Change Order Number 3
Exhibit 4.75
Change
Order Number 3
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. | |
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 order number 2 dated 8th of June
2006 shall remain in full force and effect.
3. The value of this Change Order shall be £29,620
in direct fees and £260,795 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 1 March 2007
|
DATE 28 February 2007 | |
SIGNED Xxxx Xxxxx
|
SIGNED Xxxx Xxxxx |
Appendix 1
1. Introduction
The main changes to the project specifications are the following:
• | The patient numbers have been amended from 240 to 290 enrolled | |
• | The clinical team allocation has been revised in line with the planned monitoring visit schedule (table 4) thus allowing for a reduced number of monitoring visits | |
• | Study sites have decreased from 30 to 27 from July 2006 (reduced by 1 in Italy, 1 in UK and 1 in Portugal) | |
• | The official Close Out visits will now be performed as part of the Open Label extension study as agreed with Amarin. It is assumed that during the last monitoring visit for the core study an additional 4 hours time on site will be added to allow for the final collection of all the core study data (as the close out visits will be deferred to the end of the extension phase). Therefore, costs associated with resource and travel for the close out activity has been removed from this revised costing. | |
• | Study Timelines: The overall study timelines have been decreased in line with the revised milestone dates as outlined in the table 1 below. This allows for further cost reductions | |
• | Staff Allocation: The revised staff allocation in presented in table 3. This is now in line with the revised study timelines and planned monitoring visit schedule. | |
• | Medical Writing Cost for both studies (AN01.01.0011 and AN01.01.0012) not previously included in the contract are now included in this change order. These costs have been previously presented to and agreed by Amarin Neuroscience and attached hereafter as Appendix 3 (Cost Proposal Medical Writing Version 1, 4 July 2006). | |
• | Data Management: The Data Management specifications have now been revised to include additional activities related to the increased patient numbers. The revised costs also include a reduction of month activities due to the revised study timelines (reduced by 1 month) | |
• | Pass Through Cost: The pass through costs have been revised. This includes a reduction for CRA travel and an increase for Investigator fees | |
• | Inclusion of a number of unscheduled visits: These visits will be performed at sites where issues have arisen. These visits will help to resolve any issue regarding Monitoring and Case Report Form query collection and resolution. The ICON clinical team have proposed the inclusion of 14 additional visits for the core study for these activities. It is anticipated that these visits may be required close to database lock. Each additional monitoring visit in additional to the monitoring visit plan as presented in table 4, will be billed to Amarin at a rate of £1,119 per visit. This unit cost based on 8 hours time on site, 6 hours travel time and 4 hours preparation/follow up (18 hrs/unit). |
2. Revised
Clinical Project Specifications
The revised study timelines are presented below:
Milestones for Study Extension
|
Timelines
|
|
ICON involvement begin
|
1st of April 2005 | |
First patient in
|
15th of December 2005 | |
Last patient screened (if
applicable)
|
End June 2006 | |
Last patient randomized (if
applicable)
|
End July 2006 | |
Last patient off treatment
|
End January 2007 | |
Last patient out
|
End February 2007 | |
DBL
|
End March 2007 | |
Double Blind Study completed
|
End June 2007 |
Table 1
The site, country and patient distribution is detailed in the
table below.
Country
|
Sites | Number of Patients | ||||||
Austria
|
2 | 29 | ||||||
Germany
|
9 | 87 | ||||||
Italy
|
3 | 52 | ||||||
Portugal
|
1 | 6 | ||||||
Spain
|
4 | 30 | ||||||
UK
|
8 | 86 | ||||||
Total
|
27 | 290 |
Table
2
Staff Allocation:
Based on the requested changes and patient distribution the
clinical study team allocation has been revised as follows:
FTE
|
Staff
|
Time Allocation
|
||||
0.4 | Project Manager | Allocated in April 2005 | ||||
0.8 | Project Manager | Allocated from 1st of May 2005 through 31st of December 2005 | ||||
0.6 | Project Manager | Allocated from 1st of January 2006 through 31st of March 2006 | ||||
0.8 | Project Manager | Allocated from 1st of April 2006 through 31st of 31st March 2007 | ||||
0.2 | Project Manager | Allocated from 1st of April 2007 through 31st of June 2007 | ||||
1.5 | Clinical Research Associates | Allocated in April 2005 | ||||
3.0 | Clinical Research Associates | Allocated from 1st of May 2005 through 31st of December 2005 | ||||
2.8 | Clinical Research Associates | Allocated from 1st of January 2006 through 31st of March 2006 | ||||
4.6 | Clinical Research Associates | Allocated from 1st of April 2006 through 30th of September 2006 | ||||
3.6 | Clinical Research Associates | Allocated from 1st of October 2006 through 31st of December 2006. | ||||
3.5 | Clinical Research Associates | Allocated from 1st of January 2007 through 28th of February 2007. | ||||
3.0 | Clinical Research Associates | Allocated in March 2007 | ||||
0.8 | Clinical Research Associates | Allocated in April 2007 | ||||
0.7 | Clinical Research Assistant | Allocated in April 2005 | ||||
1.4 | Clinical Research Assistants | Allocated from 1st of May 2005 through 31st of December 2005 | ||||
1.2 | Clinical Research Assistants | Allocated from 1st of January 2006 through 31st of March 2006 | ||||
1.4 | Clinical Research Assistants | Allocation from 1st of April 2006 through 30th of September 2006 | ||||
1.3 | Clinical Research Assistants | Allocation from 1st of October 2006 through 28th of February 2007 | ||||
1.1 | Clinical Research Assistants | Allocated in March 2007 | ||||
0.6 | Clinical Research Assistants | Allocated in April 2007 | ||||
Therapeutic Director | Allocated for 5 days for study duration | |||||
Clinical Regulatory Compliance Associate | Allocated for 17 days for study duration | |||||
Accounting Administrator | Allocated for 69 days for study duration |
Table
3
3. Detailed
monitoring visit plan
The table below represents the detailed monitoring visit
schedules as discussed with the Amarin Clinical team
CRA
|
Country
|
Site | Oct | days | Nov | days | Dec | days | Jan | days | Feb | days | ||||||||||||||||||||||||||||||||||
Xxxxx
|
UK | 11 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||||||||||||||||||||||||||||||||||
UK | 12 | 1 | 2 | 1 | 2 | |||||||||||||||||||||||||||||||||||||||||
UK | 14 | 1 | 1 | 1 | 1 | 1 | 1 | |||||||||||||||||||||||||||||||||||||||
UK | 15 | 1 | 2 | 1 | 2 | 1 | 2 | |||||||||||||||||||||||||||||||||||||||
UK | 16 | 1 | 2 | 1 | 2 | 1 | 1 | |||||||||||||||||||||||||||||||||||||||
UK | 18 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |||||||||||||||||||||||||||||||||||||
UK | 2 | 2 | 4 | 4 | 3 | 3 | 6 | 6 | 3 | 3 | ||||||||||||||||||||||||||||||||||||
Leena
|
UK | 13 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||||||||||||||||||||||||||||||||
UK | 17 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |||||||||||||||||||||||||||||||||||||
UK | 1 | 1 | 1 | 1 | 2 | 2 | 2 | 2 | 2 | 2 | ||||||||||||||||||||||||||||||||||||
Ger | 31 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | |||||||||||||||||||||||||||||||||||||
Corinna
|
Ger | 35 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||||||||||||||||||||||||||||||||||
Ger | 37 | 1 | 3 | 1 | 1 | 1 | 1 | 1 | 1 | |||||||||||||||||||||||||||||||||||||
Ger | 39 | 1 | 1 | 1 | 1 | |||||||||||||||||||||||||||||||||||||||||
Aus | 91 | 1 | 4 | 1 | 1 | |||||||||||||||||||||||||||||||||||||||||
Aus | 92 | 1 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | |||||||||||||||||||||||||||||||||||||
Ger | 4 | 4 | 2 | 2 | 4 | 4 | 6 | 6 | 3 | 3 | ||||||||||||||||||||||||||||||||||||
Ger | 32 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 1 | |||||||||||||||||||||||||||||||||||||
Xxxxx
|
Ger | 33 | 1 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||||||||||||||||||||||||||||||||
Ger | 34 | 1 | 1 | 1 | 1 | 1 | 1 | |||||||||||||||||||||||||||||||||||||||
Ger | 36 | 1 | 1 | 1 | 1 | |||||||||||||||||||||||||||||||||||||||||
Ger | 38 | 1 | 1 | 1 | 1 | 1 | 1 | |||||||||||||||||||||||||||||||||||||||
Ger | 5 | 5 | 2 | 2 | 4 | 4 | 4 | 4 | 1 | 1 | ||||||||||||||||||||||||||||||||||||
Port | 41 | 1 | 1 | 1 | 1 | 1 | 1 | |||||||||||||||||||||||||||||||||||||||
Xxxxx
|
ESP | 61 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||||||||||||||||||||||||||||||||
ESP | 62 | 1 | 1 | 1 | 1 | |||||||||||||||||||||||||||||||||||||||||
ESP | 63 | 1 | 1 | 1 | 1 | 1 | 1 | |||||||||||||||||||||||||||||||||||||||
ESP | 64 | 1 | 1 | 1 | 1 | 1 | 1 | |||||||||||||||||||||||||||||||||||||||
0 | 5 | 5 | 1 | 1 | 5 | 5 | 4 | 4 | ||||||||||||||||||||||||||||||||||||||
Xxxxxx
|
ITA | 71 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | ||||||||||||||||||||||||||||||||||||
ITA | 74 | 1 | 1 | 1 | 1 | 2 | 2 | 3 | 3 | 1 | 1 | |||||||||||||||||||||||||||||||||||
ITA | 73 | 1 | 1 | 1 | 3 | 1 | 5 | 1 | 3 | 1 | 1 | |||||||||||||||||||||||||||||||||||
3 | 3 | 2 | 2 | 4 | 4 | 5 | 5 | 3 | 3 | |||||||||||||||||||||||||||||||||||||
Totals
|
15 | 35 | 16 | 40 | 18 | 41 | 28 | 60 | 16 | 33 |
Table
4
4.
Revised Cost Estimates (Clinical)
Number of |
Price per |
|||||||||||||||
Clinical Research Management
|
Units | Units | Unit* | Total (STG£) | ||||||||||||
Clinical Research Associate
|
Days | (84 | ) | 513 | (43,076 | ) | ||||||||||
Clinical Research Assistant
|
Days | (23 | ) | 400 | (9,211 | ) | ||||||||||
CLINICAL RESEARCH MANAGEMENT
SUB-TOTAL
|
£(52,851 | ) | ||||||||||||||
Number of |
Price per |
|||||||||||||
Estimated Pass-Through Costs
|
Units
|
Units | Unit | Total (STG£) | ||||||||||
Travel
|
||||||||||||||
Site Visit Unit Cost Adjustment
|
Visits | (25 | ) | 300 | (7,500 | ) | ||||||||
Investigator Fees
|
||||||||||||||
Investigator Fees
|
Patient | 50 | 4,900 | 245,000 | ||||||||||
Pharmacy Fees
|
Site | (3 | ) | 340 | (1,020 | ) | ||||||||
Hospital Overheads
|
0% per patie | 50 | 490 | 24,500 | ||||||||||
Other
|
||||||||||||||
Mobile phones
|
CRA per mo | (4.4 | ) | 42 | (185 | ) | ||||||||
£260,795 | ||||||||||||||
CLINICAL RESEARCH
TOTAL
|
£(52,851 | ) | ||||||||||||
ESTIMATED PASS THROUGH
COSTS
|
£260,795 | |||||||||||||
OVERALL TOTAL
|
£207,944 | |||||||||||||
Table
5
Note: Cost for each additional monitoring visit will be billed
at a rate of £1,119 per unit (visit).
5. Revised
Cost Estimates (Data Management)
Data Management Activity
|
Description
|
Resource/Time/Duration
|
CO Value | |||||
Project Management
|
Increase in Project Management due to the increase in the number of pages processed. (reduction in the project timelines by one month has been included in the costs) | Additional Project Management Time Required | £6,765 | |||||
Scanning: increase in number of
pages: 5008
|
Increase in the number of pages | Additional Resource Time Required. | £2,934 | |||||
Data Entry: increase in number of
pages: 5008
|
Increase in the number of pages | Additional Resource Time Required. | £9,354 | |||||
Validation: increase in number of
pages 5008. Cost includes increase in obvious corrections
and Data Listings also.
|
Increase in the number of pages | Additional Resource Time Required. | £17,430 | |||||
Queries: increase in number of
queries from 2182 to 2682. Total increase 500.
|
Increase in the number of queries | Additional Resource Time Required. | £4,636 | |||||
Coding: increase in number of
coded terms from 4680 to 5802. Total increase 1122
|
Increase in the number of coded terms | Additional Resource Time Required. | £971 | |||||
Close Out Activity
|
Additional Resource Time Required. | £1,727 | ||||||
Total
|
£43,816 | |||||||
NOTE: Awaiting confirmation of Biostats Specs/Costs are not
included in the above grid. Stats Timelines may change
6. Change
Order Cost Summary
ICON Service
|
Total Cost (GBP) | |||
Clinical Research Management Europe
|
(52,851 | ) | ||
Data Management
|
43,816 | |||
Medical Writing AN01.01.0011
|
20,999 | |||
Medical Writing AN01.01.0012
|
17,656 | |||
Sub-total
(ICON Service)
|
£29,620 | |||
Estimated Pass-Through Costs
|
Total Cost (GBP) | |||
Clinical Research Management Europe
|
260,795 | |||
Sub-total
(ICON Service)
|
£260,795 | |||
Total Study Cost
Estimate
|
£290,415 | |||
Appendix 2-Payment
Schedule
Change Order Clinical Direct
Fee Value: −£52,851
|
||||
Initial Payment 10% on signature
of Change Order (Feb 07)
|
£(5,282 | ) | ||
Monthly Payments x 1 months
in Feb 07 (for period Jan 07 — Feb 07)
|
£(15,856 | ) | ||
Monthly Payments x 4 months
(Mar07 — Jun07) −£7,928 per month
|
£(31,712 | ) | ||
Change Order Direct Fee Value:
£82,471
|
||||
Initial Payment 10% on signature
of Change Order (Feb 07)
|
£8,247 | |||
Monthly Payments x 1 month in
Feb 07 ( for the period Jan ’07 to Feb ’07)
|
£24,742 | |||
Monthly Payments x 4 months
(Mar ’07 to June ’07) £12,371 per month
|
£49,484 | |||
SUMMARY: Change Order 2 Payment
Schedule
|
||||
Change Order Direct Fee Value:
Clinical
|
£82,473 | |||
Change Order Direct Fee Value:
Data Management
|
£(52,850 | ) | ||
£29,623 | ||||
SUMMARY OF COSTS (CHANGE
ORDER #3)
|
||||
10% upon signature
|
£2,962 | |||
Monthly Payments x 1 month in
Feb 07 (for the period Jan 07 — Feb 07 )
|
£8,886 | |||
Monthly Payments x 4 months
(Mar ’07 to Jun ’07) £4,443 per month
|
£17,772 | |||
£29,620 |
REVISED
ICON EU PAYMENT SCHEDULED (CHANGE ORDER #3)
Milestone
Payments
Task Completed
|
Contract Value | |||
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 | |||
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
|
£1,399,147 | |||
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 | ||||||||||||
Total Monthly
payments
|
£603,064 | |||||||||||||||
Total payments
|
£2,002,211 | |||||||||||||||