Ulcer
Conditions
Keywords
ibuprofen, famotidine, ulcers, NSAIDS, pain, arthritis, chronic regional pain syndrome, chronic soft tissue pain, osteoarthritis, rheumatoid arthritis, chronic low back pain
Brief summary
The purpose of this study is to evaluate whether HZT-501 is effective in reducing the rate of development of ibuprofen-associated ulcers in patients who require long-term daily use of ibuprofen.
Detailed description
HZT-501 is a combination product including ibuprofen and the acid reducing agent famotidine. The study is designed to determine whether the combination product reduces the rate of ulcer development in subjects who require long-term daily use of ibuprofen. Subjects will be assigned randomly, in approximately a 2:1 ratio, to treatment with either HZT-501 (ibuprofen 800 mg/famotidine 26.6 mg) or ibuprofen (800 mg) three times daily for a 24 week treatment period or until they develop either an endoscopically-diagnosed upper gastrointestinal ulcer and/or prohibitive toxicity. Subjects will visit the study center for Screening and at Weeks 4, 8, 16, and 24. Physical exams will be performed, and clinical laboratory measurements made, at selected times during the study. Endoscopic exams will be performed during Screening and at Weeks 8, 16, and 24. Subjects will be contacted four weeks following study completion. Study with completed results acquired from Horizon in 2024.
Interventions
DRUGIbuprofen/famotidine
HZT-501: Ibuprofen800mg/famotidine 26.6mg administered orally 3 times daily for 24 weeks
DRUGIbuprofen
Ibuprofen 800mg administered orally 3 times daily for 24 weeks
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Expected to require daily administration of an NSAID for at least the coming six months for conditions such as osteoarthritis, rheumatoid arthritis, chronic low back pain, chronic regional pain syndrome, and chronic soft tissue pain. * Did not use a NSAID within the 30 days prior to study entry
Exclusion criteria
* History of erosive esophagitis * History of any of the following serious gastrointestinal complications: * perforation of ulcers, * gastric outlet obstruction due to ulcers, or * gastrointestinal bleeding. * Active cardiac, renal, and/or hepatic disease * Current Helicobacter pylori (H. pylori) infection * Use of an acid suppressant agent, misoprostol, or more than 325 mg/day of aspirin within the 14 days prior to study entry. * Uncontrolled diabetes * Uncontrolled hypertension * Positive pregnancy test at screening * Positive test at Screening for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. * Currently participating, or participation within 30 days prior to study entry, in an investigational drug study Please note that there are other additional criteria. The study center will determine if patients meet all of the criteria.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Develop Endoscopically-diagnosed Gastric Ulcers | 24 weeks | The primary efficacy endpoint was the number of participants with gastric ulcer at any time throughout 24 weeks of treatment. An ulcer was defined as a mucosal break of at least 3 mm in diameter with unequivocal depth. A participant is considered to have completed the study if all scheduled assessments up through the Week 24 visit have been performed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Develop Endoscopically-diagnosed Upper Gastrointestinal (UGI) Ulcers During the 24-week Treatment Period. | 24 weeks | The secondary efficacy endpoint was the number of participants with UGI (i.e., gastric and/or duodenal) ulcer at any time throughout 24 weeks of treatment. An ulcer was defined as a mucosal break of at least 3 mm in diameter with unequivocal depth. A participant is considered to have completed the study if all scheduled assessments up through the Week 24 visit have been performed. |
| Number of Participants Who Develop Endoscopically-diagnosed Duodenal Ulcers During the 24-week Treatment Period. | 24 weeks | The secondary efficacy endpoint was the number of participants with duodenal ulcer at any time throughout 24 weeks of treatment. An ulcer was defined as a mucosal break of at least 3 mm in diameter with unequivocal depth. A participant is considered to have completed the study if all scheduled assessments up through the Week 24 visit have been performed. |
| The Number of Participants Developing Non-steroidal Anti-inflammatory (NSAID)Associated Serious Gastrointestinal Complications (Perforation of Ulcers, Gastric Outlet Obstruction Due to Ulcers, Gastrointestinal Bleeding) | 24 weeks | The secondary efficacy endpoint was the number of participants developing a NSAID-associated serious gastrointestinal complication at any time throughout 24 weeks of treatment. A NSAID-associated serious gastrointestinal complication was defined as a perforation of ulcers, gastric outlet obstruction due to ulcers, and/or gastrointestinal bleeding. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HZT-501 HZT-501: Ibuprofen 800mg/famotidine 26.6mg | 607 |
| Ibuprofen Ibuprofen 800mg | 299 |
| Total | 906 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 38 | 23 |
| Overall Study | Lost to Follow-up | 16 | 9 |
| Overall Study | misc | 21 | 20 |
| Overall Study | upper gastrointestinal (UGI) ulcer | 51 | 51 |
| Overall Study | Withdrawal by Subject | 48 | 26 |
Baseline characteristics
| Characteristic | Ibuprofen | HZT-501 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 59 Participants | 107 Participants | 166 Participants |
| Age, Categorical Between 18 and 65 years | 240 Participants | 500 Participants | 740 Participants |
| Age, Continuous | 55.9 years STANDARD_DEVIATION 9.3 | 55.5 years STANDARD_DEVIATION 9.2 | 55.6 years STANDARD_DEVIATION 9.2 |
| Region of Enrollment United States | 299 participants | 607 participants | 906 participants |
| Sex: Female, Male Female | 208 Participants | 416 Participants | 624 Participants |
| Sex: Female, Male Male | 91 Participants | 191 Participants | 282 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 342 / 607 | 184 / 299 |
| serious Total, serious adverse events | 22 / 607 | 13 / 299 |
Outcome results
Primary
Number of Participants Who Develop Endoscopically-diagnosed Gastric Ulcers
The primary efficacy endpoint was the number of participants with gastric ulcer at any time throughout 24 weeks of treatment. An ulcer was defined as a mucosal break of at least 3 mm in diameter with unequivocal depth. A participant is considered to have completed the study if all scheduled assessments up through the Week 24 visit have been performed.
Time frame: 24 weeks
Population: All randomized participants who received at least one dose of study drug and who underwent a baseline endoscopic examination and at least the Week 8 endoscopic examination. Participants were assigned according to the treatment to which they were randomized; 2:1 randomization, HZT-501:ibuprofen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HZT-501 | Number of Participants Who Develop Endoscopically-diagnosed Gastric Ulcers | 55 participants |
| Ibuprofen | Number of Participants Who Develop Endoscopically-diagnosed Gastric Ulcers | 52 participants |
Comparison: The primary efficacy endpoint was the number of participants developing gastric ulcers throughout 24 weeks of treatment. A summary, including cumulative frequency and percentage with associated 95% confidence intervals was produced for the observational incidences of gastric ulcers at 24 weeks. The cumulative number of participants developing gastric ulcers at 24 weeks was analyzed using the Cochran-Mantel-Haenszel (CMH) test stratified by use of low-dose aspirin and prior UGI ulcer history.p-value: <0.000195% CI: [4.4, 15.3]Cochran-Mantel-Haenszel
Secondary
Number of Participants Who Develop Endoscopically-diagnosed Duodenal Ulcers During the 24-week Treatment Period.
The secondary efficacy endpoint was the number of participants with duodenal ulcer at any time throughout 24 weeks of treatment. An ulcer was defined as a mucosal break of at least 3 mm in diameter with unequivocal depth. A participant is considered to have completed the study if all scheduled assessments up through the Week 24 visit have been performed.
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HZT-501 | Number of Participants Who Develop Endoscopically-diagnosed Duodenal Ulcers During the 24-week Treatment Period. | 8 participants |
| Ibuprofen | Number of Participants Who Develop Endoscopically-diagnosed Duodenal Ulcers During the 24-week Treatment Period. | 14 participants |
Comparison: The secondary efficacy endpoint was the number of participants developing duodenal ulcers throughout 24 weeks of treatment. A summary, including cumulative frequency and percentage with associated 95% confidence intervals was produced for the observational incidences of duodenal ulcers at 24 weeks. The cumulative number of participants developing duodenal ulcers at 24 weeks was analyzed using the CMH test stratified by use of low-dose aspirin and prio UGI ulcer history at randomization.p-value: 0.000695% CI: [1, 6.8]Cochran-Mantel-Haenszel
Secondary
Number of Participants Who Develop Endoscopically-diagnosed Upper Gastrointestinal (UGI) Ulcers During the 24-week Treatment Period.
The secondary efficacy endpoint was the number of participants with UGI (i.e., gastric and/or duodenal) ulcer at any time throughout 24 weeks of treatment. An ulcer was defined as a mucosal break of at least 3 mm in diameter with unequivocal depth. A participant is considered to have completed the study if all scheduled assessments up through the Week 24 visit have been performed.
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HZT-501 | Number of Participants Who Develop Endoscopically-diagnosed Upper Gastrointestinal (UGI) Ulcers During the 24-week Treatment Period. | 63 participants |
| Ibuprofen | Number of Participants Who Develop Endoscopically-diagnosed Upper Gastrointestinal (UGI) Ulcers During the 24-week Treatment Period. | 61 participants |
Comparison: The secondary efficacy endpoint was the number of participants developing UGI (i.e., gastric and/or duodenal) ulcers throughout 24 weeks of treatment. A summary, including cumulative frequency and percentage with associated 95% confidence intervals was produced for the observational incidences of UGI ulcers at 24 weeks. The cumulative number of participants developing UGI ulcers at 24 weeks was analyzed using the CMH test stratified by use of low-dose aspirin and prior UGI ulcer history.p-value: <0.000195% CI: [6.1, 17.6]Cochran-Mantel-Haenszel
Secondary
The Number of Participants Developing Non-steroidal Anti-inflammatory (NSAID)Associated Serious Gastrointestinal Complications (Perforation of Ulcers, Gastric Outlet Obstruction Due to Ulcers, Gastrointestinal Bleeding)
The secondary efficacy endpoint was the number of participants developing a NSAID-associated serious gastrointestinal complication at any time throughout 24 weeks of treatment. A NSAID-associated serious gastrointestinal complication was defined as a perforation of ulcers, gastric outlet obstruction due to ulcers, and/or gastrointestinal bleeding.
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HZT-501 | The Number of Participants Developing Non-steroidal Anti-inflammatory (NSAID)Associated Serious Gastrointestinal Complications (Perforation of Ulcers, Gastric Outlet Obstruction Due to Ulcers, Gastrointestinal Bleeding) | 3 particpants |
| Ibuprofen | The Number of Participants Developing Non-steroidal Anti-inflammatory (NSAID)Associated Serious Gastrointestinal Complications (Perforation of Ulcers, Gastric Outlet Obstruction Due to Ulcers, Gastrointestinal Bleeding) | 0 particpants |