VLZ-MD-23: A Study of Vilazodone in Pediatric Patients With Major Depressive Disorder

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02436239
• Collaborator: (none)
• Enrollment: 330
• Locations: 56
• Arm: 1
• Actual Duration (Months): 38.7
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the long-term safety and tolerability of vilazodone for the treatment of MDD in pediatric outpatients (7-17 years).

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Vilazodone	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 330 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Long-term Safety Study of Vilazodone in Pediatric Patients With Major Depressive Disorder
• Actual Study Start Date: May 2, 2015
• Actual Primary Completion Date: Jul 23, 2018
• Actual Study Completion Date: Jul 23, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vilazodone	Drug: Vilazodone; Vilazodone tablets, once daily, oral administration; Other Names: Viibryd

Outcome Measures

Primary Outcome Measures

1. Number of Participants to Experience a Treatment Emergent Adverse Event (TEAE) [Visit 1 (Week -1) to up to Visit 16 (Week 26)]

   The number of Participants who experienced a treatment emergent adverse events during the 27 week period from screening to the end of the open-label treatment period

Secondary Outcome Measures

1. Change From Baseline in the CDRS-R Total Score [Baseline (Week 0) to Week 26]

   The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 133 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.

2. Change From Baseline in the CGI-S Score [Baseline (Week 0) to Week 26]

   The Clinical Global Impressions-Severity (CGI-S) is a clinician-rated instrument used to rate the severity of the patient's current state of mental illness compared with the clinician's total experience with patients with major depressive disorder (MDD). The severity of the patient's MDD was rated on a scale from 1 to 7, with 1 indicating a normal state and 7 indicating a patient who is among the most extremely ill patients.

3. Change From Baseline in Clinical Global Impressions-Improvement (CGI-I) [Baseline (Week 0) to Week 26]

   The Clinical Global Impressions-Improvement is a clinician-rated instrument that was used to rate total improvement or worsening of mental illness, regardless of whether the Investigator considered it to be a result of treatment with the investigational product. The CGI-I was used to rate the patient's improvement on a scale from 1 to 7, with 1 indicating that the patient was very much improved (with a score of 4 indicating no change) and 7 indicating the patient was very much worse.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or Female outpatients betw een 7-17 years of age

• Primary diagnosis of major depressive disorder (MDD)

• Children's Depression Rating Scale-Revised (CDRS-R) score of 40 or greater

• Clinical Global Impressions-Severity (CGI-S) score of 4 or greater

Exclusion Criteria:

• Current (past 3 months) principal Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision based diagnosis of an Axis I disorder other than MDD that is the primary focus of treatment (de novo patients only)

• History of suicidal behavior, or requires precaution against suicide

• Not generally healthy medical condition

• Seizure disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alliance Clinical Research	Birmingham	Alabama	United States	35213
2	Harmonex Neuroscience Research	Dothan	Alabama	United States	36303
3	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
4	Woodland International Research Group, INC	Little Rock	Arkansas	United States	72211
5	CITrials - Bellflower	Bellflower	California	United States	90706
6	ATP Clinical Research	Costa Mesa	California	United States	92626
7	Behavioral Research Specialists, LLC	Glendale	California	United States	91206
8	PCSD - Feighner Research	San Diego	California	United States	92108
9	Pacific Clinical Research Medical Group	Hartford	Connecticut	United States	06106
10	Children's National Medical Center	Washington	District of Columbia	United States	20010
11	Palm Springs Research, LLC	Hialeah	Florida	United States	33012
12	IMIC Inc.	Homestead	Florida	United States	33030
13	Clinical Neuroscience Solutions, Inc.	Jacksonville	Florida	United States	32256
14	Innovative Clinical Research, Inc.	Lauderhill	Florida	United States	33319
15	Clinical Neuroscience Solutions, Inc.	Orlando	Florida	United States	32801
16	Institute for Advanced Medical Research	Alpharetta	Georgia	United States	30005
17	Atlantic Center for Medical Research	Atlanta	Georgia	United States	30331
18	Northwest Behavioral Research Center	Marietta	Georgia	United States	30060
19	Capstone Clinical Research	Libertyville	Illinois	United States	60048
20	Baber Research Group	Naperville	Illinois	United States	60563
21	Neuroscience Research Institute Inc.	Oak Park	Illinois	United States	60301
22	Psychiatric Associates	Overland Park	Kansas	United States	66211
23	Lake Charles Clinical Trials	Lake Charles	Louisiana	United States	70629
24	Hugo W Moser Research Institute at Kennedy Krieger, Inc.	Baltimore	Maryland	United States	21205
25	Pharmsite Research Inc.	Baltimore	Maryland	United States	21208
26	NeuroScientific Insights	Rockville	Maryland	United States	20852
27	Baystate Medical Center	Springfield	Massachusetts	United States	01199
28	Adams Clinical Trials, LLC	Watertown	Massachusetts	United States	02472
29	Millennium Psychiatric Associates	Creve Coeur	Missouri	United States	63141
30	St. Charles Psychiatric Associates - Midwest Research Group	Saint Charles	Missouri	United States	63304
31	Erie County Medical Center/State University of New York of Buffalo Affiliate	Buffalo	New York	United States	14215
32	BioScience Research LLC	Mount Kisco	New York	United States	10549
33	Manhattan Behavioral Medicine	New York	New York	United States	10022
34	Finger Lakes Clinical research	Rochester	New York	United States	14618
35	Richmond Behavioral Associates	Staten Island	New York	United States	10312
36	Haidar Almhana Nieding LLC	Avon Lake	Ohio	United States	44012
37	Neuro-Behavioral Clinical Research, Inc	Canton	Ohio	United States	44718
38	University of Cincinnati	Cincinnati	Ohio	United States	45219
39	University Hospitals Cleveland Medical Center, Psychiatr	Cleveland	Ohio	United States	44106
40	Ohio State Univ. Dept of Psychiatry	Columbus	Ohio	United States	43210
41	Professional Psychiatric Services	Mason	Ohio	United States	45040
42	IPS Research Company	Oklahoma City	Oklahoma	United States	73103
43	Cutting Edge Research Group	Oklahoma City	Oklahoma	United States	73116
44	Research Strategies of Memphis LLC	Memphis	Tennessee	United States	38119
45	BioBehavioral Research of Austin, PC	Austin	Texas	United States	78759
46	UT Health Science Center at Houston	Houston	Texas	United States	77054
47	Houston Endoscopy and Research Ctr	Houston	Texas	United States	77079
48	Research Across America	Plano	Texas	United States	75093
49	Focus and Balance	San Antonio	Texas	United States	78229
50	Family Psychiatry of The Woodlands	The Woodlands	Texas	United States	77381
51	Ericksen Research and Development	Clinton	Utah	United States	84015
52	UVA Center for Psychopharmacology Research in Youth	Charlottesville	Virginia	United States	22903
53	Northwest Clinical Research Center	Bellevue	Washington	United States	98007
54	Core Clinical Research	Kirkland	Washington	United States	98033
55	Okanagan Clinical Trials Inc.	Kelowna	British Columbia	Canada	V1Y1Z9
56	Paediatric Sleep Research Inc	Toronto	Ontario	Canada	M6J3S3

Sponsors and Collaborators

• Forest Laboratories

Investigators

• Study Director: Emily McCusker, PhD, Forest Research Institute, Inc., an affiliate of Allergan, plc

Study Documents (Full-Text)

• Study Protocol - Nov 2, 2016
• Statistical Analysis Plan - Feb 10, 2016

More Information

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT02436239
• Other Study ID Numbers: VLZ-MD-23
• First Posted: May 6, 2015
• Last Update Posted: Sep 11, 2019
• Last Verified: Sep 1, 2019

• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Vilazodone Hydrochloride

Study Results

Participant Flow

Pre-assignment Detail	Patients who completed lead-in study VLZ-MD-22 (NCT02372799) had already completed a down-taper period at the end of study VLZ-MD-22 and were not required to undergo a washout period in VLZ-MD-23. For de novo patients, the screening/washout period was generally 1 week prior to Baseline.

Arm/Group Title	Placebo/Vilazodone	Vilazodone/Vilazodone	Fluoxetine/Vilazodone	De Novo/Vilazodone
Arm/Group Description	Participants who received placebo during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received vilazodone during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received Fluoxetine during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Newly enrolled participants received vilazodone tablets once daily, oral administration.
Period Title: Open-Lable Treatment Period
STARTED	122	131	65	12
COMPLETED	89	97	38	7
NOT COMPLETED	33	34	27	5
Period Title: Open-Lable Treatment Period
STARTED	90	103	44	6
COMPLETED	86	99	43	4
NOT COMPLETED	4	4	1	2

Baseline Characteristics

Arm/Group Title	Placebo/Vilazodone	Vilazodone/Vilazodone	Fluoxetine/Vilazodone	De Novo/Vilazodone	Total
Arm/Group Description	Participants who received placebo during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received vilazodone during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received Fluoxetine during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Newly enrolled participants received vilazodone tablets once daily, oral administration.	Total of all reporting groups
Overall Participants	122	131	65	12	330
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	13.2 (2.9)	13.3 (2.8)	13.2 (2.8)	13.0 (2.9)	13.3 (2.9)
Age, Customized (Count of Participants)
Age 7-11 Years	37 30.3%	35 26.7%	19 29.2%	4 33.3%	95 28.8%
Age 12-17 Years	83 68%	93 71%	46 70.8%	8 66.7%	230 69.7%
Age 18 Years	2 1.6%	3 2.3%	0 0%	0 0%	5 1.5%
Sex: Female, Male (Count of Participants)
Female	68 55.7%	89 67.9%	33 50.8%	7 58.3%	197 59.7%
Male	54 44.3%	42 32.1%	32 49.2%	5 41.7%	133 40.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	16 13.1%	16 12.2%	8 12.3%	2 16.7%	42 12.7%
Not Hispanic or Latino	106 86.9%	115 87.8%	57 87.7%	10 83.3%	288 87.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	5 4.1%	1 0.8%	1 1.5%	0 0%	7 2.1%
Native Hawaiian or Other Pacific Islander	0 0%	2 1.5%	0 0%	0 0%	2 0.6%
Black or African American	32 26.2%	40 30.5%	20 30.8%	1 8.3%	93 28.2%
White	82 67.2%	84 64.1%	42 64.6%	11 91.7%	219 66.4%
More than one race	3 2.5%	4 3.1%	2 3.1%	0 0%	9 2.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	57.98 (23.54)	62.67 (25.26)	59.36 (18.93)	60.34 (17.87)	60.17 (23.26)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	22.73 (6.59)	24.75 (7.96)	23.30 (5.37)	23.90 (6.20)	23.69 (6.98)
CDRS-R total score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	55.7 (9.6)	59.3 (9.5)	57.8 (8.7)	59.7 (9.1)	58.4 (9.3)
CGI-S score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.6 (0.6)	4.7 (0.7)	4.6 (0.6)	4.2 (0.4)	4.6 (0.6)

Outcome Measures

1. Primary Outcome

Title	Number of Participants to Experience a Treatment Emergent Adverse Event (TEAE)
Description	The number of Participants who experienced a treatment emergent adverse events during the 27 week period from screening to the end of the open-label treatment period
Time Frame	Visit 1 (Week -1) to up to Visit 16 (Week 26)

Outcome Measure Data

Analysis Population Description

The Safety Population consisted of the 330 participants who took at least 1 dose of open-label investigational product.

Arm/Group Title	Placebo/Vilazodone	Vilazodone/Vilazodone	Fluoxetine/Vilazodone	De Novo/Vilazodone
Arm/Group Description	Participants who received placebo during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received vilazodone during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received Fluoxetine during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Newly enrolled participants received vilazodone tablets once daily, oral administration.
Measure Participants	122	131	65	12
Count of Participants [Participants]	90 73.8%	89 67.9%	48 73.8%	10 83.3%

2. Secondary Outcome

Title	Change From Baseline in the CDRS-R Total Score
Description	The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 133 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.
Time Frame	Baseline (Week 0) to Week 26

Outcome Measure Data

Analysis Population Description

The Change From Baseline in the CDRS-R Total Score was assessed in the Intent to Treat study population, comprised of the 325 patients in the Safety Population who had a baseline and at least 1 postbaseline assessment of the CDRS-R total score.

Arm/Group Title	Placebo/Vilazodone	Vilazodone/Vilazodone	Fluoxetine/Vilazodone	De Novo/Vilazodone
Arm/Group Description	Participants who received placebo during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received vilazodone during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received Fluoxetine during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Newly enrolled participants received vilazodone tablets once daily, oral administration.
Measure Participants	121	130	63	11
Mean (Standard Deviation) [units on a scale]	-29.2 (11.9)	-30.1 (12.2)	-29.4 (12.2)	-24.5 (10.3)

3. Secondary Outcome

Title	Change From Baseline in the CGI-S Score
Description	The Clinical Global Impressions-Severity (CGI-S) is a clinician-rated instrument used to rate the severity of the patient's current state of mental illness compared with the clinician's total experience with patients with major depressive disorder (MDD). The severity of the patient's MDD was rated on a scale from 1 to 7, with 1 indicating a normal state and 7 indicating a patient who is among the most extremely ill patients.
Time Frame	Baseline (Week 0) to Week 26

Outcome Measure Data

Analysis Population Description

The CGI-S was assessed in the Intent to Treat study population, comprised of the 325 patients in the Safety Population who had a baseline and at least 1 postbaseline assessment of the CDRS-R total score.

Arm/Group Title	Placebo/Vilazodone	Vilazodone/Vilazodone	Fluoxetine/Vilazodone	De Novo/Vilazodone
Arm/Group Description	Participants who received placebo during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received vilazodone during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received Fluoxetine during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Newly enrolled participants received vilazodone tablets once daily, oral administration.
Measure Participants	121	130	63	11
Mean (Standard Deviation) [units on a scale]	-2.5 (1.3)	-2.6 (1.4)	-2.5 (1.4)	-1.7 (1.2)

4. Secondary Outcome

Title	Change From Baseline in Clinical Global Impressions-Improvement (CGI-I)
Description	The Clinical Global Impressions-Improvement is a clinician-rated instrument that was used to rate total improvement or worsening of mental illness, regardless of whether the Investigator considered it to be a result of treatment with the investigational product. The CGI-I was used to rate the patient's improvement on a scale from 1 to 7, with 1 indicating that the patient was very much improved (with a score of 4 indicating no change) and 7 indicating the patient was very much worse.
Time Frame	Baseline (Week 0) to Week 26

Outcome Measure Data

Analysis Population Description

The CGI-I was assessed in the Intent to Treat study population, comprised of the 325 patients in the Safety Population who had a baseline and at least 1 postbaseline assessment of the CDRS-R total score.

Arm/Group Title	Placebo/Vilazodone	Vilazodone/Vilazodone	Fluoxetine/Vilazodone	De Novo/Vilazodone
Arm/Group Description	Participants who received placebo during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received vilazodone during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Participants who received Fluoxetine during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.	Newly enrolled participants received vilazodone tablets once daily, oral administration.
Measure Participants	121	130	63	11
Mean (Standard Deviation) [units on a scale]	2.1 (1.2)	2.0 (1.3)	2.0 (1.2)	2.2 (1.2)

Adverse Events

Time Frame	Adverse event data was collected for up to 28 weeks, which consists of the screening visit (1 week), the 26 week open label treatment period and during the 1 week down taper period.
Arm/Group Title	Placebo/Vilazodone		Vilazodone/Vilazodone		Fluoxetine/Vilazodone		De Novo/Vilazodone
Arm/Group Description	Participants who received placebo during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.		Participants who received vilazodone during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.		Participants who received Fluoxetine during the lead in study, VLZ-MD-22, were given vilazodone tablets once daily, oral administration.		Newly enrolled participants received vilazodone tablets once daily, oral administration.
All Cause Mortality
	Placebo/Vilazodone		Vilazodone/Vilazodone		Fluoxetine/Vilazodone		De Novo/Vilazodone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/122 (0%)		0/131 (0%)		1/65 (1.5%)		0/12 (0%)
Serious Adverse Events
	Placebo/Vilazodone		Vilazodone/Vilazodone		Fluoxetine/Vilazodone		De Novo/Vilazodone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/122 (4.9%)		0/131 (0%)		1/65 (1.5%)		0/12 (0%)
Infections and infestations
Appendicitis	1/122 (0.8%)		0/131 (0%)		0/65 (0%)		0/12 (0%)
Injury, poisoning and procedural complications
Gun Shot Wound	0/122 (0%)		0/131 (0%)		1/65 (1.5%)		0/12 (0%)
Psychiatric disorders
Suicidal ideation	2/122 (1.6%)		0/131 (0%)		0/65 (0%)		0/12 (0%)
Abnormal behaviour	1/122 (0.8%)		0/131 (0%)		0/65 (0%)		0/12 (0%)
Aggression	1/122 (0.8%)		0/131 (0%)		0/65 (0%)		0/12 (0%)
Suicide attempt	1/122 (0.8%)		0/131 (0%)		0/65 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Placebo/Vilazodone		Vilazodone/Vilazodone		Fluoxetine/Vilazodone		De Novo/Vilazodone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	79/122 (64.8%)		81/131 (61.8%)		41/65 (63.1%)		10/12 (83.3%)
Ear and labyrinth disorders
Ear Pain	0/122 (0%)		1/131 (0.8%)		0/65 (0%)		2/12 (16.7%)
Gastrointestinal disorders
Nausea	27/122 (22.1%)		16/131 (12.2%)		8/65 (12.3%)		2/12 (16.7%)
Vomiting	15/122 (12.3%)		8/131 (6.1%)		3/65 (4.6%)		0/12 (0%)
Abdominal pain upper	12/122 (9.8%)		6/131 (4.6%)		4/65 (6.2%)		0/12 (0%)
Infections and infestations
Nasopharyngitis	5/122 (4.1%)		11/131 (8.4%)		2/65 (3.1%)		0/12 (0%)
Gastroenteritis	6/122 (4.9%)		3/131 (2.3%)		3/65 (4.6%)		1/12 (8.3%)
Sinusitis	1/122 (0.8%)		5/131 (3.8%)		2/65 (3.1%)		1/12 (8.3%)
Investigations
Weight increased	7/122 (5.7%)		15/131 (11.5%)		4/65 (6.2%)		1/12 (8.3%)
Nervous system disorders
Headache	21/122 (17.2%)		28/131 (21.4%)		8/65 (12.3%)		2/12 (16.7%)
Dizziness	3/122 (2.5%)		9/131 (6.9%)		4/65 (6.2%)		0/12 (0%)
Migraine	3/122 (2.5%)		3/131 (2.3%)		1/65 (1.5%)		1/12 (8.3%)
Syncope	0/122 (0%)		0/131 (0%)		0/65 (0%)		2/12 (16.7%)
Amnesia	0/122 (0%)		0/131 (0%)		0/65 (0%)		1/12 (8.3%)
Psychiatric disorders
Insomnia	13/122 (10.7%)		11/131 (8.4%)		2/65 (3.1%)		0/12 (0%)
Irritability	4/122 (3.3%)		3/131 (2.3%)		0/65 (0%)		1/12 (8.3%)
Agitation	0/122 (0%)		2/131 (1.5%)		0/65 (0%)		1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Dysmenorrhea	3/122 (2.5%)		4/131 (3.1%)		3/65 (4.6%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

All data generated in this study are the property of the sponsor. An integrated clinical and statistical report will be prepared at the completion of the study. Publication of the results by the Investigator will be subject to mutual agreement between the Investigator and the sponsor and will follow sponsor's standard operating procedures on publications.