Trial Outcomes & Findings for Evaluation of N1539 Following Abdominoplasty Surgery (NCT NCT02678286)

Last Updated: 2018-02-14

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

219 participants

Primary outcome timeframe

24 Hours

Results posted on

2018-02-14

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	110	109
Treatment Phase (48 Hours Post-Dose 1) COMPLETED	108	107
Treatment Phase (48 Hours Post-Dose 1) NOT COMPLETED	2	2
Study Overall (28 Day Follow-Up) STARTED	110	109
Study Overall (28 Day Follow-Up) COMPLETED	104	105
Study Overall (28 Day Follow-Up) NOT COMPLETED	6	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	2	1
Treatment Phase (48 Hours Post-Dose 1) Adverse Event	0	1
Study Overall (28 Day Follow-Up) Lack of Efficacy	1	0
Study Overall (28 Day Follow-Up) Withdrawal by Subject	3	2
Study Overall (28 Day Follow-Up) Lost to Follow-up	2	2

Baseline Characteristics

Evaluation of N1539 Following Abdominoplasty Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	N1539 30 mg n=110 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=109 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo	Total n=219 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	110 Participants n=5 Participants	107 Participants n=7 Participants	217 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Age, Continuous	38.9 years STANDARD_DEVIATION 8.40 • n=5 Participants	41.0 years STANDARD_DEVIATION 9.63 • n=7 Participants	40.0 years STANDARD_DEVIATION 9.08 • n=5 Participants
Sex: Female, Male Female	109 Participants n=5 Participants	106 Participants n=7 Participants	215 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	42 Participants n=5 Participants	45 Participants n=7 Participants	87 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	68 Participants n=5 Participants	64 Participants n=7 Participants	132 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	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	37 Participants n=5 Participants	36 Participants n=7 Participants	73 Participants n=5 Participants
Race (NIH/OMB) White	69 Participants n=5 Participants	69 Participants n=7 Participants	138 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	110 participants n=5 Participants	109 participants n=7 Participants	219 participants n=5 Participants
Body Mass Index (BMI)	26.5 kg/m^2 STANDARD_DEVIATION 3.08 • n=5 Participants	26.9 kg/m^2 STANDARD_DEVIATION 3.16 • n=7 Participants	26.7 kg/m^2 STANDARD_DEVIATION 3.12 • n=5 Participants
Time from End of Surgery to First Dose	0.853 hours STANDARD_DEVIATION 0.5708 • n=5 Participants	0.855 hours STANDARD_DEVIATION 0.5256 • n=7 Participants	0.854 hours STANDARD_DEVIATION 0.5475 • n=5 Participants
Baseline Pain Intensity	7.2 units on a scale STANDARD_DEVIATION 1.57 • n=5 Participants	7.4 units on a scale STANDARD_DEVIATION 1.68 • n=7 Participants	7.3 units on a scale STANDARD_DEVIATION 1.63 • n=5 Participants

PRIMARY outcome

Timeframe: 24 Hours

Population: Intent-to-Treat (ITT) population

Outcome measures

Outcome measures
Measure	N1539 30 mg n=110 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=109 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Summed Pain Intensity Difference Over the First 24 Hours (SPID24)	-4262.1 units on a scale Standard Error 214.19	-3535.7 units on a scale Standard Error 215.05

SECONDARY outcome

Timeframe: 48 Hours

Population: ITT Population

Outcome measures

Outcome measures
Measure	N1539 30 mg n=110 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=109 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)	-607.00 units on a scale Standard Error 52.45	-510.90 units on a scale Standard Error 52.66
Summed Pain Intensity Difference (SPID) at Other Intervals SPID12 (Hour 0-12)	-1763.8 units on a scale Standard Error 104.77	-1471.1 units on a scale Standard Error 105.18
Summed Pain Intensity Difference (SPID) at Other Intervals SPID48 (Hour 0-48)	-10600 units on a scale Standard Error 442.31	-8829.2 units on a scale Standard Error 444.08
Summed Pain Intensity Difference (SPID) at Other Intervals SPID24-48 (Hour 24-48)	-6337.8 units on a scale Standard Error 251.36	-5293.5 units on a scale Standard Error 252.36

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=110 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=109 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Time to First Dose of Rescue Analgesia	1.08 hours Interval 1.03 to 1.23	1.09 hours Interval 1.03 to 1.17

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=110 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=109 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Number of Subjects Utilizing Rescue Analgesia Day 1 (Hour 0-24)	97 Participants	98 Participants
Number of Subjects Utilizing Rescue Analgesia Day 2 (Hour 24-48)	60 Participants	81 Participants
Number of Subjects Utilizing Rescue Analgesia Hour 0-48	97 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=110 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=109 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Number of Doses of Rescue Analgesia Utilized Per Subject Day 1 (Hour 0-24)	3.66 doses of rescue analgesia Standard Error 0.24	4.38 doses of rescue analgesia Standard Error 0.24
Number of Doses of Rescue Analgesia Utilized Per Subject Day 2 (Hour 24-48)	1.75 doses of rescue analgesia Standard Error 0.21	2.72 doses of rescue analgesia Standard Error 0.21
Number of Doses of Rescue Analgesia Utilized Per Subject Hour 0-48	5.38 doses of rescue analgesia Standard Error 0.41	7.07 doses of rescue analgesia Standard Error 0.41

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=110 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=109 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Time to Perceptible Pain Relief (TTPPR)	0.76 hours Interval 0.5 to 0.89	1.28 hours Interval 0.96 to Upper 95% CI not reportable due to number of subjects censored.

SECONDARY outcome

Timeframe: 12 Hours

Population: ITT Population

Outcome measures

Outcome measures
Measure	N1539 30 mg n=110 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=109 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Time to Meaningful Pain Relief (TTMPR)	3.02 hours Interval 2.01 to 4.43	2.92 hours Interval 1.71 to Upper 95% CI not reportable due to the number of subjects censored

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=110 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=109 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Subjects With ≥ 30% Improvement in Pain From Baseline to Hour 6	40 Participants	34 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=110 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=109 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Subjects With ≥ 30% Improvement in Pain From Baseline to Hour 24	79 Participants	62 Participants

SECONDARY outcome

Timeframe: 6 Hours

Population: ITT Population

Outcome measures

Outcome measures
Measure	N1539 30 mg n=110 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=109 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Subjects With ≥ 50% Improvement in Pain From Baseline to Hour 6	15 Participants	9 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=110 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=109 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Subjects With ≥ 50% Improvement in Pain From Baseline to Hour 24	31 Participants	20 Participants

SECONDARY outcome

Timeframe: 24 Hours

Population: ITT Population

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=110 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=109 Participants IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Patient Global Assessment (PGA) of Pain Control at Hour 24 0 - Poor	6 Participants	10 Participants
Patient Global Assessment (PGA) of Pain Control at Hour 24 1 - Fair	11 Participants	25 Participants
Patient Global Assessment (PGA) of Pain Control at Hour 24 2 - Good	37 Participants	27 Participants
Patient Global Assessment (PGA) of Pain Control at Hour 24 3 - Very Good	38 Participants	34 Participants
Patient Global Assessment (PGA) of Pain Control at Hour 24 4 - Excellent	16 Participants	11 Participants
Patient Global Assessment (PGA) of Pain Control at Hour 24 Not Done	2 Participants	2 Participants

SECONDARY outcome

Timeframe: 48 Hours

Population: ITT Population

Outcome measures

Outcome measures
Measure	N1539 30 mg n=110 Participants N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=109 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	5 Participants	3 Participants
Patient Global Assessment (PGA) of Pain Control at Hour 48 1 - Fair	7 Participants	14 Participants
Patient Global Assessment (PGA) of Pain Control at Hour 48 2 - Good	16 Participants	28 Participants
Patient Global Assessment (PGA) of Pain Control at Hour 48 3 - Very Good	32 Participants	36 Participants
Patient Global Assessment (PGA) of Pain Control at Hour 48 4 - Excellent	47 Participants	21 Participants
Patient Global Assessment (PGA) of Pain Control at Hour 48 Not Done	3 Participants	7 Participants

Adverse Events

N1539 30 mg

Serious events: 1 serious events

Other events: 50 other events

Deaths: 0 deaths

IV Placebo

Serious events: 3 serious events

Other events: 74 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	N1539 30 mg n=110 participants at risk N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=109 participants at risk IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Infections and infestations Postoperative wound infection	0.00% 0/110 • AEs collected from time of first dose through last followup (30 days)	0.92% 1/109 • Number of events 1 • AEs collected from time of first dose through last followup (30 days)
Injury, poisoning and procedural complications Post procedural haemorrhage	0.91% 1/110 • Number of events 1 • AEs collected from time of first dose through last followup (30 days)	0.92% 1/109 • Number of events 1 • AEs collected from time of first dose through last followup (30 days)
Injury, poisoning and procedural complications Post procedural pulmonary embolism	0.00% 0/110 • AEs collected from time of first dose through last followup (30 days)	0.92% 1/109 • 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

Phone: 484-35-2470

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=110 participants at risk N1539 (Intravenous meloxicam) 30 mg every 24 hours for up to 3 doses. N1539	IV Placebo n=109 participants at risk IV Placebo every 24 hours for up to 3 doses. Intravenous Placebo
Cardiac disorders Tachycardia	1.8% 2/110 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)	0.00% 0/109 • AEs collected from time of first dose through last followup (30 days)
Gastrointestinal disorders Constipation	1.8% 2/110 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)	1.8% 2/109 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)
Gastrointestinal disorders Nausea	27.3% 30/110 • Number of events 32 • AEs collected from time of first dose through last followup (30 days)	37.6% 41/109 • Number of events 42 • AEs collected from time of first dose through last followup (30 days)
Gastrointestinal disorders Vomiting	4.5% 5/110 • Number of events 5 • AEs collected from time of first dose through last followup (30 days)	9.2% 10/109 • Number of events 10 • AEs collected from time of first dose through last followup (30 days)
Gastrointestinal disorders Chills	0.00% 0/110 • AEs collected from time of first dose through last followup (30 days)	1.8% 2/109 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)
General disorders Induration	1.8% 2/110 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)	0.00% 0/109 • AEs collected from time of first dose through last followup (30 days)
General disorders Injection site pain	1.8% 2/110 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)	0.00% 0/109 • AEs collected from time of first dose through last followup (30 days)
General disorders Pyrexia	0.00% 0/110 • AEs collected from time of first dose through last followup (30 days)	2.8% 3/109 • Number of events 3 • AEs collected from time of first dose through last followup (30 days)
Infections and infestations Upper respiratory tract infection	0.00% 0/110 • AEs collected from time of first dose through last followup (30 days)	1.8% 2/109 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)
Injury, poisoning and procedural complications Contusion	0.91% 1/110 • Number of events 1 • AEs collected from time of first dose through last followup (30 days)	2.8% 3/109 • Number of events 3 • AEs collected from time of first dose through last followup (30 days)
Injury, poisoning and procedural complications Seroma	0.00% 0/110 • AEs collected from time of first dose through last followup (30 days)	1.8% 2/109 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)
Investigations Alanine aminotransferase increased	1.8% 2/110 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)	1.8% 2/109 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)
Investigations Aspartate aminotransferase increased	1.8% 2/110 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)	0.92% 1/109 • Number of events 1 • AEs collected from time of first dose through last followup (30 days)
Investigations Hepatic enzyme increased	0.91% 1/110 • Number of events 1 • AEs collected from time of first dose through last followup (30 days)	2.8% 3/109 • Number of events 3 • AEs collected from time of first dose through last followup (30 days)
Metabolism and nutrition disorders Decreased appetite	1.8% 2/110 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)	2.8% 3/109 • Number of events 3 • AEs collected from time of first dose through last followup (30 days)
Musculoskeletal and connective tissue disorders Back pain	0.91% 1/110 • Number of events 1 • AEs collected from time of first dose through last followup (30 days)	3.7% 4/109 • Number of events 4 • AEs collected from time of first dose through last followup (30 days)
Nervous system disorders Dizziness	3.6% 4/110 • Number of events 4 • AEs collected from time of first dose through last followup (30 days)	9.2% 10/109 • Number of events 10 • AEs collected from time of first dose through last followup (30 days)
Nervous system disorders Headache	11.8% 13/110 • Number of events 13 • AEs collected from time of first dose through last followup (30 days)	16.5% 18/109 • Number of events 19 • AEs collected from time of first dose through last followup (30 days)
Skin and subcutaneous tissue disorders Hyperhidrosis	1.8% 2/110 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)	0.92% 1/109 • Number of events 1 • AEs collected from time of first dose through last followup (30 days)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/110 • AEs collected from time of first dose through last followup (30 days)	1.8% 2/109 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)
Skin and subcutaneous tissue disorders Pruritus generalised	1.8% 2/110 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)	0.92% 1/109 • Number of events 1 • AEs collected from time of first dose through last followup (30 days)
Vascular disorders Hot flush	0.00% 0/110 • AEs collected from time of first dose through last followup (30 days)	1.8% 2/109 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)
Vascular disorders Hypertension	0.00% 0/110 • AEs collected from time of first dose through last followup (30 days)	2.8% 3/109 • Number of events 3 • AEs collected from time of first dose through last followup (30 days)
Vascular disorders Hypotension	1.8% 2/110 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)	1.8% 2/109 • Number of events 2 • AEs collected from time of first dose through last followup (30 days)