Clinical trial NCT04005755: Maxigesic® IV Phase 3 Exposure Study
Official title: A Phase 3, Open-Label, Multiple-Dose, Single-Arm Exposure Study of Maxigesic® IV in Patients With Acute Pain Following Orthopedic, General or Plastic Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Postoperative Pain
Keywords: Analgesic
Lead sponsor: AFT Pharmaceuticals, Ltd.
Sponsor class: INDUSTRY
First posted: 2019-07-02
Enrollment: 232
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of TEAEs (Treatment-emergent Adverse Events)
timeFrame: During treatment period (≥ 48 hours - 5 days)
Secondary outcomes:
measure: Time Course of TEAEs
timeFrame: 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.
measure: Incidence of TRAEs (Treatment-related Adverse Events)
timeFrame: During treatment period (≥ 48 hours - 5 days)
measure: Incidence of TEAEs of Interest
timeFrame: During treatment period (≥ 48 hours - 5 days)
measure: Changes in Blood Pressure
timeFrame: From the baseline (Day 1 prior to surgery) until 7 days after the last dose
measure: Changes in Heart Rate
timeFrame: From the baseline (Day 1 prior to surgery) until 7 days after the last dose
measure: Changes in Temperature
timeFrame: From the baseline (Day 1 prior to surgery) until 7 days after the last dose
measure: Changes in Respiratory Rate
timeFrame: From the baseline (Day 1 prior to surgery) until 7 days after the last dose
measure: Changes in Hematology Values (Hemoglobin)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Hematology Values (Hematocrit)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Hematology Values (Platelet Count)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Hematology Values (Red Blood Cell Count)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Hematology Values (White Blood Cell Count)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Hematology Values (Differential Leukocyte Count)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Blood Biochemistry Values (Sodium)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Blood Biochemistry Values (Potassium)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Blood Biochemistry Values (Urea)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Blood Biochemistry Values (Creatinine)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Blood Biochemistry Values (Phosphate)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Blood Biochemistry Values (Glucose)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Blood Biochemistry Values (Albumin)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Blood Biochemistry Values (Total Protein)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Blood Biochemistry Values (Alkaline Phosphates)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Blood Biochemistry Values (Gamma-glutamyl Transferase)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Blood Biochemistry Values (Aspartate Transaminase)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Blood Biochemistry Values (Alanine Transaminase)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Blood Biochemistry Values (Bilirubin)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in ECG (Electrocardiography) Status (Normal/Abnormal)
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Changes in Hepatic Enzymes From Baseline to the End of the Treatment
timeFrame: Prior to surgery, on Day 1 and at discharge (Day 5)
measure: Patient's Global Evaluation of the Study Drug
timeFrame: 5 days after the first dose
Other outcomes:
Locations:
city: Pasadena
country: United States
facility: Chesapeake Reserach Group
state: Maryland
city: Chapel Hill
country: United States
facility: Chapel Hill Research Group
state: North Carolina
city: Christchurch
country: New Zealand
facility: Canterbury Geriatric Medical Research Trust
city: Christchurch
country: New Zealand
facility: Southern Clinical Trials
Study officials:
affiliation: Chesapeake Research Group
name: Ira Gottlieb, DPM
role: PRINCIPAL_INVESTIGATOR
affiliation: Southern Clinical Trials Ltd
name: Simon Carson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chapel Hill Research Group
name: Gregory L Ruff, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CGM Research Trust
name: Nigel Gilchrist, MD
role: PRINCIPAL_INVESTIGATOR
References: