NSAID-induced Gastroduodenal Injury, Osteoarthritis, Rheumatoid Arthritis, Ulcers
Conditions
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.
Interventions
DRUGCobiprostone
18 mcg cobiprostone capsules for oral administration
DRUGPlacebo
Matching placebo capsules for oral administration
Any marketed non-steroidal anti-inflammatory drug used by the participants as standard care.
Sponsors
Sucampo Pharma Americas, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Gastric Ulcers | at 20 months |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Duodenal and Gastroduodenal Ulcers | at 20 months |
| Number of Participants With Gastric, Duodenal, and Gastroduodenal Ulcers | at Week 4 |
| Size of Ulcers/Erosions | at 20 Months |
Countries
United States
Participant flow
Pre-assignment details
Of 124 participants recruited, only 121 were actually enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo | 32 |
| Cobiprostone QD Cobiprostone 18 mcg once daily (QD) | 30 |
| Cobiprostone BID Cobiprostone 18 mcg twice daily (BID) | 31 |
| Cobiprostone TID Cobiprostone 18 mcg three times daily (TID) | 31 |
| Total | 124 |
Baseline characteristics
| Characteristic | Cobiprostone QD | Cobiprostone BID | Placebo | Cobiprostone TID | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 4 Participants | 3 Participants | 2 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 27 Participants | 29 Participants | 29 Participants | 112 Participants |
| Age, Continuous | 53.9 years STANDARD_DEVIATION 8.01 | 54.6 years STANDARD_DEVIATION 8.28 | 54.1 years STANDARD_DEVIATION 7.9 | 53.3 years STANDARD_DEVIATION 8.18 | 54.0 years STANDARD_DEVIATION 8.01 |
| Region of Enrollment United States | 30 Participants | 31 Participants | 32 Participants | 31 Participants | 124 Participants |
| Sex: Female, Male Female | 20 Participants | 23 Participants | 23 Participants | 24 Participants | 90 Participants |
| Sex: Female, Male Male | 10 Participants | 8 Participants | 9 Participants | 7 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 30 | 18 / 30 | 22 / 31 | 21 / 30 |
| serious Total, serious adverse events | 22 / 30 | 23 / 30 | 25 / 31 | 26 / 30 |
Outcome results
Primary
Number of Participants With Gastric Ulcers
Time frame: at 20 months
Population: Intention to treat (ITT) population, defined as all participants enrolled in the trial
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Gastric Ulcers | 7 Participants |
| Cobiprostone QD | Number of Participants With Gastric Ulcers | 5 Participants |
| Cobiprostone BID | Number of Participants With Gastric Ulcers | 7 Participants |
| Cobiprostone TID | Number of Participants With Gastric Ulcers | 4 Participants |
Secondary
Number of Participants With Duodenal and Gastroduodenal Ulcers
Time frame: at 20 months
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Duodenal and Gastroduodenal Ulcers | 1 Participants |
| Cobiprostone QD | Number of Participants With Duodenal and Gastroduodenal Ulcers | 4 Participants |
| Cobiprostone BID | Number of Participants With Duodenal and Gastroduodenal Ulcers | 1 Participants |
| Cobiprostone TID | Number of Participants With Duodenal and Gastroduodenal Ulcers | 2 Participants |
Secondary
Number of Participants With Gastric, Duodenal, and Gastroduodenal Ulcers
Time frame: at Week 4
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Gastric, Duodenal, and Gastroduodenal Ulcers | 7 Participants |
| Cobiprostone QD | Number of Participants With Gastric, Duodenal, and Gastroduodenal Ulcers | 8 Participants |
| Cobiprostone BID | Number of Participants With Gastric, Duodenal, and Gastroduodenal Ulcers | 8 Participants |
| Cobiprostone TID | Number of Participants With Gastric, Duodenal, and Gastroduodenal Ulcers | 6 Participants |
Secondary
Size of Ulcers/Erosions
Time frame: at 20 Months
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Size of Ulcers/Erosions | 8.5 mm | Standard Deviation 20.49 |
| Cobiprostone QD | Size of Ulcers/Erosions | 4.7 mm | Standard Deviation 2.63 |
| Cobiprostone BID | Size of Ulcers/Erosions | 3.5 mm | Standard Deviation 2.35 |
| Cobiprostone TID | Size of Ulcers/Erosions | 2.6 mm | Standard Deviation 1.54 |