Pain, Post-operative
Conditions
Keywords
Pain, Analgesia, N1539, Phase 3
Brief summary
The primary objective of this study is to evaluate the safety and tolerability of N1539 in a variety of post-surgical conditions.
Interventions
DRUGN1539
DRUGIntravenous Placebo
Sponsors
Baudax Bio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Voluntarily provide written informed consent. * Male or female between 18 and 80 years of age, inclusive. * Be planning to undergo major elective surgery, and be expected to require intravenous analgesia and remain in an inpatient setting for at least 24-48 hours and are expected to receive at least two study doses. * Female subjects are eligible only if all the following apply: * Not pregnant; * Not breastfeeding; * Not able to become pregnant; * Not planning to become pregnant during the study or 28 day follow up; * Commit to the use of an acceptable form of birth control for the duration of the study. * Have a body mass index ≤40 kg/m2 * Be able to understand the study procedures, comply with all study procedures, and agree to participate in the study program. * For oncology cases, have a histologically confirmed diagnosis of a primary solid tumor, affecting any one of the following organs: breast, skin, colon, prostate, uterus, ovaries, urethra, penis, or vulva; AND based on clinical, laboratory, radiologic, pathologic, and surgical findings, the tumor is confined to the primary organ, without evidence of local, regional or distal spread; AND have a performance status such that they are able to carry on normal activities of daily life without limitations.
Exclusion criteria
* Have a known allergy to meloxicam or any excipient of N1539, aspirin, other non-steroidal anti-inflammatory drugs (NSAIDs). * Be scheduled to undergo cranial surgery, open heart procedure, any type of coronary artery bypass graft, organ transplant, or any other surgical procedure in which NSAIDs are contraindicated. * Planned or actual admission to the intensive care unit at any time during study participation. * Have clinically significant laboratory abnormalities. * Have a history of myocardial infarction within the preceding 12 months. * Have history of HIV, or hepatitis B or C. * Have a history or clinical manifestations of significant renal, hepatic, cardiovascular, metabolic, neurologic, psychiatric, respiratory, or other condition that would preclude participation in the study. * Have active or recent (within 6 months) gastrointestinal ulceration or bleeding * Have a known bleeding disorder which may be worsened with the administration of a NSAID. * Have evidence of a clinically significant 12 lead ECG abnormality. * Have a history of alcohol abuse (regularly drinks \> 4 units of alcohol per day; 8 oz. beer, 3 oz. wine, 1 oz. spirits) or a history of prescription/illicit drug abuse within the past 5 years. * Have positive results on the urine drug screen for cocaine or PCP or alcohol breath test indicative of illicit drug or alcohol abuse. * Unable to discontinue medications, that have not been at a stable dose for at least 14 days prior to the scheduled surgical procedure, within 5 half-lives of the specific prior medication (or, if half-life is not known, within 48 hours) before dosing with study medication. * Be unable to discontinue herbal medications at least 7 days prior to surgery through last dose of study medication. * Be receiving lithium, or a combination of furosemide with either an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker * Be currently receiving treatment with oral meloxicam (Mobic®) or other NSAID within 7 days prior to surgery. * Have received any investigational product within 30 days before dosing with study medication. * Have previously received N1539 in clinical trials, or had major surgery in the last 3 months that would interfere with study assessments. * Have undergone or be expected to undergo radiation therapy, chemotherapy, or other biological therapy for cancer treatment, within 60 days prior to screening, through the last study visit, approximately 30 days after dosing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Adverse Events | 28 Days | Number of subjects reporting 1 or more treatment-emergent adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Investigator Satisfaction With Surgical Wound Healing | Up to 7 days after last study dose | Investigators assessed their satisfaction with the healing of the surgical wound according to an 11-point numeric rating scale (0-10) where a score of 0 was completely unsatisfied (worse outcome), and a score of 10 was completely satisfied (better outcome). |
| Postoperative Opioid Use | Up to 7 days | Postoperative opioid use was measured throughout the inpatient phase and converted to the total IV morphine equivalent dose |
Countries
Australia, Canada, New Zealand, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| N1539 30 mg N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 7 doses.
N1539 | 538 |
| IV Placebo IV Placebo every 24 hours for up to 7 doses.
Intravenous Placebo | 183 |
| Total | 721 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 8 | 3 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Subject unable to return for visit | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | N1539 30 mg | IV Placebo | Total |
|---|---|---|---|
| Advanced Age (>65) with Impaired Renal Function (GFR<90) | 88 Participants | 31 Participants | 119 Participants |
| Age, Categorical <=18 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical >=65 years | 120 Participants | 43 Participants | 163 Participants |
| Age, Categorical Between 18 and 65 years | 416 Participants | 140 Participants | 556 Participants |
| Age, Continuous | 52.9 years STANDARD_DEVIATION 13.56 | 53.0 years STANDARD_DEVIATION 13.77 | 53.0 years STANDARD_DEVIATION 13.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 76 Participants | 29 Participants | 105 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 462 Participants | 154 Participants | 616 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 4 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 68 Participants | 21 Participants | 89 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 459 Participants | 155 Participants | 614 Participants |
| Region of Enrollment Australia | 23 participants | 10 participants | 33 participants |
| Region of Enrollment Canada | 5 participants | 3 participants | 8 participants |
| Region of Enrollment New Zealand | 8 participants | 2 participants | 10 participants |
| Region of Enrollment United States | 502 participants | 168 participants | 670 participants |
| Sex: Female, Male Female | 315 Participants | 113 Participants | 428 Participants |
| Sex: Female, Male Male | 223 Participants | 70 Participants | 293 Participants |
| Surgery Site/Type Abdominal/Pelvic | 254 Participants | 87 Participants | 341 Participants |
| Surgery Site/Type Orthopedic | 273 Participants | 93 Participants | 366 Participants |
| Surgery Site/Type Other | 1 Participants | 0 Participants | 1 Participants |
| Surgery Site/Type Spinal | 10 Participants | 3 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 538 | 0 / 183 |
| other Total, other adverse events | 227 / 538 | 85 / 183 |
| serious Total, serious adverse events | 14 / 538 | 10 / 183 |
Outcome results
Primary
Number of Subjects With Adverse Events
Number of subjects reporting 1 or more treatment-emergent adverse events
Time frame: 28 Days
Population: All Treated Subjects (Safety Analysis Set)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| N1539 30 mg | Number of Subjects With Adverse Events | 339 Participants |
| IV Placebo | Number of Subjects With Adverse Events | 119 Participants |
Secondary
Investigator Satisfaction With Surgical Wound Healing
Investigators assessed their satisfaction with the healing of the surgical wound according to an 11-point numeric rating scale (0-10) where a score of 0 was completely unsatisfied (worse outcome), and a score of 10 was completely satisfied (better outcome).
Time frame: Up to 7 days after last study dose
Population: All Treated Subjects (Safety Analysis Set)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N1539 30 mg | Investigator Satisfaction With Surgical Wound Healing | One day after last study dose/Discharge | 9.5 score on a scale | Standard Deviation 0.88 |
| N1539 30 mg | Investigator Satisfaction With Surgical Wound Healing | 7 Days after last study dose | 9.3 score on a scale | Standard Deviation 1.18 |
| IV Placebo | Investigator Satisfaction With Surgical Wound Healing | One day after last study dose/Discharge | 9.4 score on a scale | Standard Deviation 0.97 |
| IV Placebo | Investigator Satisfaction With Surgical Wound Healing | 7 Days after last study dose | 9.4 score on a scale | Standard Deviation 0.86 |
Secondary
Postoperative Opioid Use
Postoperative opioid use was measured throughout the inpatient phase and converted to the total IV morphine equivalent dose
Time frame: Up to 7 days
Population: All Treated Subjects (Safety Analysis Set)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N1539 30 mg | Postoperative Opioid Use | Day 1 (Hour 0-24) | 17.0 mg (IV Morphine Equivalent Dose) | Standard Deviation 22.1 |
| N1539 30 mg | Postoperative Opioid Use | Day 2 (Hour 24-48) | 8.6 mg (IV Morphine Equivalent Dose) | Standard Deviation 19.15 |
| N1539 30 mg | Postoperative Opioid Use | Day 3 (Hour 48-72) | 4.1 mg (IV Morphine Equivalent Dose) | Standard Deviation 16.6 |
| N1539 30 mg | Postoperative Opioid Use | Day 1-2 (Hour 0-48) | 25.3 mg (IV Morphine Equivalent Dose) | Standard Deviation 36.96 |
| N1539 30 mg | Postoperative Opioid Use | Day 1-3 (Hour 0-72) | 27.4 mg (IV Morphine Equivalent Dose) | Standard Deviation 44.67 |
| N1539 30 mg | Postoperative Opioid Use | During Treatment | 28.8 mg (IV Morphine Equivalent Dose) | Standard Deviation 57.39 |
| IV Placebo | Postoperative Opioid Use | Day 1-3 (Hour 0-72) | 35.9 mg (IV Morphine Equivalent Dose) | Standard Deviation 52.77 |
| IV Placebo | Postoperative Opioid Use | Day 1 (Hour 0-24) | 21.8 mg (IV Morphine Equivalent Dose) | Standard Deviation 24.7 |
| IV Placebo | Postoperative Opioid Use | Day 1-2 (Hour 0-48) | 32.7 mg (IV Morphine Equivalent Dose) | Standard Deviation 41.44 |
| IV Placebo | Postoperative Opioid Use | Day 2 (Hour 24-48) | 11.3 mg (IV Morphine Equivalent Dose) | Standard Deviation 21.82 |
| IV Placebo | Postoperative Opioid Use | During Treatment | 37.5 mg (IV Morphine Equivalent Dose) | Standard Deviation 66.06 |
| IV Placebo | Postoperative Opioid Use | Day 3 (Hour 48-72) | 6.2 mg (IV Morphine Equivalent Dose) | Standard Deviation 21.83 |
p-value: <0.05ANCOVA