Pain, Post-operative
Conditions
Keywords
Bunion, Bunionectomy, Pain, Analgesia, N1539
Brief summary
The primary objective of this study is to evaluate the safety of N1539 in subjects with acute moderate to severe pain following unilateral bunionectomy.
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Voluntarily provide written informed consent. * Male or female between 18 and 75 years of age, inclusive. * Be scheduled to undergo a primary unilateral first metatarsal bunionectomy repair * Be American Society of Anesthesiology (ASA) physical class 1 or 2. * Female subject are eligible only if all the following apply: * Not pregnant; * Not lactating; * Not planning to become pregnant during the study; * Commit to the use of an acceptable form of birth control for the duration of the study through Day 30. * Have a body mass index ≤35 kg/m2 * Be able to understand the study procedures, comply with all study procedures, and agree to participate in the study program.
Exclusion criteria
* Have a known allergy to meloxicam or any excipient of N1539, D5W, aspirin, other non-steroidal anti-inflammatory drugs (NSAIDs) or to any peri- or postoperative medications used in this study. * Have a clinically significant abnormal clinical laboratory test value. * Have history of or positive test results for HIV, or hepatitis B or C. * Have a history or clinical manifestations of significant renal, hepatic, cardiovascular, metabolic, neurologic, psychiatric, or other condition that would preclude participation in the study. * Have a history of migraine or frequent headaches, seizures, or are currently taking anticonvulsants. * Have another painful physical condition that may confound the assessments of post operative pain. * Have a history of syncope or other syncopal attacks. * 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 prescription/illicit drug abuse.. * Have positive results on the urine drug screen or alcohol breath test indicative of illicit drug or alcohol abuse. * Have been receiving or have received chronic opioid therapy defined as greater than 15 morphine equivalents units per day for greater than 3 out of 7 days per week over a one-month period within 12 months. * Use concurrent therapy that could interfere with the evaluation of efficacy or safety, such as any drugs which in the investigator's opinion may exert significant analgesic properties or act synergistically with N1539. * Unable to discontinue medications, that have not been at a stable dose for at least 14 days prior to the scheduled bunionectomy procedure, within 5 half lives of the specific prior medication (or, if half life is not known, within 48 hours) before dosing. * Have utilized corticosteroids, either systemically, inhalational either intranasally or oral, or by intra-articular injection, within 14 days prior to the study. * Have received any investigational product within 30 days before dosing with study medication. * Be receiving warfarin, 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®) * Have previously received N1539 in clinical trials, or had bunionectomy in the last 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Adverse Events | Through Day 30 Follow-up | Number of subjects reporting treatment emergent adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect Size of N1539 Doses Using the Summed Pain Intensity Difference Over the First 48 Hours (SPID48) | 48 Hours | Effect size was estimated based on SPID48 derived using 2-hour windowed last observation carried forward (W2LOCF) method and an analysis of covariance (ANCOVA) model that included treatment and baseline PI score. |
| Summed Pain Intensity Difference Over the First 48 Hours (SPID48) | 48 Hours | Pain intensity was recorded using a Numeric Pain Rating Scale (Range 0-10) where 0 equates to no pain (better), and 10 equates to the worst pain imaginable (worse). Pain intensity scores were to be recorded at the following time points: 0.25, 0.5, 0.75, 1, 2, 4, and 6 hours post Dose 1. Thereafter pain assessments were to be recorded every 2 hours until 48 hours post Dose 1. Pain intensity differences from baseline at each time point were calculated and a time weighted summed pain intensity difference (SPID) was then calculated. Time weighted SPID calculations were computed by multiplying a weight factor to each score prior to summation. The weight factor at each time point was the time elapsed since the previous observation. A smaller SPID was better. |
| Summed Pain Intensity Difference (SPID) at Other Intervals | 48 Hours | Pain intensity was recorded using a Numeric Pain Rating Scale (Range 0-10) where 0 equates to no pain (better), and 10 equates to the worst pain imaginable (worse). Pain intensity scores were to be recorded at the following time points: 0.25, 0.5, 0.75, 1, 2, 4, and 6 hours post Dose 1. Thereafter pain assessments were to be recorded every 2 hours until 48 hours post Dose 1. Pain intensity differences from baseline at each time point were calculated and a time weighted summed pain intensity difference (SPID) was then calculated. Time weighted SPID calculations were computed by multiplying a weight factor to each score prior to summation. The weight factor at each time point was the time elapsed since the previous observation. A smaller SPID was better. |
| Number of Subjects With Use of Rescue Medication (Oral Opioids) | 48 hours | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| N1539 30mg N1539 (Intravenous meloxicam) 30mg every 24 hours for up to 3 doses.
N1539 | 20 |
| N1539 60mg N1539 (Intravenous meloxicam) 60mg every 24 hours for up to 3 doses.
N1539 | 20 |
| IV Placebo IV Placebo every 24 hours for up to 3 doses.
Intravenous Placebo | 19 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | N1539 30mg | N1539 60mg | IV Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical >=65 years | 1 Participants | 3 Participants | 2 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 16 Participants | 16 Participants | 51 Participants |
| Age, Continuous | 47.6 years STANDARD_DEVIATION 12.66 | 44.9 years STANDARD_DEVIATION 16.67 | 49.2 years STANDARD_DEVIATION 12.81 | 47.2 years STANDARD_DEVIATION 14.06 |
| Baseline Pain Intensity (0-10 NPRS) | 7.7 units on a scale STANDARD_DEVIATION 2 | 7.4 units on a scale STANDARD_DEVIATION 1.9 | 7.7 units on a scale STANDARD_DEVIATION 2.24 | 7.6 units on a scale STANDARD_DEVIATION 2.02 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 20 Participants | 19 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 9 Participants | 11 Participants | 30 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 10 Participants | 8 Participants | 28 Participants |
| Region of Enrollment United States | 20 participants | 20 participants | 19 participants | 59 participants |
| Sex: Female, Male Female | 16 Participants | 18 Participants | 14 Participants | 48 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 20 | 10 / 20 | 10 / 19 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 19 |
Outcome results
Primary
Number of Subjects With Adverse Events
Number of subjects reporting treatment emergent adverse events
Time frame: Through Day 30 Follow-up
Population: All subjects treated with ≥1 dose of study medication (Safety analysis set)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| N1539 30mg | Number of Subjects With Adverse Events | 12 Participants |
| N1539 60mg | Number of Subjects With Adverse Events | 10 Participants |
| IV Placebo | Number of Subjects With Adverse Events | 10 Participants |
Secondary
Effect Size of N1539 Doses Using the Summed Pain Intensity Difference Over the First 48 Hours (SPID48)
Effect size was estimated based on SPID48 derived using 2-hour windowed last observation carried forward (W2LOCF) method and an analysis of covariance (ANCOVA) model that included treatment and baseline PI score.
Time frame: 48 Hours
Population: All subjects treated with ≥1 dose of study medication and who had baseline PI and at least one post baseline PI (mITT analysis set; efficacy analysis set)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| N1539 30mg | Effect Size of N1539 Doses Using the Summed Pain Intensity Difference Over the First 48 Hours (SPID48) | -9241.9 units on a scale | Standard Error 1411.74 |
| N1539 60mg | Effect Size of N1539 Doses Using the Summed Pain Intensity Difference Over the First 48 Hours (SPID48) | -8350.6 units on a scale | Standard Error 1413.3 |
| IV Placebo | Effect Size of N1539 Doses Using the Summed Pain Intensity Difference Over the First 48 Hours (SPID48) | -1991.3 units on a scale | Standard Error 1448.2 |
Secondary
Number of Subjects With Use of Rescue Medication (Oral Opioids)
Time frame: 48 hours
Population: mITT analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| N1539 30mg | Number of Subjects With Use of Rescue Medication (Oral Opioids) | Hour 24-48 | 11 Participants |
| N1539 30mg | Number of Subjects With Use of Rescue Medication (Oral Opioids) | Hour 0-24 | 20 Participants |
| N1539 30mg | Number of Subjects With Use of Rescue Medication (Oral Opioids) | Hour 0-48 | 20 Participants |
| N1539 60mg | Number of Subjects With Use of Rescue Medication (Oral Opioids) | Hour 24-48 | 10 Participants |
| N1539 60mg | Number of Subjects With Use of Rescue Medication (Oral Opioids) | Hour 0-24 | 18 Participants |
| N1539 60mg | Number of Subjects With Use of Rescue Medication (Oral Opioids) | Hour 0-48 | 18 Participants |
| IV Placebo | Number of Subjects With Use of Rescue Medication (Oral Opioids) | Hour 0-24 | 19 Participants |
| IV Placebo | Number of Subjects With Use of Rescue Medication (Oral Opioids) | Hour 0-48 | 19 Participants |
| IV Placebo | Number of Subjects With Use of Rescue Medication (Oral Opioids) | Hour 24-48 | 14 Participants |
Secondary
Summed Pain Intensity Difference Over the First 48 Hours (SPID48)
Pain intensity was recorded using a Numeric Pain Rating Scale (Range 0-10) where 0 equates to no pain (better), and 10 equates to the worst pain imaginable (worse). Pain intensity scores were to be recorded at the following time points: 0.25, 0.5, 0.75, 1, 2, 4, and 6 hours post Dose 1. Thereafter pain assessments were to be recorded every 2 hours until 48 hours post Dose 1. Pain intensity differences from baseline at each time point were calculated and a time weighted summed pain intensity difference (SPID) was then calculated. Time weighted SPID calculations were computed by multiplying a weight factor to each score prior to summation. The weight factor at each time point was the time elapsed since the previous observation. A smaller SPID was better.
Time frame: 48 Hours
Population: mITT analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| N1539 30mg | Summed Pain Intensity Difference Over the First 48 Hours (SPID48) | -9241.9 units on a scale | Standard Error 1411.74 |
| N1539 60mg | Summed Pain Intensity Difference Over the First 48 Hours (SPID48) | -8350.6 units on a scale | Standard Error 1413.3 |
| IV Placebo | Summed Pain Intensity Difference Over the First 48 Hours (SPID48) | -1991.3 units on a scale | Standard Error 1448.2 |
p-value: 0.0049t-test, 2 sided
p-value: 0.0076t-test, 2 sided
Secondary
Summed Pain Intensity Difference (SPID) at Other Intervals
Pain intensity was recorded using a Numeric Pain Rating Scale (Range 0-10) where 0 equates to no pain (better), and 10 equates to the worst pain imaginable (worse). Pain intensity scores were to be recorded at the following time points: 0.25, 0.5, 0.75, 1, 2, 4, and 6 hours post Dose 1. Thereafter pain assessments were to be recorded every 2 hours until 48 hours post Dose 1. Pain intensity differences from baseline at each time point were calculated and a time weighted summed pain intensity difference (SPID) was then calculated. Time weighted SPID calculations were computed by multiplying a weight factor to each score prior to summation. The weight factor at each time point was the time elapsed since the previous observation. A smaller SPID was better.
Time frame: 48 Hours
Population: mITT analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| N1539 30mg | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID6 (Hour 0-6) | -793.87 units on a scale | Standard Error 172.45 |
| N1539 30mg | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID12 (Hour 0-12) | -1655.1 units on a scale | Standard Error 338.78 |
| N1539 30mg | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID24 (Hour 0-24) | -3024.0 units on a scale | Standard Error 644.63 |
| N1539 30mg | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID12-24 (Hour 12-24) | -1368.9 units on a scale | Standard Error 343.34 |
| N1539 30mg | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID12-48 (Hour 12-48) | -7586.8 units on a scale | Standard Error 1121.12 |
| N1539 30mg | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID24-48 (Hour 24-48) | -6217.9 units on a scale | Standard Error 817.22 |
| N1539 60mg | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID24-48 (Hour 24-48) | -5557.3 units on a scale | Standard Error 818.12 |
| N1539 60mg | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID6 (Hour 0-6) | -663.17 units on a scale | Standard Error 172.64 |
| N1539 60mg | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID12-24 (Hour 12-24) | -1458.4 units on a scale | Standard Error 343.72 |
| N1539 60mg | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID12-48 (Hour 12-48) | -7015.7 units on a scale | Standard Error 1122.35 |
| N1539 60mg | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID12 (Hour 0-12) | -1334.9 units on a scale | Standard Error 339.15 |
| N1539 60mg | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID24 (Hour 0-24) | -2793.3 units on a scale | Standard Error 645.34 |
| IV Placebo | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID12 (Hour 0-12) | 319.67 units on a scale | Standard Error 347.53 |
| IV Placebo | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID24 (Hour 0-24) | 276.46 units on a scale | Standard Error 661.28 |
| IV Placebo | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID24-48 (Hour 24-48) | -2267.8 units on a scale | Standard Error 838.33 |
| IV Placebo | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID12-24 (Hour 12-24) | -43.21 units on a scale | Standard Error 352.21 |
| IV Placebo | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID6 (Hour 0-6) | 146.22 units on a scale | Standard Error 176.91 |
| IV Placebo | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID12-48 (Hour 12-48) | -2311.0 units on a scale | Standard Error 1150.07 |
p-value: <0.05t-test, 2 sided
p-value: <0.05t-test, 2 sided