Exhibit 4.53


 


Certain portions of this Exhibit have been omitted
pursuant to a request for "Confidential Treatment" under Rule 24b-2
of the Securities and Exchange Commission. 
Such portions have been redacted and bracketed in the request and appear
as [*] in the text of this Exhibit.  The
omitted confidential information has been filed with the Securities and
Exchange Commission.


 


CLINICAL TRIAL AGREEMENT


 


THIS Agreement is entered
into on March 18th 2005 by and between AMARIN NEUROSCIENCE LIMITED, a limited
company incorporated in Scotland with offices located at Kings Park House,
Laurelhill Business Park, Stirling, UK, FK7 9PQ (“Sponsor”) and the UNIVERSITY OF ROCHESTER (“Institution”), a not-for-profit
educational institution established under the laws of New York State, with
business offices located at 5th Floor Hylan Building, RC Box 270140,
Rochester, NY 14627.


 


RECITALS


 


A.           Sponsor is
engaged in the business of (inter alia) the development of pharmaceutical
products, and the Institution is engaged in the business (inter alia) of
providing clinical research and development services, including the provision
of investigators who conduct clinical trials for the pharmaceutical industry,
the management of clinical trials, clinical data management and statistical
analysis.


 


B.             Sponsor
desires Institution to study the safety and/or efficacy of Miraxion TM (formerly
Lax-101)(“Study Drug”) via a Phase III Clinical program and Institution
is willing to perform a clinical study of the Study Drug; and


 


C.             The
Study (as defined below) is of mutual interest and benefit to Sponsor and
Institution, and will further the Institution’s instructional and research
objectives in a manner consistent with its status as a not-for-profit
tax-exempt educational institution;


 


Now therefore, in
consideration of the promises and mutual covenants herein contained, Sponsor
and Institution hereby agree as follows:


 


1.               STATEMENT
OF WORK.


 


1.1                                 The
Institution shall exercise best efforts to carry out or to facilitate the
carrying out of the clinical trial research study set forth in the research
protocol dated 2005 and entitled  “A
Multi Center, Double Blind, Randomized, Parallel Group, Placebo-Controlled
Trial of (ethyl-EPA) Miraxion TM in Patients with Mild to Moderate Huntington’s
Disease” (the “Study”), which is attached hereto as Exhibit A (the “Protocol”)
and hereby incorporated into this Agreement by reference.  The Study shall be conducted under the
direction of Dr. Ira Shoulson as principal investigator and Dr. Christopher
Ross and Dr. Blair Leavitt as Co-Principal


 


1





















 


Investigators
(together the “Principal Investigators”) in accordance with this
Agreement.  The Institution shall procure
that each of the Principal Investigators enters into an agreement containing
the provisions set out in Exhibit D (as may be amended by mutual agreement
as between the Institution and the Sponsor) prior to the commencement of the
Study.


 


1.2                                 The Institution shall
perform the services described in Exhibit B to this Agreement (the “Services”).
All obligations which Sponsor
desires to delegate to Institution
are specified in Exhibit B under Assignment of Responsibilities and Institution shall assume the
responsibility for such delegated obligations as Sponsor under the Federal Food, Drug and Cosmetic Act.  Any obligation not delegated to Institution
pursuant to this Agreement and its Exhibits shall be retained by the Sponsor.


 


1.3                                 Institution acknowledges
that time shall be of the essence in relation to the timetable set out as part
of the Budget attached hereto as Exhibit C.


 


Notwithstanding
the above, Sponsor acknowledges that the Institution’s activities
may be delayed by events or circumstances outside of its control, including,
but not limited to: delays in Study Drug supply; changes to the Protocol or
other related Study documents; regulatory or audit issues; and competing
enrollments in the geographic areas served by investigators conducting the
Study.


 


1.4                                 In
the event that Sponsor requires
for any reason to add to or vary the scope of the Services it shall notify Institution in writing to that effect
and Institution shall, within
ten business days of receipt of such notice, submit its proposals, including
revised costings and timelines, as appropriate, for the performance of such
Services.  If acceptable to Sponsor, the parties shall amend the
Exhibits to this Agreement accordingly.


 


1.5                                 In
performing the Services, the Institution shall (where appropriate), and the
Institution agrees to be responsible for ensuring that its investigators (the “Investigators”), comply
with and procure compliance with the following:


 


1.5.1                        the Protocol and any subsequent
amendments;


 


1.5.2                        the ICH Harmonised Tripartite
Guideline for Good Clinical Practice or its local equivalent (“GCP”);


 


1.5.3                        part 312 Title 21 of the Code
of Federal Regulations issued by the U.S. Food and Drug Administration (“FDA”);


 


1.5.4                        the standard operating
procedures of Institution to be
agreed in advance by Sponsor ;


 


1.5.5                        all applicable national and
local laws, rules and regulations, including but not limited to the U.S.
Federal Food, Drug and Cosmetic Act and


 


2





















 


Regulations
of the FDA, and those promulgated by any relevant regulatory authority, and
relevant professional standards;


 


1.5.6                        all reasonable  written and verbal instructions of Sponsor;


 


and the Institution shall
ensure that:


 


1.5.7                        the Investigators will permit
monitoring, auditing or inspection of their activities by or on behalf of the
Sponsor and the regulatory  authorities;


 


1.5.8                        the Investigators  will
permit direct access to case report forms (“CRFs”), source data and  documentation
(including patient notes) to persons performing trial-related  monitoring,
audits, ethical review or regulatory inspection.  The expected frequency
of monitoring visits will be as agreed between the parties from time to time;


 


1.5.9                        Investigators understand any
persons delegated trial related duties are  suitably qualified and aware
of the requirements of the Protocol, ICH GCP and the appropriate regulatory
requirements and are adequately informed  about the Study Drug;


 


1.5.10                  the Investigators have adequate
facilities, resources  and time are available to conduct the Study;


 


1.5.11                  adequate drug  storage
facilities and drug accountability procedures are in  place;


 


1.5.12                  Study CRFs and other relevant Study
documents are completed on an ongoing basis throughout the duration of the
Study and are completed accurately and legibly and are consistent with the
source documents;


 


1.5.13                  Investigators notify all adverse
events and serious adverse events  (including suspected unexpected serious adverse
events) occurring during the course of the Study to Institution, the Sponsor
and any company contracted by the Sponsor to manage the reports and ensure
onward reporting to Regulatory Authorities;


 


1.5.14                  the Investigators assist in the
preparation of ethics submissions and  ensuring
that local ethical approvals are in place;


 


1.5.15                  the storing of essential Study
documents (as defined by ICH GCP) is in a suitable  archive for the period
required by ICH  GCP guidelines;


 


and that all such responsibilities will be
contained in a written agreement  between the Institution and its
Investigators in a form approved by the Sponsor in writing.


 


3





















 


1.6                                 Institution shall perform the Services
with reasonable care and skill and shall ensure that personnel engaged by it in
the provision of the Services are competent and have appropriate professional
qualifications, training and experience.


 


1.7                                 Each
party shall from time to time by notice to the other nominate (a) representative(s)
for primary liaison relating to the Services, which from the date of this
Agreement shall be as follows:


 


	
  For Sponsor:

  	
  Bimmie Strausser MD

  
	
   

  	
  Consultant

  
	
  For Institution

  	
  Dr. Ira Shoulson

  
	
   

  	
  Principal Investigator

  



 


1.8                                 Institution agrees that all personnel
performing the Services shall be employees or sub-contractors of Institution and that nothing in this
Agreement shall be deemed to create a contract of employment between Sponsor and any employee or
sub-contractor of Institution.


 


1.9                                 Sponsor agrees to provide in good time
to Institution all data, advice
and information reasonably necessary for the performance of the Services in
accordance with this Agreement.


 


1.10                           Institution agrees (provided Sponsor has given it adequate notice
in advance) to allow Sponsor to
attend the site(s) where the Services are being conducted for the purpose of
monitoring and reviewing the performance of the Services at times and dates
mutually acceptable to all parties and to give Sponsor its full co-operation in
this regard.


 


1.11                           In
the event of any inconsistency between this Agreement and the Protocol, the
terms of this Agreement shall govern. 
Changes in the Protocol may be made only through prior written agreement
between the Sponsor and the Institution.


 


1.12                           The
Institution agrees to screen sufficient numbers of patients into the Study to
allow for 300 patients to be randomised into the Study.


 


1.13                           The
Sponsor reserves the right to amend in writing the numbers of patients to be
randomised as set out in Article 1.12, in accordance with the provisions
of Article 1.4.


 


2.               PERIOD
OF PERFORMANCE.


 


The Period of Performance
under this Agreement shall commence on the date of this Agreement and shall remain
in force (subject to earlier termination pursuant to Article 14) until the
completion of the Services in accordance with the terms of this Agreement. The
Study may not in any event begin until approval is received from the
Institution’s Institutional Review Board (“IRB”) and Regulatory Authority.


 


4





















 


3.               PAYMENT.


 


3.1                                 Sponsor
shall pay the Institution in accordance with the budget and milestone schedule attached
hereto as Exhibit C and incorporated herein by reference (the “Budget”).  The parties estimate that the payments
provided for in the Budget will be sufficient to support the Study, but
Institution may submit to Sponsor and/or the Sponsor may request a revised
budget in the event that costs may reasonably be projected to exceed or be less
than the Budget.  Except as otherwise
provided in this Agreement, Sponsor will not be required to make any payment in
excess of the Budget without Sponsor’s prior written approval.


 


3.2                                 Regardless
of whether it is included in the Budget, the Sponsor understands and agrees
that it is responsible for paying the Institution’s nonrefundable Institutional
Review Board fees and for reimbursing to the Institution any Institutional
Review Board fees payable to any third party in respect of any site taking part
on the Study, and shall pay such fees within thirty (30) days of the date of
receipt of the invoice except as otherwise provided in the Budget.


 


3.3                                 Sponsor
shall in addition reimburse Institution for reasonable and necessary
pre-approved travel and other out-of-pocket expenses properly and necessarily
incurred in the performance of the Services as set out in Exhibit B(the “Expenses”),
provided that the Institution produces copy invoices or other substantiating
documentation and, in the case of any individual item of expenditure exceeding
the sum of $500, Sponsor’s prior
written approval has been given to such expenditure.


 


3.4                                 Institution
shall render invoices in respect of installments of the Budget and in respect
of Milestones (once achieved), when payable, and monthly invoices in arrears in
respect of the Expenses. Payment shall be due within 30 days of the date of
receipt of the Institution’s invoice.


 


3.5                                 Checks
shall be made payable to the University of Rochester and sent to:


 


University of Rochester


Clinical
Trials Coordination Center


1351 Mt. Hope Avenue, Suite 223


Rochester, NY  14620


ATTN:   Finance Department.


 


3.6                                 For
purposes of identification, each payment shall include the title of the project
and the name of the Principal Investigator.


 


5





















 


3.7                                 Payments
will be made by the Sponsor to the Institution and from the Institution to
participating Study sites upon (i) completion of CRF’s for evaluable
patients, and (ii) inclusion of such CRF’s in the Study database.


 


4.               SUPPLIES.


 


Sponsor will provide Institution, at no charge, with a sufficient
quantity of the Study Drug and matching placebo necessary to conduct the Study,
as well as any other compounds, materials, equipment, and information, which
the Protocol specifies as being provided by Sponsor to Institution, or which
Sponsor and Institution deem necessary to conduct the Study.  All such Study Drug, compounds, materials,
and equipment remain the sole property of Sponsor, unless otherwise designated.


 


5.               INVESTIGATOR’S
ASSURANCE.


 


5.1                                 The
Institution acknowledges that the Principal Investigator agrees to undertake
certain obligations as prescribed in Exhibit B and as required by
applicable government regulations.


 


5.2                                 Sponsor
acknowledges that the responsibility to comply with and perform under the
provisions of Exhibit B where indicated as being the responsibility of the
Principal Investigator shall rest with the Principal Investigators as required
by the Food and Drug Administration (FDA).


 


6.         NOTICES.


 


Any notices related to
this Agreement or required herein shall be in writing and delivered by first
class mail, postage prepaid, or by facsimile (facsimile notice to be confirmed
by letter posted within 24 hours of transmission) to the address of the other
party as set out below (or such other address as may have been notified in
writing to the other party), and any such notice shall be deemed to have been
served at the time of delivery (if delivered) or upon the expiration of 96
hours after posting (if sent by post) or upon the expiration of 12 hours after
transmission (if sent by facsimile)


 


6





















 


	
  INSTITUTION

  Gunta J. Liders,

  Associate VP for Research Administration

  University of Rochester

  Office of Research & Project Administration

  5th Floor Hylan Bldg.

  Rochester, NY 14627

  Phone: (585) 275-4031

  FAX: (585) 275-9492

  	
   

  	
  SPONSOR

  

  General Counsel & Company Secretary
 Amarin Corporation plc;

  7 Curzon Street;

  Mayfair;

  London

  W1J 5HG

  U.K

  Phone +44 (0)20 7907 2447

  FAX: +44 (0)20 7499 9004 

  



 


7.               INDEPENDENT
CONTRACTOR.  The Institution is an
independent contractor and not an agent, joint venturer, or partner of Sponsor.


 


8.               INDEPENDENT
RESEARCH.  Nothing in this Agreement
shall be construed to limit the freedom of the Principal Investigators and/or
Institution, its employees and agents, whether paid under this Agreement or
not, to engage in similar inquiries made independently under other grants,
contracts or agreements with parties other than Sponsor.


 


9.               CONFIDENTIAL
INFORMATION.   All information
designated at the time of disclosure, in writing, by either party as
confidential (“Confidential Information”) shall not be used by the other party
other than for purposes of this Agreement.  Each party agrees to treat Confidential
Information received from the other party with the same degree of care with
which it would treat its own Confidential Information of a similar nature and
further agrees not to disclose such Confidential Information to a third party
without prior written consent of the other party, for a period of five (5) years
following disclosure.  The foregoing
obligations of non-disclosure do not apply to Confidential Information which:


 


(a)          is in the
public domain at the time of disclosure;


(b)         was known
to the other party prior to disclosure;


(c)          was
received from a third party not under an obligation of confidence to Sponsor;


(d)         is required
to be disclosed by law or at the request of a governmental authority, but only
to the extent that such disclosure has been so directed or requested and
provided that Sponsor has been given sufficient advance notice of any such
proposed disclosure in order to enable it to take appropriate measures to
protect the confidentiality of the Confidential Information; or


(e)          is
disclosed by either party to its employees and sub-contractors who reasonably
require access to it and use of it for the purpose of carrying out that party’s
rights and obligations under this Agreement, and who have a contractual
obligation to that party to (i) protect the confidentiality of information
such as the Confidential Information on terms no less onerous than as set out
in this Agreement; and (ii) to assign all


 


7





















 


Intellectual Property (as defined below) arising from
such individuals work on behalf of that party to that party upon request.


 


10.         DATA
OWNERSHIP AND INTELLECTUAL PROPERTY. 
The Institution agrees that all data, inventions and discoveries
generated by any party (to include for the avoidance of doubt any Subcontractor
or Investigator) during the course of the activities described in the Exhibits
hereto shall be the sole and exclusive property of Sponsor.  The Institution shall execute any documents
or undertake any further actions if requested by Sponsor to evidence transfer
of title thereto.  Sponsor shall
reimburse the Institution, Principal Investigators or Subcontractors for any
reasonable expenses incurred at Sponsor’s request to secure title or legal
protection for any such Inventions. 
Notwithstanding the above, the Institution and its Subcontractors may
retain a copy of the data, inventions and discoveries for their own education
and non-commercial research purposes. 
The Institution shall also own the copyright to all of its standard forms previously
created by the Institution, including those modified for use by Sponsor.


 


11.         PUBLICATION.   Sponsor acknowledges that Institution is
dedicated to free scholarly exchange and to public dissemination of the results
of its scholarly activities.  Therefore,
Institution shall have the right at its reasonable discretion to publish in
writing, material resulting from or related to the Study.  The Institution shall furnish Sponsor with a
copy of any proposed written publication or presentation of such material at
least thirty (30) days prior to the submission for publication. Within said
period, Sponsor shall review such proposed publication for any designated
proprietary information and, by written notice to the Institution, identify
with specificity the sentence(s) or figure(s) in the proposed publication which
Sponsor contends contains such proprietary information or which cannot be
disclosed for legal or administrative reasons so that the proposed publication
shall be edited appropriately by the Institution to remove it/them before
publication.  If the Sponsor determines
that the proposed publication contains patentable subject matter which requires
protection, the Sponsor may require delay of submission for publication for a
period of time not to exceed sixty (60) days for the purpose of filing patent
applications.  The Institution shall give
the Sponsor and /or Sponsor’s personnel appropriate credit and / or recognition
for co-authorship in accordance with academic standards for any direct
contribution made by them, subject to their prior consent.


 


12.         SITE
MONITORING AND AUDITING Sponsor and the Institution acknowledge that
routine site monitoring is not included in the Institution’s Work Scope,
attached as Exhibit B, and will be performed by a sub-contractor of
Sponsor. Should Sponsor elect to conduct additional audits, inspections or
reviews of the Investigators and/or sites participating in this Study (“quality
assurance”, “validation” or other Sponsor related audits) over and above
routine monitoring, which places an undue burden on the relevant Investigators
and/or sites participating in this Study then Sponsor agrees that a reasonable
fee shall be due and owing to the Investigator/site so audited.  This fee shall not apply in the event of an
FDA or Sponsor


 


8





















 


“for
cause” inspection and shall not in any event exceed $1,000 where such audit,
inspection or review is two days or less.


 


13.         PUBLICITY.  Neither party shall use the name of the other
in connection with any products, promotion, or advertising related to this
Study without the prior written permission of the other party save to the
extent as is properly required to be disclosed by law or at the request of a governmental
authority.  This does not include the
existence of the Agreement for internal reporting requirements.


 


14.         TERMINATION.


 


14.1                           This
Agreement may be terminated without cause by either party at any time during
the term of the Agreement on ninety (90) days prior written notice to the other
party.  In the event that Agreement is
terminated for any reason by the Institution, the Institution will use its best
efforts to promptly conclude and/or upon Sponsor’s request, transfer the
responsibility for the Study to Sponsor or their designee. Sponsor will use its
best efforts to accept the transfer of responsibility from Institution in a
timely fashion.  The Institution will
take all necessary steps to accomplish the orderly transfer of Study
responsibilities and to minimize disruption of day-to-day Study activities,
particularly those activities involving Study participants.  At Sponsor’s request, the Institution shall
promptly deliver to Sponsor or their designee all data, information, materials
and any and all documentation relating to the work or the services performed or
to be performed hereunder.


 


14.2                           Either
party shall be entitled forthwith to terminate this Agreement by notice to the
other if:


 


14.2.1                  that other party commits any material
breach of any of the provisions of this Agreement and, in the case where the
breach is capable of remedy, fails to remedy the same within thirty (30) days
of receipt of notice from the party seeking to terminate, specifying the breach
and requiring it to be remedied; or


 


14.2.2                  the other party compounds or makes
arrangements with its creditors or is adjudged insolvent or goes into
liquidation (other than for the purposes of a bona fide reconstruction) or has
a  receiver appointed over most of its
property or assets or any event occurs in any jurisdiction in relation to that
party which is analogous to the foregoing events.


 


14.2.3                  in the reasonable judgment or the
parties and the Principal Investigators, the Institution’s IRB, or the Food and
Drug Administration it is determined to be inappropriate, impractical, or
inadvisable to continue due to a safety issue.


 


9





















 


14.3.                        The exercise of the rights to
terminate this Agreement given by this Article 14 shall not prejudice legal
rights or remedies either party may have against the other in respect of any
breach of the terms of this Agreement.


 


14.4                           All
provisions of this Agreement that by their terms require performance by one or
both parties following expiration or termination of this Agreement shall
survive such expiration or termination. 
Such provisions shall include, but not be limited to, Articles, 3, 5, 6,
9, 10, 11, 13, 15,17 ,24, 25 ,26 and 27.


 


15            POST TERMINATION CONSEQUENCES


 


15.1                           In
the event of termination for any reason of this Agreement pursuant to Article 14
above:


 


15.1.1                  the parties
shall promptly meet in good faith to discuss and endeavour to agree on the
steps required to effect an orderly closure of all outstanding Services;


 


15.1.2                  to the extent
that any part of the fee for the Services has been paid in advance and such fee
is recoupable in accordance with any relevant agreement, the Institution shall
promptly re-pay such fee to Sponsor, having made deduction only of a sum
representing payment for the Services calculated pro rata to the date of
termination, together with any third party costs reasonably and necessarily
incurred or committed up to the date of termination, and any further sum agreed
to be paid to the Sponsor pursuant to this Article;


 


15.1.3                  to the extent
that the any fees for the Services are paid in arrears the Sponsor shall pay to
the Institution a proportion of such  fee
calculated pro rata up to the date of termination, together with any third
party costs reasonably and necessarily incurred or committed up to the date of
termination, and shall compensate the Institution for its reasonable costs
associated with such termination at a rate to be agreed between the parties.


 


15.2                           In
the event of expiry or termination for any reason of this Agreement the
Institution shall promptly provide to the Sponsor at the Sponsor’s expense all
Confidential Information and other data, materials (including unused Study
Drug) provided to the Institution or generated by the provision of the
Services.  Notwithstanding the above,
Institution may retain one copy of all Confidential Information and other data,
materials (not including unused Study Drug) for the purpose of demonstrating
its obligations under this Agreement.


 


16.         INDEMNIFICATION.


 


16.1                           Sponsor
shall indemnify, defend and hold harmless the Institution and its agents,
representatives, trustees, officers and employees (“Institution Indemnitees”)
from


 


10





















 


and
against any demands, actions, claims, judgments or settlements (“Claims”) that
may be made or instituted against any of them (including the reasonable
attorneys’ fees and other costs and expenses of defense), by reason of personal
injury (including but not limited to death) or property damage which arises out
of or is connected with the performance of this Study under the Protocol;
provided, however, that Sponsor shall not be liable for any loss or damage
resulting from an Institution Indemnitee’s (a) failure to adhere to the
material terms of the Protocol or this Agreement; (b) failure to comply
with any applicable FDA or other government requirement; and/or (c) negligence
or willful misconduct.


 


16.2                           The
Institution agrees to indemnify and hold harmless the Sponsor and its agents,
representatives, trustees, officers and employees (the “Sponsor Indemnitees”)
from and against any Claims (including reasonable legal costs) that may be made
or instituted against any of them (including the reasonable attorneys’ fees and
other costs and expenses of defense), by reason of personal injury (including
but not limited to death) or property damage which arises out of or is
connected with the Institution’s negligence or willful misconduct during
the  performance of this Study under the
Protocol, provided, however, that Institution shall not be liable for any loss
or damage resulting from the Sponsor’s (a) failure to adhere to the
material terms of the Protocol or this Agreement; (b) failure to comply
with any applicable FDA or other government requirement; and/or (c) negligence
or willful misconduct.


 


16.3                           The indemnities above
shall be subject to the following provisions:


(a)                                  a party (including its indemnities) claiming under one of the indemnities
above ( the “Indemnified Party”) shall 
fully and promptly inform the other party (the “Indemnifying Party”) of
any third party claim made against it or one of its indemnities covered by the
indemnity;


(b)                                 the Indemnified Party shall take all reasonable steps to mitigate its
loss in relation to the indemnity;


(c)                                  the Indemnified Party shall make no admission of liability to any third
party in relation to any Claim made against it covered by the indemnity;


(d)                                 the
Indemnified Party shall permit Indemnifying Party to take full control of such Claim or
proceedings;


(e)                                  the Indemnified
Party shall assist in the investigation and defense of such Claim or
proceedings.


 


16.4                           Neither
party shall be liable for delay in performing or failure to perform obligations
under this Agreement if such delay or failure results from circumstances outside
its reasonable control (including, without limitation, any act of God,
governmental action, accident, strike, lock-out or other form of industrial
action) promptly notified to the other party (“Force Majeure”). An incident of
Force Majeure shall not constitute a breach of this Agreement and the time for
performance shall be extended accordingly; however, if it persists for more
than thirty (30) days:


 


11





















 


16.4.1                  the parties may
enter into discussions with a view to alleviating its affects and, if possible,
agreeing on such alternative arrangements as may be reasonable in all of the
circumstances; or


 


16.4.2                  the party not in
default may forthwith on notice to the other party terminate this Agreement and
the provisions of Articles 14 and 15 shall apply.


 


16.5                           In
addition, Sponsor shall reimburse Institution for reasonable and necessary
medical expenses incurred in treating research subjects for injuries or adverse
reactions caused by manufacturing defects or malfunctions of the Study Drug,
supplied by Sponsor following its use in accordance with the Study Protocol or
by required study procedures, provided that:


(a)          the
Institution uses the Study Drug in accordance with the Study Protocol,


(b)         such
expenses are not covered by the research subject’s medical or hospital
insurance coverage and,


(c)          such
expenses do not  arise as a result of
Institution’s failure to adhere to the material terms of the Protocol or this
Agreement; failure to comply with any applicable FDA or other government
requirement; and/or negligence or willful misconduct.


 


17.         INSURANCE.   Sponsor shall, at its sole cost and expense,
procure and maintain commercial general liability insurance or equivalent self
insurance in amounts not less than those agreed by the parties.  Such commercial general liability insurance
or equivalent self insurance shall provide contractual liability coverage for
Sponsor’s indemnification.   Upon
request, Sponsor shall provide Institution with written evidence of such
insurance prior to commencement of the Study. 
Sponsor shall provide Institution with written notice at least fifteen
(15) days prior to the cancellation, non-renewal or material change in such
insurance; if Sponsor does not obtain replacement insurance providing
comparable coverage within such fifteen (15) day period, Institution shall have
the right to terminate this Agreement effective at the end of such fifteen (15)
day period without notice of any additional waiting periods.


 


18.         COMPLIANCE
WITH HIPAA. It is understood and agreed that Institution, as a covered
entity under the Health Insurance Portability and Accountability Act of 1996 (“HIPAA”),
may not use or disclose protected health information (“PHI”), as defined in
HIPAA and its implementing regulations, for purposes other than treatment,
payment, or health care operations without first obtaining authorization from
the individual concerned.  Institution
agrees to obtain authorization from individuals enrolled in the Study which
permits disclosure to and use of PHI by Sponsor for purposes of conducting and
overseeing the Study. Sponsor agrees that it shall not disclose PHI to any
person or entity except as permitted by the HIPAA authorization.


 


19.         DEBARMENT
AND DISQUALIFICATION


 


19.1                           The
Institution represents and warrants that:


 


12





















 


19.1.1                  neither the Institution nor any of
its employees or sub-contractors engaged in the performance of the Services is
under investigation by the FDA for debarment action or is debarred pursuant to
the U.S. Generic Drug Enforcement Act of 1992 (21 USC 301 et seq.), or has a
disqualification hearing pending or has been disqualified by the FDA pursuant
to 21 CFR Section 312.70; and


 


19.1.2                  it has not engaged in conduct or activity
which could lead to any of the events described in this Article 19.1.


 


19.2             The
Institution the shall forthwith notify the Sponsor in the event that during the
term of this Agreement the Institution becomes aware that it or any employee or
sub-contractor engaged in the provision of Services:


 


19.2.1                  comes under investigation by the FDA
for debarment action or disqualification or is debarred or disqualified; or


19.2.2                  engages in any conduct or activity
which could lead to any of the disqualification or debarment actions described
in Article 19.1 above.


 


20.         WARRANTIES.  THE INSTITUTION MAKES NO WARRANTIES, EXPRESS,
OR IMPLIED, CONCERNING THE RESULTS OF THIS STUDY OR THE OWNERSHIP,
MERCHANTABILITY, OR FITNESS FOR A PARTICULAR PURPOSE OF SUCH RESULTS.  Neither party shall be liable to the other for
any direct, consequential, or other damages suffered by the other or any other
entity or individual as a result of the Study.


 


21.         NO
WAIVER.  The waiver of any breach or
default hereunder by either party shall not operate or be construed as a waiver
of any repetition of such breach or default or of any other breach or default.


 


22.         DISPUTES.  If a dispute arises out of or relates to this
Agreement, or breach thereof, and if said dispute cannot be settled through
negotiation and mutual agreement, the parties agree first to try in good faith
to settle the dispute by mediation, before resorting to arbitration,
litigation, or some other dispute resolution procedure.  The forum for such proceedings will be Monroe
County, New York.


 


23.         ENTIRE
AGREEMENT.  This Agreement describes
the entire agreement between the parties concerning the subject matter hereof
and supersedes all prior or contemporaneous agreements, representations or
understandings, written or oral.  This
Agreement may not be amended, changed or modified except in a writing signed by
both parties hereto.


 


24.         ASSIGNMENT.  Neither party may assign this Agreement
without the prior written consent of the other party; provided, however, that
Sponsor may assign this Agreement to a successor in ownership of at least 51%
of its assets or to a company within the same group of companies as the
Sponsor, provided that such successor or group company expressly assumes, in
writing, the obligation to perform in accordance with the terms and conditions
of this Agreement.   Any attempt by
either party to assign this Agreement without such consent shall be void.


 


13





















 


25.         SEVERABILITY.  If any provision of this Agreement shall be
or become invalid under any provision of federal, state or local law, or by a
court of competent jurisdiction, such invalidity shall have no effect on the
validity or enforceability of the remaining provisions of this Agreement, and
they shall continue in full force and effect.


 


26.         GOVERNING
LAW.  This Agreement shall be
interpreted in accordance with, and governed by, the laws of the State of New
York, without regard to its conflict of laws rules, and irrespective of the
domicile or residence of the parties or of the location of any property
affected hereby.  The venue for any
action to interpret or enforce this Agreement shall be in Monroe County, New
York.


 


27.         OTHER PROVISIONS


 


27.1                           No
variation to the terms of this Agreement shall be effective unless in writing
and signed on behalf of each party by a director or other authorized person.


 


27.2                           If
any term or provision of this Agreement is held by any court or other competent
authority to be void or unenforceable in whole or in part, the other provisions
of this Agreement and the remainder of the affected provision shall continue to
be valid.


 


27.3                           Failure
by either party on one or more occasions to avail itself of a right conferred
by this Agreement shall not be construed as a waiver of such party’s right to
enforce such right or any other right.


 


27.4                           The
Schedules and Exhibits to this Agreement form part of and shall be deemed to be
incorporated in this Agreement and the term “Agreement” shall be construed
accordingly.


 


27.5                           This
Agreement contains the whole agreement between the parties and supersedes all
previous agreements and understandings between the parties with respect to the
subject matter of this Agreement.


 


27.6                           Each
party acknowledges that, in entering into this Agreement, it does not do so on
the basis of and does not rely on any representation or warranty (whether made
orally or in writing) except as expressly provided in this Agreement.


 


14





















 


IN WITNESS WHEREOF, the
parties hereto have executed this Agreement in duplicate by proper persons
thereunto duly authorized.


 


	
  SPONSOR

  	
   

  	
  UNIVERSITY
  OF ROCHESTER

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  By:

  	
   

  	
   

  	
  By:

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  Name:

  	
   

  	
   

  	
  Name:

  	
  Gunta J. Liders

  	
   

  
	
   

  	
   

  	
   

  
	
  Title:

  	
   

  	
   

  	
  Title:

  	
  Associate VP for
  Research Administration

  	
   

  
	
   

  	
   

  	
   

  
	
  Date:

  	
   

  	
   

  	
  Date:

  	
   

  	
   

  
												



 


15





















 


I have read and agree
with the terms of this Agreement.


 


PRINCIPAL INVESTIGATOR


 


 


	
  By:

  	
   

  	
   

  
	
   

  
	
   

  
	
  Name:

  	
   

  	
   

  
	
   

  
	
   

  
	
  Title:

  	
   

  	
   

  
	
   

  
	
   

  
	
  Date:

  	
   

  	
   

  
						



 


16





















 


EXHIBIT A


 


THE PROTOCOL


 


17





















 


	
  Study
  Drug: ethyl-EPA

  	
   

  	
  CONFIDENTIAL

  



 


Clinical Study
Protocol:  AN01.01.0011


 


Clinical
Study Protocol No: AN01.01.0011


 


[ * ]


 


March 3, 2005


 


 


18





















 


SIGNATURE(S)
OF INVESTIGATOR(S)


 


Confidentiality and Investigator Statement


 


I agree to abide by the
statement of confidentiality.


 


I agree to conduct the
study according to this protocol and have read and agree to comply with the
Investigator’s Responsibilities (Appendix VIII). Any changes in procedure will
only be made if necessary to protect the safety, rights or welfare of subjects.


 


I agree to comply with
current International Conference on Harmonisation Tripartite Guideline on Good
Clinical Practice plus appropriate FDA CFRs and local regulatory requirements.


 


I agree to conduct the
study in person or to supervise the study.


 


I agree to ensure that
all who assist me in the conduct of the study have access to the study protocol
and any amendments and are aware of their obligations.


 


I will ensure that the
drugs supplied by Amarin Neuroscience Ltd will be used only for administration
to patients included in this trial protocol and for no other purpose.


 


 


	
   

  	
   

  	
   

  
	
  Principal
  Investigator

  	
  Date

  



 


19





















 


TABLE OF
CONTENTS


 


[ * ]


 


20





















 


TREND-HD
PROTOCOL SYNOPSIS


 


[ *8 ]


 


21





















 


TREND-IID
SCHEDULE OF ACTIVITIES


 


[ * ]


 


22





















 


List of
Abbreviations and Definitions of Terms


 


[ * ]


 


23





















 


1.0                               INTRODUCTION


 


[ * ]


 


24





















 


APPENDICES


 


Appendix
I Unified Huntington’s Disease Rating Scale


 


25





















 


Appendix II                                   Clinical
Global Impression Scale


 


26





















 


Appendix III                               Beck
Depression Inventory – II


 


27










 













Appendix IV                              Mini-Mental
State Examination


 


28





















 


Appendix
V                                  Declaration
of Helsinki


 


World Medical Association Declaration
of Helsinki: Recommendations Guiding Medical


 


Doctors
in Biomedical Research Involving Human Subjects


 


Adopted by the 18th World Medical
Assembly, Helsinki, Finland, June 1964


 


and amended by the


 


29th World Medical Assembly, Tokyo,
Japan, October 1975,


 


35th World Medical Assembly, Venice,
Italy, October 1983.


 


41st World Medical Assembly, Hong
Kong, September 1989,


 


and the 48th General
Assembly, Somerset West, Republic of South Africa, October 1996


 


Introduction


 


It is the mission of the
physician to safeguard the health of the people. His or her knowledge and
conscience are dedicated the fulfillment of this mission.


 


The Declaration of Geneva
of the World Medical Assembly binds the physician with the words, “The health
of my patient will be my first consideration,” and the International Code of
Medical Ethics declares that, “A physician shall act only in the subject’s
interest when providing medical care might have the effect of weakening the
physical and mental condition of the subject.”


 


The purpose of biomedical
research involving human subjects must be to improve diagnostic, therapeutic
and prophylactic procedures and the understanding of the etiology and
pathogenesis of disease.


 


In current medical
practice most diagnostic, therapeutic or prophylactic procedures involve
hazards. This applies especially to biomedical research.


 


Medical progress is based
on research which ultimately must rest in part on experimentation involving
human subjects.


 


In the field of
biomedical research a fundamental distinction must be recognized between
medical research in which the aim is essentially diagnostic or therapeutic for
a subject, and medical research, the essential object of which is purely
scientific and without implying direct diagnostic or therapeutic value to the
person subjected to the research.


 


Special caution must be
exercised in the conduct of research which may effect the environment, and the
welfare of animals used for research must be respected.


 


29





















 


Because it is essential
that the results of laboratory experiments be applied to human beings to
further scientific knowledge and to help suffering humanity, the World Medical
Association has prepared the following recommendations as a guide to every
physician in biomedical research involving human subjects. They should be kept
under review in the future. It must be stressed that the standards as drafted
are only a guide to physicians all over the world. Physicians are not relieved
from criminal, civic and ethical responsibilities under the laws of their own
countries.


 


1. Basic
Principles


 


1. Biomedical research
involving human subjects must conform to generally accepted scientific
principles and should be based on adequately performed laboratory and animal
experimentation and on a thorough knowledge of the scientific literature.


 


2. The design and
performance of each experimental procedure involving human subjects should be
clearly formulated in an experimental protocol which should be transmitted for
consideration, comment and guidance to a specially appointed committee
independent of the Investigator and the sponsor provided that this independent
committee is in conformity with the laws and regulations of the country in
which the research experiment is performed.


 


3. Biomedical research
involving human subjects should be conducted only by scientifically qualified
persons and under the supervision of a clinically competent medical person. The
responsibility for the human subject must always rest with a medically
qualified person and never rest on the subject of the research, even though the
subject has given his or her consent.


 


4. Biomedical research
involving human subjects cannot legitimately be carried out unless the
importance of  the objective is in
proportion to the inherent risk to the subject.


 


5. Every biomedical
research involving human subjects should be preceded by careful assessment or
predictable risks in comparison with foreseeable benefits to the subject or to
others. Concern for the interest of the subject must always prevail over the
interests of science and society.


 


6. The right of the
research subject to safeguard his or her integrity must always be respected.
Every precaution should be taken to respect the privacy of the subject and to
minimize the impact of the study on the subject’s physical and mental integrity
and on the personality of the subject.


 


7. Physicians should
abstain from engaging in research projects involving human subjects unless they
are satisfied that the hazards involved are believed to be predictable.
Physicians should cease any investigation if the hazards are found to outweigh
the potential benefits.


 


30





















 


8. In publication of the
results of his or her research, the physician is obliged to preserve the
accuracy of the results. Reports of experimentation not in accordance with the
principles laid down in this Declaration should not be accepted for
publication.


 


9. In any research on
human beings, each potential subject must be adequately informed of the aims,
methods, anticipated benefits and potential hazards of the study and the
discomfort it may entail. He or she should be informed that he or she is a
liberty to abstain from participation in the study and that he or she is free
to withdraw his or her consent to participation at any time. The physician should
then obtain the subject’s freely-given informed consent, preferably in writing.


 


10. When obtaining
informed consent for the research project the physician should be particularly
cautious if the subject is in a dependent relationship to him or her or may
consent under duress. In that case the informed consent should be contained by
a physician who is not engaged in the investigation and who is completely
independent of this official relationship.


 


11. In case of  legal incompetence, informed consent should
be obtained from the legal guardian in accordance with national legislation.
Where physical or mental incapacity makes it impossible to obtain informed
consent, or when the subject is a minor, permission from the responsible
relative replaces that of the subject in accordance with national legislation.
Whenever the minor child is in fact able to give consent, the minor’s consent
must be obtained in addition to the consent of the minor’s legal guardian.


 


12. The research protocol
should always contain a statement of the ethical considerations involved and
should indicate that the principles enunciated in the present Declaration are
complied with.


 


II.
Medical research combined with clinical care


 


(Clinical
research)


 


1. In the treatment of the sick person, the physician must be free to
use a new diagnostic and therapeutic measure, if in his or her judgment it
offers hope of saving life, reestablishing health or alleviating suffering.


 


2. The Potential benefits, hazards and discomfort of a new method
should be weighed against the advantages of the best current diagnostic and
therapeutic methods.


 


3. In any medical study, every subject – including those of a control
group, if any – should be assured of the best proven diagnostic and therapeutic
method. This does not exclude the use of inert placebo in studies where no
proven diagnostic or therapeutic method exists.


 


4. The refusal of the subject to participate in a study must never
interfere with the physician-subject relationship.


 


31





















 


5. If the physician
considers it essential not to obtain informed consent, the specific reasons for
this proposal should be stated in the experimental protocol for transmission to
the independent committee.


 


6. They physician can combine
medical research with professional care, the objective being the acquisition of
new medical knowledge, only to the extent that medical research is justified by
its potential diagnostic or therapeutic value for the subject.


 


III.
Non-therapeutic biomedical research involving human subjects




(Non-clinical
biomedical research)


 


1. In the purely scientific application of medical research carried out
on a human being, it is the duty of the physician to remain the protector of
the life and health of that person on whom biomedical research is being carried
out.


 


2. The subjects should be volunteers – either healthy persons or
subjects for whom the experimental design is not related to the subject’s
illness.


 


3. The investigator or the investigating team should discontinue the
research if in his/her or their judgement it may, if continued, be harmful to
the individual.


 


4. In research on man, the interest of science and society should never
take precedence over considerations related to the well being of the subject.


 


32





















 


Appendix VI          Responsibility
of Clinical Trial Sponsor


 


[ * ]


 


33





















 


Appendix VII         Responsibility
of Clinical Trial Monitor


 


[ * ]


 


34





















 


Appendix VI          Responsibility
of Clinical Trial Investigators


 


[ * ]


 


35





















 


Appendix IX          Documents
Required Prior to Initiation of the Study


 


[ * ]


 


36





















 


Appendix X           Content
of Investigator File


 


[ * ]


 


37





















 


EXHIBIT B


 


SCOPE OF WORK/ASSIGNMENT OF RESPONSIBILITIES


 


38





















 


Confidential


 


Amarin/HSG


Planning Workscope


Final 2/3/05


 


University of Rochester


Department of Neurology


Clinical Trials
Coordination center


 


Amarin Neuroscience and
Miraxion


 


	
   

  	
  Task/Description

  	
   

  	
  HSG

  	
   

  	
  Amarin

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  A.

  	
  Protocol
  Development

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  1

  	
  [*]

  	
   

  	
  X

  	
   

  	
  X

  	
   

  
	
  2

  	
  [*]

  	
   

  	
  X

  	
   

  	
  X

  	
   

  
	
  3

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  
	
  4

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  
	
  B.

  	
  Study
  Preparation

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  5

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  
	
  6

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  
	
  7

  	
  [*]

  	
   

  	
  X

  	
   

  	
  X

  	
  (1)

  
	
  8

  	
  [*]

  	
   

  	
  X

  	
   

  	
  X

  	
  (1)

  
	
  9

  	
  [*]

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  10

  	
  [*]

  	
   

  	
  X

  	
   

  	
  X

  	
  (1)

  
	
  11

  	
  [*]

  	
   

  	
  X

  	
   

  	
  X

  	
  (1)

  
	
  12

  	
  [*]

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  13

  	
  [*]

  	
   

  	
  X

  	
   

  	
  X

  	
   

  
	
  14

  	
  [*]

  	
   

  	
  X

  	
   

  	
  X

  	
  (1)

  
	
  15

  	
  [*]

  	
   

  	
  X

  	
   

  	
  X

  	
  (1)

  
	
  16

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  
	
  17

  	
  [*]

  	
   

  	
  X

  	
   

  	
  X

  	
   

  
	
  18

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  
	
  19

  	
  [*]

  	
   

  	
  X

  	
   

  	
  X

  	
   

  
	
  20

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  
	
  21

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  
	
  22

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  
	
  23

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  
	
  C.

  	
  Packaging
  and Distribution of Drug

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  24

  	
  [*]

  	
   

  	
  X

  	
   

  	
  X

  	
  (1)

  
	
  25

  	
  [*]

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  26

  	
  Develop plan for
  emergency replacement of drug (e.g., damaged, missing, lost).

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  27

  	
  [*]

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  28

  	
  [*]

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  29

  	
  [*]

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  30

  	
  [*]

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  31

  	
  [*]

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  32

  	
  [*]

  	
   

  	
   

  	
   

  	
  X

  	
   

  



 










(1)Primary responsibility
assumed when X marked for both parties, otherwise, shared responsibility


 


39





















 


	
   

  	
  Task/Description

  	
   

  	
  HSG

  	
   

  	
  Amarin

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  33

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  34

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  35

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  36

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  37

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  D.

  	
  Development
  and Distribution of Case Report Forms (CRFs)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  38

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  
	
  39

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  
	
  40

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  
	
  E.

  	
  Site
  Monitoring

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  41

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
  X

  	
  (1)

  
	
  42

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  43

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
  X

  	
  (1)

  
	
  F.

  	
  Operations
  Manual

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  44

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  
	
  45

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  
	
  46

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  
	
  G.

  	
  Data
  Management Plan

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  47

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  
	
  48

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  
	
  49

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  
	
  50

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
  X

  	
  (1)

  	
   

  	
  X

  	
   

  
	
  51

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  
	
  52

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  
	
  53

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  54

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  H.

  	
  Statistical
  Analysis Plan for Publication

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  55

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  
	
  56

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  
	
  57

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  
	
  58

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  
	
  I.

  	
  Statistical
  Analysis Plan for Technical Reports

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  59

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  60

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  61

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  62

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  
	
  J.

  	
  Finance
  and Administration

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  63

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  
	
  64

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  



 










(1)Primary responsibility
assumed when X marked for both parties, otherwise, shared responsibility


 


40





















 


	
   

  	
  Task/Description

  	
   

  	
  HSG

  	
   

  	
  Amarin

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  65

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  
	
  K.

  	
  Site
  Selection and Establishment

  	
   

  	
   

  	
   

  	
   

  
	
  66

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  
	
  67

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  
	
  68

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  
	
  69

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  
	
  70

  	
  [*]

  	
   

  	
   

  	
   

  	
  X

  
	
  71

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  
	
  72

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  
	
  73

  	
  [*]

  	
   

  	
   

  	
   

  	
  X

  
	
  74

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  
	
  L.

  	
  Orientation
  Meeting Planning and Conduct

  	
   

  	
   

  	
   

  	
   

  
	
  75

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  
	
  76

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  
	
  77

  	
  [*]

  	
   

  	
   

  	
   

  	
  X

  
	
  78

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  
	
  79

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  
	
  80

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  
	
  81

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  
	
  82

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  
	
  M.

  	
  Public
  Relations/Recruitment Campaign

  	
   

  	
   

  	
   

  	
   

  
	
  83

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  
	
  84

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  
	
  85

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  
	
  86

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  
	
  87

  	
  [*]

  	
   

  	
  X

  	
   

  	
   

  



 










(1)Primary responsibility
assumed when X marked for both parties, otherwise, shared responsibility


 


41





















 


EXHIBIT C


BUDGET, TIMELINE, PAYMENT SCHEDULE


 


42





















 


University of Rochester


Clinical Trials Coordination Center


Budget for Miraxion


Sponsor : Amarin


 


N = 300


SITES = 40


Duration = 12
months


TIME PERIOD = 38
months (Dec 04 - Jan 08)


Version #6 January 31,
2005


 


	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  BUDGET

  	
   

  
	
  HSG Personnel Costs :

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
  Clinical Operations

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Biostatistics

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Computer Systems and Support:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Operating and Supplies Cost :

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
  General Office

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Telecom/Fax

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Postage/Courier

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Photocopying

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Ops Manuals

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  CRF Binders

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Screening Packets

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Other:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Data Entry

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Consulting

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
  Co-PI (Ross)

  	
   

  	
  $79,167

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Co-PI (Leavitt)

  	
   

  	
  $79,167

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Steering Committee

  	
   

  	
  $79,167

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  DSMB

  	
   

  	
  $22,750

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Record Preparation and Return

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Subtotal of Direct Costs

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  University of Rochester
  Indirect Rate of 30%

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Per Subject Fee 300 Subjects

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
  Seven visits pers subject charged as follows

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Screening

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Baseline V1

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Phone T1

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Visit 2

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Visit 3

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Phone T2

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Visit 4

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Visit 5

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Phone T3

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Unsched Visit

  	
   

  	
  [*]

  	
   

  	
  (Not
  Included in above Total)

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  U of R 30% Indirect on 1st
  $25,000 of each Site Subcontract

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Study Budget

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Less Payment Received on 1-28-05

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Total HSG Cost Forward

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
													



 


	
  Additional Costs to be Borne by Amarin

  
	
   

  	
  •

  	
  Central Laboratory costs

  
	
   

  	
  •

  	
  Drug packaging, labeling,
  distribution and resupply, including IVRS if applicable

  
	
   

  	
  •

  	
  Central ECG reading costs

  
	
   

  	
  •

  	
  Per Subject Fees Not Included above,
  that will be charged per occurrence:

  
	
   

  	
   

  	
  •
  Screen Failures, will be charged for the full screening visit ($1,580)

  
	
   

  	
   

  	
  •
  Premature Withdrawals will be liable for visits incurred plus Visit 5
  ($1,651)

  
	
   

  	
   

  	
  •
  Unscheduled visits will be charged at $683

  
	
   

  	
  •

  	
  Monitoring Costs and Travel

  
	
   

  	
  •

  	
  Institutional Review Board Fees will
  be billed to Amarin as charges (initial, renewal and amendments) are received
  by HSG

  
	
   

  	
  •

  	
  Travel and Conference costs
  including:

  
	
   

  	
   

  	
  •
  Orientation and steering committee meetings

  
	
   

  	
   

  	
  •
  Investigator/coordinator close out meeting

  
	
   

  	
   

  	
  •
  Other meeting costs and study related travel

  
	
   

  	
  •

  	
  Public Relations Program for subject
  recruitment if desired

  
	
   

  	
  •

  	
  Fees to use copyrighted / proprietary
  data collection instruments

  
	
   

  	
  •

  	
  Assumes use of HSG database standards
  and CRFs, would require adjustment of fees commensurate with degree of
  changes

  



 


HSG Amarin Budget V6 1-31-2005


 


43





















 


Budget for Miraxion


Version #6 January 31,
2005


 


	
  Consultant Costs

  	
   

  	
  Planning

  	
   

  	
  Conduct

  	
   

  	
  Analysis / Pub

  	
   

  	
  TOTAL

  	
   

  
	
  Steering Cmte (5 members at [*] / year)

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  DSMB (Qtrly Meetings, Chair at [*] 3 Members @ [*]
  per mtg)

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
  CO-PI (Ross, [*] / year + indirects on summary)

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  CO-PI (Leavitt, [*] / year + indirects on summary)

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
  TOTAL

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Computer Systems and Support

  	
   

  	
  Planning

  	
   

  	
  Conduct

  	
   

  	
  Analysis / Pub

  	
   

  	
  TOTAL

  	
   

  
	
  CTCC Computing Costs (~15%)

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
  TOTAL

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Operating and Supplies Cost

  	
   

  	
  Planning

  	
   

  	
  Conduct

  	
   

  	
  Analysis / Pub

  	
   

  	
  TOTAL

  	
   

  
	
  -General Office

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  -Telecommunications/Fax

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  -Postage/Courier

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  -Photocopying

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  -Operations Manual (114 @ $40/each)

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
  -CRF Binders (330 @ $90/each)

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
  -Screening Packets (375 @ $25/each)

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
  TOTAL

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Other Costs

  	
   

  	
  Planning

  	
   

  	
  Conduct

  	
   

  	
  Analysis / Pub

  	
   

  	
  TOTAL

  	
   

  
	
  -Data Entry

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
  -Record Preparation and Return

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  -Site Monitoring Travel

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
  -DSMB Travel

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  
	
  TOTAL

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  



 


44





















 


Amarin
Miraxion 


January 31,
2005, Version 6 


 


	
   

  	
   

  	
   

  	
   

  	
  % Effort

  	
   

  	
  % Effort

  	
   

  	
  % Effort

  	
   

  
	
  Staff
  Effort

  	
   

  	
  Title

  	
   

  	
  Planning

  (6 mo.) 12/1/2004 - 5/31/05

  	
   

  	
  Study Conduct - DB Lock

  (26 mo.) 6/1/05 - 7/31/07

  	
   

  	
  Analysis & Publication

  (6.0 mo.) 8/1/07 - 1/31/08

  	
   

  
	
  Name

  
	
  Shoulson, Ira

  	
   

  	
  PI

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Kieburtz, Karl

  	
   

  	
  Director CTCC

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Kayson, Elise

  	
   

  	
  Director Proj
  Coordinator

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  DeBlieck, Lisa

  	
   

  	
  Sr. Proj
  Coordinator

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Laskowski, Letty

  	
   

  	
  Asst. Coordinator

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Trimble, Gene

  	
   

  	
  Director Data
  Manager

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  TBD

  	
   

  	
  Sr Data Base
  Programmer

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  TBD

  	
   

  	
  Info Analyst

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  TBD

  	
   

  	
  Data Control
  Clerk

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Henderson, Sue

  	
   

  	
  Administrative
  Assistant

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Dean, Becky

  	
   

  	
  Meeting Planner

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Renter, Michelle

  	
   

  	
  Finance

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  TBD

  	
   

  	
  Medical Monitor

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Oakes, David

  	
   

  	
  Biostat

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Beck, Chris

  	
   

  	
  Asst Biostat

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Watts, Art

  	
   

  	
  Sr. Biostats
  Programmer

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  TBD

  	
   

  	
  Biostats Res Asst

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Janciurus, Joanne

  	
   

  	
  Biostats
  Programmer

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Kamp, Cornelia

  	
   

  	
  Director Research
  Operations

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Edicola, John

  	
   

  	
  Director
  Strategic Development

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Shinaman, Aileen

  	
   

  	
  HSG Executive Director
  / Legal

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  



 


45





















 


Payment Schedule for
Miraxion (Exclusive of quarterly Site Payments)


 


	
  Total Due from Amarin

  	
   

  	
  [*]

  	
   

  
	
  Less Site Payments (and UR Indirect on Payments)

  	
   

  	
  [*]

  	
   

  
	
  Total HSG Operating Costs to Invoice

  	
   

  	
  [*]

  	
   

  



 


	
  Milestone

  	
   

  	
  Percent Due

  	
   

  	
  Amount Due

  	
   

  	
  Balance Remaining

  	
   

  
	
  Execution of Contract

  	
   

  	
  [*]

  	
  %

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  First Patient Dosed

  	
   

  	
  [*]

  	
  %

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Enrollment 25% Complete

  	
   

  	
  [*]

  	
  %

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Enrollment 75% Complete

  	
   

  	
  [*]

  	
  %

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Data Transfer to Amarin - All Subj 6 Mo. Complete

  	
   

  	
  [*]

  	
  %

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Final DB Transfer to Amarin

  	
   

  	
  [*]

  	
  %

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
  Final Study Results Available

  	
   

  	
  [*]

  	
  %

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  100

  	
  %

  	
  [*]

  	
   

  	
  [*]

  	
   

  



 


Prepared: 3-9-2005
J. Edicola


 


	
  University
  of Rochester Confidential

  	
   

  	
  3/16/2005

  	
   

  	
   

  



 


46





















 


EXHIBIT D


 


PRINCIPAL INVESTIGATOR AGREEMENT


 


Protocol
Title:  “A Multi Center,
Double Blind, Randomized, Parallel Group, Placebo-Controlled Trial of
(ethyl-EPA) Miraxion TM in Patients with Mild to Moderate Huntington’s Disease”
(the “Study”), (the “Protocol”).


 


Protocol
No. [                   ]


 


Principal
Investigator’s Name:  
[                    ]
(the “Investigator”)


 


The Investigator has
agreed to act as [Principal Investigator/ Co-Principal Investigator (as applicable] in the Study. This
Agreement sets out the terms and conditions of our agreements as follows:


 


1.               The
Study will be carried out in compliance with the Protocol, and any subsequent
amendments made and approved in accordance with the clinical trial agreement
(the “CTA”) dated [     ] 2005 and made
between Amarin Neuroscience Limited (the “Sponsor”) and the University Of
Rochester (“Institution”).


 


2.               The
Investigator shall provide such services (the “Services”) as are reasonably
delegated to him by the Sponsor and the Institution in respect of the Study as
are agreed from time to time to include, without limitation, the Investigator
assisting the Institution and the Sponsor in respect of:


 


(i)                                     the
organization, supervision and conduct of the practical aspects of the Study;


 


(ii)                                  the
conducting of the Study in accordance with the Protocol and the ICH Harmonized
Tripartite Guideline for Good Clinical Practice or its local equivalent (“GCP”).


 


3.               In
performing the Services, the Investigator shall comply with the following:


 


(i)                                     the
Protocol and GCP;


(ii)                                  part
312 Title 21 of the Code of Federal Regulations issued by the U.S. Food and
Drug Administration (“FDA”);


(iii)                               the standard operating
procedures of Institution;


(iv)                              all
applicable national and local laws, rules and regulations, including but
not limited to the U.S. Federal Food, Drug and Cosmetic Act and Regulations of
the FDA, and those promulgated by any relevant regulatory authority, and
relevant professional standards;


(v)                                 all
reasonable  written and verbal
instructions of Sponsor;


 


4.               The
Investigator shall perform the Services with reasonable care and skill.


 


5.               The
Investigator agrees that all data, inventions and discoveries generated by him
during the course of the activities described in this Agreement shall be the
sole and exclusive property of the Sponsor. 
The Investigator shall execute any documents or undertake any further
actions if requested by Sponsor to evidence transfer of title thereto. Sponsor
shall reimburse the Investigators for any reasonable expenses incurred at
Sponsor’s request to secure title or legal protection for any such Inventions.


 


6.               All
information designated at the time of disclosure, in writing, by either party
as confidential (“Confidential Information”) shall not be used by the other
party other than for purposes of this Agreement.  Each party agrees to treat Confidential
Information received from the other party with the same degree of care with
which it would treat its own Confidential Information of a similar nature and
further agrees not to disclose such Confidential Information to a third party
without prior written consent of the other party, for a period of five (5) years


 


47





















 


following disclosure. 
The foregoing obligations of non-disclosure do not apply to Confidential
Information which:


 


(a)          is
in the public domain at the time of disclosure;


(b)         was
known to the other party prior to disclosure;


(c)          was
received from a third party not under an obligation of confidence to Sponsor;


(d)         is
required to be disclosed by law or at the request of a governmental authority.


 


 


	
  Signed by the Investigator

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  Name

  	
   

  	
  Date

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  Signed
  on behalf of

  	
   

  	
   

  	
   

  
	
  The
  Institution

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Signature

  	
   

  	
   

  	
  Position

  	
   

  
	
  Date

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  Signed
  on behalf of

  	
   

  	
   

  	
   

  
	
  The
  Sponsor

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Signature

  	
   

  	
   

  	
  Position

  	
   

  
	
  Date

  	
   

  	
   

  	
   

  	
   

  
									



 


48