Opioid-induced Bowel Dysfunction (OBD) Pivotal Assessment of Lubiprostone (OPAL)

• Sponsor: Sucampo Pharma Americas, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01298219
• Collaborator: Sucampo Pharmaceuticals, Inc. (Industry)
• Enrollment: 439
• Locations: 142
• Arms: 2
• Duration (Months): 11
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The primary purpose of the study is to evaluate the efficacy and safety of lubiprostone administration in subjects with Opioid-induced Bowel Dysfunction.

Condition or Disease	Intervention/Treatment	Phase
Opioid-induced Bowel Dysfunction	Drug: Lubiprostone; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 439 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Care provider and outcomes assessor were also blinded for this double-blind trial.
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Placebo-controlled, Double-blinded Study of the Efficacy and Safety of Lubiprostone in Subjects With Opioid-induced Bowel Dysfunction
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Nov 1, 2011
• Actual Study Completion Date: Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lubiprostone 24 mcg capsules twice daily (BID)	Drug: Lubiprostone; 24 mcg administered orally twice daily (BID); Other Names: Amitiza
Placebo Comparator: Placebo 0 mcg capsules twice daily (BID)	Drug: Placebo; Matching placebo, 0 mcg administered orally twice daily (BID); Other Names: No other names

Outcome Measures

Primary Outcome Measures

1. Number of Participants Classified as Treatment Responders Within 12 Weeks [12 weeks]

   Spontaneous bowel movement (SBM) is defined as any BM that does not occur within 24 hours after use of rescue medication. To be classified as responders, participants are required to demonstrate at least moderate response (≥ 1 SBM improvement over baseline SBM frequency) for all treatment weeks for which observed data are available, and must additionally demonstrate a full response (≥ 3 SBMs per week) for at least 9 of the 12 treatment weeks.

Secondary Outcome Measures

1. Number of SBMs Per Week at Week 8 [at Week 8]

2. Number of Participants Who Experienced First SBM Within 48 Hours After Dose Initiation [within 48 hours post-dose]

3. Number of SBMs Per Week at Week 12 [at Week 12]

4. Number of SBMs Per Week Overall [within 14 weeks]

   Overall is defined as the length of time from first dose to last follow-up within 2 weeks after last dose.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

A patient can be considered for eligibility to participate if he/she:

• Has been consistently treated for chronic, noncancer-related pain with any oral, transdermal, intravenous, or subcutaneous opioid for at least 30 days prior to screening

• Is diagnosed with OBD

• Is capable of utilizing an electronic diary to report daily spontaneous bowel movements (SBMs)

• Is willing to continue opioid therapy and discontinue the use of laxatives, stool softeners, and other concomitant medications affecting gastrointestinal motility throughout the study

Exclusion Criteria:

A patient cannot be considered for eligibility to participate if he/she:

• Uses opioids for the treatment of cancer-related pain, abdominal pain, mechanical bowel obstructions, bowel disorders, and constipation not arising from opioid use, but instead attributable to dietary, neurologic, congenital, or endocrine disorders, scleroderma, and/or for the management of drug addiction

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	North Alabama Research Center	Athens	Alabama	United States	35811
2	Innovative Clinical Trials, Inc.	Birmingham	Alabama	United States	35205
3	Achieve Clinical Research	Birmingham	Alabama	United States	35216
4	Alabama Clinical Therapeutics	Birmingham	Alabama	United States	35235
5	G&L Research, LLC	Foley	Alabama	United States	36535
6	Healthscan Research	Montgomery	Alabama	United States	36109
7	River Region Research	Tallassee	Alabama	United States	36078
8	Anasazi Internal Medicine PC	Phoenix	Arizona	United States	85032
9	Aureas Research, Inc	Little Rock	Arkansas	United States	72212
10	Certified Clinical Research	Carmichael	California	United States	95608
11	California Clinical Research, Inc.	Davis	California	United States	95616
12	Family Medical Center	Foothill Ranch	California	United States	92610
13	South Orange County Surgical Medical Group	Laguna Hills	California	United States	92653
14	Clinical Trials Research	Lincoln	California	United States	95648
15	Clear Vision Research	Long Beach	California	United States	90805
16	Long Beach VA Medical Center	Long Beach	California	United States	90822
17	Clear Vision Research	Los Angeles	California	United States	90023
18	Facey Medical Foundation	Mission Hills	California	United States	91345
19	North County Clinical Research	Oceanside	California	United States	92056
20	SDS Clinical Trials, Inc.	Orange	California	United States	92868
21	Probe Clinical Research Corporation	Riverside	California	United States	92501
22	Probe Clinical Research Corporation - Santa Ana	Santa Ana	California	United States	92701
23	Westlake Medical Research	Westlake Village	California	United States	91361
24	Mountain View Clinical Research	Denver	Colorado	United States	80209
25	Meridien Research	Bradenton	Florida	United States	34208
26	Coastal Orthopedics & Pain Management	Bradenton	Florida	United States	34209
27	Florida Research & Testing, LLC	Clearwater	Florida	United States	33755
28	Avail Clinical Research	DeLand	Florida	United States	32720
29	S&W Clinical Research	Fort Lauderdale	Florida	United States	33306
30	Palm Springs Research Institute	Hialeah	Florida	United States	33012
31	Kendall South Medical Center, Inc.	Miami	Florida	United States	33175
32	Gastroenterology Group of Naples	Naples	Florida	United States	34102
33	Physicians Regional Medical Group	Naples	Florida	United States	34119
34	Ocala Rheumatology Research Center	Ocala	Florida	United States	34474
35	Paddock Park Clinical Research	Ocala	Florida	United States	34474
36	Journey Research, Inc.	Oldsmar	Florida	United States	34677
37	Compass Research	Orlando	Florida	United States	32806
38	Andres Patron, DO, PA	Pembroke Pines	Florida	United States	30026
39	Advent Clinical Research Centers	Pinellas Park	Florida	United States	33781
40	Gold Coast Research, LLC	Plantation	Florida	United States	33317
41	Orthopedic Research Institite	Royal Palm Beach	Florida	United States	33411
42	IC Research	Sanford	Florida	United States	32771
43	Sarasota Memorial Pain Care Center	Sarasota	Florida	United States	34238
44	Tampa Clinical Research	Tampa	Florida	United States	33624
45	Southeastern Regional Research Group	Columbus	Georgia	United States	31904
46	Better Health Clinical Research	Newnan	Georgia	United States	30265
47	Clinical Research Atlanta	Stockbridge	Georgia	United States	30281
48	Advanced Clinical Research	Boise	Idaho	United States	83642
49	Sonora Clinical Research	Boise	Idaho	United States	83702
50	Nautical Clinical Research	Meridian	Idaho	United States	83642
51	Anesthesia/Pain Control Indiana University School of Medicine	Chicago	Illinois	United States	60657
52	Knight Center for Integrated Health	Peoria	Illinois	United States	61614
53	Ridge Family Practice	Council Bluffs	Iowa	United States	51503
54	Lee Research Institute	Lenexa	Kansas	United States	66215
55	Kentucky Medical Research Center	Lexington	Kentucky	United States	40504
56	Bluegrass Internal Medicine	Owensboro	Kentucky	United States	42303
57	Horizon Research Group	Baton Rouge	Louisiana	United States	70809
58	Miray Medical Center	Brockton	Massachusetts	United States	02301
59	The Research Institute	Springfield	Massachusetts	United States	01107
60	Coastal Research	Weymouth	Massachusetts	United States	02190
61	Ashok Jain, MD	Dearborn	Michigan	United States	48124
62	Shores Medical Associates	Saint Clair Shores	Michigan	United States	48081
63	Mid-America Clinical Research LLC	Saint Louis	Missouri	United States	63139
64	Montana Medical Research, Inc.	Missoula	Montana	United States	59808
65	Independent Clinical Researchers	Las Vegas	Nevada	United States	89106
66	AB Clinical Trials	Las Vegas	Nevada	United States	89119
67	Clinical Research of South Nevada	Las Vegas	Nevada	United States	89121
68	Clinical Research Advantage, Inc.	Las Vegas	Nevada	United States	89128
69	Lab2Marche	Las Vegas	Nevada	United States	89149
70	Aloha Medical Center	Las Vegas	Nevada	United States	89183
71	Edison Medical Group	Edison	New Jersey	United States	08817
72	Clinical Research Program	Marlton	New Jersey	United States	08053
73	Albuquerque Clinical Trials	Albuquerque	New Mexico	United States	87102
74	Drug Trials America	Hartsdale	New York	United States	10530
75	Family Health Medical Services PLLC	Jamestown	New York	United States	14701
76	U of Rochester	Rochester	New York	United States	14618
77	Medical Frontiers	Carlisle	Ohio	United States	45005
78	Hightop Medical Research Center	Cincinnati	Ohio	United States	45224
79	Community Research	Cincinnati	Ohio	United States	45227
80	Community Research	Cincinnati	Ohio	United States	45245
81	Rapid Medical Research, Inc.	Cleveland	Ohio	United States	44122
82	Parsons Avenue Medical Center	Columbus	Ohio	United States	43207
83	Hometown Urgent Care	Groveport	Ohio	United States	43125
84	Northstar Medical Research, LLC	Middleburg Heights	Ohio	United States	44130
85	Pharmacotherpy Research Associates Inc	Zanesville	Ohio	United States	43701
86	COR Clinical Research, LLC	Oklahoma City	Oklahoma	United States	73103
87	Sooner Clinical Research	Oklahoma City	Oklahoma	United States	73112
88	Sunstone Medical Research	Medford	Oregon	United States	97504
89	Fanno Creek Clinic	Portland	Oregon	United States	97219
90	McMillen & Magargle	Mechanicsburg	Pennsylvania	United States	17055
91	Omega Medical Research	Warwick	Rhode Island	United States	02886
92	Hartwell Research Group	Anderson	South Carolina	United States	29621
93	Degarmo Institute of Medical Research	Greer	South Carolina	United States	29651
94	Pain Specialists of Charleston	North Charleston	South Carolina	United States	29406
95	Health Concepts	Rapid City	South Dakota	United States	57702
96	InvestiClin Research	Brentwood	Tennessee	United States	37027
97	SCRI Research Center	Germantown	Tennessee	United States	38138
98	Prevention & Strengthening Solutions, Inc.	Humboldt	Tennessee	United States	38343
99	FutureSearch Trials of Neurology & Sleep Lab	Austin	Texas	United States	78756
100	Jaron Winston, MD	Austin	Texas	United States	78757
101	KRK Medical Research	Dallas	Texas	United States	75230
102	FutureSearch Trials of Dallas, LP	Dallas	Texas	United States	75231
103	Pillar Clinical Research, LLC	Dallas	Texas	United States	75243
104	Galenos Research	Dallas	Texas	United States	75251
105	Diversified Medical Practice, P.A.	Houston	Texas	United States	77027
106	Clinical Trial Network	Houston	Texas	United States	77074
107	Dependable Clinical Research	Houston	Texas	United States	77074
108	Pioneer Research Solutions, Inc.	Houston	Texas	United States	77098
109	Bobby Huynh	Richardson	Texas	United States	75080
110	Sun Research Institute	San Antonio	Texas	United States	78215
111	Spring Clinical Research	Sugar Land	Texas	United States	77478
112	Pioneer Research Solutions	Sugar Land	Texas	United States	77479
113	Lifetree Clinical Research	Salt Lake City	Utah	United States	84106
114	ACR Research Salt Lake City	West Jordan	Utah	United States	84088
115	Virginia Research Center, LLC	Midlothian	Virginia	United States	23114
116	Pain Clinic-Heilig Hart Ziekenhuis Roeselare	Roeselare	Westlaan 123	Belgium	8800
117	Huisartsenpraktijk De Regenboog	Antwerp		Belgium	2100
118	Dr Capiau - GP Practice	Wetteren		Belgium	9230
119	St. Anne's University Hospital - centrum pro	Brno		Czechia	656 91
120	Nemocnice Jablonec nad Nisou, p.o.	Jablonec nad Nisou		Czechia	466 60
121	Ambulance bolesti, Krajska nemocnice Liberec	Liberec		Czechia	460 63
122	Klaudianova nemocnice Mlada Boleslav	Mlada Boleslav		Czechia	293 50
123	Clintrial s.r.o.	Praha 10		Czechia	108 00
124	Neurologicka ambulance	Praha 6		Czechia	160 00
125	Regional Hospital T. B., a.s.	Zlin		Czechia	762 75
126	Schmerzzentrum Berlin	Berlin		Germany	10435
127	Schmerztherapeutische- Ärztezentrum Nordstadt	Hannover		Germany	30167
128	Schmerz und Palliativzentrum	Wiesbaden		Germany	65189
129	NZOZ Dom Sue Ryder prowadzony przez Pallmed Sp. z o.o.	Bydgoszcz		Poland	85-796
130	Hagakliniken	Gothenburg		Sweden	13 28
131	Karolinska University Hospita- Dept of Anaesthesia, Pain Div.	Stockholm		Sweden	4186
132	S3 Clinical Research Centers	Vällingby		Sweden	Stockholm 162 68
133	ElyBridge Surgery	ELY	Cardiff	United Kingdom	CF5 4AE
134	Randalstown Medical Practice	Randalstown	Co Antrim	United Kingdom	BT41 3AE
135	Sea Road Surgery	Bexhill on Sea	E.Sussex	United Kingdom	TN40 1JJ
136	Sheepcot Medical Centre,	Watford	Herts	United Kingdom	WD25 0EA
137	Fylde Coast Clinical Research Ltd	Blackpool	Lancsashire	United Kingdom	FY3 7EN
138	Ballygomartin Group Practice	Belfast	Northern Ireland	United Kingdom	BT13 3BW
139	The Waterfront Medical Centre	Barry	Wales	United Kingdom	CF63 4AR
140	Valleyfield Health Center	Dunfermline		United Kingdom	KY12 8SJ
141	Frome Medical Practice	Frome		United Kingdom	BA11 1EZ
142	Mortimer Surgery	Reading		United Kingdom	RG7 3SG

Sponsors and Collaborators

• Sucampo Pharma Americas, LLC
• Sucampo Pharmaceuticals, Inc.

Investigators

• Study Director: Clinical Study Leader, Mallinckrodt

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sucampo Pharma Americas, LLC
• ClinicalTrials.gov Identifier: NCT01298219
• Other Study ID Numbers: OBD1033
• First Posted: Feb 17, 2011
• Last Update Posted: Feb 11, 2020
• Last Verified: Feb 1, 2013

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Intestinal Diseases; Gastrointestinal Diseases; Opioid-Induced Constipation; Lubiprostone

Study Results

Participant Flow

Recruitment Details	Recruitment period: 07 December 2010 to 16 November 2011 Recruitment sites: 91 U.S. investigative sites and 14 E.U. investigative sites
Pre-assignment Detail	Safety evaluable population includes all subjects who were randomized and dosed. Intention to treat (ITT) population includes only those subjects who were dosed and provided at least one post-treatment efficacy assessment.

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description	24 mcg capsules twice daily (BID) Lubiprostone: 24 mcg administered orally twice daily (BID)	0 mcg capsules twice daily (BID) Placebo: Matching placebo, 0 mcg administered orally twice daily (BID)
Period Title: Overall Study
STARTED	219	220
Intention to Treat (ITT)	219	220
Safety Analysis Set	219	220
COMPLETED	169	184
NOT COMPLETED	50	36

Baseline Characteristics

Arm/Group Title	Lubiprostone	Placebo	Total
Arm/Group Description	24 mcg capsules twice daily (BID) Lubiprostone: 24 mcg administered orally twice daily (BID)	0 mcg capsules twice daily (BID) Placebo: Matching placebo, 0 mcg administered orally twice daily (BID)	Total of all reporting groups
Overall Participants	219	220	439
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.9 (9.01)	51.5 (11.68)	51.7 (10.42)
Sex: Female, Male (Count of Participants)
Female	138 63%	138 62.7%	276 62.9%
Male	81 37%	82 37.3%	163 37.1%
Region of Enrollment (participants) [Number]
Czech Republic	6 2.7%	8 3.6%	14 3.2%
Belgium	2 0.9%	2 0.9%	4 0.9%
United States	202 92.2%	203 92.3%	405 92.3%
Poland	2 0.9%	2 0.9%	4 0.9%
United Kingdom	3 1.4%	2 0.9%	5 1.1%
Germany	4 1.8%	3 1.4%	7 1.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Classified as Treatment Responders Within 12 Weeks
Description	Spontaneous bowel movement (SBM) is defined as any BM that does not occur within 24 hours after use of rescue medication. To be classified as responders, participants are required to demonstrate at least moderate response (≥ 1 SBM improvement over baseline SBM frequency) for all treatment weeks for which observed data are available, and must additionally demonstrate a full response (≥ 3 SBMs per week) for at least 9 of the 12 treatment weeks.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description	24 mcg capsules twice daily (BID) Lubiprostone: 24 mcg administered orally twice daily (BID)	0 mcg capsules twice daily (BID) Placebo: Matching placebo, 0 mcg administered orally twice daily (BID)
Measure Participants	219	220
Count of Participants [Participants]	59 26.9%	41 18.6%

2. Secondary Outcome

Title	Number of SBMs Per Week at Week 8
Time Frame	at Week 8

Outcome Measure Data

Analysis Population Description

Intention to treat with data at Week 8

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description	24 mcg capsules twice daily (BID) Lubiprostone: 24 mcg administered orally twice daily (BID)	0 mcg capsules twice daily (BID) Placebo: Matching placebo, 0 mcg administered orally twice daily (BID)
Measure Participants	168	182
Mean (Standard Deviation) [SBMs/week]	2.9 (3.18)	2.5 (3.03)

3. Secondary Outcome

Title	Number of Participants Who Experienced First SBM Within 48 Hours After Dose Initiation
Time Frame	within 48 hours post-dose

Outcome Measure Data

Analysis Population Description

Intention to treat

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description	24 mcg capsules twice daily (BID) Lubiprostone: 24 mcg administered orally twice daily (BID)	0 mcg capsules twice daily (BID) Placebo: Matching placebo, 0 mcg administered orally twice daily (BID)
Measure Participants	219	220
within 24 Hours	110 50.2%	84 38.2%
within 48 Hours	157 71.7%	134 60.9%

4. Secondary Outcome

Title	Number of SBMs Per Week at Week 12
Time Frame	at Week 12

Outcome Measure Data

Analysis Population Description

Intention to treat with data at Week 12

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description	24 mcg capsules twice daily (BID) Lubiprostone: 24 mcg administered orally twice daily (BID)	0 mcg capsules twice daily (BID) Placebo: Matching placebo, 0 mcg administered orally twice daily (BID)
Measure Participants	159	180
Mean (Standard Deviation) [SBMs/week]	3.1 (3.13)	2.7 (3.34)

5. Secondary Outcome

Title	Number of SBMs Per Week Overall
Description	Overall is defined as the length of time from first dose to last follow-up within 2 weeks after last dose.
Time Frame	within 14 weeks

Outcome Measure Data

Analysis Population Description

Intention to treat with data at Week 14

Arm/Group Title	Lubiprostone	Placebo
Arm/Group Description	24 mcg capsules twice daily (BID) Lubiprostone: 24 mcg administered orally twice daily (BID)	0 mcg capsules twice daily (BID) Placebo: Matching placebo, 0 mcg administered orally twice daily (BID)
Measure Participants	213	218
Mean (Standard Deviation) [SBMs/week]	4.3 (2.96)	3.7 (2.53)

Adverse Events

Time Frame	Treatment-emergent adverse events (AEs): 14 weeks (from time of first dose to 14 days post-treatment)
Adverse Event Reporting Description	Number of participants at risk represents the Safety Evaluable population. Safety Evaluable population includes all subjects who were randomized and dosed. ITT population (in Participant Flow) includes only subjects who dosed and provided at least one post-treatment efficacy assessment.
Arm/Group Title	Lubiprostone		Placebo
Arm/Group Description	24 mcg capsules twice daily (BID) Lubiprostone: 24 mcg administered orally twice daily (BID)		0 mcg capsules twice daily (BID) Placebo: Matching placebo, 0 mcg administered orally twice daily (BID)
All Cause Mortality
	Lubiprostone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/219 (0.5%)		0/220 (0%)
Serious Adverse Events
	Lubiprostone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/219 (3.2%)		6/220 (2.7%)
Cardiac disorders
Cardiac Failure Congestive	0/219 (0%)		1/220 (0.5%)
Coronary Artery Disease	0/219 (0%)		1/220 (0.5%)
Gastrointestinal disorders
Abdominal Pain	1/219 (0.5%)		0/220 (0%)
Abdominal Pain Upper	0/219 (0%)		1/220 (0.5%)
Fecaloma	0/219 (0%)		1/220 (0.5%)
Nausea	1/219 (0.5%)		0/220 (0%)
Vomiting	1/219 (0.5%)		0/220 (0%)
General disorders
Chest Pain	0/219 (0%)		1/220 (0.5%)
Injury, poisoning and procedural complications
Ankle Fracture	1/219 (0.5%)		0/220 (0%)
Contusion	0/219 (0%)		1/220 (0.5%)
Drug Toxicity	1/219 (0.5%)		0/220 (0%)
Investigations
Hepatic Enzyme Increased	1/219 (0.5%)		0/220 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	1/219 (0.5%)		1/220 (0.5%)
Muscle Spasms	0/219 (0%)		1/220 (0.5%)
Nervous system disorders
Syncope	1/219 (0.5%)		1/220 (0.5%)
Migraine	1/219 (0.5%)		0/220 (0%)
Renal and urinary disorders
Nephrolithiasis	1/219 (0.5%)		0/220 (0%)
Renal Failure Acute	0/219 (0%)		1/220 (0.5%)
Other (Not Including Serious) Adverse Events
	Lubiprostone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	72/219 (32.9%)		44/220 (20%)
Gastrointestinal disorders
Diarrhea	24/219 (11%)		8/220 (3.6%)
Nausea	21/219 (9.6%)		10/220 (4.5%)
Vomiting	9/219 (4.1%)		11/220 (5%)
Abdominal Pain	15/219 (6.8%)		0/220 (0%)
Flatulence	6/219 (2.7%)		5/220 (2.3%)
Infections and infestations
Urinary Tract Infection	7/219 (3.2%)		6/220 (2.7%)
Upper Respiratory Tract Infection	4/219 (1.8%)		5/220 (2.3%)
Investigations
Gamma-Glutamyltransferase Increased	5/219 (2.3%)		4/220 (1.8%)
Musculoskeletal and connective tissue disorders
Back Pain	6/219 (2.7%)		5/220 (2.3%)
Arthralgia	5/219 (2.3%)		4/220 (1.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.