Trial Outcomes & Findings for Evaluation of N1539 Following Bunionectomy Surgery (NCT NCT02675907)

Last Updated: 2017-11-17

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

201 participants

Primary outcome timeframe

48 Hours

Results posted on

2017-11-17

Participant Flow

Participant milestones

Participant milestones
Measure	N1539 30 mg N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Treatment Phase (48 Hours Post-Dose 1) STARTED	100	101
Treatment Phase (48 Hours Post-Dose 1) COMPLETED	95	96
Treatment Phase (48 Hours Post-Dose 1) NOT COMPLETED	5	5
Study Overall STARTED	100	101
Study Overall COMPLETED	97	97
Study Overall NOT COMPLETED	3	4

Reasons for withdrawal

Reasons for withdrawal
Measure	N1539 30 mg N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Treatment Phase (48 Hours Post-Dose 1) Lack of Efficacy	4	4
Treatment Phase (48 Hours Post-Dose 1) Withdrawal by Subject	1	1
Study Overall Lack of Efficacy	1	0
Study Overall Withdrawal by Subject	2	2
Study Overall Lost to Follow-up	0	2

Baseline Characteristics

Evaluation of N1539 Following Bunionectomy Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	N1539 30 mg n=100 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=101 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo	Total n=201 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	92 Participants n=5 Participants	92 Participants n=7 Participants	184 Participants n=5 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Age, Continuous	46.7 years STANDARD_DEVIATION 12.79 • n=5 Participants	48.4 years STANDARD_DEVIATION 12.17 • n=7 Participants	47.6 years STANDARD_DEVIATION 12.48 • n=5 Participants
Sex: Female, Male Female	84 Participants n=5 Participants	87 Participants n=7 Participants	171 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	28 Participants n=5 Participants	36 Participants n=7 Participants	64 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	72 Participants n=5 Participants	65 Participants n=7 Participants	137 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Black or African American	32 Participants n=5 Participants	26 Participants n=7 Participants	58 Participants n=5 Participants
Race (NIH/OMB) White	61 Participants n=5 Participants	68 Participants n=7 Participants	129 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	100 Participants n=5 Participants	101 Participants n=7 Participants	201 Participants n=5 Participants
Body Mass Index (BMI)	26.9 kg/m^2 STANDARD_DEVIATION 4.80 • n=5 Participants	28.3 kg/m^2 STANDARD_DEVIATION 4.02 • n=7 Participants	27.6 kg/m^2 STANDARD_DEVIATION 4.46 • n=5 Participants
Time from End of Surgery to First Dose	0.514 hours STANDARD_DEVIATION 0.2397 • n=5 Participants	0.485 hours STANDARD_DEVIATION 0.2001 • n=7 Participants	0.500 hours STANDARD_DEVIATION 0.2206 • n=5 Participants
Baseline Pain Intensity	6.7 units on a scale STANDARD_DEVIATION 1.90 • n=5 Participants	7.0 units on a scale STANDARD_DEVIATION 1.82 • n=7 Participants	6.8 units on a scale STANDARD_DEVIATION 1.86 • n=5 Participants

PRIMARY outcome

Timeframe: 48 Hours

Population: Intent-to-Treat (ITT) population

Outcome measures

Outcome measures
Measure	N1539 30 mg n=100 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=101 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Summed Pain Intensity Difference Over the First 48 Hours (SPID48)	-6956.0 units on a scale Standard Error 521.69	-4829.3 units on a scale Standard Error 519.56

SECONDARY outcome

Timeframe: 48 Hours

Population: ITT Population

Outcome measures

Outcome measures
Measure	N1539 30 mg n=100 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=101 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Summed Pain Intensity Difference (SPID) at Other Intervals SPID6 (Hour 0-6)	-510.78 units on a scale Standard Error 66.22	-288.33 units on a scale Standard Error 65.95
Summed Pain Intensity Difference (SPID) at Other Intervals SPID12 (Hour 0-12)	-957.83 units on a scale Standard Error 123.30	-480.15 units on a scale Standard Error 122.80
Summed Pain Intensity Difference (SPID) at Other Intervals SPID24 (Hour 0-24)	-2071.0 units on a scale Standard Error 247.01	-1167.9 units on a scale Standard Error 246.00
Summed Pain Intensity Difference (SPID) at Other Intervals SPID12-48 (Hour 12-48)	-5998.2 units on a scale Standard Error 439.21	-4349.1 units on a scale Standard Error 437.42
Summed Pain Intensity Difference (SPID) at Other Intervals SPID24-48 (Hour 24-48)	-4885.1 units on a scale Standard Error 313.60	-3661.4 units on a scale Standard Error 312.32

SECONDARY outcome

Timeframe: 48 Hours

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	N1539 30 mg n=100 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=101 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Time to First Dose of Rescue Analgesia	1.99 hours Interval 1.53 to 4.12	2.09 hours Interval 1.15 to 3.31

SECONDARY outcome

Timeframe: 48 Hours

Population: ITT Population

Rescue analgesia (oral oxycodone 5 mg) was available to subjects with inadequately controlled pain upon request.

Outcome measures

Outcome measures
Measure	N1539 30 mg n=100 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=101 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Number of Subjects Utilizing Rescue Analgesia Hour 0-24	83 Participants	99 Participants
Number of Subjects Utilizing Rescue Analgesia Hour 24-48	48 Participants	71 Participants
Number of Subjects Utilizing Rescue Analgesia Hour 0-48	83 Participants	99 Participants

SECONDARY outcome

Timeframe: 48 Hours

Population: ITT Population

Rescue analgesia (oral oxycodone 5 mg) was available to subjects with inadequately controlled pain upon request.

Outcome measures

Outcome measures
Measure	N1539 30 mg n=100 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=101 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Number of Doses of Rescue Analgesia Utilized Per Subject Hour 0-24	3.97 doses of rescue analgesia Standard Error 0.26	5.06 doses of rescue analgesia Standard Error 0.26
Number of Doses of Rescue Analgesia Utilized Per Subject Hour 24-48	1.63 doses of rescue analgesia Standard Error 0.25	2.51 doses of rescue analgesia Standard Error 0.25
Number of Doses of Rescue Analgesia Utilized Per Subject Hour 0-48	5.45 doses of rescue analgesia Standard Error 0.46	7.49 doses of rescue analgesia Standard Error 0.46

SECONDARY outcome

Timeframe: 12 Hours

Population: ITT Population

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).

Outcome measures

Outcome measures
Measure	N1539 30 mg n=100 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=101 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Time to Perceptible Pain Relief (TTPPR)	0.52 hours Interval 0.35 to 0.74	1.59 hours Interval 0.48 to 2.0

SECONDARY outcome

Timeframe: 12 Hours

Population: ITT Population

Outcome measures

Outcome measures
Measure	N1539 30 mg n=100 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=101 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Time to Meaningful Pain Relief (TTMPR)	2.16 hours Interval 1.0 to 12.01	3.19 hours Interval 2.39 to 4.82

SECONDARY outcome

Timeframe: 6 Hours

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	N1539 30 mg n=100 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=101 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Subjects With ≥ 30% Improvement in Pain From Baseline to Hour 6	32 Participants	20 Participants

SECONDARY outcome

Timeframe: 24 Hours

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	N1539 30 mg n=100 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=101 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Subjects With ≥ 30% Improvement in Pain From Baseline to Hour 24	37 Participants	21 Participants

SECONDARY outcome

Timeframe: 6 Hours

Population: ITT Population

Outcome measures

Outcome measures
Measure	N1539 30 mg n=100 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=101 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Subjects With ≥ 50% Improvement in Pain From Baseline to Hour 6	16 Participants	8 Participants

SECONDARY outcome

Timeframe: 24 Hours

Population: ITT Population

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.

Outcome measures

Outcome measures
Measure	N1539 30 mg n=100 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=101 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Subjects With ≥ 50% Improvement in Pain From Baseline to Hour 24	13 Participants	5 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	N1539 30 mg n=95 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=97 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Patient Global Assessment (PGA) of Pain Control at Hour 24 1 - Fair	23 Participants	26 Participants
Patient Global Assessment (PGA) of Pain Control at Hour 24 2 - Good	28 Participants	26 Participants
Patient Global Assessment (PGA) of Pain Control at Hour 24 3 - Very Good	17 Participants	13 Participants
Patient Global Assessment (PGA) of Pain Control at Hour 24 4 - Excellent	10 Participants	3 Participants
Patient Global Assessment (PGA) of Pain Control at Hour 24 0 - Poor	17 Participants	29 Participants

SECONDARY outcome

Timeframe: 48 Hours

Outcome measures

Outcome measures
Measure	N1539 30 mg n=95 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=96 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Patient Global Assessment (PGA) of Pain Control at Hour 48 0 - Poor	7 Participants	15 Participants
Patient Global Assessment (PGA) of Pain Control at Hour 48 1 - Fair	8 Participants	18 Participants
Patient Global Assessment (PGA) of Pain Control at Hour 48 2 - Good	26 Participants	25 Participants
Patient Global Assessment (PGA) of Pain Control at Hour 48 3 - Very Good	30 Participants	30 Participants
Patient Global Assessment (PGA) of Pain Control at Hour 48 4 - Excellent	24 Participants	8 Participants

Adverse Events

N1539 30 mg

Serious events: 0 serious events

Other events: 44 other events

Deaths: 0 deaths

IV Placebo

Serious events: 2 serious events

Other events: 54 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	N1539 30 mg n=100 participants at risk N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=101 participants at risk IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
General disorders Sudden death	0.00% 0/100 • AEs collected from time of first dose through last followup (30 days)	0.99% 1/101 • Number of events 1 • AEs collected from time of first dose through last followup (30 days)
Injury, poisoning and procedural complications Fracture	0.00% 0/100 • AEs collected from time of first dose through last followup (30 days)	0.99% 1/101 • Number of events 1 • AEs collected from time of first dose through last followup (30 days)

Other adverse events

Additional Information

Randall Mack

Recro Pharma, Inc.

Phone: 484-395-2470

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Discussion and/or publication of data generated is not permitted without the prior written consent of the sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	N1539 30 mg n=100 participants at risk N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=101 participants at risk IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Gastrointestinal disorders Nausea	20.0% 20/100 • Number of events 30 • AEs collected from time of first dose through last followup (30 days)	25.7% 26/101 • Number of events 31 • AEs collected from time of first dose through last followup (30 days)
Gastrointestinal disorders Constipation	4.0% 4/100 • Number of events 4 • AEs collected from time of first dose through last followup (30 days)	5.0% 5/101 • Number of events 5 • AEs collected from time of first dose through last followup (30 days)
Gastrointestinal disorders Diarrhoea	2.0% 2/100 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)	0.00% 0/101 • AEs collected from time of first dose through last followup (30 days)
Gastrointestinal disorders Vomiting	3.0% 3/100 • Number of events 3 • AEs collected from time of first dose through last followup (30 days)	8.9% 9/101 • Number of events 11 • AEs collected from time of first dose through last followup (30 days)
General disorders Injection site erythema	0.00% 0/100 • AEs collected from time of first dose through last followup (30 days)	2.0% 2/101 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)
General disorders Injection site pain	1.0% 1/100 • Number of events 1 • AEs collected from time of first dose through last followup (30 days)	2.0% 2/101 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)
General disorders Oedema peripheral	2.0% 2/100 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)	0.00% 0/101 • AEs collected from time of first dose through last followup (30 days)
Infections and infestations Cellulitis	2.0% 2/100 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)	0.00% 0/101 • AEs collected from time of first dose through last followup (30 days)
Infections and infestations Incision site cellulitis	0.00% 0/100 • AEs collected from time of first dose through last followup (30 days)	2.0% 2/101 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)
Infections and infestations Wound infection	0.00% 0/100 • AEs collected from time of first dose through last followup (30 days)	2.0% 2/101 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)
Injury, poisoning and procedural complications Skin abrasion	2.0% 2/100 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)	2.0% 2/101 • Number of events 3 • AEs collected from time of first dose through last followup (30 days)
Investigations Alanine aminotransferase increased	0.00% 0/100 • AEs collected from time of first dose through last followup (30 days)	3.0% 3/101 • Number of events 3 • AEs collected from time of first dose through last followup (30 days)
Investigations Aspartate aminotransferase increased	0.00% 0/100 • AEs collected from time of first dose through last followup (30 days)	2.0% 2/101 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)
Investigations Blood alkaline phosphatase increased	0.00% 0/100 • AEs collected from time of first dose through last followup (30 days)	2.0% 2/101 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)
Metabolism and nutrition disorders Decreased appetite	2.0% 2/100 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)	6.9% 7/101 • Number of events 8 • AEs collected from time of first dose through last followup (30 days)
Nervous system disorders Dizziness	3.0% 3/100 • Number of events 3 • AEs collected from time of first dose through last followup (30 days)	4.0% 4/101 • Number of events 4 • AEs collected from time of first dose through last followup (30 days)
Nervous system disorders Headache	8.0% 8/100 • Number of events 8 • AEs collected from time of first dose through last followup (30 days)	11.9% 12/101 • Number of events 14 • AEs collected from time of first dose through last followup (30 days)
Nervous system disorders Somnolence	3.0% 3/100 • Number of events 3 • AEs collected from time of first dose through last followup (30 days)	2.0% 2/101 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)
Psychiatric disorders Insomnia	0.00% 0/100 • AEs collected from time of first dose through last followup (30 days)	2.0% 2/101 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)
Renal and urinary disorders Pollakiuria	1.0% 1/100 • Number of events 1 • AEs collected from time of first dose through last followup (30 days)	2.0% 2/101 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)
Skin and subcutaneous tissue disorders Blister	2.0% 2/100 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)	0.00% 0/101 • AEs collected from time of first dose through last followup (30 days)
Skin and subcutaneous tissue disorders Hyperhidrosis	2.0% 2/100 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)	0.99% 1/101 • Number of events 1 • AEs collected from time of first dose through last followup (30 days)
Skin and subcutaneous tissue disorders Pruritus	8.0% 8/100 • Number of events 8 • AEs collected from time of first dose through last followup (30 days)	3.0% 3/101 • Number of events 3 • AEs collected from time of first dose through last followup (30 days)
Skin and subcutaneous tissue disorders Pruritus generalised	2.0% 2/100 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)	0.00% 0/101 • AEs collected from time of first dose through last followup (30 days)
Vascular disorders Flushing	3.0% 3/100 • Number of events 4 • AEs collected from time of first dose through last followup (30 days)	0.99% 1/101 • Number of events 3 • AEs collected from time of first dose through last followup (30 days)