Postoperative Pain
Conditions
Keywords
Analgesic
Brief summary
The study aims to determine the tolerability of repeated doses of Maxigesic® IV over an extended period of exposure.
Detailed description
Combined administration of acetaminophen and ibuprofen has been shown to provide superior analgesia over administration of comparable doses of either component alone or placebo, when given as an intravenous formulation or as a solid oral tablet in the postoperative setting. The superior efficacy of the combination does not appear to come at the expense of tolerability. A previous study of Maxigesic® IV in bunionectomy patients found that there were no differences between patients treated with repeated doses of Maxigesic® IV and those treated with intravenous acetaminophen, ibuprofen or placebo in the rate of discontinuations due to adverse events (AEs), the overall incidence of treatment-emergent AEs (TEAEs) or the severity of TEAEs. The incidence of common TEAEs (affecting ≥ 10% of the study population), including gastrointestinal disorders, nervous system disorders, general disorders and administration site conditions, and skin and subcutaneous tissue disorders, was not changed due to combined administration of acetaminophen and ibuprofen in Maxigesic® IV. This study aims to determine the tolerability of repeated doses of Maxigesic® IV over an extended period of exposure (≥ 48 hours).
Interventions
DRUGMaxigesic® IV
acetaminophen 1000 mg + ibuprofen 300 mg, 100 ml solution for infusion
Sponsors
AFT Pharmaceuticals, Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Is male or female ≥ 18 years of age. * Is classified by the anesthesiologist as P1 to P2 in the American Society of Anesthesiologists (ASA) Physical Status Classification System. * Requires multiple doses of parenterally administered nonopioid analgesics over multiple days as a result of surgery (non-laparoscopic general, plastic or orthopedic surgery). * Has an expected stay in facility ≥ 48 hours. * Has a body weight ≥ 45 kg. * If female and of childbearing potential, is nonlactating and nonpregnant. * If female, is either not of childbearing potential (defined as postmenopausal for at least 1 year or surgically sterile \[bilateral tubal ligation, bilateral oophorectomy, or hysterectomy\]) or practicing 1 of the following medically acceptable methods of birth control: i) Hormonal methods such as oral, implantable, injectable, or transdermal contraceptives for a minimum of 1 full cycle (based on the subject's usual menstrual cycle period) before study drug administration; ii) Total abstinence from sexual intercourse since the last menses before study drug administration through completion of final study visit; iii) Intrauterine device (IUD); iv) Double-barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream). * Is able to provide written informed consent to participate in the study and able to understand the procedures and study requirements. * Must voluntarily sign and date an informed consent form (ICF) that is approved by an Institutional Review Board (IRB) before the conduct of any study procedure. * Is willing and able to remain at the study site for at least 48 hours and to attend a follow-up visit at 7 ± 2 days after the last dose of study drug.
Exclusion criteria
* Has a known history of allergic reaction or clinically significant intolerance to acetaminophen, aspirin, opioids, or any nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen); history of NSAID-induced bronchospasm (subjects with the triad of asthma, nasal polyps, and chronic rhinitis are at greater risk for bronchospasm and should be considered carefully); or hypersensitivity, allergy, or significant reaction to sulfa (including sulfonamide) medicines, ingredients of the study drug, or any other drugs used in the study including anesthetics and antibiotics that may be required on the day of surgery. * Has experienced any surgical complications or other issues that, in the opinion of the Investigator, could compromise the safety of the subject if he or she participates in the study or could confound the results of the study. * Has a known or suspected history of alcoholism or drug abuse or misuse within 2 years of screening or evidence of tolerance or physical dependence before dosing with study drug. * Has any clinically significant unstable cardiac, respiratory, neurological, immunological, hematological, or renal disease or any other condition that, in the opinion of the Investigator, could compromise the subject's welfare, ability to communicate with the study staff, or otherwise contraindicate study participation. * Has a history or current diagnosis of a significant psychiatric disorder that, in the opinion of the Investigator, would affect the subject's ability to comply with the study requirements. * Has tested positive either on the urine drug screen or on the alcohol breathalyzer test. Subjects who test positive and can produce a prescription for the medication from their physician may be considered for study enrolment at the discretion of the Investigator. * Has a history of a clinically significant (Investigator opinion) gastrointestinal (GI) event within 6 months before screening or has any history of peptic or gastric ulcers or GI bleeding. * Has a surgical or medical condition of the GI or renal system that might significantly alter the absorption, distribution, or excretion of any drug substance. * Is considered by the Investigator, for any reason to be an unsuitable candidate to receive the study drug. * Is receiving systemic chemotherapy, has an active malignancy of any type, or has been diagnosed with cancer within 5 years before Screening (excluding treated squamous or basal cell carcinoma of the skin). * Is currently receiving anticoagulants (e.g. heparin or warfarin). * Has received a course of systemic corticosteroids (either oral or parenteral) within 3 months before screening (inhaled nasal steroids and regional/limited area application of topical corticosteroids (Investigator discretion) are allowed). * Has a history of chronic use (defined as daily use for \> 2 weeks) of NSAIDs, opiates, or glucocorticoids (except inhaled nasal steroids and regional/limited topical corticosteroids), for any condition within 6 months before study drug administration. Aspirin at a daily dose of ≤ 325 mg is allowed for cardiovascular prophylaxis if the subject has been on a stable dose regimen for ≥ 30 days before screening and has not experienced any relevant medical problem. * Has a significant renal or hepatic disease, as indicated by clinical laboratory assessment (results ≥ 3 times the upper limit of normal \[ULN\] for any liver function test, including aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], or creatinine ≥ 1.5 times the ULN). * Has any clinically significant laboratory finding at screening that, in the opinion of the Investigator, contraindicates study participation. * Previously participated in another clinical study of Maxigesic® IV or received any investigational drug or device or investigational therapy within 30 days before Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of TEAEs (Treatment-emergent Adverse Events) | During treatment period (≥ 48 hours - 5 days) | The incidence of treatment-emergent adverse events associated with exposure Maxigesic® IV |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time Course of TEAEs | After receiving the first dose of study medication until 7 days after the last dose, a total of approximately 9 days for subjects who received the treatment for 48 hours and 12 days for subjects who received the treatment for 5 days. | The incidence of treatment-emergent adverse events associated with exposure Maxigesic® IV during various study time periods |
| Incidence of TRAEs (Treatment-related Adverse Events) | During treatment period (≥ 48 hours - 5 days) | The incidence of treatment-related adverse events (TEAEs considered by the investigator to be probably or definitely related to the study drug) associated with exposure Maxigesic® IV |
| Incidence of TEAEs of Interest | During treatment period (≥ 48 hours - 5 days) | The incidence of TEAEs of interest (cardiovascular, gastrointestinal, renal, hepatic, administration site conditions and bleeding-related events) |
| Changes in Blood Pressure | From the baseline (Day 1 prior to surgery) until 7 days after the last dose | Systolic and Diastolic Blood Pressured Measured every 24 hours |
| Changes in Heart Rate | From the baseline (Day 1 prior to surgery) until 7 days after the last dose | Measured every 24 hours |
| Changes in Temperature | From the baseline (Day 1 prior to surgery) until 7 days after the last dose | Measured every 24 hours |
| Changes in Respiratory Rate | From the baseline (Day 1 prior to surgery) until 7 days after the last dose | Respiratory Rate Measured every 24 hours |
| Changes in Hematology Values (Hemoglobin) | Prior to surgery, on Day 1 and at discharge (Day 5) | Measured at screening visit and at the end of the treatment |
| Changes in Hematology Values (Hematocrit) | Prior to surgery, on Day 1 and at discharge (Day 5) | Measured at screening visit and at the end of the treatment |
| Changes in Hematology Values (Platelet Count) | Prior to surgery, on Day 1 and at discharge (Day 5) | Measured at screening visit and at the end of the treatment |
| Changes in Hematology Values (White Blood Cell Count) | Prior to surgery, on Day 1 and at discharge (Day 5) | Measured at screening visit and at the end of the treatment |
| Changes in Hematology Values (Differential Leukocyte Count) | Prior to surgery, on Day 1 and at discharge (Day 5) | Hematology test was Measured at screening visit and at the end of the treatment |
| Changes in Blood Biochemistry Values (Sodium) | Prior to surgery, on Day 1 and at discharge (Day 5) | Measured at screening visit and at the end of the treatment |
| Changes in Blood Biochemistry Values (Potassium) | Prior to surgery, on Day 1 and at discharge (Day 5) | Measured at screening visit and at the end of the treatment |
| Changes in Hematology Values (Red Blood Cell Count) | Prior to surgery, on Day 1 and at discharge (Day 5) | Measured at screening visit and at the end of the treatment |
| Changes in Blood Biochemistry Values (Creatinine) | Prior to surgery, on Day 1 and at discharge (Day 5) | Measured at screening visit and at the end of the treatment |
| Changes in Blood Biochemistry Values (Phosphate) | Prior to surgery, on Day 1 and at discharge (Day 5) | Measured at screening visit and at the end of the treatment |
| Changes in Blood Biochemistry Values (Glucose) | Prior to surgery, on Day 1 and at discharge (Day 5) | Measured at screening visit and at the end of the treatment |
| Changes in Blood Biochemistry Values (Albumin) | Prior to surgery, on Day 1 and at discharge (Day 5) | Measured at screening visit and at the end of the treatment |
| Changes in Blood Biochemistry Values (Total Protein) | Prior to surgery, on Day 1 and at discharge (Day 5) | Measured at screening visit and at the end of the treatment |
| Changes in Blood Biochemistry Values (Alkaline Phosphates) | Prior to surgery, on Day 1 and at discharge (Day 5) | Measured at screening visit and at the end of the treatment |
| Changes in Blood Biochemistry Values (Gamma-glutamyl Transferase) | Prior to surgery, on Day 1 and at discharge (Day 5) | Blood Biochemistry was Measured at screening visit and at the end of the treatment |
| Changes in Blood Biochemistry Values (Aspartate Transaminase) | Prior to surgery, on Day 1 and at discharge (Day 5) | Blood Chemistry (AST) was Measured at screening visit and at the end of the treatment |
| Changes in Blood Biochemistry Values (Alanine Transaminase) | Prior to surgery, on Day 1 and at discharge (Day 5) | Blood Chemistry (ALT) was Measured at screening visit and at the end of the treatment |
| Changes in Blood Biochemistry Values (Bilirubin) | Prior to surgery, on Day 1 and at discharge (Day 5) | Measured at screening visit and at the end of the treatment |
| Changes in ECG (Electrocardiography) Status (Normal/Abnormal) | Prior to surgery, on Day 1 and at discharge (Day 5) | All components of the ECG will be analysed to assess safety (P wave, QRS Complex, QT interval, PR interval, T wave, ST segment, U wave, PR segment) in 5 categories of the shift from baseline to the end of treatment from: Normal to Normal Normal to Abnormal NCS (Non-clinically Significant) Abnormal NCS to Normal Abnormal NCS to Abnormal NCS Missing |
| Changes in Hepatic Enzymes From Baseline to the End of the Treatment | Prior to surgery, on Day 1 and at discharge (Day 5) | The elevation in hepatic enzymes (ALP, ALT, AST, GGT) from baseline to the end of the treatment |
| Patient's Global Evaluation of the Study Drug | 5 days after the first dose | Summary of the patients' ratings of the study medication (1 = Poor; 2 = Fair; 3 = Good; 4 = Very Good; 5 = Excellent) |
| Changes in Blood Biochemistry Values (Urea) | Prior to surgery, on Day 1 and at discharge (Day 5) | Measured at screening visit and at the end of the treatment |
Countries
New Zealand, United States
Participant flow
Recruitment details
323 subjects were screened, of whom 90 subjects were screening failures, and a total of 233 subjects were enrolled. 1 subject was enrolled but not dosed due to receiving prohibited concomitant medications during surgery, therefore a total of 232 subjects were administered at least one dose of the study drug. 17 subjects discontinued from the study, including 14 discontinuations during the treatment period, and 3 discontinuations during the follow-up period. 215 subjects completed the full study
Participants by arm
| Arm | Count |
|---|---|
| Maxigesic® IV Acetaminophen 10 mg/ml + ibuprofen 3 mg/ml in 100 ml solution for infusion. The study drug will be administered by injection into a dedicated indwelling venous cannula, infused over 15 minutes. The study drug will be administered every 6 hours (q6h) for a minimum of 48 hours up to at least 5 days, with a maximum of 4 doses within a 24 hour period.
Maxigesic® IV: acetaminophen 1000 mg + ibuprofen 300 mg, 100 ml solution for infusion | 232 |
| Total | 232 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative reason, temporary site closure due to COVID-19 | 4 |
| Overall Study | Adverse Event | 6 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Maxigesic® IV |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 61 Participants |
| Age, Categorical Between 18 and 65 years | 171 Participants |
| Age, Continuous | 53.4 years STANDARD_DEVIATION 15.3 |
| BMI | 29.7 kg/m^2 STANDARD_DEVIATION 5.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 223 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 91 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 131 Participants |
| Region of Enrollment New Zealand | 85 participants |
| Region of Enrollment United States | 147 participants |
| Sex: Female, Male Female | 144 Participants |
| Sex: Female, Male Male | 88 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 232 |
| other Total, other adverse events | 164 / 232 |
| serious Total, serious adverse events | 2 / 232 |
Outcome results
Primary
Incidence of TEAEs (Treatment-emergent Adverse Events)
The incidence of treatment-emergent adverse events associated with exposure Maxigesic® IV
Time frame: During treatment period (≥ 48 hours - 5 days)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maxigesic® IV | Incidence of TEAEs (Treatment-emergent Adverse Events) | Incidence of TEAEs ( 2 days treatment) | 256 Treatment-Emergent Adverse Events |
| Maxigesic® IV | Incidence of TEAEs (Treatment-emergent Adverse Events) | Incidence of TEAEs (5 days treatment) | 38 Treatment-Emergent Adverse Events |
Secondary
Changes in Blood Biochemistry Values (Alanine Transaminase)
Blood Chemistry (ALT) was Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Blood Biochemistry Values (Alanine Transaminase) | 4.5 IU/L | Standard Deviation 25.2 |
Secondary
Changes in Blood Biochemistry Values (Albumin)
Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Blood Biochemistry Values (Albumin) | -4.9 g/L | Standard Deviation 3.2 |
Secondary
Changes in Blood Biochemistry Values (Alkaline Phosphates)
Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Blood Biochemistry Values (Alkaline Phosphates) | -2.1 IU/L | Standard Deviation 15.1 |
Secondary
Changes in Blood Biochemistry Values (Aspartate Transaminase)
Blood Chemistry (AST) was Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Blood Biochemistry Values (Aspartate Transaminase) | 7.1 IU/L | Standard Deviation 23.3 |
Secondary
Changes in Blood Biochemistry Values (Bilirubin)
Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Blood Biochemistry Values (Bilirubin) | 0.0 μmol/L | Standard Deviation 3.9 |
Secondary
Changes in Blood Biochemistry Values (Creatinine)
Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Blood Biochemistry Values (Creatinine) | -3.9 μmol/L | Standard Deviation 9.5 |
Secondary
Changes in Blood Biochemistry Values (Gamma-glutamyl Transferase)
Blood Biochemistry was Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Blood Biochemistry Values (Gamma-glutamyl Transferase) | 4.3 IU/L | Standard Deviation 16.5 |
Secondary
Changes in Blood Biochemistry Values (Glucose)
Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Blood Biochemistry Values (Glucose) | 0.7 mmol/L | Standard Deviation 1.5 |
Secondary
Changes in Blood Biochemistry Values (Phosphate)
Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Blood Biochemistry Values (Phosphate) | -0.1 mmol/L | Standard Deviation 0.2 |
Secondary
Changes in Blood Biochemistry Values (Potassium)
Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Blood Biochemistry Values (Potassium) | -0.1 mmol/L | Standard Deviation 0.4 |
Secondary
Changes in Blood Biochemistry Values (Sodium)
Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Blood Biochemistry Values (Sodium) | -0.6 mmol/L | Standard Deviation 2.3 |
Secondary
Changes in Blood Biochemistry Values (Total Protein)
Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Blood Biochemistry Values (Total Protein) | -5.8 g/L | Standard Deviation 5.3 |
Secondary
Changes in Blood Biochemistry Values (Urea)
Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Blood Biochemistry Values (Urea) | -0.7 mmol/L | Standard Deviation 1.4 |
Secondary
Changes in Blood Pressure
Systolic and Diastolic Blood Pressured Measured every 24 hours
Time frame: From the baseline (Day 1 prior to surgery) until 7 days after the last dose
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maxigesic® IV | Changes in Blood Pressure | Systolic Blood Pressure change from the baseline | -0.9 mmHg | Standard Deviation 18.98 |
| Maxigesic® IV | Changes in Blood Pressure | Diastolic Blood Pressure change from the baseline | -0.5 mmHg | Standard Deviation 11.31 |
Secondary
Changes in ECG (Electrocardiography) Status (Normal/Abnormal)
All components of the ECG will be analysed to assess safety (P wave, QRS Complex, QT interval, PR interval, T wave, ST segment, U wave, PR segment) in 5 categories of the shift from baseline to the end of treatment from: Normal to Normal Normal to Abnormal NCS (Non-clinically Significant) Abnormal NCS to Normal Abnormal NCS to Abnormal NCS Missing
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Maxigesic® IV | Changes in ECG (Electrocardiography) Status (Normal/Abnormal) | Shift from Baseline to the end of treatment Missing | 2 Participants |
| Maxigesic® IV | Changes in ECG (Electrocardiography) Status (Normal/Abnormal) | Shift from Baseline to the end of treatment Normal to Normal | 83 Participants |
| Maxigesic® IV | Changes in ECG (Electrocardiography) Status (Normal/Abnormal) | Shift from Baseline to the end of treatment Normal to Abnormal NCS | 18 Participants |
| Maxigesic® IV | Changes in ECG (Electrocardiography) Status (Normal/Abnormal) | Shift from Baseline to the end of treatment Abnormal NCS to Normal | 44 Participants |
| Maxigesic® IV | Changes in ECG (Electrocardiography) Status (Normal/Abnormal) | Shift from Baseline to the end of treatment Abnormal NCS to Abnormal NCS | 85 Participants |
Secondary
Changes in Heart Rate
Measured every 24 hours
Time frame: From the baseline (Day 1 prior to surgery) until 7 days after the last dose
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Heart Rate | 3.4 beats/min | Standard Deviation 11.86 |
Secondary
Changes in Hematology Values (Differential Leukocyte Count)
Hematology test was Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maxigesic® IV | Changes in Hematology Values (Differential Leukocyte Count) | Basophils | -0.00 billions/L | Standard Deviation 0.02 |
| Maxigesic® IV | Changes in Hematology Values (Differential Leukocyte Count) | Eosinophils | 0.05 billions/L | Standard Deviation 0.13 |
| Maxigesic® IV | Changes in Hematology Values (Differential Leukocyte Count) | Lymphocytes | -0.2 billions/L | Standard Deviation 0.5 |
| Maxigesic® IV | Changes in Hematology Values (Differential Leukocyte Count) | Monocytes | 0.2 billions/L | Standard Deviation 0.2 |
| Maxigesic® IV | Changes in Hematology Values (Differential Leukocyte Count) | Neutrophils | 1.5 billions/L | Standard Deviation 1.7 |
Secondary
Changes in Hematology Values (Hematocrit)
Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Hematology Values (Hematocrit) | -0.03 proportion of red blood cells in blood | Standard Deviation 0.04 |
Secondary
Changes in Hematology Values (Hemoglobin)
Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Hematology Values (Hemoglobin) | -11.6 g/L | Standard Deviation 13.4 |
Secondary
Changes in Hematology Values (Platelet Count)
Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Hematology Values (Platelet Count) | -12.8 billions/L | Standard Deviation 40.1 |
Secondary
Changes in Hematology Values (Red Blood Cell Count)
Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Hematology Values (Red Blood Cell Count) | -0.4 trillions/L | Standard Deviation 0.5 |
Secondary
Changes in Hematology Values (White Blood Cell Count)
Measured at screening visit and at the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Hematology Values (White Blood Cell Count) | 6.2 billions/L | Standard Deviation 1.7 |
Secondary
Changes in Hepatic Enzymes From Baseline to the End of the Treatment
The elevation in hepatic enzymes (ALP, ALT, AST, GGT) from baseline to the end of the treatment
Time frame: Prior to surgery, on Day 1 and at discharge (Day 5)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received. The number of participants analyzed are reporting the number of participants who experienced the shifts from Normal to Abnormal.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Maxigesic® IV | Changes in Hepatic Enzymes From Baseline to the End of the Treatment | Shifts from Normal to High Upper Limit of Normal (ULN) <3.0 | ALP | 1 Participants |
| Maxigesic® IV | Changes in Hepatic Enzymes From Baseline to the End of the Treatment | Shifts from Normal to High Upper Limit of Normal (ULN) <3.0 | ALT | 24 Participants |
| Maxigesic® IV | Changes in Hepatic Enzymes From Baseline to the End of the Treatment | Shifts from Normal to High Upper Limit of Normal (ULN) <3.0 | AST | 22 Participants |
| Maxigesic® IV | Changes in Hepatic Enzymes From Baseline to the End of the Treatment | Shifts from Normal to High Upper Limit of Normal (ULN) <3.0 | GGT | 12 Participants |
| Maxigesic® IV | Changes in Hepatic Enzymes From Baseline to the End of the Treatment | Shift from Normal to High ULN ≥ 3.0, <5.0 | ALP | 0 Participants |
| Maxigesic® IV | Changes in Hepatic Enzymes From Baseline to the End of the Treatment | Shift from Normal to High ULN ≥ 3.0, <5.0 | ALT | 4 Participants |
| Maxigesic® IV | Changes in Hepatic Enzymes From Baseline to the End of the Treatment | Shift from Normal to High ULN ≥ 3.0, <5.0 | AST | 5 Participants |
| Maxigesic® IV | Changes in Hepatic Enzymes From Baseline to the End of the Treatment | Shift from Normal to High ULN ≥ 3.0, <5.0 | GGT | 0 Participants |
| Maxigesic® IV | Changes in Hepatic Enzymes From Baseline to the End of the Treatment | Shift from Normal to High ULN ≥ 5.0 | ALP | 0 Participants |
| Maxigesic® IV | Changes in Hepatic Enzymes From Baseline to the End of the Treatment | Shift from Normal to High ULN ≥ 5.0 | ALT | 2 Participants |
| Maxigesic® IV | Changes in Hepatic Enzymes From Baseline to the End of the Treatment | Shift from Normal to High ULN ≥ 5.0 | AST | 0 Participants |
| Maxigesic® IV | Changes in Hepatic Enzymes From Baseline to the End of the Treatment | Shift from Normal to High ULN ≥ 5.0 | GGT | 0 Participants |
Secondary
Changes in Respiratory Rate
Respiratory Rate Measured every 24 hours
Time frame: From the baseline (Day 1 prior to surgery) until 7 days after the last dose
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Respiratory Rate | 0.5 breaths/min | Standard Deviation 2.43 |
Secondary
Changes in Temperature
Measured every 24 hours
Time frame: From the baseline (Day 1 prior to surgery) until 7 days after the last dose
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maxigesic® IV | Changes in Temperature | 0.2 degree Celsius | Standard Deviation 0.38 |
Secondary
Incidence of TEAEs of Interest
The incidence of TEAEs of interest (cardiovascular, gastrointestinal, renal, hepatic, administration site conditions and bleeding-related events)
Time frame: During treatment period (≥ 48 hours - 5 days)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maxigesic® IV | Incidence of TEAEs of Interest | Gastrointestinal disorders | 67 Treatment-Emergent Adverse Events |
| Maxigesic® IV | Incidence of TEAEs of Interest | Renal and urinary disorders | 12 Treatment-Emergent Adverse Events |
| Maxigesic® IV | Incidence of TEAEs of Interest | Abnormal hepatic function lab results | 25 Treatment-Emergent Adverse Events |
| Maxigesic® IV | Incidence of TEAEs of Interest | General disorders and administration site conditions | 78 Treatment-Emergent Adverse Events |
| Maxigesic® IV | Incidence of TEAEs of Interest | Cardiac Disorders | 3 Treatment-Emergent Adverse Events |
| Maxigesic® IV | Incidence of TEAEs of Interest | Vascular disorders | 7 Treatment-Emergent Adverse Events |
Secondary
Incidence of TRAEs (Treatment-related Adverse Events)
The incidence of treatment-related adverse events (TEAEs considered by the investigator to be probably or definitely related to the study drug) associated with exposure Maxigesic® IV
Time frame: During treatment period (≥ 48 hours - 5 days)
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maxigesic® IV | Incidence of TRAEs (Treatment-related Adverse Events) | Not related | 103 Treatment-Emergent Adverse Events |
| Maxigesic® IV | Incidence of TRAEs (Treatment-related Adverse Events) | Unlikely | 89 Treatment-Emergent Adverse Events |
| Maxigesic® IV | Incidence of TRAEs (Treatment-related Adverse Events) | Possible | 34 Treatment-Emergent Adverse Events |
| Maxigesic® IV | Incidence of TRAEs (Treatment-related Adverse Events) | Probable | 17 Treatment-Emergent Adverse Events |
| Maxigesic® IV | Incidence of TRAEs (Treatment-related Adverse Events) | Definite | 51 Treatment-Emergent Adverse Events |
Secondary
Patient's Global Evaluation of the Study Drug
Summary of the patients' ratings of the study medication (1 = Poor; 2 = Fair; 3 = Good; 4 = Very Good; 5 = Excellent)
Time frame: 5 days after the first dose
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Maxigesic® IV | Patient's Global Evaluation of the Study Drug | Poor | 4 Participants |
| Maxigesic® IV | Patient's Global Evaluation of the Study Drug | Fair | 12 Participants |
| Maxigesic® IV | Patient's Global Evaluation of the Study Drug | Good | 40 Participants |
| Maxigesic® IV | Patient's Global Evaluation of the Study Drug | Very Good | 82 Participants |
| Maxigesic® IV | Patient's Global Evaluation of the Study Drug | Excellent | 93 Participants |
| Maxigesic® IV | Patient's Global Evaluation of the Study Drug | Missing | 1 Participants |
Secondary
Time Course of TEAEs
The incidence of treatment-emergent adverse events associated with exposure Maxigesic® IV during various study time periods
Time frame: After receiving the first dose of study medication until 7 days after the last dose, a total of approximately 9 days for subjects who received the treatment for 48 hours and 12 days for subjects who received the treatment for 5 days.
Population: The safety analysis was on all participants who were administered at least one dose of study medication, with treatment allocation for analysis based on the actual treatment the participant received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maxigesic® IV | Time Course of TEAEs | Treatment-Emergent Adverse Events Day 1 | 166 Treatment-Emergent Adverse Events |
| Maxigesic® IV | Time Course of TEAEs | Treatment-Emergent Adverse Events Day 2 | 90 Treatment-Emergent Adverse Events |
| Maxigesic® IV | Time Course of TEAEs | Treatment-Emergent Adverse Events Day 3 | 9 Treatment-Emergent Adverse Events |
| Maxigesic® IV | Time Course of TEAEs | Treatment-Emergent Adverse Events Day 4 | 12 Treatment-Emergent Adverse Events |
| Maxigesic® IV | Time Course of TEAEs | Treatment-Emergent Adverse Events Day 5 | 17 Treatment-Emergent Adverse Events |