Bunion, Pain, Postoperative
Conditions
Keywords
Moderate Post-Operative Pain, Severe Post-Operative Pain, Bunionectomy
Brief summary
The primary objective of this study is to show the effectiveness of repeated doses of COV795 versus placebo, using the summed pain intensity difference over the first 48 hours in subjects with acute moderate to severe pain following bunionectomy.
Interventions
DRUGCOV795
2 tablets taken every 12 hours
DRUGPlacebo
2 tablets taken every 12 hours
Sponsors
Mallinckrodt
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Complete the informed consent process as documented by signed informed consent form(s). 2. Be in generally good health. 3. Be 18 to 75 years of age, inclusively at the time of screening. 4. Be scheduled for a primary unilateral first metatarsal bunionectomy (with no collateral procedures). 5. Have a body mass index ≤33 kg/m2. 6. Female subjects are eligible only if not pregnant, not lactating, not planning to become pregnant for the duration of the study, surgically sterile or at least two years postmenopausal, or practicing an acceptable form of birth control for at least 2 months 7. Male subjects must be sterile or commit to the use of a reliable method of birth control 8. Be classified as Physical status 1 (PS-1) to PS-2 by the American Society of Anesthetists (ASA) Physical Status Classification System. 9. Be willing to complete the pain evaluations and return to the clinic as scheduled.
Exclusion criteria
1. Have an uncontrolled medical condition, serious intercurrent illness, clinically significant general health condition, or extenuating circumstance that may significantly decrease study compliance or otherwise preclude their participation in the study. 2. Have a clinically significant abnormal electrocardiogram (ECG) at screening 3. Have had any type of gastric bypass surgery or have a gastric band. 4. Have previous abdominal surgery within the past year or history of abdominal adhesions, known or suspected paralytic ileus. 5. Have a history of any medical condition that would alter the absorption, distribution, metabolism or excretion of COV795 6. Have a history of severe bronchial asthma, hypercarbia, or hypoxia 7. Have a clinically significant abnormality on their clinical laboratory values 8. Have Addison's disease, benign prostatic hyperplasia, or kidney disease 9. Have donated blood or blood components within 3 months prior to the screening visit. 10. Have a known allergy or hypersensitivity to any opioid analgesics, anesthetics, acetaminophen, Non-steroid anti-inflammatory drugs (NSAIDs). 11. Have a history of intolerance to short term opioid use. 12. Unwilling to discontinue certain prohibited medications within the allotted time before surgery and throughout the duration of the study. Have taken certain drugs within the indicated times before surgery. 13. Have a history of substance or alcohol abuse and/or a positive result on drug screening. 14. Have a positive test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) at the screening visit. 15. Have dysphagia and/or cannot swallow study medication whole. 16. Have a history of migraine or frequent headaches, seizures, or are currently taking anticonvulsants. 17. Have previously participated in a clinical trial using COV795 or had a bunionectomy in the last 3 months. 18. Received any investigational drugs or devices within 4 weeks prior to the screening visit. 19. Other criteria as specified in the trial protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SPID48 (Summed Pain Intensity Difference) | 48 hours | Pain intensity (PI) is measured using the 11-point (0-10) Numeric Pain Rating Scale (NPRS) score. PID is the arithmetic difference in NPRS score at the time point of interest from the baseline score. SPID48 is the sum of time-weighted PID scores measured 22 times over the 48 hour assessment period, with a total score ranging from -480 (worst) to 480 (best). A higher SPID value indicates greater pain relief. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| COV795 2 tablets taken every 12 hours | 166 |
| Placebo 2 tablets taken every 12 hours | 163 |
| Total | 329 |
Baseline characteristics
| Characteristic | COV795 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 42.3 years STANDARD_DEVIATION 13.17 | 44.6 years STANDARD_DEVIATION 14.14 | 43.4 years STANDARD_DEVIATION 13.69 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 38 Participants | 44 Participants | 82 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 128 Participants | 119 Participants | 247 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 11 Participants | 24 Participants |
| Race (NIH/OMB) Black or African American | 51 Participants | 47 Participants | 98 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 98 Participants | 103 Participants | 201 Participants |
| Sex: Female, Male Female | 145 Participants | 135 Participants | 280 Participants |
| Sex: Female, Male Male | 21 Participants | 28 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 89 / 166 | 35 / 163 |
| serious Total, serious adverse events | 3 / 235 | 1 / 94 |
Outcome results
Primary
SPID48 (Summed Pain Intensity Difference)
Pain intensity (PI) is measured using the 11-point (0-10) Numeric Pain Rating Scale (NPRS) score. PID is the arithmetic difference in NPRS score at the time point of interest from the baseline score. SPID48 is the sum of time-weighted PID scores measured 22 times over the 48 hour assessment period, with a total score ranging from -480 (worst) to 480 (best). A higher SPID value indicates greater pain relief.
Time frame: 48 hours
Population: The analysis population for the primary outcome measure was the modified intent-to-treat population (mITT). The mITT analysis population includes 303 subjects from Cohort 2. Missing pain intensity difference scores were imputed using a multiple imputation method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| COV795 | SPID48 (Summed Pain Intensity Difference) | 114.9 scores on a scale | Standard Error 7.64 |
| Placebo | SPID48 (Summed Pain Intensity Difference) | 66.9 scores on a scale | Standard Error 7.6 |