EXHIBIT 10.45
AMENDMENT #4
Protocol # V1T 02-08961X
PRA Project ID #1600
THIS AMENDMENT #4 ("Amendment #4"), dated as of the 18 th day of August, 2003 (the "Effective Date"), by and between CroMedica Global, Inc. ("CroMedica") and ISTA Pharmaceuticals (formerly known as Advanced Corneal Systems, Inc. (hereinafter "Sponsor").
W I T N E S S E T H:
WHEREAS, under the terms of a certain Contract for Clinical Research Agreement (the "Agreement"), dated the 8 th day of September, 1998 as amended by Amendment #1, dated October 11, 2000, Amendment #2, dated February 21, 2001, and Amendment #3, dated December 5, 2001 by and between the parties, Sponsor agreed to retain CroMedica, and CroMedica agreed to be retained by Sponsor, to perform the Services as more particularly described in the Agreement pursuant to the terms of the Agreement; and
WHEREAS, the parties hereto have entered into certain additional agreements with respect to modification of the Agreement, and which they desire to memorialize in this Amendment #4;
NOW, THEREFORE, in consideration of the premises and of the following mutual promises, covenants and conditions hereinafter set forth, the parties hereto agree as follows:
1. Change in Name of CroMedica. The parties acknowledge that CroMedica Global Inc. is now doing business as Pharmaceutical Research Associates, Inc. ("PRA"), and that this change of name does not alter the terms and conditions set forth in the Agreement. All references to CroMedica in the Agreement shall now be construed to mean references to PRA. The terms of the Agreement are only modified to the extent of the amendments set forth below.
2. Payment and Performance Schedule. The Services to be provided by PRA pursuant to the Agreement are hereby amended to reflect that Sponsor has assumed responsibility for monitoring certain investigative sites, and to reflect PRA's monitoring visits and safety reporting through December 2002. These changes to the Services are described in the revised Attachment 2, which is attached hereto and incorporated herein by reference.
3. Ratification of Balance of Agreement. In all other respects, the terms of the Agreement are hereby ratified and affirmed by each of the parties hereto.
4. Headings. The headings in this Amendment #4 are for convenience of reference only and shall not affect its interpretation.
Page 1 of 15
IN WITNESS WHEREOF, the parties hereto, each by a duly authorized representative, have executed this Amendment #4 as of the date first written above.
PHARMACEUTICAL RESEARCH
ASSOCIATES, INC. ISTA PHARMACEUTICALS
By:
/s/ Greg A. Johnson By:
/s/ Risa L. Grillone
Greg A. Johnson
Authorized Signature
Title: Vice President, Operations
Title: Vice President, Clinical Research
Date: 22 Aug 2003
Date: 16 Sept 03
Page 2 of 15
REVISED ATTACHMENT 2
AMENDED PROJECT SPECIFICATIONS
Unit Cost
Original
Study Total
Adjustment
Amendment
2
Revised
Study Total
($US)
Adjustment
Amendment
3 Occurring
to Nov.
2001
Adjustment
Amendment
3 Occurring
post Nov.
2001
Revised
Study Total
($US)
Adjustment
Amendment
4
Revised
Study Total
($US)
Amendment
2
Amendment
#3
Amendment
#4
Up front (20%) 563,525.00 563,525.00 563,525.00 563,525.00 Australia Regulatory Submission 10,000.00 10,000.00 10,000.00 10,000.00 10,000.00
CRF Finalization 8,580.00 8,580.00 8,580.00 8,580.00 8,580.00
Site Recruitment:
Canadian 200.00 2,400.00 2,400.00 2,400.00 (2,400.00 ) 0.00
U.S. 240.00 2,880.00 2,880.00 2,880.00 (2,880.00 ) 0.00
Australia 240.00 2,400.00 2,400.00 2,400.00 (2,400.00 ) 0.00
AMENDMENT #4 ADJUSTMENT: Revised based on actual number of site identifications performed: 5 Canadian, 12 US, 8 Australian.
Canadian 200.00 1,000.00 1,000.00
U.S. 240.00 2,880.00 2,880.00
Australia 240.00 1,920.00 1,920.00
Initiation Visits:
Canadian 600.00 7,200.00 7,200.00 7,200.00 (7,200.00 ) 0.00
U.S. 720.00 18,720.00 18,720.00 18,720.00 (18,720.00 ) 0.00
Australia 1,080.00 10,800.00 10,800.00 10,800.00 (10,800.00 ) 0.00 AMENDMENT #4 ADJUSTMENT: Revised based on actual number of initiations performed: 9 Canadian, 31 US, 8 Australian.
Canadian 600.00 5,400.00 5,400.00
U.S. 720.00 22,320.00 22,320.00
Australia 1,080.00 8,640.00 8,640.00
Page 3 of 15 Unit Cost
Original
Study Total
Adjustment
Amendment
2
Revised
Study Total
($US)
Adjustment
Amendment
3 Occurring
to Nov.
2001
Adjustment
Amendment
3 Occurring
post Nov.
2001
Revised
Study Total
($US)
Adjustment
Amendment
4
Revised
Study Total
($US)
Amendment
2
Amendment
#3
Amendment
#4
Interim Visits:
Canadian 1,200.00 183,600.00
U.S. 1,440.00 1,156,680.00
Australia 1,280.00 124,800.00 124,800.00
AMENDMENT 2 ADD: 7 additional monitoring visits per site related to 3 interim analyses and resolution of clinical review queries not originally contracted:
Canadian
11 sites x 7 visits 92,400.00 276,000.00
AMENDMENT #2
ADJUSTMENT: Per visit rate adjusted to $1800/visit for visits occurring post-March, 2001 due to increased patient population, extensive CRF changes, increased on site effort
58 x $1,200 = 69,600
38 x $1,800 = 68,400
134 x $1,800 = 241,200
Total $379,200 22,800.00 80,400.00 379,200.00 (379,200.00 ) 0.00
U.S.
58 sites x 7 visits 584,640.00 1,741,320.00
AMENDMENT #2
ADJUSTMENT: Per visit rate adjusted to $2160/visit for visits occurring post-March, 2001 due to increased patient population, extensive CRF changes, increased on site effort
608 x $1,440 = 875,520
Page 4 of 15 Unit Cost
Original
Study Total Adjustment
Amendment
2
Revised
Study Total
($US)
Adjustment
Amendment
3 Occurring
to Nov.
2001
Adjustment
Amendment
3 Occurring
post Nov.
2001
Revised
Study Total
($US)
Adjustment
Amendment
4
Revised
Study Total
($US)
Amendment
2
Amendment
#3
Amendment
#4
212 x $2,160 = 457,920
389 x $2,160 = 840,240
Total $2,173,680 152,640.00 279,720.00 2,173,680.00 (2,173,680.00 ) 0.00
AMENDMENT 3 ADD: North America: 2.25 visits per site to take total visits per site to 22 over life of study Australia: 5 visits per site to take total visits per site to 16 over life of study
Canadian
11 sites x 2.25 visits 1,800.00 44,550.00 44,550.00 (44,550.00 ) 0.00
U.S.
58 sites x 2.25 visits 2,160.00 281,880.00 281,880.00 (281,880.00 ) 0.00
Australia
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