Pain, Post-operative
Conditions
Keywords
Bunion, Bunionectomy, Pain, Analgesia, N1539, Phase 3
Brief summary
The primary objective of this study is to evaluate the analgesic efficacy 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. * 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 myocardial infarction or coronary artery bypass graft surgery within the preceding 12 months * Have a history of migraine or frequent headaches, seizures, or are currently taking anticonvulsants. * Have active or recent (within 6 months) gastrointestinal ulceration or bleeding. * Have a known bleeding disorder or be taking agents affecting coagulation * Have another painful physical condition that may confound the assessments of post operative pain. * 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) within the past 5 years or a history of 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 of surgery. * 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 with study medication. * Have utilized corticosteroids, either systemically or by intra-articular injection, within 6 weeks prior to the surgical procedure. * 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®) within 7 days prior to surgery * Have previously received N1539 in clinical trials, or had major surgery in the last 3 months that would interfere with study outcomes or increase the risk of study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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, and 2 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 value (i.e. more negative) was better. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Dose of Rescue Analgesia | 48 Hours | Rescue analgesia (oral oxycodone 5 mg) was available to subjects with inadequately controlled pain upon request. Time to first rescue was calculated as the elapsed time from administration of Dose 1 to the administration of the first dose of rescue analgesia. |
| Number of Subjects Utilizing Rescue Analgesia | 48 Hours | Rescue analgesia (oral oxycodone 5 mg) was available to subjects with inadequately controlled pain upon request. |
| Number of Doses of Rescue Analgesia Utilized Per Subject | 48 Hours | Rescue analgesia (oral oxycodone 5 mg) was available to subjects with inadequately controlled pain upon request. |
| Time to Perceptible Pain Relief (TTPPR) | 12 Hours | Time to perceptible and meaningful pain relief was measured using the double stopwatch method. For each randomized subject, two stopwatches were started immediately after administration of the first study dose (Hour 0). The subject was to stop the first watch when they first perceived pain relief to occur (time to perceptible relief). Once the first watch was stopped, the second stopwatch was given to the subject with the instructions to stop the watch when they first experienced meaningful pain relief (time to meaningful relief). |
| Time to Meaningful Pain Relief (TTMPR) | 12 Hours | Time to perceptible and meaningful pain relief was measured using the double stopwatch method. For each randomized subject, two stopwatches were started immediately after administration of the first study dose (Hour 0). The subject was to stop the first watch when they first perceived pain relief to occur (time to perceptible relief). Once the first watch was stopped, the second stopwatch was given to the subject with the instructions to stop the watch when they first experienced meaningful pain relief (time to meaningful relief). |
| 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, and 2 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 value (i.e. more negative) was better. |
| Subjects With ≥ 30% Improvement in Pain From Baseline to Hour 24 | 24 Hours | Percent improvement in pain is the cumulative pain intensity percent reduction from baseline over the defined interval (6 or 24 hours), calculated as SPID for the defined interval (SPID6 or SPID24) divided by the baseline pain intensity (BaselinePI) extrapolated across that interval. Example: % Improvement through Hour 24 = 100 \* SPID24 / (BaselinePI \* 24 \* 60), and SPID24 \< 0 as an indication for improvement. |
| Subjects With ≥ 50% Improvement in Pain From Baseline to Hour 6 | 6 Hours | Percent improvement in pain is the cumulative pain intensity percent reduction from baseline over the defined interval (6 or 24 hours), calculated as SPID for the defined interval (SPID6 or SPID24) divided by the baseline pain intensity (BaselinePI) extrapolated across that interval. Example: % Improvement through Hour 6 = 100 \* SPID6 / (BaselinePI \* 6 \* 60), and SPID6 \< 0 as an indication for improvement. |
| Subjects With ≥ 50% Improvement in Pain From Baseline to Hour 24 | 24 Hours | Percent improvement in pain is the cumulative pain intensity percent reduction from baseline over the defined interval (6 or 24 hours), calculated as SPID for the defined interval (SPID6 or SPID24) divided by the baseline pain intensity (BaselinePI) extrapolated across that interval. Example: % Improvement through Hour 24 = 100 \* SPID24 / (BaselinePI \* 24 \* 60), and SPID24 \< 0 as an indication for improvement. |
| Patient Global Assessment (PGA) of Pain Control at Hour 24 | 24 Hours | PGA of pain control was evaluated at Hour 24 and Hour 48 with subject reported degree of pain control over the preceding interval according to a 5 point scale (0-4) with categories of 0-poor, 1-fair, 2-good, 3-very good, or 4-excellent. |
| Patient Global Assessment (PGA) of Pain Control at Hour 48 | 48 Hours | PGA of pain control was evaluated at Hour 24 and Hour 48 with subject reported degree of pain control over the preceding interval according to a 5 point scale (0-4) with categories of 0-poor, 1-fair, 2-good, 3-very good, or 4-excellent. |
| Subjects With ≥ 30% Improvement in Pain From Baseline to Hour 6 | 6 Hours | Percent improvement in pain is the cumulative pain intensity percent reduction from baseline over the defined interval (6 or 24 hours), calculated as SPID for the defined interval (SPID6 or SPID24) divided by the baseline pain intensity (BaselinePI) extrapolated across that interval. Example: % Improvement through Hour 6 = 100 \* SPID6 / (BaselinePI \* 6 \* 60), and SPID6 \< 0 as an indication for improvement. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| N1539 30 mg N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses.
N1539 | 100 |
| IV Placebo IV Placebo every 24 hours for up to 3 doses.
Intravenous Placebo | 101 |
| Total | 201 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Study Overall | Lack of Efficacy | 1 | 0 |
| Study Overall | Lost to Follow-up | 0 | 2 |
| Study Overall | Withdrawal by Subject | 2 | 2 |
| Treatment Phase (48 Hours Post-Dose 1) | Lack of Efficacy | 4 | 4 |
| Treatment Phase (48 Hours Post-Dose 1) | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | IV Placebo | N1539 30 mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 8 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 92 Participants | 92 Participants | 184 Participants |
| Age, Continuous | 48.4 years STANDARD_DEVIATION 12.17 | 46.7 years STANDARD_DEVIATION 12.79 | 47.6 years STANDARD_DEVIATION 12.48 |
| Baseline Pain Intensity | 7.0 units on a scale STANDARD_DEVIATION 1.82 | 6.7 units on a scale STANDARD_DEVIATION 1.9 | 6.8 units on a scale STANDARD_DEVIATION 1.86 |
| Body Mass Index (BMI) | 28.3 kg/m^2 STANDARD_DEVIATION 4.02 | 26.9 kg/m^2 STANDARD_DEVIATION 4.8 | 27.6 kg/m^2 STANDARD_DEVIATION 4.46 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 36 Participants | 28 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 65 Participants | 72 Participants | 137 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 26 Participants | 32 Participants | 58 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 68 Participants | 61 Participants | 129 Participants |
| Region of Enrollment United States | 101 Participants | 100 Participants | 201 Participants |
| Sex: Female, Male Female | 87 Participants | 84 Participants | 171 Participants |
| Sex: Female, Male Male | 14 Participants | 16 Participants | 30 Participants |
| Time from End of Surgery to First Dose | 0.485 hours STANDARD_DEVIATION 0.2001 | 0.514 hours STANDARD_DEVIATION 0.2397 | 0.500 hours STANDARD_DEVIATION 0.2206 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 100 | 1 / 101 |
| other Total, other adverse events | 44 / 100 | 54 / 101 |
| serious Total, serious adverse events | 0 / 100 | 2 / 101 |
Outcome results
Primary
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, and 2 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 value (i.e. more negative) was better.
Time frame: 48 Hours
Population: Intent-to-Treat (ITT) population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| N1539 30 mg | Summed Pain Intensity Difference Over the First 48 Hours (SPID48) | -6956.0 units on a scale | Standard Error 521.69 |
| IV Placebo | Summed Pain Intensity Difference Over the First 48 Hours (SPID48) | -4829.3 units on a scale | Standard Error 519.56 |
p-value: 0.0034t-test, 2 sided
Secondary
Number of Doses of Rescue Analgesia Utilized Per Subject
Rescue analgesia (oral oxycodone 5 mg) was available to subjects with inadequately controlled pain upon request.
Time frame: 48 Hours
Population: ITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| N1539 30 mg | Number of Doses of Rescue Analgesia Utilized Per Subject | Hour 0-24 | 3.97 doses of rescue analgesia | Standard Error 0.26 |
| N1539 30 mg | Number of Doses of Rescue Analgesia Utilized Per Subject | Hour 24-48 | 1.63 doses of rescue analgesia | Standard Error 0.25 |
| N1539 30 mg | Number of Doses of Rescue Analgesia Utilized Per Subject | Hour 0-48 | 5.45 doses of rescue analgesia | Standard Error 0.46 |
| IV Placebo | Number of Doses of Rescue Analgesia Utilized Per Subject | Hour 0-24 | 5.06 doses of rescue analgesia | Standard Error 0.26 |
| IV Placebo | Number of Doses of Rescue Analgesia Utilized Per Subject | Hour 24-48 | 2.51 doses of rescue analgesia | Standard Error 0.25 |
| IV Placebo | Number of Doses of Rescue Analgesia Utilized Per Subject | Hour 0-48 | 7.49 doses of rescue analgesia | Standard Error 0.46 |
p-value: <0.05ANCOVA
p-value: <0.05ANCOVA
p-value: <0.05ANCOVA
Secondary
Number of Subjects Utilizing Rescue Analgesia
Rescue analgesia (oral oxycodone 5 mg) was available to subjects with inadequately controlled pain upon request.
Time frame: 48 Hours
Population: ITT Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| N1539 30 mg | Number of Subjects Utilizing Rescue Analgesia | Hour 0-24 | 83 Participants |
| N1539 30 mg | Number of Subjects Utilizing Rescue Analgesia | Hour 24-48 | 48 Participants |
| N1539 30 mg | Number of Subjects Utilizing Rescue Analgesia | Hour 0-48 | 83 Participants |
| IV Placebo | Number of Subjects Utilizing Rescue Analgesia | Hour 0-24 | 99 Participants |
| IV Placebo | Number of Subjects Utilizing Rescue Analgesia | Hour 24-48 | 71 Participants |
| IV Placebo | Number of Subjects Utilizing Rescue Analgesia | Hour 0-48 | 99 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.01Cochran-Mantel-Haenszel
p-value: <0.01Cochran-Mantel-Haenszel
Secondary
Patient Global Assessment (PGA) of Pain Control at Hour 24
PGA of pain control was evaluated at Hour 24 and Hour 48 with subject reported degree of pain control over the preceding interval according to a 5 point scale (0-4) with categories of 0-poor, 1-fair, 2-good, 3-very good, or 4-excellent.
Time frame: 24 Hours
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| N1539 30 mg | Patient Global Assessment (PGA) of Pain Control at Hour 24 | 0 - Poor | 17 Participants |
| N1539 30 mg | Patient Global Assessment (PGA) of Pain Control at Hour 24 | 3 - Very Good | 17 Participants |
| N1539 30 mg | Patient Global Assessment (PGA) of Pain Control at Hour 24 | 2 - Good | 28 Participants |
| N1539 30 mg | Patient Global Assessment (PGA) of Pain Control at Hour 24 | 4 - Excellent | 10 Participants |
| N1539 30 mg | Patient Global Assessment (PGA) of Pain Control at Hour 24 | 1 - Fair | 23 Participants |
| IV Placebo | Patient Global Assessment (PGA) of Pain Control at Hour 24 | 4 - Excellent | 3 Participants |
| IV Placebo | Patient Global Assessment (PGA) of Pain Control at Hour 24 | 0 - Poor | 29 Participants |
| IV Placebo | Patient Global Assessment (PGA) of Pain Control at Hour 24 | 2 - Good | 26 Participants |
| IV Placebo | Patient Global Assessment (PGA) of Pain Control at Hour 24 | 3 - Very Good | 13 Participants |
| IV Placebo | Patient Global Assessment (PGA) of Pain Control at Hour 24 | 1 - Fair | 26 Participants |
p-value: 0.107Cochran-Mantel-Haenszel
Secondary
Patient Global Assessment (PGA) of Pain Control at Hour 48
PGA of pain control was evaluated at Hour 24 and Hour 48 with subject reported degree of pain control over the preceding interval according to a 5 point scale (0-4) with categories of 0-poor, 1-fair, 2-good, 3-very good, or 4-excellent.
Time frame: 48 Hours
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| N1539 30 mg | Patient Global Assessment (PGA) of Pain Control at Hour 48 | 1 - Fair | 8 Participants |
| N1539 30 mg | Patient Global Assessment (PGA) of Pain Control at Hour 48 | 2 - Good | 26 Participants |
| N1539 30 mg | Patient Global Assessment (PGA) of Pain Control at Hour 48 | 3 - Very Good | 30 Participants |
| N1539 30 mg | Patient Global Assessment (PGA) of Pain Control at Hour 48 | 4 - Excellent | 24 Participants |
| N1539 30 mg | Patient Global Assessment (PGA) of Pain Control at Hour 48 | 0 - Poor | 7 Participants |
| IV Placebo | Patient Global Assessment (PGA) of Pain Control at Hour 48 | 4 - Excellent | 8 Participants |
| IV Placebo | Patient Global Assessment (PGA) of Pain Control at Hour 48 | 0 - Poor | 15 Participants |
| IV Placebo | Patient Global Assessment (PGA) of Pain Control at Hour 48 | 1 - Fair | 18 Participants |
| IV Placebo | Patient Global Assessment (PGA) of Pain Control at Hour 48 | 3 - Very Good | 30 Participants |
| IV Placebo | Patient Global Assessment (PGA) of Pain Control at Hour 48 | 2 - Good | 25 Participants |
p-value: 0.0046Cochran-Mantel-Haenszel
Secondary
Subjects With ≥ 30% Improvement in Pain From Baseline to Hour 24
Percent improvement in pain is the cumulative pain intensity percent reduction from baseline over the defined interval (6 or 24 hours), calculated as SPID for the defined interval (SPID6 or SPID24) divided by the baseline pain intensity (BaselinePI) extrapolated across that interval. Example: % Improvement through Hour 24 = 100 \* SPID24 / (BaselinePI \* 24 \* 60), and SPID24 \< 0 as an indication for improvement.
Time frame: 24 Hours
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| N1539 30 mg | Subjects With ≥ 30% Improvement in Pain From Baseline to Hour 24 | 37 Participants |
| IV Placebo | Subjects With ≥ 30% Improvement in Pain From Baseline to Hour 24 | 21 Participants |
p-value: 0.0107Cochran-Mantel-Haenszel
Secondary
Subjects With ≥ 30% Improvement in Pain From Baseline to Hour 6
Percent improvement in pain is the cumulative pain intensity percent reduction from baseline over the defined interval (6 or 24 hours), calculated as SPID for the defined interval (SPID6 or SPID24) divided by the baseline pain intensity (BaselinePI) extrapolated across that interval. Example: % Improvement through Hour 6 = 100 \* SPID6 / (BaselinePI \* 6 \* 60), and SPID6 \< 0 as an indication for improvement.
Time frame: 6 Hours
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| N1539 30 mg | Subjects With ≥ 30% Improvement in Pain From Baseline to Hour 6 | 32 Participants |
| IV Placebo | Subjects With ≥ 30% Improvement in Pain From Baseline to Hour 6 | 20 Participants |
p-value: 0.0451Cochran-Mantel-Haenszel
Secondary
Subjects With ≥ 50% Improvement in Pain From Baseline to Hour 24
Percent improvement in pain is the cumulative pain intensity percent reduction from baseline over the defined interval (6 or 24 hours), calculated as SPID for the defined interval (SPID6 or SPID24) divided by the baseline pain intensity (BaselinePI) extrapolated across that interval. Example: % Improvement through Hour 24 = 100 \* SPID24 / (BaselinePI \* 24 \* 60), and SPID24 \< 0 as an indication for improvement.
Time frame: 24 Hours
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| N1539 30 mg | Subjects With ≥ 50% Improvement in Pain From Baseline to Hour 24 | 13 Participants |
| IV Placebo | Subjects With ≥ 50% Improvement in Pain From Baseline to Hour 24 | 5 Participants |
p-value: 0.043Cochran-Mantel-Haenszel
Secondary
Subjects With ≥ 50% Improvement in Pain From Baseline to Hour 6
Percent improvement in pain is the cumulative pain intensity percent reduction from baseline over the defined interval (6 or 24 hours), calculated as SPID for the defined interval (SPID6 or SPID24) divided by the baseline pain intensity (BaselinePI) extrapolated across that interval. Example: % Improvement through Hour 6 = 100 \* SPID6 / (BaselinePI \* 6 \* 60), and SPID6 \< 0 as an indication for improvement.
Time frame: 6 Hours
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| N1539 30 mg | Subjects With ≥ 50% Improvement in Pain From Baseline to Hour 6 | 16 Participants |
| IV Placebo | Subjects With ≥ 50% Improvement in Pain From Baseline to Hour 6 | 8 Participants |
p-value: 0.0781Cochran-Mantel-Haenszel
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, and 2 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 value (i.e. more negative) was better.
Time frame: 48 Hours
Population: ITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| N1539 30 mg | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID24 (Hour 0-24) | -2071.0 units on a scale | Standard Error 247.01 |
| N1539 30 mg | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID6 (Hour 0-6) | -510.78 units on a scale | Standard Error 66.22 |
| N1539 30 mg | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID12-48 (Hour 12-48) | -5998.2 units on a scale | Standard Error 439.21 |
| N1539 30 mg | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID24-48 (Hour 24-48) | -4885.1 units on a scale | Standard Error 313.6 |
| N1539 30 mg | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID12 (Hour 0-12) | -957.83 units on a scale | Standard Error 123.3 |
| IV Placebo | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID24-48 (Hour 24-48) | -3661.4 units on a scale | Standard Error 312.32 |
| IV Placebo | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID6 (Hour 0-6) | -288.33 units on a scale | Standard Error 65.95 |
| IV Placebo | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID24 (Hour 0-24) | -1167.9 units on a scale | Standard Error 246 |
| IV Placebo | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID12-48 (Hour 12-48) | -4349.1 units on a scale | Standard Error 437.42 |
| IV Placebo | Summed Pain Intensity Difference (SPID) at Other Intervals | SPID12 (Hour 0-12) | -480.15 units on a scale | Standard Error 122.8 |
p-value: <0.05t-test, 2 sided
p-value: <0.01t-test, 2 sided
p-value: <0.01t-test, 2 sided
p-value: <0.01t-test, 2 sided
p-value: <0.01t-test, 2 sided
Secondary
Time to First Dose of Rescue Analgesia
Rescue analgesia (oral oxycodone 5 mg) was available to subjects with inadequately controlled pain upon request. Time to first rescue was calculated as the elapsed time from administration of Dose 1 to the administration of the first dose of rescue analgesia.
Time frame: 48 Hours
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| N1539 30 mg | Time to First Dose of Rescue Analgesia | 1.99 hours |
| IV Placebo | Time to First Dose of Rescue Analgesia | 2.09 hours |
p-value: 0.0076Log Rank
Secondary
Time to Meaningful Pain Relief (TTMPR)
Time to perceptible and meaningful pain relief was measured using the double stopwatch method. For each randomized subject, two stopwatches were started immediately after administration of the first study dose (Hour 0). The subject was to stop the first watch when they first perceived pain relief to occur (time to perceptible relief). Once the first watch was stopped, the second stopwatch was given to the subject with the instructions to stop the watch when they first experienced meaningful pain relief (time to meaningful relief).
Time frame: 12 Hours
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| N1539 30 mg | Time to Meaningful Pain Relief (TTMPR) | 2.16 hours |
| IV Placebo | Time to Meaningful Pain Relief (TTMPR) | 3.19 hours |
p-value: 0.1048Log Rank
Secondary
Time to Perceptible Pain Relief (TTPPR)
Time to perceptible and meaningful pain relief was measured using the double stopwatch method. For each randomized subject, two stopwatches were started immediately after administration of the first study dose (Hour 0). The subject was to stop the first watch when they first perceived pain relief to occur (time to perceptible relief). Once the first watch was stopped, the second stopwatch was given to the subject with the instructions to stop the watch when they first experienced meaningful pain relief (time to meaningful relief).
Time frame: 12 Hours
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| N1539 30 mg | Time to Perceptible Pain Relief (TTPPR) | 0.52 hours |
| IV Placebo | Time to Perceptible Pain Relief (TTPPR) | 1.59 hours |
p-value: 0.1228Log Rank