Peptic 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
DRUGHZT-501
HZT-501: Ibuprofen 800mg/famotidine 26.6mg orally 3 times daily for 24 weeks
DRUGIbuprofen
Ibuprofen 800mg 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 a nonsteroidal anti-inflammatory drug (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, * 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 Subjects Who Develop Endoscopically-diagnosed Upper Gastrointestinal Ulcers Confirmed by Endoscopy. | 24 weeks | The primary efficacy endpoint was the number of subjects with upper gastrointestinal (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 subject 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 Subjects Who Develop Endoscopically-diagnosed Gastric Ulcers During the 24-week Treatment Period. | 24 weeks | The secondary efficacy endpoint was the number of subjects 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 subject is considered to have completed the study if all scheduled assessments up through the Week 24 visit have been performed. |
| Number of Subjects Who Develop Endoscopically-diagnosed Duodenal Ulcers During the 24-week Treatment Period. | 24 weeks | The secondary efficacy endpoint was the number of subjects with duodenal ulcer at any time throughout the 24 weeks of treatment. An ulcer was defined as a mucosal break of at least 3 mm in diameter with unequivocal depth. A subject is considered to have completed the study if all scheduled assessments up through the Week 24 visit have been performed. |
| The Incidence Rate of NSAID-associated Serious Gastrointestinal Complications. | 24 weeks | The secondary efficacy endpoint was the number of subjects developing a NSAID-associated serious GI complication at any time throughout 6 months of treatment. A NSAID-associated serious GI complication was defined as a perforation of ulcers, gastric outlet obstruction due to ulcers, and/or GI bleeding. |
Participant flow
Recruitment details
A multi-center US study in which 80 sites recruited subjects between March 2007 and February 2008.
Pre-assignment details
Following screening for eligibility and wash-out of restricted medications, subjects were assigned according to the treatment to which they were randomized in a 2:1 ratio (HZT-501:ibuprofen).
Participants by arm
| Arm | Count |
|---|---|
| HZT-501 HZT-501: Ibuprofen 800mg/Famotidine 26.6mg | 415 |
| Ibuprofen Ibuprofen 800mg | 212 |
| Total | 627 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 24 | 15 |
| Overall Study | Lost to Follow-up | 22 | 5 |
| Overall Study | misc | 21 | 10 |
| Overall Study | UGI ulcer | 33 | 34 |
| Overall Study | Withdrawal by Subject | 43 | 26 |
Baseline characteristics
| Characteristic | Ibuprofen | HZT-501 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 39 Participants | 73 Participants | 112 Participants |
| Age, Categorical Between 18 and 65 years | 173 Participants | 342 Participants | 515 Participants |
| Age, Continuous | 55.7 years STANDARD_DEVIATION 9.5 | 55.3 years STANDARD_DEVIATION 9 | 55.4 years STANDARD_DEVIATION 9.1 |
| Region of Enrollment United States | 212 participants | 415 participants | 627 participants |
| Sex: Female, Male Female | 152 Participants | 272 Participants | 424 Participants |
| Sex: Female, Male Male | 60 Participants | 143 Participants | 203 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 220 / 415 | 116 / 212 |
| serious Total, serious adverse events | 11 / 415 | 4 / 212 |
Outcome results
Primary
Number of Subjects Who Develop Endoscopically-diagnosed Upper Gastrointestinal Ulcers Confirmed by Endoscopy.
The primary efficacy endpoint was the number of subjects with upper gastrointestinal (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 subject 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 subjects who received at least one dose of study drug and who underwent a baseline endoscopic examination and at least the Week 8 endoscopic examination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HZT-501 | Number of Subjects Who Develop Endoscopically-diagnosed Upper Gastrointestinal Ulcers Confirmed by Endoscopy. | 40 participants |
| Ibuprofen | Number of Subjects Who Develop Endoscopically-diagnosed Upper Gastrointestinal Ulcers Confirmed by Endoscopy. | 38 participants |
Comparison: The primary efficacy endpoint was the proportion of subjects developing UGI (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 proportion of subjects developing UGI ulcers at 24 weeks was analyzed using the CMH test stratified by use of low-dose aspirin and prior UGI ulcer history at randomization.p-value: 0.001895% CI: [3, 15.9]Cochran-Mantel-Haenszel
Secondary
Number of Subjects Who Develop Endoscopically-diagnosed Duodenal Ulcers During the 24-week Treatment Period.
The secondary efficacy endpoint was the number of subjects with duodenal ulcer at any time throughout the 24 weeks of treatment. An ulcer was defined as a mucosal break of at least 3 mm in diameter with unequivocal depth. A subject 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 Subjects Who Develop Endoscopically-diagnosed Duodenal Ulcers During the 24-week Treatment Period. | 3 participants |
| Ibuprofen | Number of Subjects Who Develop Endoscopically-diagnosed Duodenal Ulcers During the 24-week Treatment Period. | 9 participants |
Comparison: The secondary efficacy endpoint was the proportion of subjects 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 proportion of subjects developing duodenal ulcers at 24 weeks was analyzed using the CMH test stratified by use of low-dose aspirin and prior UGI ulcer history at randomization.p-value: 0.001795% CI: [0.8, 7.1]Cochran-Mantel-Haenszel
Secondary
Number of Subjects Who Develop Endoscopically-diagnosed Gastric Ulcers During the 24-week Treatment Period.
The secondary efficacy endpoint was the number of subjects 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 subject 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: The secondary efficacy endpoint was the number of subjects 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 subject is considered to have completed the study if all scheduled assessments up through the Week 24 visit were performed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HZT-501 | Number of Subjects Who Develop Endoscopically-diagnosed Gastric Ulcers During the 24-week Treatment Period. | 37 participants |
| Ibuprofen | Number of Subjects Who Develop Endoscopically-diagnosed Gastric Ulcers During the 24-week Treatment Period. | 34 participants |
p-value: 0.005195% CI: [1.9, 14.4]Cochran-Mantel-Haenszel
Secondary
The Incidence Rate of NSAID-associated Serious Gastrointestinal Complications.
The secondary efficacy endpoint was the number of subjects developing a NSAID-associated serious GI complication at any time throughout 6 months of treatment. A NSAID-associated serious GI complication was defined as a perforation of ulcers, gastric outlet obstruction due to ulcers, and/or GI bleeding.
Time frame: 24 weeks
Population: All randomized subjects who received at least one dose of study drug and who underwent a baseline endoscopic exam. Subjects were assigned according to the treatment to which they received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HZT-501 | The Incidence Rate of NSAID-associated Serious Gastrointestinal Complications. | 0 participants |
| Ibuprofen | The Incidence Rate of NSAID-associated Serious Gastrointestinal Complications. | 0 participants |