A Study of the Safety and Tolerability of Pimavanserin (ACP-103) in Patients With Parkinson's Disease Psychosis

• Sponsor: ACADIA Pharmaceuticals Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00550238
• Collaborator: (none)
• Enrollment: 459
• Locations: 135
• Arm: 1
• Duration (Months): 131
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

To assess the long-term safety and tolerability of ACP-103 in subjects with Parkinson's disease psychosis.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease Psychosis	Drug: Pimavanserin tartrate (ACP-103)	Phase 3

Detailed Description

This study did not have a fixed duration, and the duration of individual subject participation was determined based on investigator assessment of subject tolerability and continued benefit until such time as either the drug was commercially available in the US, or an alternate treatment extension was available in non-US regions. For this reason, no subjects, therefore, were considered to have "completed" the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 459 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Open-Label Extension Study to Examine the Safety and Tolerability of ACP-103 in the Treatment of Psychosis in Parkinson's Disease
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: May 30, 2018
• Actual Study Completion Date: May 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pimavanserin tartrate (ACP-103) Tablets taken once daily by mouth for as long as ACP-103 is considered to be tolerated and beneficial to subjects	Drug: Pimavanserin tartrate (ACP-103); Tablets taken once daily by mouth for as long as ACP-103 is considered to be tolerated and beneficial to subjects

Outcome Measures

Primary Outcome Measures

1. Safety: Number (%) of Patients With Drug-related Treatment-emergent Adverse Events (AEs) [From first to last study drug dose plus 30 days]

   Number (%) of patients with drug-related treatment-emergent AEs (i.e. AEs reported by the Investigator as possibly, probably, or highly probably related to study drug)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject has completed the treatment period of a previous blinded study of pimavanserin

• The subject is willing and able to provide consent

• Caregiver is willing and able to accompany the subject to all visits

Exclusion Criteria:

• Subject has current evidence of a serious and or unstable cardiovascular, respiratory, gastrointestinal, renal, hematologic or other medical disorder

• Subject is judged by the Investigator to be inappropriate for the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Gilbert	Arizona	United States	85234
2		Phoenix	Arizona	United States	85013
3		Tucson	Arizona	United States	84724
4		Berkeley	California	United States	94705
5		Carson	California	United States	90746
6		Fountain Valley	California	United States	92708
7		Fresno	California	United States	93720
8		Irvine	California	United States	92697
9		La Habra	California	United States	90631
10		La Jolla	California	United States	92037
11		Laguna Hills	California	United States	92653
12		Loma Linda	California	United States	92354
13		Oxnard	California	United States	93030
14		Pasadena	California	United States	91105
15		Reseda	California	United States	91335
16		Sunnyvale	California	United States	94085
17		Ventura	California	United States	93003
18		Englewood	Colorado	United States	80113
19		Danbury	Connecticut	United States	06810
20		Fairfield	Connecticut	United States	06824
21		Farmington	Connecticut	United States	06030
22		Boca Raton	Florida	United States	33486
23		Bradenton	Florida	United States	34205
24		Deerfield Beach	Florida	United States	33064
25		Gainesville	Florida	United States	32610
26		Jacksonville	Florida	United States	32209
27		Miami	Florida	United States	33136
28		Naples	Florida	United States	34102
29		Orlando	Florida	United States	32806
30		Ormond Beach	Florida	United States	32174
31		Panama City	Florida	United States	32405
32		Pompano Beach	Florida	United States	33060
33		Port Charlotte	Florida	United States	33980
34		Saint Petersburg	Florida	United States	33701
35		Sarasota	Florida	United States	34233
36		Tampa	Florida	United States	33606
37		Augusta	Georgia	United States	30912
38		Decatur	Georgia	United States	30033
39		Glenview	Illinois	United States	60026
40		Springfield	Illinois	United States	62794
41		Kansas City	Kansas	United States	66160
42		Louisville	Kentucky	United States	40202
43		Scarborough	Maine	United States	04074
44		Baltimore	Maryland	United States	21287
45		Boston	Massachusetts	United States	02215
46		Worcester	Massachusetts	United States	01655
47		Clinton Township	Michigan	United States	48037
48		Detroit	Michigan	United States	48201
49		East Lansing	Michigan	United States	48824
50		Roseville	Michigan	United States	48066
51		Traverse City	Michigan	United States	49684
52		West Bloomfield	Michigan	United States	48334
53		Columbia	Missouri	United States	65201
54		Saint Louis	Missouri	United States	63110
55		Missoula	Montana	United States	59802
56		Toms River	New Jersey	United States	08755
57		Albany	New York	United States	12208
58		Commack	New York	United States	11725
59		Kingston	New York	United States	12401
60		Rochester	New York	United States	14618
61		Asheville	North Carolina	United States	28806
62		Charlotte	North Carolina	United States	28204
63		Durham	North Carolina	United States	27705
64		New Bern	North Carolina	United States	28562
65		Salisbury	North Carolina	United States	28144
66		Cincinnati	Ohio	United States	45210
67		Cleveland	Ohio	United States	44195
68		Columbus	Ohio	United States	43210
69		Toledo	Ohio	United States	43614
70		Greensburg	Pennsylvania	United States	15601
71		Philadelphia	Pennsylvania	United States	19131
72		Providence	Rhode Island	United States	02906
73		Brentwood	Tennessee	United States	37027
74		Houston	Texas	United States	77030
75		Salt Lake City	Utah	United States	84108
76		Burlington	Vermont	United States	05401
77		Alexandria	Virginia	United States	22311
78		Richmond	Virginia	United States	23229
79		Roanoke	Virginia	United States	24018
80		Virginia Beach	Virginia	United States	23456
81		Kirkland	Washington	United States	98034
82		Spokane	Washington	United States	99204
83		Milwaukee	Wisconsin	United States	53233
84		Innsbruck		Austria	6020
85		Vienna		Austria	1090
86		Roeselare		Belgium	8800
87		London	Ontario	Canada	N6A 5A5
88		Ottawa	Ontario	Canada	K1G 4G3
89		Clermont Ferrand		France	63003
90		Marseille		France	13385
91		Nantes Cedex		France	44093
92		Pessac		France	33604
93		Strasbourg		France	67091
94		Bangalore		India	560 034
95		Chennai		India	600 006
96		Hyderabad		India	500003
97		Madurai		India	625 020
98		Mangalore		India	575 001
99		Mangalore		India	575 002
100		Mumbai		India	400 016
101		Mumbai		India	400 026
102		Pune		India	411 004
103		Pune		India	411 030
104		Visakhapatnam		India	530 002
105		Chieti		Italy	66013
106		Grosseto		Italy	58100
107		Rome		Italy	00163
108		Rome		Italy	00185
109		Bydgoszcz		Poland	85796
110		Katowice		Poland	40-752
111		Lublin		Poland	20-090
112		Coimbra		Portugal	3000-548
113		Lisboa		Portugal	1649-028
114		Porto		Portugal	4099-001
115		Kazan		Russian Federation	420061
116		Kirov		Russian Federation	610014
117		Moscow		Russian Federation	125284
118		Pyatigorsk		Russian Federation	357538
119		Samara		Russian Federation	443095
120		Smolensk		Russian Federation	214018
121		St. Petersburg		Russian Federation	194044
122		Belgrade		Serbia	11000
123		Novi Sad		Serbia	21000
124		Stockholm		Sweden	SE-112 45
125		Kharkov		Ukraine	61068
126		Kiev		Ukraine	04080
127		Kiev		Ukraine	04114
128		Lugansk		Ukraine	91045
129		Lviv		Ukraine	79010
130		Vinnitsia		Ukraine	21005
131		Barnsley		United Kingdom	S75 2EP
132		Blackburn		United Kingdom	BB2 3HH
133		London		United Kingdom	NW3 20G
134		Newcastle		United Kingdom	NE4 6BE
135		North Shields		United Kingdom	NE21 8NH

Sponsors and Collaborators

• ACADIA Pharmaceuticals Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jul 16, 2010
• Statistical Analysis Plan - Aug 5, 2014

More Information

Publications

• Mathis MV, Muoio BM, Andreason P, Avila AM, Farchione T, Atrakchi A, Temple RJ. The US Food and Drug Administration's Perspective on the New Antipsychotic Pimavanserin. J Clin Psychiatry. 2017 Jun;78(6):e668-e673. doi: 10.4088/JCP.16r11119. Review.

• Responsible Party: ACADIA Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT00550238
• Other Study ID Numbers: ACP-103-015
• First Posted: Oct 29, 2007
• Last Update Posted: Jun 24, 2019
• Last Verified: May 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by ACADIA Pharmaceuticals Inc.: Parkinson's Disease Psychosis
• Additional relevant MeSH terms: Parkinson Disease; Psychotic Disorders; Mental Disorders; Pimavanserin

Study Results

Participant Flow

Recruitment Details	Eligible patients were adult males or females with Parkinson's Disease Psychosis who had completed a prior double blind study with pimavanserin and were determined by the treating physician (Investigator) to benefit from continued treatment. This study did not have a fixed duration. Thus, no patients were considered to have "completed" the study.
Pre-assignment Detail	Patients could be enrolled in this study as early as the final visit of the previous double-blind study, or up to 28 days following completion of the treatment period of the previous double-blind study.

Arm/Group Title	Pimavanserin
Arm/Group Description	Pimavanserin tartrate (ACP-103) tablets taken once daily by mouth for as long as the drug is considered to be tolerated and beneficial to patients
Period Title: Overall Study
STARTED	459
COMPLETED	0
NOT COMPLETED	459

Baseline Characteristics

Arm/Group Title	Pimavanserin
Arm/Group Description	Pimavanserin tartrate (ACP-103) tablets taken once daily by mouth for as long as the drug is considered to be tolerated and beneficial to patients
Overall Participants	459
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.2 (8.19)
Sex: Female, Male (Count of Participants)
Female	176 38.3%
Male	283 61.7%
Race/Ethnicity, Customized (Count of Participants)
White	423 92.2%
Black/African American	4 0.9%
Asian	19 4.1%
Other	13 2.8%
Region of Enrollment (participants) [Number]
North America	321 69.9%
Europe	120 26.1%
India	18 3.9%

Outcome Measures

1. Primary Outcome

Title	Safety: Number (%) of Patients With Drug-related Treatment-emergent Adverse Events (AEs)
Description	Number (%) of patients with drug-related treatment-emergent AEs (i.e. AEs reported by the Investigator as possibly, probably, or highly probably related to study drug)
Time Frame	From first to last study drug dose plus 30 days

Outcome Measure Data

Analysis Population Description

Enrolled patients who received at least 1 dose of study drug

Arm/Group Title	Pimavanserin
Arm/Group Description	Pimavanserin tartrate (ACP-103) tablets taken once daily by mouth for as long as the drug is considered to be tolerated and beneficial to patients
Measure Participants	459
Count of Participants [Participants]	180 39.2%

Adverse Events

Time Frame	From first to last study drug dose plus 30 days
Arm/Group Title	Pimavanserin
Arm/Group Description	Pimavanserin tartrate (ACP-103) tablets taken once daily by mouth for as long as the drug is considered to be tolerated and beneficial to patients
All Cause Mortality
	Pimavanserin
	Affected / at Risk (%)	# Events
Total	59/459 (12.9%)
Serious Adverse Events
	Pimavanserin
	Affected / at Risk (%)	# Events
Total	188/459 (41%)
Blood and lymphatic system disorders
Anaemia	2/459 (0.4%)	2
Leukocytosis	1/459 (0.2%)	1
Cardiac disorders
Acute myocardial infarction	5/459 (1.1%)	5
Cardiac arrest	3/459 (0.7%)	3
Cardiac failure congestive	3/459 (0.7%)	3
Angina pectoris	2/459 (0.4%)	2
Cardiac failure	2/459 (0.4%)	2
Cardio-respiratory arrest	2/459 (0.4%)	2
Cardiopulmonary failure	2/459 (0.4%)	2
Coronary artery disease	2/459 (0.4%)	2
Myocardial infarction	2/459 (0.4%)	2
Atrial flutter	1/459 (0.2%)	1
Atrioventricular block complete	1/459 (0.2%)	1
Bradycardia	1/459 (0.2%)	1
Cardiomyopathy	1/459 (0.2%)	1
Myocardial ischaemia	1/459 (0.2%)	1
Sick sinus syndrome	1/459 (0.2%)	1
Eye disorders
Visual acuity reduced	1/459 (0.2%)	1
Gastrointestinal disorders
Rectal haemorrhage	2/459 (0.4%)	2
Small intestinal obstruction	2/459 (0.4%)	2
Abdominal pain	1/459 (0.2%)	1
Constipation	1/459 (0.2%)	1
Crohn's disease	1/459 (0.2%)	1
Dyschezia	1/459 (0.2%)	1
Faecaloma	1/459 (0.2%)	1
Gastric ulcer	1/459 (0.2%)	1
Gastrointestinal haemorrhage	1/459 (0.2%)	1
Hiatus hernia	1/459 (0.2%)	1
Inguinal hernia	1/459 (0.2%)	1
Lower gastrointestinal haemorrhage	1/459 (0.2%)	1
Melaena	1/459 (0.2%)	1
Pancreatitis	1/459 (0.2%)	1
Pancreatitis acute	1/459 (0.2%)	1
Presbyoesophagus	1/459 (0.2%)	1
Rectal prolapse	1/459 (0.2%)	1
Umbilical hernia	1/459 (0.2%)	1
General disorders
Chest pain	6/459 (1.3%)	6
Death	2/459 (0.4%)	2
Asthenia	1/459 (0.2%)	1
Axillary pain	1/459 (0.2%)	1
Inflammation	1/459 (0.2%)	1
Non-cardiac chest pain	1/459 (0.2%)	1
Pyrexia	1/459 (0.2%)	1
Hepatobiliary disorders
Cholecystitis	2/459 (0.4%)	2
Bile duct obstruction	1/459 (0.2%)	1
Cholecystitis acute	1/459 (0.2%)	1
Infections and infestations
Pneumonia	21/459 (4.6%)	23
Urinary tract infection	17/459 (3.7%)	19
Sepsis	7/459 (1.5%)	7
Cellulitis	4/459 (0.9%)	5
Clostridium difficile colitis	3/459 (0.7%)	3
Diverticulitis	3/459 (0.7%)	3
Respiratory tract infection	3/459 (0.7%)	3
Bacterial sepsis	2/459 (0.4%)	2
Candiduria	2/459 (0.4%)	2
Coccidioidomycosis	2/459 (0.4%)	2
Septic shock	2/459 (0.4%)	2
Urosepsis	2/459 (0.4%)	2
Abscess limb	1/459 (0.2%)	1
Bacteraemia	1/459 (0.2%)	1
Enterococcal sepsis	1/459 (0.2%)	1
Escherichia bacteraemia	1/459 (0.2%)	1
Escherichia urinary tract infection	1/459 (0.2%)	1
Fungal infection	1/459 (0.2%)	1
Gangrene	1/459 (0.2%)	1
Gastroenteritis viral	1/459 (0.2%)	1
Gastrointestinal infection	1/459 (0.2%)	1
Pneumonia viral	1/459 (0.2%)	1
Injury, poisoning and procedural complications
Hip fracture	10/459 (2.2%)	10
Fall	6/459 (1.3%)	8
Femoral neck fracture	4/459 (0.9%)	4
Femure fracture	4/459 (0.9%)	5
Contusion	2/459 (0.4%)	2
Humerus fracture	2/459 (0.4%)	2
Spinal compression fracture	2/459 (0.4%)	2
Clavicle fracture	1/459 (0.2%)	1
Craniocerebral injury	1/459 (0.2%)	1
Head injury	1/459 (0.2%)	1
Joint dislocation	1/459 (0.2%)	1
Laceration	1/459 (0.2%)	1
Lumbar vertebral fracture	1/459 (0.2%)	1
Overdose	1/459 (0.2%)	1
Post procedural complication	1/459 (0.2%)	1
Post procedural haemorrhage	1/459 (0.2%)	1
Road traffic accident	1/459 (0.2%)	1
Soft tissue injury	1/459 (0.2%)	1
Spinal fracture	1/459 (0.2%)	1
Stress fracture	1/459 (0.2%)	1
Subdural haemorrhage	1/459 (0.2%)	1
Thoracic vertebral fracture	1/459 (0.2%)	1
Toxicity to various agents	1/459 (0.2%)	1
Investigations
Nuclear magnetic resonance imaging	1/459 (0.2%)	1
Metabolism and nutrition disorders
Dehydration	9/459 (2%)	9
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis	4/459 (0.9%)	4
Osteoarthritis	3/459 (0.7%)	4
Intervertebral disc disorder	2/459 (0.4%)	2
Arthritis	1/459 (0.2%)	1
Exostosis	1/459 (0.2%)	1
Osteochondrosis	1/459 (0.2%)	1
Rhabdomyolysis	1/459 (0.2%)	1
Scoliosis	1/459 (0.2%)	1
Spinal column stenosis	1/459 (0.2%)	1
Spinal osteoarthritis	1/459 (0.2%)	1
Spondylolysis	1/459 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	3/459 (0.7%)	3
Bladder cancer	1/459 (0.2%)	1
Brain neoplasm	1/459 (0.2%)	1
Colon cancer stage III	1/459 (0.2%)	1
Hepatic neoplasm malignant	1/459 (0.2%)	1
Meningioma benign	1/459 (0.2%)	1
Multiple myeloma	1/459 (0.2%)	1
Paraproteinaemia	1/459 (0.2%)	1
Recurrent cancer	1/459 (0.2%)	1
Nervous system disorders
Parkinson's disease	10/459 (2.2%)	10
Syncope	8/459 (1.7%)	9
Dementia	7/459 (1.5%)	7
Cerebrovascular accident	5/459 (1.1%)	6
Transient ischaemic attack	4/459 (0.9%)	4
Convulsion	3/459 (0.7%)	3
Metabolic encephalopathy	3/459 (0.7%)	3
Presyncope	3/459 (0.7%)	3
Encephalopathy	2/459 (0.4%)	2
Subarachnoid haemorrhage	2/459 (0.4%)	2
Toxic encephalopathy	2/459 (0.4%)	2
Autonomic nervous system imbalance	1/459 (0.2%)	1
Burning sensation	1/459 (0.2%)	1
Cerebral haemorrhage	1/459 (0.2%)	1
Haemorrhagic stroke	1/459 (0.2%)	1
Ischaemic stroke	1/459 (0.2%)	1
Lethargy	1/459 (0.2%)	1
Neuroleptic malignant syndrome	1/459 (0.2%)	1
On and off phenomenon	1/459 (0.2%)	1
Parkinsonism	1/459 (0.2%)	1
Sciatica	1/459 (0.2%)	1
Psychiatric disorders
Mental status change	7/459 (1.5%)	7
Psychotic disorder	7/459 (1.5%)	7
Hallucination	6/459 (1.3%)	6
Hallucination, visual	2/459 (0.4%)	2
Abnormal behaviour	1/459 (0.2%)	1
Aggression	1/459 (0.2%)	1
Anxiety	1/459 (0.2%)	1
Confusional state	1/459 (0.2%)	1
Delirium	1/459 (0.2%)	1
Delusion	1/459 (0.2%)	1
Jealous delusion	1/459 (0.2%)	1
Major depression	1/459 (0.2%)	1
Panic attack	1/459 (0.2%)	1
Suicide attempt	1/459 (0.2%)	1
Renal and urinary disorders
Renal failure acute	2/459 (0.4%)	2
Urinary retention	2/459 (0.4%)	2
Bladder neck obstruction	1/459 (0.2%)	1
Calculus ureteric	1/459 (0.2%)	1
Haematuria	1/459 (0.2%)	1
Nephrolithiasis	1/459 (0.2%)	1
Renail failure	1/459 (0.2%)	1
Renal failure chronic	1/459 (0.2%)	1
Urinary tract obstrcution	1/459 (0.2%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/459 (0.2%)	1
Vaginal prolapse	1/459 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration	11/459 (2.4%)	13
Pulmonary embolism	8/459 (1.7%)	8
Acute respiratory failure	5/459 (1.1%)	5
Respiratory failure	3/459 (0.7%)	3
Chronic obstructive pulmonary disease	2/459 (0.4%)	2
Dyspnoea	2/459 (0.4%)	2
Aspiration	1/459 (0.2%)	1
Atelectasis	1/459 (0.2%)	1
Atypical pneumonia	1/459 (0.2%)	1
Choking	1/459 (0.2%)	1
Hydropneumothorax	1/459 (0.2%)	1
Hypoxia	1/459 (0.2%)	1
Pleural effusion	1/459 (0.2%)	1
Pulmonary haemorrhage	1/459 (0.2%)	1
Respiratory distress	1/459 (0.2%)	1
Surgical and medical procedures
Deep brain stimulation	1/459 (0.2%)	1
Skin neoplasm excision	1/459 (0.2%)	1
Vascular disorders
Orthostatic hypotension	5/459 (1.1%)	6
Hypertension	4/459 (0.9%)	4
Deep vein thrombosis	2/459 (0.4%)	2
Aortic aneurysm	1/459 (0.2%)	1
Aortic dissection	1/459 (0.2%)	1
Circulatory collapse	1/459 (0.2%)	1
Hypertensive crisis	1/459 (0.2%)	2
Hypotension	1/459 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Pimavanserin
	Affected / at Risk (%)	# Events
Total	328/459 (71.5%)
Blood and lymphatic system disorders
Anaemia	35/459 (7.6%)	37
Gastrointestinal disorders
Constipation	46/459 (10%)	54
Dysphagia	43/459 (9.4%)	46
Nausea	39/459 (8.5%)	49
General disorders
Oedema peripheral	43/459 (9.4%)	52
Infections and infestations
Urinary tract infection	79/459 (17.2%)	160
Injury, poisoning and procedural complications
Fall	145/459 (31.6%)	326
Contusion	37/459 (8.1%)	55
Laceration	36/459 (7.8%)	51
Excoriation	23/459 (5%)	41
Investigations
Weight decreased	57/459 (12.4%)	65
Metabolism and nutrition disorders
Dehydration	25/459 (5.4%)	34
Musculoskeletal and connective tissue disorders
Arthralgia	31/459 (6.8%)	42
Back pain	28/459 (6.1%)	38
Nervous system disorders
Dizziness	43/459 (9.4%)	50
Dementia	30/459 (6.5%)	33
Somnolence	29/459 (6.3%)	33
Parkinson's disease	27/459 (5.9%)	30
Headache	23/459 (5%)	30
Tremor	23/459 (5%)	26
Psychiatric disorders
Hallucination	62/459 (13.5%)	89
Confusional state	50/459 (10.9%)	65
Anxiety	41/459 (8.9%)	47
Depression	39/459 (8.5%)	41
Insomnia	34/459 (7.4%)	36
Psychotic disorder	33/459 (7.2%)	39
Agitation	32/459 (7%)	37
Cognitive disorder	28/459 (6.1%)	33
Vascular disorders
Orthostatic hypertension	40/459 (8.7%)	48
Hypertension	34/459 (7.4%)	36

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Investigator may publish the study results, relative to his/her own patients, only after review, comment and approval by the sponsor. No publication of confidential information shall be made without the sponsor's prior written consent. At least 60 days prior to submitting a manuscript or prior to any public presentation, a copy of the manuscript or presentation will be provided to the sponsor for review and comment. The sponsor has 60 days to review and comment.