

    Revised
    Staff Allocation:

 

	 	 	 	 	 	 	 	 	 
	

    FTE

	
 
	
 
	

    Staff

	
 
	

    Time Allocation

	
 
	

    Main Tasks to be Performed

	 

	
 
	
    0.6
	
 
	
 
	
    Project Manager
    
	
 
	
    Allocated in April 2007
    
	
 
	
    General Management: Status
    tracking, Finance, Drug supply, Team training and follow up of
    1 month follow up visit. Hand Over preparation.
    

	
 
	
    0.3
	
 
	
 
	
    Project Manager
    
	
 
	
    Allocated in May 2007
    
	
 
	
    General Management and Hand Over
    activities.
    

	
 
	
    —
	
 
	
 
	
    Project Manager
    
	
 
	
    Allocated in June 2007
    
	
 
	
    Allocation for the core study as
    presented in C/O#3 will apply during this period. No additional
    allocation was assigned
    

	
 
	
    0.3
	
 
	
 
	
    Lead CRA
    
	
 
	
    Allocated from
    1st of
    May 2007 through
    31st of
    May 2008
    
	
 
	
    Starting May 2007 with handover
    activities. General Management of extension study
    (teleconferences, status updates and team management).
    

	
 
	
    0.6
	
 
	
 
	
    Clinical Research Associate
    
	
 
	
    Allocated from
    1st of
    July 2006 through
    31st of
    December 2006
    
	
 
	
    Set up time applied July-Sept now
    extended from July-Dec 06. Preparation of documentation and
    assist in submission to EC/CA, collection of essential
    documents, investigator agreements and Study Initiation.
    

	
 
	
    —
	
 
	
 
	
    Clinical Research Associate
    
	
 
	
    1st of
    January 2007 through
    31st of
    March 2007
    
	
 
	
    Additional clinical team
    allocation for study extension was not assigned during this
    period
    

	
 
	
    2.6
	
 
	
 
	
    Clinical Research Associates
    
	
 
	
    Allocated in April 2007
    
	
 
	
    Site visits to monitor informed
    consent, SAEs/AEs, for 20% of patients, performance of a full
    check of CRF data versus source and monitoring month 7 follow up
    visit.
    

	
 
	
    1.4
	
 
	
 
	
    Clinical Research Associates
    
	
 
	
    Allocated from
    1st of
    May 2007 through
    30th of
    June 2007
    
	
 
	
    Follow up activities from April
    2007.
    

 

	 	 	 	 	 	 	 	 	 
	

    FTE

	
 
	
 
	

    Staff

	
 
	

    Time Allocation

	
 
	

    Main Tasks to be Performed

	 

	
 
	
    2.6
	
 
	
 
	
    Clinical Research Associates
    
	
 
	
    Allocated from
    1st of
    July 2007 through
    31st of
    August 2007
    
	
 
	
    All sites to be visited to collect
    4 month safety follow up data, including SAEs/AEs and for
    20% of patients, performance of a full check of CRF data versus
    source.
    

	
 
	
    0.6
	
 
	
 
	
    Clinical Research Associates
    
	
 
	
    Allocated from
    1st of
    September 2007 through
    31st of
    December 2007
    
	
 
	
    General tasks will be preformed
    during this period
    

	
 
	
    2.6
	
 
	
 
	
    Clinical Research Associates
    
	
 
	
    Allocated from
    1st of
    January 2008 through
    31st of
    May 2008
    
	
 
	
    In Jan and Feb all sites will need
    to be visited to collect 12 month follow up data. From
    March through May all sites will need to be visited for formal
    close out. Performance of study closure activities including
    study file finalization/reconciliation.
    

	
 
	
    1.2
	
 
	
 
	
    Clinical Research Assistant
    
	
 
	
    Allocated from
    15th of
    April 2007 through
    31st of
    May 2007
    
	
 
	
    Overall support to Lead CRA and
    CRAs; Set up and maintenance of ICOTrack,  Main study file,
    Monitoring files, Document control, CRF distribution, Drug
    supply tracking, Investigator Payments and support to sites.
    

	
 
	
    0.7
	
 
	
 
	
    Clinical Research Assistant
    
	
 
	
    Allocated from
    1st of
    June 2007 through
    31st of
    August 2007
    
	
 
	
    As above
    

	
 
	
    0.5
	
 
	
 
	
    Clinical Research Assistant
    
	
 
	
    Allocated from
    1st of
    September 2007 end
    30th of
    November 2007
    
	
 
	
    As above
    

	
 
	
    0.7
	
 
	
 
	
    Clinical Research Assistant
    
	
 
	
    Allocated from
    1st of
    December 2007 end
    30th of
    April 2008
    
	
 
	
    In addition to above, final study
    file preparation/reconciliation.
    

	
 
	
 
	
 
	
 
	
    Clinical Regulatory Compliance
    Associate
    
	
 
	
    Allocated for 12 days for the
    extension study duration
    
	
 
	
 

	
 
	
 
	
 
	
 
	
    Accounting Administrator
    
	
 
	
    Allocated for 30 days for the
    extension study duration
    
	
 
	
 

 

 

			
	
    Note: 		
    General site management, in-house study management and status
    reporting is calculated from April 07 onwards Some time per
    month is calculated for regular team teleconferences and 1:1
    conversations with Lead CRA

 

    Table 3

 

		
	
    2.2  
	
    Direct
    Cost Estimates (Clinical)

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	
    Clinical Research

    
	
 
	
 
	
 
	
    Number of

    
	
 
	
 
	
    Price per

    
	
 
	
 
	
 
	
 

	

    Management

	
 
	
    Units
	
 
	
    Units
	
 
	
 
	
    Unit*
	
 
	
 
	
    Total (STG£)
	
 

	 

	

    Project Manager
    

	
 
	
    Days
    
	
 
	
 
	
    17
	
 
	
 
	
 
	
    970
	
 
	
 
	
 
	
    16,484
	
 

	

    Lead CRA
    

	
 
	
    Days
    
	
 
	
 
	
    74
	
 
	
 
	
 
	
    696
	
 
	
 
	
 
	
    51,548
	
 

	

    Clinical Research Associate
    

	
 
	
    Days
    
	
 
	
 
	
    562
	
 
	
 
	
 
	
    529
	
 
	
 
	
 
	
    297,089
	
 

	

    Clinical Research Assistant
    

	
 
	
    Days
    
	
 
	
 
	
    169
	
 
	
 
	
 
	
    407
	
 
	
 
	
 
	
    68,746
	
 

	

    Clinical Regulatory Compliance
    Associate
    

	
 
	
    Days
    
	
 
	
 
	
    12
	
 
	
 
	
 
	
    561
	
 
	
 
	
 
	
    6,728
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    CLINICAL RESEARCH MANAGEMENT
    SUB-TOTAL

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £440,595
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	
 
	
 
	
 
	
 
	
    Number of

    
	
 
	
 
	
    Price per

    
	
 
	
 
	
 
	
 

	

    Support Services

	
 
	
    Units
	
 
	
    Units
	
 
	
 
	
    Unit*
	
 
	
 
	
    Total (STG£)
	
 

	 

	

    Local Ethics Committee Study
    Extension Submissions
    

	
 
	
    Sites
    
	
 
	
 
	
    21
	
 
	
 
	
 
	
    276
	
 
	
 
	
 
	
    5,797
	
 

	

    Central Ethics Committee Study
    Extension Submission
    

	
 
	
    Sites
    
	
 
	
 
	
    6
	
 
	
 
	
 
	
    414
	
 
	
 
	
 
	
    2,484
	
 

	

    Regulatory Submission for Study
    Extension
    

	
 
	
    Submission
    
	
 
	
 
	
    6
	
 
	
 
	
 
	
    1,502
	
 
	
 
	
 
	
    9,015
	
 

	

    ICOTrack Maintenance
    

	
 
	
    Months
    
	
 
	
 
	
    24
	
 
	
 
	
 
	
    177
	
 
	
 
	
 
	
    4,238
	
 

	

    SUPPORT SERVICES
    SUB-TOTAL

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £21,534
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    ICON CLINICAL RESEARCH
    MANAGEMENT FEE

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £462,129
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

 

 

			
	
    * 		
    Figures in the “Price per unit” column have been
    rounded, figures in the “Total” column are Correct.

 

    Table 4

 

 

		
	
    2.3  
	
    Pass-through
    Estimates (Clinical)

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	
 
	
 
	
 
	
 
	
    Number of

    
	
 
	
 
	
    Price per

    
	
 
	
 
	
 
	
 

	

    Estimated Pass-Through Costs

	
 
	

    Units

	
 
	
    Units
	
 
	
 
	
    Unit
	
 
	
 
	
    Total (STG£)
	
 

	 

	

    Travel

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Site Visit Unit Cost Adjustment
    

	
 
	
    Visits
    
	
 
	
 
	
    81
	
 
	
 
	
 
	
    300
	
 
	
 
	
 
	
    24,300
	
 

	

    Team Meetings
    

	
 
	
    Meetings
    
	
 
	
 
	
    1
	
 
	
 
	
 
	
    629
	
 
	
 
	
 
	
    629
	
 

	

    Sponsor Meetings
    

	
 
	
    Meetings
    
	
 
	
 
	
    2
	
 
	
 
	
 
	
    1,118
	
 
	
 
	
 
	
    2,236
	
 

	

    Translations

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Protocol synopsis (1,000 words)
    

	
 
	
    Language
    
	
 
	
 
	
    5
	
 
	
 
	
 
	
    391
	
 
	
 
	
 
	
    1,953
	
 

	

    Informed consent document
    

	
 
	
    Language
    
	
 
	
 
	
    5
	
 
	
 
	
 
	
    783
	
 
	
 
	
 
	
    3,917
	
 

	

    EC documents
    

	
 
	
    Submission
    
	
 
	
 
	
    21
	
 
	
 
	
 
	
    433
	
 
	
 
	
 
	
    9,085
	
 

	

    Medication instructions
    

	
 
	
    Language
    
	
 
	
 
	
    5
	
 
	
 
	
 
	
    120
	
 
	
 
	
 
	
    600
	
 

	

    Regulatory documents
    

	
 
	
    Submission
    
	
 
	
 
	
    5
	
 
	
 
	
 
	
    866
	
 
	
 
	
 
	
    4,330
	
 

	

    Patient Cards
    

	
 
	
    Language
    
	
 
	
 
	
    5
	
 
	
 
	
 
	
    53
	
 
	
 
	
 
	
    265
	
 

	

    Investigator Contracts
    

	
 
	
    Site
    
	
 
	
 
	
    19
	
 
	
 
	
 
	
    800
	
 
	
 
	
 
	
    15,200
	
 

	

    Other

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Teleconferencing (3 lines)
    

	
 
	
    Meetings
    
	
 
	
 
	
    48
	
 
	
 
	
 
	
    84
	
 
	
 
	
 
	
    4,025
	
 

	

    Investigator Fees
    

	
 
	
    Patients
    
	
 
	
 
	
    261
	
 
	
 
	
 
	
    950
	
 
	
 
	
 
	
    247,950
	
 

	

    Ethics Committee Fees
    

	
 
	
    Sites
    
	
 
	
 
	
    27
	
 
	
 
	
 
	
    559
	
 
	
 
	
 
	
    15,094
	
 

	

    Regulatory Fees
    

	
 
	
    Submission
    
	
 
	
 
	
    6
	
 
	
 
	
 
	
    800
	
 
	
 
	
 
	
    4,800
	
 

	

    Courier
    

	
 
	
    per site/month
    
	
 
	
 
	
    648
	
 
	
 
	
 
	
    15
	
 
	
 
	
 
	
    9,631
	
 

	

    Mobile phones
    

	
 
	
    per CRA per month
    
	
 
	
 
	
    30
	
 
	
 
	
 
	
    42
	
 
	
 
	
 
	
    1,243
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £345,259
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

 

    Table 5

 

		
	
    3.  
	
    Data
    Management

 

		
	
    3.1  
	
    Data
    Management Specifications

 

    ICON Data Management will apply the same standards and implement
    the same processes for the extension study as we are currently
    using for the core study. The specifications for the extension
    study are outlined below:

 

	 	 	 	 	 
	

    Activity

	
 
	

    Unit Type

	
 
	

    Specification

	 

	

    Project Management

	
 
	
 
	
 
	
 

	

    Study Duration:
    

	
 
	
    Month
    
	
 
	
    12*
    

	

    Frequency of Status Reports:
    

	
 
	
    Monthly
    
	
 
	
    12
    

	

    Meetings

	
 
	
 
	
 
	
 

	

    Teleconferences with Amarin
    (weekly):
    

	
 
	
    Hours/Meeting
    
	
 
	
    1 x 48
    

	

    Face to Face Meetings:
    

	
 
	
    Hours/Meeting
    
	
 
	
    1 x 20
    

	

    Project
    Set-up

	
 
	
 
	
 
	
 

	

    Updates to study documentation:
    

	
 
	
    Documentation
    
	
 
	
    Yes
    

	

    Modification of existing database:
    

	
 
	
    Database Panel
    
	
 
	
    18
    

	

    Modification of existing data
    listings:
    

	
 
	
    Listings
    
	
 
	
    Yes
    

	

    Additional edit check programs:
    

	
 
	
    Program
    
	
 
	
    220
    

	

    Program External Data and
    Review

	
 
	
 
	
 
	
 

	

    Central laboratory interface:
    

	
 
	
    Laboratory
    
	
 
	
    12
    

	

    Genetic & EFA interface:
    

	
 
	
    Interface
    
	
 
	
    No
    

	

    Data Processing

	
 
	
 
	
 
	
 

	

    Total Number of Patients
    

	
 
	
 
	
 
	
 

	

    Drop-out patients:
    

	
 
	
    Patient
    
	
 
	
    0
    

	

    Completed patients:
    

	
 
	
    Patient
    
	
 
	
    261 (ext)
    

	

    Total pages processed:
    

	
 
	
    Page
    
	
 
	
    7830
    

	

    Coding

	
 
	
 
	
 
	
 

	

    Coded Terms (60% autoencode):
    

	
 
	
    Item
    
	
 
	
    1436
    

	

    Query Processing

	
 
	
 
	
 
	
 

	

    Data Queries:
    

	
 
	
    Query
    
	
 
	
    783
    

	

    Data Transfers to
    Amarin

	
 
	
 
	
 
	
 

	

    Final Transfer:
    

	
 
	
    Transfer
    
	
 
	
    1
    

	

    Quality Control
    Reviews

	
 
	
 
	
 
	
 

	

    100% Reviews of CRFs:
    

	
 
	
    Patients
    
	
 
	
    16
    

	

    Critical Variable Reviews (20
    items):
    

	
 
	
    Patients
    
	
 
	
    261
    

	

    Closeout Activities

	
 
	
 
	
 
	
 

	

    Return of CRFs to Amarin:
    

	
 
	
    Pages
    
	
 
	
    7830
    

	

    Other Activities

	
 
	
 
	
 
	
 

	

    SAE Reconciliation:
    

	
 
	
    SAE
    
	
 
	
    30
    

 

 

			
	
    * 		
    Please note that we have included an additional 12 project
    months for the extension study on the basis that costs up to
    JUNE 2007 are including in the main study.

 

    Note: ICON has assumed the number of coded terms and the
    query rate based on previous experience. If ICON finds there is
    a significant differences in these figures throughout course of
    the study, Amarin will be notified immediately and a review of
    the costs associated with these items shall occur.

 

    Note: Total Number of Pages are based on the following
    assumption: that the extension study runs for one year it is
    estimated that all patients will complete the first 4
    visits — Visit 4(5 pages), Telephone Visit (5), Visit
    5 (9) and Visit 6 (11).

 

 

    Table
    6

 

    Reconciliation
    of Serious Adverse Events

 

    ICON will perform SAE reconciliation. ICON will perform SAE
    Reconciliation between the Clinical Database and the Kendle
    Database. This will be done on a monthly basis. It will take
    approximately 1 hour to reconcile each SAE.

 

    Case
    Record Form Scanning

 

    ICON will scan all CRFs received into the OptICON system. ICON
    will file and store the CRFs in a secure and confidential manner
    throughout the course of the study.

 

		
	
    3.2  
	
    CRF
    Design Specifications

 

    ICON will design two additional unique Case Record Form (CRF)
    pages for the extension study (using Framemaker). Amarin will
    review and approve these pages prior to release.

 

		
	
    3.3  
	
    Direct
    Cost Estimates (Data Management)

 

    These costs are based on the assumption that Data Management
    will be done in Europe

 

	 	 	 	 	 
	

    Data Management Activity

	
 
	
    Costs GBP
	
 

	 

	

    Project Management
    

	
 
	
 
	
    £20,975
	
 

	

    Revisions to database and
    development of new edit checks
    

	
 
	
 
	
    £12,816
	
 

	

    Meetings and teleconferences
    

	
 
	
 
	
    £6,940
	
 

	

    External Data Review and
    Reconciliation
    

	
 
	
 
	
    £891
	
 

	

    CRF Page Scanning
    

	
 
	
 
	
    £4,567
	
 

	

    Data Entry
    

	
 
	
 
	
    £14,588
	
 

	

    Validation
    

	
 
	
 
	
    £29,372
	
 

	

    Queries
    

	
 
	
 
	
    £8,658
	
 

	

    Coding
    

	
 
	
 
	
    £1,517
	
 

	

    Data Transfers
    

	
 
	
 
	
    £348
	
 

	

    SAE Reconciliation
    

	
 
	
 
	
    £2,428
	
 

	

    Quality Reviews
    

	
 
	
 
	
    £5,357
	
 

	

    CRF Redesign Costs
    

	
 
	
 
	
    £2,572
	
 

	
 
	
 
	
 
	
 
	
 

	

    TOTAL ADDITIONAL DATA
    MANAGEMENT COSTS

	
 
	
 
	
    £111,029
	
 

	
 
	
 
	
 
	
 
	
 

 

 

    NOTE 1: Data Management costs are based on the
    specifications outlined in section 3.1 and may be deemed as
    “ballpark” until the final specifications for the
    extension study have been agreed.

 

    NOTE 2: Biostatistics costs have not been included at
    this time as we await confirmation of ICON’s involvement in
    this activity and agreement of the final specifications.

 

    Table 7

 

		
	
    3.4  
	
    Pass-through
    Costs Estimates (Data Management)

 

	 	 	 	 	 
	
 
	
 
	
    Total Cost

    
	
 

	

    Activity

	
 
	
    (GBP)
	
 

	 

	

    Teleconferencing
    

	
 
	
 
	
    £874
	
 

	

    Communication
    

	
 
	
 
	
    £2,524
	
 

	

    Travel
    

	
 
	
 
	
    £3,747
	
 

	

    CRF Printing
    

	
 
	
 
	
    £11,096
	
 

	

    CRF Distribution
    

	
 
	
 
	
    £1,000
	
 

	
 
	
 
	
 
	
 
	
 

	

    Total Cost

	
 
	
 
	
    £19,241
	
 

	
 
	
 
	
 
	
 
	
 

 

    Table 8

 

		
	
    4.  
	
    Cost
    Summary

 

	 	 	 	 	 
	

    ICON Service

	
 
	
    Total Cost (GBP)
	
 

	 

	

    Clinical Research Management Europe
    

	
 
	
 
	
    462,129
	
 

	

    Data Management
    

	
 
	
 
	
    111,029
	
 

	
 
	
 
	
 
	
 
	
 

	

    Sub-total
    (ICON Service)

	
 
	
 
	
    £573,158
	
 

	
 
	
 
	
 
	
 
	
 

 

	 	 	 	 	 
	

    Estimated Pass-Through Costs

	
 
	
    Total Cost (GBP)
	
 

	 

	

    Clinical Research Management Europe
    

	
 
	
 
	
    345,259
	
 

	

    Data Management
    

	
 
	
 
	
    19,241
	
 

	
 
	
 
	
 
	
 
	
 

	

    Sub-total
    (ICON Service)

	
 
	
 
	
    £364,500
	
 

	
 
	
 
	
 
	
 
	
 

	

    Total Study Cost
    Estimate

	
 
	
 
	
    £937,658
	
 

	
 
	
 
	
 
	
 
	
 

 

    Table
    9

 

    Appendix 2-Payment
    Schedule

 

	 	 	 	 	 
	

    Change Order Clinical Direct
    Fee Value: £462,129

	
 
	
 
	
 
	
 

	

    Initial Payment 10% on signature
    of Change Order (Feb 07)
    

	
 
	
 
	
    £46,213
	
 

	

    Monthly Payments x 1 month
    Feb 07 (for the period July06 — Feb 07)
    

	
 
	
 
	
    £138,640
	
 

	

    Monthly Payments x 16 months
    (Mar07 — Jun08) £17,330 per month
    

	
 
	
 
	
    £277,280
	
 

	

    Change Order Direct Fee Value:
    £111,029

	
 
	
 
	
 
	
 

	

    Initial Payment 10% on signature
    of Change Order (Feb 07)
    

	
 
	
 
	
    £11,103
	
 

	

    Monthly Payments x 1 month
    Feb 07 (for the period July06 — Feb 07)
    

	
 
	
 
	
    £33,304
	
 

	

    Monthly Payments x 16 months
    (Mar07 — Jun08) £4,163 per month
    

	
 
	
 
	
    £66,608
	
 

	

    SUMMARY: Change Order 2 Payment
    Schedule

	
 
	
 
	
 
	
 

	

    Change Order Direct Fee Value:
    Clinical
    

	
 
	
 
	
    £462,133
	
 

	

    Change Order Direct Fee Value:
    Data Management
    

	
 
	
 
	
    £111,015
	
 

	
 
	
 
	
 
	
    £573,148
	
 

	

    SUMMARY OF COSTS (CHANGE
    ORDER #4)

	
 
	
 
	
 
	
 

	

    10% upon signature
    

	
 
	
 
	
    £57,315
	
 

	

    Monthly Payments x 1 month
    Feb 07 (for the period July06 — Feb 07)
    

	
 
	
 
	
    £171,944
	
 

	

    Monthly Payments x 16 months
    £21,493 (Mar07 — Jun08)
    

	
 
	
 
	
    £343,888
	
 

	
 
	
 
	
 
	
 
	
 

	
 
	
 
	
 
	
    £573,147
	
 

	
 
	
 
	
 
	
 
	
 

 

    REVISED
    ICON EU PAYMENT SCHEDULED (CHANGE ORDER #4)

 

	 	 	 	 	 
	

    Milestone Payments

	
 
	
    Contract Value
	
 

	 

	

    Task Completed

	
 
	
 
	
 
	
 

	

    Contract Signed
    

	
 
	
 
	
    342,550
	
 

	

    All sites initiated
    

	
 
	
 
	
    192,684
	
 

	

    50% of patients enrolled
    

	
 
	
 
	
    192,684
	
 

	

    Initial Payment 10% on signature
    of C/O#2
    

	
 
	
 
	
    25,984
	
 

	

    Initial Payment 10% on signature
    of C/O#3
    

	
 
	
 
	
    2,962
	
 

	

    Initial Payment 10% on signature
    of C/O#4
    

	
 
	
 
	
    57,315
	
 

	

    100% of patients enrolled
    

	
 
	
 
	
    192,684
	
 

	

    Mid-point of treatment phase
    

	
 
	
 
	
    192,684
	
 

	

    All patients completed and data at
    DM
    

	
 
	
 
	
    192,684
	
 

	

    All sites closed
    

	
 
	
 
	
    38,537
	
 

	

    Final Tables & Listings
    

	
 
	
 
	
    25,691
	
 

	
 
	
 
	
 
	
 
	
 

	

    Total Milestones
    payments

	
 
	
 
	
    £1,456,462
	
 

	
 
	
 
	
 
	
 
	
 

 

	 	 	 	 	 	 	 	 	 	 	 	 	 	 	 
	

     Monthly Payments

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Monthly Payments contract
    

	
 
	
    April ‘05 - Jan’ 07
    
	
 
	
 
	
    22
	
 
	
 
	
 
	
    15,570
	
 
	
 
	
 
	
    342,550
	
 

	

    Monthly Payments change
    order #2
    

	
 
	
    Jun ‘06 - May’ 07
    
	
 
	
 
	
    12
	
 
	
 
	
 
	
    19,488
	
 
	
 
	
 
	
    233,856
	
 

	

    Monthly Payments change
    order #3
    

	
 
	
    Feb’ 07
    
	
 
	
 
	
    1
	
 
	
 
	
 
	
    8,886
	
 
	
 
	
 
	
    8,886
	
 

	

    Monthly Payments change
    order #3
    

	
 
	
    Mar ‘07 - June’ 07
    
	
 
	
 
	
    4
	
 
	
 
	
 
	
    4,443
	
 
	
 
	
 
	
    17,772
	
 

	

    Monthly Payments change
    order #4
    

	
 
	
    Feb’ 07
    
	
 
	
 
	
    1
	
 
	
 
	
 
	
    171,944
	
 
	
 
	
 
	
    171,944
	
 

	

    Monthly Payments change
    order #4
    

	
 
	
    Mar ‘07 - June’ 08
    
	
 
	
 
	
    16
	
 
	
 
	
 
	
    21,493
	
 
	
 
	
 
	
    343,888
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Total Monthly
    payments

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £1,118,896
	
 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	

    Total payments

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
    £2,575,358exv4w73

 

    Exhibit 4.73

 

     

    7 Curzon Street, London, W1J 5HG

    Tel: +44 (0)20 7499 9009 Fax: +44 (0)20 7499 9004

 

    Addendum
    to Amarin Executive Employment Contracts — Alan
    Cooke

 

    Sickness

 

    If you are ill and unfit for work, you must personally contact
    your manager as early as possible on the first day and comply
    with the absence policy as detailed in the handbook.

 

    If you are ill for less than 7 consecutive days (including
    weekends) you must complete a self certification form. For
    longer periods of illness a Doctor’s certificate must be
    supplied and additional ones sent to cover the whole period of
    sickness.

 

    Company Sick Pay may be paid at the Company’s absolute
    discretion as follows in a rolling 12 month period:

 

	 	 	 	 	 	 
	
 
	
 
	
 
	
    Period for Which Full Pay is

    
	
 

	
 
	
 
	
 
	
    Normally Payable in a

    
	
 

	
    Length of Continuous Employment on Commencement of Absence
	
 
	
 
	
    Twelve Month Period
	
 

	

    Up to 1 year
    

	
 
	
 
	
 
	
    4 weeks
	
 

	

    Over 1 year and up to
    3 years
    

	
 
	
 
	
 
	
    8 weeks
	
 

	

    Over 3 years and up to
    5 years
    

	
 
	
 
	
 
	
    13 weeks
	
 

	

    Over 5 years
    

	
 
	
 
	
 
	
    26 weeks
	
 

	
 
	
 
	
 
	
 
	
 
	
 

 

    The Company may at any time require you to have a medical
    examination at the Company’s expense.

 

    Should you have, or develop a condition that could be described
    as a disability you have a duty to inform us so that any
    reasonable adjustment may be made to your work or working
    environment. This disclosure would be treated in strictest
    confidence and you would not be discriminated against in any way.

 

    Confidential
    Information and Company Documents

 

    The Executive shall neither during the Employment (except in the
    proper performance of his duties) nor at any time after the
    termination of the employment:

 

    (a) divulge or communicate to any person, company, business
    entity or other organisation;

 

    (b) use for his own purposes or for any other purposes
    other than those of the Company or Group Company; or

 

    (c) through any failure to exercise due care and diligence,
    permit or cause any unauthorised disclosure of any Confidential
    Information. These restrictions shall cease to apply to any
    information which shall become available to the public generally
    otherwise than through any default of the Executive.

 

    This communication and the
    information it contains are intended for the person(s) or
    organisation(s) named above and for no other person or
    organisation

    and may be confidential and
    protected by law, Unauthorised use, copying or disclosure of any
    part is strictly prohibited and may be unlawful.

 

    Amarin Corporation plc

 

		
	    Registered
    in England No 2353920	    Registered
    office: 110 Cannon Street, London EC4N 6AR

 

    All books, notes, memoranda, records, lists of customers and
    suppliers and employees, correspondence, documents, computer and
    other discs, tapes and other data storage, date listings, codes,
    designs, and drawings and other documents and material
    whatsoever (whether made or created by the executive or
    otherwise) relating to the business of the company or any Group
    Company (and copies of the same):

 

    (a) shall be and remain the property of the Company or the
    relevant Group Company; and

 

    (b) shall be handed over by the executive to the Company or
    to the relevant Group Company on demand and in any event on the
    termination of Employment

 

    Intellectual
    Property Rights

 

    It shall be part of the contractual duties of the Executive
    (whether alone or with any other employee of the Company or any
    Group Company) at all times to further the interests of the
    Company and its Group Companies and, without prejudice to the
    generality of the foregoing and to the extent as is consistent
    with the Executive’s role within the Company;

 

    (a) to make, discover and conceive inventions, processes,
    techniques, designs, improvements or developments relating to or
    capable of use or adaptation for use in connection with the
    business or any Group Company (“an Invention”)

 

    (b) to consider in what manner and by what new methods or
    devices the products, services, processes, equipment or systems
    of the Company or any Group Company with which the Executive is
    concerned or for which the Executive is responsible, might be
    improved (“a Development”);

 

    (c) promptly to give to the Company or any Group Company
    full details of any such Invention or Development which the
    Executive may from time to time make or discover in the course
    of their Employment; and

 

    (d) to further the interests of the Company’s or any
    Group Company’s undertaking with regard thereto

 

    and the Company or any Group Company shall be entitled to the
    exclusive ownership of any such Invention or Development and to
    the exclusive use thereof, provided that this clause shall take
    effect subject to any statutory rights of the Executive.

 

    The Executive shall immediately give full information to the
    Board as to such Invention or Development and the exact mode of
    working, producing, using and exploiting the same and shall also
    give all such explanations and instructions to the Board as may
    be necessary or useful to enable the Company or any Group
    Company to obtain full benefit of them and will at the expense
    of the Company or any Group Company furnish it with all
    necessary plans, drawings, formulae and models applicable to the
    same and shall at the cost and expense of the Company or any
    Group Company execute all documents and do all acts and things
    necessary to enable the Company or any Group Company (or its or
    their nominees) to apply for and obtain protection for such
    Inventions and Developments throughout the world and for vesting
    the ownership of them in the Company or any Group Company (or
    its or their nominees).

 

    The Executive shall not knowingly do anything to imperil the
    validity of any patent or protection related to the business of
    any Company or any Group Company or any application therefore
    but shall at the cost to the Company or any Group Company render
    all possible assistance to the Company or any Group Company,
    both in obtaining and in maintaining such patents or other
    protection.

 

    The Executive shall not either during Employment or any time
    after the Employment exploit or assist others to exploit any
    Invention or Development which the Executive may from time to
    time make or discover in the course of the Employment or (unless
    the same shall have become public knowledge otherwise than by
    breach by the Executive of the terms of the Appointment) make
    public or disclose any such Invention or Development or
    improvement or given any information in respect of the same
    except to the Company or any Group Company or as it may direct.

 

    The Executive hereby irrevocably appoints the Company or any
    Group Company to be the Executive’s attorney in the
    Executive’s name and on the Executive’s behalf to
    execute all documents and do all things necessary and generally
    to use the Executive’s name for the purpose of giving the
    Company or any Group Company (or its or their nominees) the full
    benefit of the provisions of this clause and in favour of any
    third party a certificate in writing

 

    signed by any director or the secretary of the Company or any
    Group Company that any instrument or act which falls within the
    authority conferred by this clause which shall be conclusive
    evidence that such is the case.

 

    Copyright and unregistered design rights in all works created by
    the Executive in the course of the Employment will, in
    accordance with the Copyright Designs and Patent Act 1988, vest
    in the Company or any Group Company. Rights in any design
    registerable pursuant to the Registered Designs Act 1949, (as
    amended) created by the Executive in the course of his
    Employment shall, in accordance with the Act, vest in the
    Company or any Group Company.

 

    Restrictions
    during Employment

 

    During the course of Employment the Executive shall not:

 

    (a) be directly or indirectly employed, engaged, concerned
    or interested in any other business or undertaking; or

 

    (b) engage in any activity which the Board reasonably
    considers may be, or become harmful to the interests of Company
    or any Group Company or which might reasonably be considered to
    interfere with the performance of the Executive’s duties
    under this Agreement.

 

    The above Clause shall not apply:

 

    (a) to the Executive holding (directly or through nominees)
    of investments listed on the London Stock Exchange or in respect
    of which dealing takes place in the Unlisted Securities Market
    on the London Stock Exchange or any recognised stock exchange as
    long as he does not hold more than 5% of the issued shares or
    other securities of any class of any one Company; or

 

    (b) to any act undertaken by the executive with the prior
    written consent of the Board; or

 

    (c) to any interest permitted with the prior approval of
    the Board (such interest not to be unreasonably withheld) for
    the Executive to serve from time to time and continue to serve
    on the Boards of and hold any other offices or positions in
    companies or organisations which will not present any conflict
    of interest with Company or any Group Company and provided that
    such activities do not materially detract from the performance
    of the Executive’s duties.

 

    Share
    Dealings

 

    The Executive shall comply fully with Amarin’s Share
    Dealing Code.

 

    I acknowledge receipt of this Addendum to my Contract of
    employment and agree to the terms and conditions as set out
    above.

 

	 	 	 
	

    Signed

	
 
	
    
    

 

    (Alan Cooke)

 

    Dated  21/Feb/2007

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