Change Order Number 4

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 Xxxxx Xxxxxx Xxxxxxxx Xxxx, Xxxxxxxxxxxx, Xxxxxx 00 (‘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 30^th 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 Xxxx Xxxxx		Xx. Xxxx Xxxxx
TITLE CFO, Director		TITLE: Executive VP Commercial & Organisational Development.
DATE 15 February 2007		DATE 29 January 2007
SIGNED Xxxx Xxxxx		SIGNED Xxxx Xxxxx

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 Xxxxxx 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													£2,575,358