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Maxigesic® IV Phase 3 Exposure Study

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ClinicalTrials.gov Identifier: NCT04005755
Recruitment Status : Recruiting
First Posted : July 2, 2019
Last Update Posted : March 13, 2020
Sponsor:
Information provided by (Responsible Party):
AFT Pharmaceuticals, Ltd.

Brief Summary:
The study aims to determine the tolerability of repeated doses of Maxigesic® IV over an extended period of exposure.

Condition or disease Intervention/treatment Phase
Postoperative Pain Drug: Maxigesic® IV Phase 3

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 225 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 22, 2019
Estimated Primary Completion Date : March 2, 2020
Estimated Study Completion Date : June 28, 2020

Arm Intervention/treatment
Experimental: 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.
Drug: Maxigesic® IV
acetaminophen 1000 mg + ibuprofen 300 mg, 100 ml solution for infusion




Primary Outcome Measures :
  1. Incidence of TEAEs (treatment-emergent adverse events) [ Time Frame: During treatment period (≥ 48 hours - 5 days) ]
    The incidence of treatment-emergent adverse events associated with exposure Maxigesic® IV


Secondary Outcome Measures :
  1. Time course of TEAEs [ Time Frame: After receiving the first dose of study medication until 7 days after the last dose ]
    The incidence of treatment-emergent adverse events associated with exposure Maxigesic® IV during various study time periods

  2. Incidence of TRAEs (treatment-related adverse events) [ Time Frame: 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

  3. Incidence of TEAEs of interest [ Time Frame: During treatment period (≥ 48 hours - 5 days) ]
    The incidence of TEAEs of interest (cardiovascular, gastrointestinal, renal, hepatic, administration site conditions and bleeding-related events)

  4. Changes in blood pressure [ Time Frame: From the baseline (Day 1 prior to surgery) until 7 days after the last dose ]
    Measured every 24 hours

  5. Changes in heart rate [ Time Frame: From the baseline (Day 1 prior to surgery) until 7 days after the last dose ]
    Measured every 24 hours

  6. Changes in temperature [ Time Frame: From the baseline (Day 1 prior to surgery) until 7 days after the last dose ]
    Measured every 24 hours

  7. Changes in respiratory rate [ Time Frame: From the baseline (Day 1 prior to surgery) until 7 days after the last dose ]
    Measured every 24 hours

  8. Changes in hematology values (hemoglobin) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  9. Changes in hematology values (hematocrit) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  10. Changes in hematology values (Platelet count) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  11. Changes in hematology values (Red blood cell count) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  12. Changes in hematology values (White blood cell count) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  13. Changes in hematology values (Differential Leukocyte count) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  14. Changes in blood biochemistry values (Sodium) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  15. Changes in blood biochemistry values (Potassium) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  16. Changes in blood biochemistry values (Urea) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  17. Changes in blood biochemistry values (Creatinine) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  18. Changes in blood biochemistry values (Phosphate) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  19. Changes in blood biochemistry values (Glucose) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  20. Changes in blood biochemistry values (Albumin) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  21. Changes in blood biochemistry values (Total protein) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  22. Changes in blood biochemistry values (Alkaline phosphates) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  23. Changes in blood biochemistry values (Gamma-glutamyl transferase) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  24. Changes in blood biochemistry values (Aspartate transaminase) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  25. Changes in blood biochemistry values (Alanine transaminase) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  26. Changes in blood biochemistry values (Bilirubin) [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Measured at screening visit and at the end of the treatment

  27. Changes in ECG status (normal/abnormal) [ Time Frame: 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.

  28. Changes in urinalysis values [ Time Frame: Prior to surgery, on Day 1 and at discharge (Day 5) ]
    Test for presence of leukocytes, blood, nitrites, urobilinogen, protein, ketones, bilirubin and glucose.

  29. Patient's global evaluation of the study drug [ Time Frame: 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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04005755


Contacts
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Contact: Jennifer Zhang, MPH + 64 9 488 0232 ext 710 jenniferz@aftpharm.com
Contact: Ioana Stanescu, Phil.Lic + 64 9 488 0232 ext 712 ioana@aftpharm.com

Locations
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United States, Maryland
Chesapeake Reserach Group Recruiting
Pasadena, Maryland, United States, 21122
Contact: Ira J Gottlieb, DPM    410-761-0118    IGottlieb@crgmd.com   
Contact: Neal Surasky    + 1 410 761 0118    NSurasky@crgmd.com   
Principal Investigator: Ira J Gottlieb, DPM         
United States, North Carolina
Chapel Hill Research Group Recruiting
Chapel Hill, North Carolina, United States, 27514
Contact: Gregory L Ruff, MD    919-967-0000    DTunick@CRGMD.com   
Contact: Deborah Tunick    443 557 0374    DTunick@CRGMD.com   
New Zealand
Canterbury Geriatric Medical Research Trust Not yet recruiting
Christchurch, New Zealand, 8083
Contact: Nigel Gilchrist    + 64 3 337 7821    Nigel.Gilchrist@cdhb.health.nz   
Contact: Deirdre Thompson    03 -337 7821    Deirdre.Thompson@gm-research.org.nz   
Southern Clinical Trials Not yet recruiting
Christchurch, New Zealand
Contact: Simon Carson, MD    + 64 9 3371 979    simon@sctrials.co.nz   
Contact: Julia Mathieson    + 64 3 3371 979    julia@sctrials.co.nz   
Principal Investigator: Simon Carson, MD         
Sponsors and Collaborators
AFT Pharmaceuticals, Ltd.
Investigators
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Principal Investigator: Ira Gottlieb, DPM Chesapeake Research Group
Principal Investigator: Simon Carson, MD Southern Clinical Trials Ltd
Principal Investigator: Gregory L Ruff, MD Chapel Hill Research Group
Principal Investigator: Nigel Gilchrist, MD CGM Research Trust
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Responsible Party: AFT Pharmaceuticals, Ltd.
ClinicalTrials.gov Identifier: NCT04005755    
Other Study ID Numbers: AFT-MXIV-11
First Posted: July 2, 2019    Key Record Dates
Last Update Posted: March 13, 2020
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AFT Pharmaceuticals, Ltd.:
Analgesic
Additional relevant MeSH terms:
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Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Neurologic Manifestations
Signs and Symptoms