Study of the Safety and Efficacy of Fixed-dose Brexpiprazole (OPC-34712) as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder With and Without Anxious Distress

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02196506
• Collaborator: H. Lundbeck A/S (Industry)
• Enrollment: 837
• Locations: 47
• Arms: 2
• Duration (Months): 22
• Patients Per Site: 17.8
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the tolerability, safety, and efficacy of brexpiprazole (2.0 mg/day) as adjunctive therapy in adult subjects with a diagnosis of MDD with and without anxious distress

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder; Depression; Depressive Disorder, Major; Mood Disorders; Mental Disorders	Drug: Placebo + ADT; Drug: Brexpiprazole +ADT	Phase 3

Detailed Description

The introduction of atypical antipsychotics has created a renewed interest in adjunctive therapy for MDD, particularly for treatment-resistant MDD. Several atypical antipsychotics have been shown to enhance the response to ADT. This is a phase 3, multicenter, randomized, double-blind, placebo-controlled, fixed-dose trial designed to assess the safety and efficacy of brexpiprazole (2.0 mg/day) as adjunctive therapy to an assigned open-label ADT in depressed subjects with and without anxious distress.

Study Design

• Study Type: Interventional
• Actual Enrollment: 837 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of the Safety and Efficacy of Fixed-dose Brexpiprazole (OPC-34712) as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder With and Without Anxious Distress
• Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: Apr 1, 2016
• Actual Study Completion Date: May 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brexpiprazole + ADT Brexpiprazole + ADT	Drug: Brexpiprazole +ADT; Brexpiprazole + ADT Tablet, Oral, 2mg brexpiprazole and FDA Approved Antidepressant (ADT)
Placebo Comparator: Placebo + ADT Placebo + ADT	Drug: Placebo + ADT; Placebo + ADT Placebo + FDA Approved Antidepressant (ADT)

Outcome Measures

Primary Outcome Measures

1. Change in the Montgomery-Asberg Depression [From baseline (end of Phase A [Week 8]) to week 14]

   To assess the change in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score from Baseline (End of Phase A [Week 8]) to Week 14. The MADRS was utilized as the primary efficacy assessment of the participant's level of depression and was administered utilizing the Structured Interview Guide for the MADRS (SIGMA). The MADRS consisted of 10 items each with 7 defined grades of severity. The rater decided whether the rating lied on predefined scale steps (0, 2, 4, 6) or between them (1, 3, 5). The 10 items were apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score was 60; 0, no symptom; 60, severely affected.

Secondary Outcome Measures

1. Change in the Sheehan Disability Scale (SDS) From Baseline to End of Treatment [From baseline (end of Phase A [Week 8]) to week 14]

   To assess the change in the Sheehan Disability Scale (SDS) Score (the mean of 3 individual item scores) from Baseline (End of Phase A [Week 8]) to Week 14 (End of Phase B). SDS was a 3-item clinician-rated questionnaire used to evaluate impairments in the domains of work, social life, and family life/home responsibility. Each item was scored using a scale of 0 to 10 (a higher score indicates symptoms have disrupted work, social life, and family life/home responsibility extremely). The maximum total score was 30; 0 = not at all, to 30 = extremely.

2. Change From End of Phase A to End of Phase B in MADRS Total Score for the Subpopulation With <25% Improvement From Baseline of Phase A to End of Phase A in MADRS Total Score [From baseline (end of Phase A [Week 8]) to week 14]

   To assess the change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit) in MADRS Total Score for the subpopulation with < 25% improvement from baseline of Phase A (Week 0) to end of Phase A (Week 8) in MADRS Total Score. The MADRS was utilized as the primary efficacy assessment of the participant's level of depression and was administered utilizing the Structured Interview Guide for the MADRS (SIGMA). The MADRS consisted of 10 items each with 7 defined grades of severity. The 10 items were apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score was 60; 0, no symptom; 60, severely affected.

3. Change From End of Phase A to End of Phase B in MADRS Total Score for the Subpopulations With Anxious Distress as Specified in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). [From baseline (end of Phase A [Week 8]) to week 14]

   To assess the change from end of Phase A (Week 8) to end of Phase B (Week 14) in MADRS Total Score for the subpopulations with anxious distress as specified in DSM-V. The MADRS was utilized as the primary efficacy assessment of the participant's level of depression and was administered utilizing the Structured Interview Guide for the MADRS (SIGMA). The MADRS consisted of 10 items each with 7 defined grades of severity. The 10 items were apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score was 60; 0, no symptom; 60, severely affected.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male and Female subjects between 18-65 years of age, with diagnosis of major depressive disorder with or without anxious distress

• Current depressive episode must be at least 8 weeks in duration

Exclusion Criteria:

• Subjects with a history of Neuroleptic Malignant Syndrome or Serotonin Syndrome

• Subjects who report an inadequate response to more than 3 antidepressant treatments in the current episode

• Subjects with a current Axis I diagnosis of: Delirium, dementia, amnestic or other cognitive disorder, Schizophrenia, schizoaffective disorder, or other psychotic disorder, Bipolar I or II disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Beverly Hills	California	United States
3		Denver	Colorado	United States
4		Hialeah	Florida	United States
5		Orlando	Florida	United States
6		Alpharetta	Georgia	United States
7		Smyrna	Georgia	United States
8		Baltimore	Maryland	United States
9		Boston	Massachusetts	United States
10		Rochester Hills	Michigan	United States
11		Cherry Hill	New Jersey	United States
12		Jamaica	New York	United States
13		New York	New York	United States
14		Staten Island	New York	United States
15		Raleigh	North Carolina	United States
16		Cincinnati	Ohio	United States
17		Edmond	Oklahoma	United States
18		Portland	Oregon	United States
19		Salem	Oregon	United States
20		Philadelphia	Pennsylvania	United States
21		Lincoln	Rhode Island	United States
22		Columbia	South Carolina	United States
23		Memphis	Tennessee	United States
24		Wichita Falls	Texas	United States
25		Murray	Utah	United States
26		Woodstock	Vermont	United States
27		Charlottesville	Virginia	United States
28		Richmond	Virginia	United States
29		Seattle	Washington	United States
30		Spokane	Washington	United States
31		Achim		Germany
32		Berlin		Germany
33		Dusseldorf		Germany
34		Frankfurt		Germany
35		Freiburg		Germany
36		Oranienburg		Germany
37		Stralsund		Germany
38		Wurzburg		Germany
39		Budapest		Hungary
40		Gyor		Hungary
41		Gdansk		Poland
42		Lubin		Poland
43		Sosnowiec		Poland
44		Warszawa		Poland
45		Bratislava		Slovakia
46		Kosice-Barca		Slovakia
47		Liptovsky Mikulas		Slovakia

Sponsors and Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.
• H. Lundbeck A/S

Investigators

• Study Director: Claudette Brewer, Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT02196506
• Other Study ID Numbers: 331-13-214
• First Posted: Jul 22, 2014
• Last Update Posted: Aug 21, 2018
• Last Verified: Aug 1, 2018

• Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.: OPC-34712; brexpiprazole; Major Depressive Disorder; Adjunctive Treatment; Anxious Distress
• Additional relevant MeSH terms: Disease; Depression; Depressive Disorder; Depressive Disorder, Major; Mental Disorders; Mood Disorders; Brexpiprazole

Study Results

Participant Flow

Recruitment Details	This trial was conducted in 837 participants at 51 trial sites in the following 5 countries:Germany,Hungary,Poland,Slovakia,andUnited States (US).A total of 1144 participants with major depressive disorder were screened for the trial, 837 enrolled into Phase A,394 were randomized into Phase B and 322 continued treatment with placebo+ADT in Phase A+
Pre-assignment Detail	Trial consisted of a screening phase and 3 phases. In phase A (8-week single-blind prospective treatment phase) and in phase A+ (Single-blind phase A Responder), there was single treatment group. In phase B (6-week double-blind randomization phase), there were 2 treatment groups. All Outcome Measures were assessed in phase B.

Arm/Group Title	Phase A: All ADT (Antidepressant Therapy)	Phase B: Brexpiprazole + ADT	Phase B: Placebo + ADT	Phase A +: ALL ADT
Arm/Group Description	Participants meeting entrance criteria who were experiencing a major depressive episode with a HAM-D17 Total Score of greater than or equal 18 at baseline were enrolled into an 8-week Single-blind Prospective Treatment Phase (Phase A). All participants received single-blind placebo plus an investigator determined, open-label, ADT. Once assigned to an ADT by the investigator, participants remained on the same ADT for the duration of the trial. At the Week 8 visit, the IWRS (Interactive web response system) determined based on scores entered by the investigator, whether a participant was a "Phase A Responder" or a "Phase A Inadequate Responder."	Participants received brexpiprazole 2 mg and ADT orally once daily for 6 weeks.	Participants received matching placebo and ADT orally once daily for 6 weeks.	Phase A+ included participants who met criteria for a response at the end of the prospective treatment phase (Week 8 visit of Phase A) and participants who were not suitable for randomization in Phase B per the judgment of the investigator or medical monitor. Treatment response in Phase A was determined at the Week 8 visit based on improvement or lack of improvement of the participant's depressive symptoms, which was confirmed by clinical criteria that prospectively defined response. Participant response was determined from clinical data that were entered into the IWRS at each visit. Participants in Phase A+ received single-blind placebo+ADT for an additional 6 weeks, for a total of 14 weeks, and attended visits at Weeks 11 and 14.
Period Title: Phase A
STARTED	837	0	0	0
COMPLETED	716	0	0	0
NOT COMPLETED	121	0	0	0
Period Title: Phase A
STARTED	0	192	202	0
COMPLETED	0	177	196	0
NOT COMPLETED	0	15	6	0
Period Title: Phase A
STARTED	0	0	0	322
COMPLETED	0	0	0	308
NOT COMPLETED	0	0	0	14

Baseline Characteristics

Arm/Group Title	Brexpiprazole + ADT	Placebo + ADT	Total
Arm/Group Description	Phase B: Brexpiprazole +Antidepressant therapy (ADT): Participants received brexpiprazole 2mg and ADT orally once daily for 6 weeks.	Phase B: Placebo + Antidepressant therapy (ADT): Participants received matching placebo and ADT orally once daily for 6 weeks	Total of all reporting groups
Overall Participants	192	202	394
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.0 (12.7)	42.7 (12.5)	42.9 (12.6)
Sex: Female, Male (Count of Participants)
Female	147 76.6%	144 71.3%	291 73.9%
Male	45 23.4%	58 28.7%	103 26.1%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	11 5.7%	9 4.5%	20 5.1%
Not Hispanic or Latino	181 94.3%	192 95%	373 94.7%
Unknown	0 0%	1 0.5%	1 0.3%
Region of Enrollment (participants) [Number]
Hungary	16 8.3%	16 7.9%	32 8.1%
United States	100 52.1%	106 52.5%	206 52.3%
Poland	26 13.5%	26 12.9%	52 13.2%
Slovakia	23 12%	25 12.4%	48 12.2%
Germany	27 14.1%	29 14.4%	56 14.2%

Outcome Measures

1. Primary Outcome

Title	Change in the Montgomery-Asberg Depression
Description	To assess the change in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score from Baseline (End of Phase A [Week 8]) to Week 14. The MADRS was utilized as the primary efficacy assessment of the participant's level of depression and was administered utilizing the Structured Interview Guide for the MADRS (SIGMA). The MADRS consisted of 10 items each with 7 defined grades of severity. The rater decided whether the rating lied on predefined scale steps (0, 2, 4, 6) or between them (1, 3, 5). The 10 items were apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score was 60; 0, no symptom; 60, severely affected.
Time Frame	From baseline (end of Phase A [Week 8]) to week 14

Outcome Measure Data

Analysis Population Description

The primary analysis was performed on Efficacy Sample which included all randomized participants who took at least one dose of trial medication in Phase B and who have both an end of Phase A (Week 8) and at least one post-randomization MADRS Total Score during Phase B.

Arm/Group Title	Brexpiprazole + ADT	Placebo + ADT
Arm/Group Description	Phase B: Brexpiprazole +Antidepressant therapy (ADT): Participants received brexpiprazole 2mg and ADT orally once daily for 6 weeks.	Phase B: Placebo + Antidepressant therapy (ADT): Participants received matching placebo and ADT orally once daily for 6 weeks
Measure Participants	191	202
Least Squares Mean (Standard Error) [Units on a scale]	-10.4 (0.63)	-8.07 (0.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brexpiprazole + ADT, Placebo + ADT
	Comments	Statistical Analysis at Week 14
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0074
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.30
	Confidence Interval	(2-Sided) 95%; -3.97 to -0.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in the Sheehan Disability Scale (SDS) From Baseline to End of Treatment
Description	To assess the change in the Sheehan Disability Scale (SDS) Score (the mean of 3 individual item scores) from Baseline (End of Phase A [Week 8]) to Week 14 (End of Phase B). SDS was a 3-item clinician-rated questionnaire used to evaluate impairments in the domains of work, social life, and family life/home responsibility. Each item was scored using a scale of 0 to 10 (a higher score indicates symptoms have disrupted work, social life, and family life/home responsibility extremely). The maximum total score was 30; 0 = not at all, to 30 = extremely.
Time Frame	From baseline (end of Phase A [Week 8]) to week 14

Outcome Measure Data

Analysis Population Description

The primary analysis was performed on Efficacy Sample which included all randomized participants who took at least one dose of trial medication in Phase B and who have both an end of Phase A (Week 8) and at least one post-randomization MADRS Total Score during Phase B.

Arm/Group Title	Brexpiprazole + ADT	Placebo + ADT
Arm/Group Description	Phase B: Brexpiprazole +Antidepressant therapy (ADT): Participants received brexpiprazole 2mg and ADT orally once daily for 6 weeks.	Phase B: Placebo + Antidepressant therapy (ADT): Participants received matching placebo and ADT orally once daily for 6 weeks
Measure Participants	187	200
Least Squares Mean (Standard Error) [Units on a scale]	-1.63 (0.18)	-1.41 (0.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brexpiprazole + ADT, Placebo + ADT
	Comments	Statistical Analysis at Week 14
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3331
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95%; -0.66 to 0.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From End of Phase A to End of Phase B in MADRS Total Score for the Subpopulation With <25% Improvement From Baseline of Phase A to End of Phase A in MADRS Total Score
Description	To assess the change from end of Phase A (Week 8 visit) to end of Phase B (Week 14 visit) in MADRS Total Score for the subpopulation with < 25% improvement from baseline of Phase A (Week 0) to end of Phase A (Week 8) in MADRS Total Score. The MADRS was utilized as the primary efficacy assessment of the participant's level of depression and was administered utilizing the Structured Interview Guide for the MADRS (SIGMA). The MADRS consisted of 10 items each with 7 defined grades of severity. The 10 items were apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score was 60; 0, no symptom; 60, severely affected.
Time Frame	From baseline (end of Phase A [Week 8]) to week 14

Outcome Measure Data

Analysis Population Description

Subpopulation of <25% Improvement Sample: Comprised of all participants in the Efficacy Sample who had <25% improvement at the end of Phase A in MADRS Total Score.

Arm/Group Title	Brexpiprazole + ADT	Placebo + ADT
Arm/Group Description	Phase B: Brexpiprazole +Antidepressant therapy (ADT): Participants received brexpiprazole 2mg and ADT orally once daily for 6 weeks.	Phase B: Placebo + Antidepressant therapy (ADT): Participants received matching placebo and ADT orally once daily for 6 weeks
Measure Participants	161	158
Least Squares Mean (Standard Error) [Units on a scale]	-11.1 (0.71)	-8.87 (0.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brexpiprazole + ADT, Placebo + ADT
	Comments	Statistical Analysis at Week 14
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0263
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.25
	Confidence Interval	(2-Sided) 95%; -4.23 to -0.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From End of Phase A to End of Phase B in MADRS Total Score for the Subpopulations With Anxious Distress as Specified in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V).
Description	To assess the change from end of Phase A (Week 8) to end of Phase B (Week 14) in MADRS Total Score for the subpopulations with anxious distress as specified in DSM-V. The MADRS was utilized as the primary efficacy assessment of the participant's level of depression and was administered utilizing the Structured Interview Guide for the MADRS (SIGMA). The MADRS consisted of 10 items each with 7 defined grades of severity. The 10 items were apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score was 60; 0, no symptom; 60, severely affected.
Time Frame	From baseline (end of Phase A [Week 8]) to week 14

Outcome Measure Data

Analysis Population Description

Subpopulation of Anxious Distress Sample: Comprised of all participants in the Efficacy Sample who had anxious distress as specified in DSM-V.

Arm/Group Title	Brexpiprazole + ADT	Placebo + ADT
Arm/Group Description	Phase B: Brexpiprazole +Antidepressant therapy (ADT): Participants received brexpiprazole 2mg and ADT orally once daily for 6 weeks.	Phase B: Placebo + Antidepressant therapy (ADT): Participants received matching placebo and ADT orally once daily for 6 weeks
Measure Participants	124	124
Least Squares Mean (Standard Error) [Units on a scale]	-11.8 (0.81)	-8.87 (0.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Brexpiprazole + ADT, Placebo + ADT
	Comments	Statistical Analysis at Week 14
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0099
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.98
	Confidence Interval	(2-Sided) 95%; -5.24 to -0.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Participants were assessed for the occurrence of adverse events (AEs) once the participant signed informed consent form through completion of the trial; up to 14-weeks after the participant entered the trial and actively monitored up to 30 (+2) days after their last dose of investigational medicinal product (this could be up to 22 weeks depending on duration of trial participation).
Adverse Event Reporting Description	Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. No adverse events were assessed or collected from Phase A or A+ participants as those phases are single-blind, non-randomized, monotherapy treatment periods of the study and are outside of the pre-specified definition of the safety sample per the trial design.
Arm/Group Title	Brexpiprazole + ADT		Placebo + ADT
Arm/Group Description	Phase B: Brexpiprazole +Antidepressant therapy (ADT): Participants received brexpiprazole 2mg and ADT orally once daily for 6 weeks.		Phase B: Placebo + Antidepressant therapy (ADT): Participants received matching placebo and ADT orally once daily for 6 weeks
All Cause Mortality
	Brexpiprazole + ADT		Placebo + ADT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/192 (0%)		0/202 (0%)
Serious Adverse Events
	Brexpiprazole + ADT		Placebo + ADT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/192 (0.5%)		0/202 (0%)
Ear and labyrinth disorders
Vertigo	1/192 (0.5%)	1	0/202 (0%)	0
Other (Not Including Serious) Adverse Events
	Brexpiprazole + ADT		Placebo + ADT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/192 (25.5%)		35/202 (17.3%)
Infections and infestations
Upper Respiratory Tract Infection	10/192 (5.2%)	11	10/202 (5%)	11
Investigations
Weight Increased	10/192 (5.2%)	10	1/202 (0.5%)	1
Nervous system disorders
Akathisia	16/192 (8.3%)	17	10/202 (5%)	12
Headache	7/192 (3.6%)	7	15/202 (7.4%)	24
Psychiatric disorders
Restlessness	16/192 (8.3%)	16	4/202 (2%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.