Cobiprostone Prevention of NSAID-induced Gastroduodenal Injury

• Sponsor: Sucampo Pharma Americas, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00597818
• Collaborator: (none)
• Enrollment: 121
• Locations: 19
• Arms: 4
• Duration (Months): 21
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The primary purpose of this study is to determine the efficacy and safety of three dose levels of cobiprostone as compared to placebo in OA/RA patients treated with an NSAID for 20 months.

Condition or Disease	Intervention/Treatment	Phase
NSAID-induced Gastroduodenal Injury; Ulcers; Rheumatoid Arthritis; Osteoarthritis	Drug: Cobiprostone; Drug: Placebo; Drug: Non-steroidal anti-inflammatory drug	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 121 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomized, Placebo-controlled, Double-blinded Study of the Efficacy and Safety of Cobiprostone for the Prevention of NSAID-induced Gastroduodenal Injury in Patients With Osteoarthritis and/or Rheumatoid Arthritis Patients
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants receive matching placebo capsules for 20 months	Drug: Placebo; Matching placebo capsules for oral administration; Other Names: Matching Placebo ; Drug: Non-steroidal anti-inflammatory drug; Any marketed non-steroidal anti-inflammatory drug used by the participants as standard care.; Other Names: Standard Care
Experimental: Cobiprostone QD Participants receive 18 mcg cobiprostone once daily (QD) for 20 months	Drug: Cobiprostone; 18 mcg cobiprostone capsules for oral administration; Other Names: SPI-8811 RU-8811 ; Drug: Non-steroidal anti-inflammatory drug; Any marketed non-steroidal anti-inflammatory drug used by the participants as standard care.; Other Names: Standard Care
Experimental: Cobiprostone BID Participants receive 18 mcg cobiprostone twice daily (BID) for 20 months	Drug: Cobiprostone; 18 mcg cobiprostone capsules for oral administration; Other Names: SPI-8811 RU-8811 ; Drug: Non-steroidal anti-inflammatory drug; Any marketed non-steroidal anti-inflammatory drug used by the participants as standard care.; Other Names: Standard Care
Experimental: Cobiprostone TID Participants receive 18 mcg cobiprostone three times daily (TID) for 20 months	Drug: Cobiprostone; 18 mcg cobiprostone capsules for oral administration; Other Names: SPI-8811 RU-8811 ; Drug: Non-steroidal anti-inflammatory drug; Any marketed non-steroidal anti-inflammatory drug used by the participants as standard care.; Other Names: Standard Care

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Gastric Ulcers [at 20 months]

Secondary Outcome Measures

1. Number of Participants With Duodenal and Gastroduodenal Ulcers [at 20 months]

2. Number of Participants With Gastric, Duodenal, and Gastroduodenal Ulcers [at Week 4]

3. Size of Ulcers/Erosions [at 20 Months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient is more than 40 and less than 70 years of age.

• Patient has confirmed osteoarthritis (OA) and/or rheumatoid arthritis (RA) and could benefit from NSAID therapy.

• No current gastrointestinal H. pylori infection.

Exclusion Criteria:

• Known allergy or hypersensitivity to NSAIDs, or has any other contraindicated condition(s) to NSAID therapy.

• Patient has undergone a gastrointestinal or abdominal surgical procedure within 90 days prior to the Screening Visit, or has had a bowel resection at any time.

• Medical history includes prior or active GI complications and/or disorders, including but not limited to Barrett's esophagus, erosive esophagitis, esophageal stricture or ring, gastric obstruction, irritable bowel syndrome (IBS), or inflammatory bowel disease (IBD).

• Active symptomatic peptic ulcer disease or GI bleeding.

• Patient has received cobiprostone (SPI-8811; RU-8811) or AMITIZA (other names: lubiprostone, SPI-0211, or RU-0211) at any time prior to participation in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Carl T Hayden VA Medical Center	Phoenix	Arizona	United States	85012
2	Gregory J. Wiener, MD PC	Chula Vista	California	United States	91910
3	Loma Linda University Physicians Medical Group	Loma Linda	California	United States	92354
4	Facey Medical Foundation	Mission Hills	California	United States	91345
5	Desert Oasis Healthcare	Palm Springs	California	United States	92262
6	Sepulveda Ambulatory Care Center	Sepulveda	California	United States	91343
7	University Clinical Research, Inc.	Pembroke Pines	Florida	United States	33024
8	University of Illinois Medical Center	Chicago	Illinois	United States	60612
9	Gulf Coast Research, LLC	Baton Rouge	Louisiana	United States	70808
10	Boston Medical Center	Boston	Massachusetts	United States	02118
11	Long Island Gastrointestinal Research Group	Great Neck	New York	United States	11023
12	Research Associates of New York	New York	New York	United States	10021
13	University of North Carolina Gastroenterology	Chapel Hill	North Carolina	United States	27599
14	Oklahoma Founddation for Digestive Research	Oklahoma City	Oklahoma	United States	73104
15	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
16	Gastroenterology Section at Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
17	Dallas VA Research Corporation, Inc.	Dallas	Texas	United States	75216
18	Houston Institute for Clinical Research	Houston	Texas	United States	77074
19	Digestive and Liver Disease Specialists	Norfolk	Virginia	United States	23502

Sponsors and Collaborators

• Sucampo Pharma Americas, LLC

Investigators

• Study Director: Global Clinical Leader, Mallinckrodt

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sucampo Pharma Americas, LLC
• ClinicalTrials.gov Identifier: NCT00597818
• Other Study ID Numbers: SU0621
• First Posted: Jan 18, 2008
• Last Update Posted: Dec 26, 2019
• Last Verified: Mar 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Arthritis; Osteoarthritis; Arthritis, Rheumatoid; Wounds and Injuries; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal

Study Results

Participant Flow

Pre-assignment Detail	Of 124 participants recruited, only 121 were actually enrolled.

Arm/Group Title	Placebo	18 mcg	36 mcg	54 mcg
Arm/Group Description	Matching placebo	Cobiprostone 18 mcg once daily (QD)	Cobiprostone 18 mcg twice daily (BID)	Cobiprostone 18 mcg three times daily (TID)
Period Title: Overall Study
STARTED	30	30	31	30
COMPLETED	12	14	12	20
NOT COMPLETED	18	16	19	10

Baseline Characteristics

Arm/Group Title	Placebo	Cobiprostone QD	Cobiprostone BID	Cobiprostone TID	Total
Arm/Group Description	Matching placebo	Cobiprostone 18 mcg once daily (QD)	Cobiprostone 18 mcg twice daily (BID)	Cobiprostone 18 mcg three times daily (TID)	Total of all reporting groups
Overall Participants	32	30	31	31	124
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	29 90.6%	27 90%	27 87.1%	29 93.5%	112 90.3%
>=65 years	3 9.4%	3 10%	4 12.9%	2 6.5%	12 9.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.1 (7.9)	53.9 (8.01)	54.6 (8.28)	53.3 (8.18)	54.0 (8.01)
Sex: Female, Male (Count of Participants)
Female	23 71.9%	20 66.7%	23 74.2%	24 77.4%	90 72.6%
Male	9 28.1%	10 33.3%	8 25.8%	7 22.6%	34 27.4%
Region of Enrollment (Count of Participants)
United States	32 100%	30 100%	31 100%	31 100%	124 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Gastric Ulcers
Time Frame	at 20 months

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population, defined as all participants enrolled in the trial

Arm/Group Title	Placebo	Cobiprostone QD	Cobiprostone BID	Cobiprostone TID
Arm/Group Description	Matching placebo	Cobiprostone 18 mcg once daily (QD)	Cobiprostone 18 mcg twice daily (BID)	Cobiprostone 18 mcg three times daily (TID)
Measure Participants	30	30	31	30
Count of Participants [Participants]	7 21.9%	5 16.7%	7 22.6%	4 12.9%

2. Secondary Outcome

Title	Number of Participants With Duodenal and Gastroduodenal Ulcers
Time Frame	at 20 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	Cobiprostone QD	Cobiprostone BID	Cobiprostone TID
Arm/Group Description	Matching placebo	Cobiprostone 18 mcg once daily (QD)	Cobiprostone 18 mcg twice daily (BID)	Cobiprostone 18 mcg three times daily (TID)
Measure Participants	30	30	31	30
Count of Participants [Participants]	1 3.1%	4 13.3%	1 3.2%	2 6.5%

3. Secondary Outcome

Title	Number of Participants With Gastric, Duodenal, and Gastroduodenal Ulcers
Time Frame	at Week 4

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	Cobiprostone QD	Cobiprostone BID	Cobiprostone TID
Arm/Group Description	Matching placebo	Cobiprostone 18 mcg once daily (QD)	Cobiprostone 18 mcg twice daily (BID)	Cobiprostone 18 mcg three times daily (TID)
Measure Participants	30	30	31	30
Count of Participants [Participants]	7 21.9%	8 26.7%	8 25.8%	6 19.4%

4. Secondary Outcome

Title	Size of Ulcers/Erosions
Time Frame	at 20 Months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Placebo	Cobiprostone QD	Cobiprostone BID	Cobiprostone TID
Arm/Group Description	Matching placebo	Cobiprostone 18 mcg once daily (QD)	Cobiprostone 18 mcg twice daily (BID)	Cobiprostone 18 mcg three times daily (TID)
Measure Participants	30	30	31	30
Mean (Standard Deviation) [mm]	8.5 (20.49)	4.7 (2.63)	3.5 (2.35)	2.6 (1.54)

Adverse Events

Time Frame	All participants were treated and followed for ulcers and other adverse events for a total of 20 months
Arm/Group Title	Placebo		Cobiprostone QD		Cobiprostone BID		Cobiprostone TID
Arm/Group Description	Matching placebo		Cobiprostone 18 mcg once daily (QD)		Cobiprostone 18 mcg twice daily (BID)		Cobiprostone 18 mcg three times daily (TID)
All Cause Mortality
	Placebo		Cobiprostone QD		Cobiprostone BID		Cobiprostone TID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Cobiprostone QD		Cobiprostone BID		Cobiprostone TID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/30 (73.3%)		23/30 (76.7%)		25/31 (80.6%)		26/30 (86.7%)
Gastrointestinal disorders
Diarrhoea	5/30 (16.7%)		4/30 (13.3%)		11/31 (35.5%)		12/30 (40%)
Nausea	4/30 (13.3%)		3/30 (10%)		5/31 (16.1%)		5/30 (16.7%)
Dyspepsia	6/30 (20%)		3/30 (10%)		2/31 (6.5%)		5/30 (16.7%)
Gastritis	5/30 (16.7%)		4/30 (13.3%)		2/31 (6.5%)		3/30 (10%)
Erosive oesophagitis	6/30 (20%)		3/30 (10%)		2/31 (6.5%)		2/30 (6.7%)
Flatulence	4/30 (13.3%)		4/30 (13.3%)		1/31 (3.2%)		2/30 (6.7%)
Abdominal pain upper	3/30 (10%)		2/30 (6.7%)		3/31 (9.7%)		2/30 (6.7%)
Duodenitis	3/30 (10%)		3/30 (10%)		1/31 (3.2%)		3/30 (10%)
Hiatus hernia	0/30 (0%)		3/30 (10%)		2/31 (6.5%)		3/30 (10%)
Gastrointestinal tract mucosal discolouration	2/30 (6.7%)		3/30 (10%)		1/31 (3.2%)		2/30 (6.7%)
Reflux oesophagitis	3/30 (10%)		3/30 (10%)		0/31 (0%)		1/30 (3.3%)
Gastritis erosive	3/30 (10%)		2/30 (6.7%)		2/31 (6.5%)		0/30 (0%)
Abdominal distension	1/30 (3.3%)		2/30 (6.7%)		1/31 (3.2%)		1/30 (3.3%)
Oesophagitis	2/30 (6.7%)		2/30 (6.7%)		0/31 (0%)		1/30 (3.3%)
Constipation	0/30 (0%)		1/30 (3.3%)		1/31 (3.2%)		2/30 (6.7%)
Gastrointestinal haemorrhage	2/30 (6.7%)		1/30 (3.3%)		0/31 (0%)		0/30 (0%)
Abdominal discomfort	2/30 (6.7%)		0/30 (0%)		0/31 (0%)		1/30 (3.3%)
Other (Not Including Serious) Adverse Events
	Placebo		Cobiprostone QD		Cobiprostone BID		Cobiprostone TID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/30 (66.7%)		18/30 (60%)		22/31 (71%)		21/30 (70%)
Gastrointestinal disorders
Diarrhoea	4/30 (13.3%)		4/30 (13.3%)		10/31 (32.3%)		11/30 (36.7%)
Nausea	3/30 (10%)		3/30 (10%)		5/31 (16.1%)		5/30 (16.7%)
Dyspepsia	5/30 (16.7%)		2/30 (6.7%)		1/31 (3.2%)		4/30 (13.3%)
Gastritis	4/30 (13.3%)		4/30 (13.3%)		2/31 (6.5%)		3/30 (10%)
Erosive Oesophagitis	5/30 (16.7%)		2/30 (6.7%)		2/31 (6.5%)		2/30 (6.7%)
Flatulence	4/30 (13.3%)		3/30 (10%)		1/31 (3.2%)		2/30 (6.7%)
Abdominal Pain Other	3/30 (10%)		2/30 (6.7%)		3/31 (9.7%)		2/30 (6.7%)
Duodenitis	3/30 (10%)		3/30 (10%)		1/31 (3.2%)		3/30 (10%)
Reflux oesphagitis	3/30 (10%)		2/30 (6.7%)		0/31 (0%)		1/30 (3.3%)
Gastritis erosive	3/30 (10%)		2/30 (6.7%)		1/31 (3.2%)		0/30 (0%)
Abdominal distension	1/30 (3.3%)		2/30 (6.7%)		1/31 (3.2%)		1/30 (3.3%)
Constipation	0/30 (0%)		0/30 (0%)		1/31 (3.2%)		2/30 (6.7%)
Oesophagitis	2/30 (6.7%)		0/30 (0%)		0/31 (0%)		1/30 (3.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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