Lurasidone - A 6-week Study of Patients With Bipolar I Depression (Monotherapy)

• Sponsor: Sunovion (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00868699
• Collaborator: (none)
• Enrollment: 505
• Locations: 55
• Arms: 3
• Duration (Months): 34
• Patients Per Site: 9.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This clinical study is designed to test the hypothesis that lurasidone is effective, tolerable, and safe for the treatment of patients with bipolar I depression

Condition or Disease	Intervention/Treatment	Phase
Bipolar Depression	Drug: lurasidone; Drug: lurasidone; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 505 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, 6-Week, Double-Blind, Placebo-Controlled, Fixed-Flexible Dose, Parallel-Group Study of Lurasidone for the Treatment of Bipolar I Depression
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: lurasidone low arm	Drug: lurasidone; lurasidone 20 mg/day for Days 1-7
Placebo Comparator: Placebo	Drug: Placebo; Placebo Comparator
Experimental: lurasidone high arm	Drug: lurasidone; lurasidone 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6 and 80 mg/day on Day 7 and 80-120 mg/day

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Endpoint (Week 6) [Baseline to Week 6]

   Montgomery-Asberg Depression Rating Scale (MADRS)is a clinician-rated assessment of a subject's level of depression. The MADRS total score ranges from a minimum of 0 to a maximum of 60. For the MADRS total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. The MADRS contains ten (10) items. The total score is computed as the sum of the scores for the 10 items.

Secondary Outcome Measures

1. Mean Change From Baseline to Endpoint (Week 6) in: Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) Score (Depression) [Baseline to Week 6]

   Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) score (depression) is a clinician-rated assessment of a subject's level of depression. The CGI depression score ranges from a minimum of 0 to a maximum of 7. For the CGI depression score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome.

2. Mean Change From Baseline to Endpoint (Week 6) in: Sheehan Disability Scale (SDS) Total Score [Baseline to Week 6]

   Sheehan Disability Scale (SDS) total score is a subject-rated assessment of a subject's level of depression. The SDS total score ranges from a minimum of 0 to a maximum of 30. For the SDS total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. The SDS contains three (3) items. The total score is computed as the sum of the scores for the 3 items.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject is diagnosed with bipolar I disorder, most resent episode depressed

• Subject must have a lifetime history of at least one bipolar manic or mixed episode

Exclusion Criteria:

• History of nonresponse to an adequate (6-week) trial of three or more antidepressants (with or without mood stabilizers) during the current episode

• Subject has been hospitalized for a manic or mixed episode within 60 days prior to randomization

• Imminent risk of suicide or injury to self, others, or property

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Synergy Escondido,710 East Grand Ave.	Escondido	California	United States	92025
2	Collaborative Neuroscience Network Inc.,12772 Valley View Street,Suite 3	Garden Grove	California	United States	92645
3	Excell Research, Inc,3998 Vista Way,Suite 100	Oceanside	California	United States	92056
4	University of California at Irvine Medical Center	Orange	California	United States	92868
5	California Neuropsychopharmacology,CNRI - Los Angeles LLC,8309 Telegraph Road	Pico Rivera	California	United States	90660
6	California Neuropsychopharmacology Clinical Research Institute, LLC,466 26th Street,6th Floor	San Diego	California	United States	92102
7	University of Colorado	Aurora	Colorado	United States	80045
8	Florida Clinical Research Center, LLC,3914 State Road 64 East	Bradenton	Florida	United States	34208
9	Florida Clinical Research Center, LLC,2300 Maitland Center Parkway,Suite 230	Maitland	Florida	United States	32751
10	Depression and Anxiety Disorders Research Institute	Tampa	Florida	United States	33613
11	Janus Center for Psychiatric Research,5601 Corporate Way,Suite 103	West Palm Beach	Florida	United States	33407
12	American Medical Research Inc.,1200 Harger Road Suite 415	Oak Brook	Illinois	United States	60523
13	Lake Charles Clinical Trials LLC,2770 3rd Avenue,Suite 340	Lake Charles	Louisiana	United States	70601
14	Sheppard Pratt Health System,6501 North Charles Street	Baltimore	Maryland	United States	21285
15	Albuquerque Neuroscience Inc., 101 Hospital Loop, NE, Suite 209	Albuquerque	New Mexico	United States	87109
16	Neurobehavioral Research, Inc.	Cedarhurst	New York	United States	11516
17	Finger Lakes Clinical Research	Rochester	New York	United States	14618
18	Richard H. Weisler., M.D., P.A., & Associates,700 Spring Forest Road,Suite 125	Raleigh	North Carolina	United States	27609
19	Mood Disorders Program-UHCMC	Cleveland	Ohio	United States	44106
20	MetroHealth System	Cleveland	Ohio	United States	44122
21	CRI Worldwide, LLC	Philadelphia	Pennsylvania	United States	19139
22	FutureSearch Clinical Trials, LLC.,4200 Marathon Blvd.,Suite 200	Austin	Texas	United States	78756
23	Medical Services Prague s.r.o.	Kolejni 429-5	Praha	Czech Republic
24	Psychiatricka ambulance	Brno - mesto		Czech Republic	602 00
25	BIALBI s.r.o., Psychiatricke Oddeleni	Litomerice		Czech Republic
26	Clintrial, s.r.o.	Praha		Czech Republic	10 100 00
27	Hopital Caremeau, Service de Psychiatrie A	Nimes Cedex		France	30 30029
28	Zans Ritter, Marcel	Orvault		France	44700
29	S V Medical College	Tirupati	Andh Prad	India	517507
30	Vijayawada Institute of Mental Health and Neurosciences, Psychiatry	Vijaywada	Andh Prad	India	520002
31	Samvedna Hospitals	Ahmedabad	Gujarat	India	380006
32	Seth K M School of P G Medicine & Research	Ahmedabad	Gujarat	India	380006
33	Mental Illness Treatment Rehabilitationi Foundation	Ahmedabad	Gujarat	India	380013
34	Spandana Nursing Home	Bangalore	Karna	India	560010
35	Sujata Birla Hospital & Research Centre	Nashik	Mahara	India	422101
36	R.K. Yadav Memorial Mental Health & De-Addiction Hospital	Jaipur	Rajasthan	India	302021
37	Manobal Med. Research Centre	Lucknow	Uttar Prad	India	226006
38	Spitalul Clinic de Urgenta Militar Central	Bucdresti		Romania	010825
39	Spitalul Clinic de Psihaiatrie Prof. Dr. Alexandru Obregia	Bucuresti		Romania	041914
40	Spitalul Clinic Judetean de Urgenta Cluj	Cluj-Napoca		Romania	400012
41	Spitalul Clinic de Neuropsihiatrie Craiova	Craiova		Romania	200620
42	Spitalul Clinic de Neurologie si Psihiatrie Oradea	Oradea		Romania	410154
43	City Psychiatric Hospital #2 of St. Nikolay Chudotvorets	St. Petersburg		Russian Federation	190121
44	Bekhterev Scientific Research Psychoneurological Institute	St. Petersburg		Russian Federation	193019
45	Psychoneurology Dispensary #4	St. Petersburg		Russian Federation	197110
46	Cape Trial Centre	Cape Town, W. Cape		South Africa	7530
47	Paarl Medical Centre	Paarl, W. Cape		South Africa	7646
48	Clinika	Port Elizabeth, E. Cape		South Africa	6000
49	Dey Clinic	Pretoria, Gauteng		South Africa	0181
50	Vereeniging Medi-Clinic	Vereeniging, Free State		South Africa	1941
51	Chair of Psychiatry and Medical Psychology	Donetsk		Ukraine	83008
52	Reg. Psychiatric Hospital	Odessa		Ukraine
53	Reg Cl.Ps.H.n.a.O.F. Malstev, Fem.Ac. Gen. Ps.D.5B	Poltava		Ukraine	36006
54	CRI Cl.Psych.Hosp. #1, Fem. Psych. Dept. #2, Male I	Simferopol		Ukraine	95006
55	Reg. Psych. Hosp.n.a.O.Yuschenko, Dept #21	Vinnitsia		Ukraine	21018

Sponsors and Collaborators

• Sunovion

Investigators

• Study Director: Medical Director, MD, Sunovion

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sunovion
• ClinicalTrials.gov Identifier: NCT00868699
• Other Study ID Numbers: D1050236; EUDRACT No. 2008-007457-13
• First Posted: Mar 25, 2009
• Last Update Posted: Apr 17, 2014
• Last Verified: Mar 1, 2014

• Keywords provided by Sunovion: Bipolar I, Depression
• Additional relevant MeSH terms: Depression; Depressive Disorder; Bipolar Disorder; Lurasidone Hydrochloride

Study Results

Participant Flow

Recruitment Details	4/29/09 to 2/1/12

Arm/Group Title	Placebo	Lurasidone High Arm	Lurasidone Low Arm
Arm/Group Description	Placebo : Placebo Comparator	lurasidone : lurasidone 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6 and 80 mg/day on Day 7 and 80-120 mg/day	lurasidone : lurasidone 20 mg/day for Days 1-7, beginning day 8 flexibly dosed 20-60 mg/day
Period Title: Overall Study
STARTED	170	169	166
Intent-to-Treat Population	162	162	161
Safety Population	168	167	164
COMPLETED	127	124	123
NOT COMPLETED	43	45	43

Baseline Characteristics

Arm/Group Title	Placebo	Lurasidone High Arm	Lurasidone Low Arm	Total
Arm/Group Description	Placebo : Placebo Comparator	lurasidone : lurasidone 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6 and 80 mg/day on Day 7 and 80-120 mg/day	lurasidone : lurasidone 20 mg/day for Days 1-7, beginning day 8 flexibly dosed 20-60 mg/day	Total of all reporting groups
Overall Participants	162	162	161	485
Age (Count of Participants)
<=18 years	0 0%	0 0%	3 1.9%	3 0.6%
Between 18 and 65 years	159 98.1%	159 98.1%	155 96.3%	473 97.5%
>=65 years	3 1.9%	3 1.9%	3 1.9%	9 1.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.2 (12.45)	42.0 (12.35)	41.3 (12.31)	41.5 (12.35)
Sex: Female, Male (Count of Participants)
Female	87 53.7%	98 60.5%	91 56.5%	276 56.9%
Male	75 46.3%	64 39.5%	70 43.5%	209 43.1%
Region of Enrollment (participants) [Number]
France	5 3.1%	4 2.5%	4 2.5%	13 2.7%
United States	58 35.8%	70 43.2%	67 41.6%	195 40.2%
Czech Republic	19 11.7%	19 11.7%	17 10.6%	55 11.3%
Ukraine	16 9.9%	17 10.5%	16 9.9%	49 10.1%
Romania	9 5.6%	2 1.2%	4 2.5%	15 3.1%
South Africa	18 11.1%	17 10.5%	19 11.8%	54 11.1%
Russian Federation	10 6.2%	10 6.2%	11 6.8%	31 6.4%
India	27 16.7%	23 14.2%	23 14.3%	73 15.1%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Endpoint (Week 6)
Description	Montgomery-Asberg Depression Rating Scale (MADRS)is a clinician-rated assessment of a subject's level of depression. The MADRS total score ranges from a minimum of 0 to a maximum of 60. For the MADRS total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. The MADRS contains ten (10) items. The total score is computed as the sum of the scores for the 10 items.
Time Frame	Baseline to Week 6

Outcome Measure Data

Analysis Population Description

Intent-to-treat population is analyzed.

Arm/Group Title	Placebo	Lurasidone High Arm	Lurasidone Low Arm
Arm/Group Description	Placebo : Placebo Comparator	lurasidone : lurasidone 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6 and 80 mg/day on Day 7 and 80-120 mg/day	lurasidone : lurasidone 20 mg/day for Days 1-7, beginning day 8 flexibly dosed 20-60 mg/day
Measure Participants	162	162	161
Least Squares Mean (Standard Error) [units on a scale]	-10.7 (0.83)	-15.4 (0.83)	-15.4 (0.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lurasidone Low Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.6
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.17
	Estimation Comments	A negative difference in least square mean change from baseline between Lurasidone group and placebo indicates a greater improvement in the Lurasidone group over the placebo group.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lurasidone High Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.6
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.17
	Estimation Comments	A negative difference in least square mean change from baseline between Lurasidone group and placebo indicates a greater improvement in the Lurasidone group over the placebo group.

2. Secondary Outcome

Title	Mean Change From Baseline to Endpoint (Week 6) in: Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) Score (Depression)
Description	Clinical Global Impression Bipolar Version, Severity of Illness (CGI-BP-S) score (depression) is a clinician-rated assessment of a subject's level of depression. The CGI depression score ranges from a minimum of 0 to a maximum of 7. For the CGI depression score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome.
Time Frame	Baseline to Week 6

Outcome Measure Data

Analysis Population Description

Intent-to-treat population is analyzed.

Arm/Group Title	Placebo	Lurasidone High Arm	Lurasidone Low Arm
Arm/Group Description	Placebo : Placebo Comparator	lurasidone : lurasidone 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6 and 80 mg/day on Day 7 and 80-120 mg/day	lurasidone : lurasidone 20 mg/day for Days 1-7, beginning day 8 flexibly dosed 20-60 mg/day
Measure Participants	162	162	161
Least Squares Mean (Standard Error) [units on a scale]	-1.14 (0.102)	-1.71 (0.101)	-1.83 (0.102)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lurasidone Low Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.69
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.143
	Estimation Comments	A negative difference in least square mean change from baseline between Lurasidone group and placebo indicates a greater improvement in the Lurasidone group over the placebo group.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lurasidone High Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.57
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.143
	Estimation Comments	A negative difference in least square mean change from baseline between Lurasidone group and placebo indicates a greater improvement in the Lurasidone group over the placebo group.

3. Secondary Outcome

Title	Mean Change From Baseline to Endpoint (Week 6) in: Sheehan Disability Scale (SDS) Total Score
Description	Sheehan Disability Scale (SDS) total score is a subject-rated assessment of a subject's level of depression. The SDS total score ranges from a minimum of 0 to a maximum of 30. For the SDS total score, low scores indicate a better outcome and high scores indicate a worse outcome. When change from baseline is considered, a negative (decrease in score) value is considered a better outcome, and a positive (increase in score) value is considered a worse outcome. The SDS contains three (3) items. The total score is computed as the sum of the scores for the 3 items.
Time Frame	Baseline to Week 6

Outcome Measure Data

Analysis Population Description

Intent-to-treat population is analyzed. Number of participants in table is not consistent with intent-to-treat population because: if one or more items are missing at a study visit, as can occur when a subject opts out of the work/school item because it does not apply, the authors of the scale recommend setting the total score to missing

Arm/Group Title	Placebo	Lurasidone High Arm	Lurasidone Low Arm
Arm/Group Description	Placebo : Placebo Comparator	lurasidone : lurasidone 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6 and 80 mg/day on Day 7 and 80-120 mg/day	lurasidone : lurasidone 20 mg/day for Days 1-7, beginning day 8 flexibly dosed 20-60 mg/day
Measure Participants	100	105	88
Least Squares Mean (Standard Error) [units on a scale]	-6.3 (0.77)	-9.8 (0.73)	-9.5 (0.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lurasidone Low Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.1
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.05
	Estimation Comments	A negative difference in least square mean change from baseline between Lurasidone group and placebo indicates a greater improvement in the Lurasidone group over the placebo group.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Lurasidone High Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.5
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.01
	Estimation Comments	A negative difference in least square mean change from baseline between Lurasidone group and placebo indicates a greater improvement in the Lurasidone group over the placebo group.

Adverse Events

Time Frame	April 29,2009 - February 1, 2012
Adverse Event Reporting Description	Safety population is analyzed.
Arm/Group Title	Placebo		Lurasidone High Arm		Lurasidone Low Arm
Arm/Group Description	Placebo : Placebo Comparator		lurasidone : lurasidone 20 mg/day for Days 1-2, 40 mg/day for Days 3-4, 60 mg/day for Days 5-6 and 80 mg/day on Day 7 and 80-120 mg/day		lurasidone : lurasidone 20 mg/day for Days 1-7, beginning day 8 flexibly dosed 20-60 mg/day
All Cause Mortality
	Placebo		Lurasidone High Arm		Lurasidone Low Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Lurasidone High Arm		Lurasidone Low Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/168 (0.6%)		5/167 (3%)		3/164 (1.8%)
Gastrointestinal disorders
Duodenal Ulcer	1/168 (0.6%)	1	0/167 (0%)	0	0/164 (0%)	0
Infections and infestations
HIV Infection	0/168 (0%)	0	1/167 (0.6%)	1	0/164 (0%)	0
Subcutaneous Absceses	0/168 (0%)	0	1/167 (0.6%)	1	0/164 (0%)	0
Injury, poisoning and procedural complications
Foot Fracture	0/168 (0%)	0	1/167 (0.6%)	1	0/164 (0%)	0
Restless Leg Syndrome	0/168 (0%)	0	1/167 (0.6%)	1	0/164 (0%)	0
Psychiatric disorders
Depression	0/168 (0%)	0	2/167 (1.2%)	2	2/164 (1.2%)	2
Panic Attack	0/168 (0%)	0	1/167 (0.6%)	1	1/164 (0.6%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Lurasidone High Arm		Lurasidone Low Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	56/168 (33.3%)		65/167 (38.9%)		57/164 (34.8%)
Gastrointestinal disorders
Nausea	13/168 (7.7%)	87	29/167 (17.4%)	38	17/164 (10.4%)	24
Nervous system disorders
Headache	20/168 (11.9%)	25	15/167 (9%)	16	23/164 (14%)	36
Akathisia	4/168 (2.4%)	6	18/167 (10.8%)	23	13/164 (7.9%)	18
Somnolence	7/168 (4.2%)	7	11/167 (6.6%)	13	7/164 (4.3%)	7
Sedation	3/168 (1.8%)	3	12/167 (7.2%)	13	5/164 (3%)	6
Dizziness	13/168 (7.7%)	13	10/167 (6%)	12	4/164 (2.4%)	5
Psychiatric disorders
Insomnia	14/168 (8.3%)	19	11/167 (6.6%)	16	8/164 (4.9%)	12

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

In addition to the <60-180 day restriction above, since this is a multicenter study, 1st publication of study results shall be made with other participating study sites as a multicenter publication; provided, if a multicenter publication is not forthcoming within 24 months following completion of study at all sites, the PI shall be free to publish.