Efficacy and Safety Study of Meloxicam Nanocrystal Injection for the Treatment of Moderate to Severe Pain

Efficacy and Safety Study of Meloxicam Nanocrystal Injection for the Treatment of Moderate to Severe Pain After Abdominal Surgery - a Multicenter, Randomized, Double-blind, Placebo-parallel Controlled, Phase III Clinical Trial

The purpose of this study is to evaluate the efficacy and safety of meloxicam nanocrystal injection in subjects with moderate to severe pain after abdominal surgery.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Meloxicam Nanocrystal Injection; Drug: Placebo

Detailed Description

In this study, a randomized, double-blind, placebo-controlled multicenter study will be conducted to evaluate the efficacy and safety of meloxicam nanocrystal injection in subjects with moderate to severe pain after abdominal surgery.

• Study Type: Interventional
• Enrollment (Actual): 192
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Wuhan, China
    • Union Hospital of Tongji Medical College of Huazhong University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18 years ≤ age ≤ 65 years, regardless of gender.
2. Elective abdominal surgery under general anesthesia.
3. ASA score of grade 1-3.
4. 18 kg/m^2 < BMI < 30 kg/m^2.
5. NRS score of ≥ 4 within 3 hours after the end of surgery (last suture).
6. Able to understand the study process and the use of pain scales, and able to communicate effectively with study personnel.
7. Written informed consent signed by subject or legal representative.

Exclusion Criteria:

1. Abnormal liver function: ALT and/or AST > 2 × ULN, or TBIL ≥ 2 × ULN.
2. Renal impairment (blood creatinine > 1.5 × ULN), or dialysis treatment within 28 days prior to the surgery.
3. Subjects at high risk of bleeding, including subjects with congenital bleeding disorders (e.g., hemophilia), thrombocytopenic subjects (platelet count less than 50 × 10^9/L), subjects with abnormal platelet function (e.g., idiopathic thrombocytopenic purpura, disseminated intravascular coagulation, congenital abnormal platelet function), or subjects with any clinically significant active bleeding.
4. Abnormal coagulation (PT>ULN+3s and/or APTT>ULN+10s).
5. Subjects with a history of severe gastrointestinal disease (e.g. ulcers, bleeding and perforation, etc.) within 1 year prior to randomization that may be worsened by the administration of NSAIDs-like drugs.
6. Myocardial infarction or coronary artery bypass grafting within 1 year prior to randomization.
7. Abnormal clinically significant 12-lead ECG during the screening period and judged by the investigator to be inappropriate for participation in this trial.
8. Combination of severe liver, kidney, cardiovascular, cerebrovascular, or metabolic system disease, which is judged by the investigator to be inappropriate for participation in this trial.
9. Subjects with combined neurological or psychiatric disorders such as migraine and seizures, which have been judged by the investigator to affect the evaluation of the efficacy of the trial drug.
10. Subjects with hypertension whose blood pressure is not satisfactorily controlled by antihypertensive medication (screening period sitting systolic blood pressure ≥ 160 mmHg, and/or screening period diastolic blood pressure ≥ 100 mmHg).
11. Sitting systolic blood pressure ≤ 90 mmHg at screening.
12. Subjects with diabetes mellitus whose blood glucose is not satisfactorily controlled (random blood glucose ≥ 11.1 mmol/L during the screening period).
13. Subjects with advanced malignancy or malignancy with extensive metastases.
14. Combined with other physical pain conditions that may confound postoperative pain evaluation.
15. Subjects with known hypersensitivity to meloxicam, any of the excipients in the study drug, aspirin, other non-steroidal anti-inflammatory drugs (NSAIDs), any perioperative drug use, or other history of anaphylactic reactions.
16. Subjects with alcohol or drug dependence within 3 months prior to screening and/or subjects whose alcohol, drug, or medication withdrawal may interfere with efficacy and safety evaluations during the study period.
17. Subjects who have undergone abdominal surgery within 6 months prior to randomization.
18. Subjects who have participated in other clinical trials and received the test drug/test device within 3 months prior to randomization.
19. Subjects with contraindications to investigational drugs, standard anesthetic practices.
20. Women who are pregnant or breastfeeding.
21. Other reasons that the investigator deems inappropriate for participation in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Meloxicam Nanocrystal Injection; The eligible subjects will receive Meloxicam Nanocrystal Injection, administered as 30 mg (1 mL) every 24 h for 2 doses.	Drug: Meloxicam Nanocrystal Injection; 30 mg (1 mL), once daily, by intravenous infusion
Placebo Comparator: Placebo; The eligible subjects will receive Placebo, administered as 1 mL Placebo every 24 h for 2 doses.	Drug: Placebo; 1 mL Placebo, once daily, by intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PID24 (Time Weighted Sum of Pain Intensity Difference Over 24 Hours Post-Dose)	The primary efficacy variable was the Pain Intensity (PI) measured by the Numerical Rating Scale (NRS); a scale from zero to 10 on which subjects circled a single number to indicate current pain level, with zero representing "No Pain" and 10 representing "Worst Possible Pain".	24 hours after first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TOTPAR (time-weighted sum of pain relief scores): TOTPAR12, TOTPAR18, TOTPAR24, TOTPAR48.	pain relief intensity was recorded using a Likert Scale (Range 0-4) where 0 equates to no pain relief (worse), and 4 equates to the completely pain relief intensity (better). pain relief intensity scores were to be recorded at the following time points: 0.25, 0.5, 1, 1.5, 2 ，3，4，6 ，8，10，12，14，16，18，24，30，36，42 and 48hours post Dose 1. pain relief intensity at each time point were calculated and a time weighted summed pain relief intensity (TOTPAR) was then calculated. Time weighted TOTPAR 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 bigger TOTPAR value was better.	0-48 hours after the first dose
SPID2、SPID6、SPID12、SPID18、SPID18-24、SPID24-48、SPID42-48、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, 1, 1.5, 2 ，3，4，6 ，8，10，12，14，16，18，24，30，36，42 and 48hours 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.	0-48 hours after the first dose
Time to the first dose of the remedial analgesia		0-48 hours after the first dose
Number of times of remedial analgesia administered 0-24h and 24-48h after the first dose		0-48 hours after the first dose
Proportion of subjects requiring remedial analgesia		0-48 hours after the first dose
The total amount of remedial analgesia used 24 h and 48 h after the first dose		0-48 hours after the first dose
The subject's analgesic treatment satisfaction score (0-4 point categorical scale score)	The subject's analgesic treatment satisfaction score was recorded using a Likert Scale (Range 0-4), A bigger value was better.	48 hours after the first dose
The investigator's satisfaction score (0-4 point categorical scale score) for the subject's analgesic treatment	The investigator's satisfaction score was recorded using a Likert Scale (Range 0-4), A bigger value was better.	48 hours after the first dose

Collaborators and Investigators

• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Investigators: Principal Investigator: Chen xiangdong, Union Hospital of Tongji Medical College of Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2023
• Primary Completion (Actual): July 11, 2023
• Study Completion (Actual): July 13, 2023

Study Registration Dates

• First Submitted: January 28, 2023
• First Submitted That Met QC Criteria: April 22, 2024
• First Posted (Actual): April 23, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Meloxicam
• Other Study ID Numbers: SYH9015-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No