Maxigesic IV Phase 3 Bunionectomy Study

NCT02689063 | Completed Phase 3 Results

• 1 other identifier: AFT-MXIV-07
• Study Type: interventional
• Target: 276
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of the study is to determine the clinical efficacy and safety of Maxigesic IV, acetaminophen IV, Ibuprofen IV versus placebo IV for the treatment of acute postoperative pain after bunionectomy

Conditions

Post Operative Pain

Keywords

Analgesic

Outcome Measures

Primary Outcomes (1)

• Summed Pain Intensity Difference (SPID)-Calculated From the Pain Intensity Scores Recorded on a 100mm Long Scale With Anchors for "no Pain" (0 mm) and "Worst Pain Imaginable" (100 mm).

  A Pain Intensity Difference (PID) is the difference between the Visual Analogue Scale (VAS) pain intensity score recorded at baseline and a score recorded at any time after the first dose of study medication. Taken together, a patient's PID scores capture the pain relief profile attributable to the assigned study medication. A high PID score indicates a better pain relief experienced. The extent of pain relief can then be calculated by the Area Under the Curve the PID scores (also referred to as the Sum of Pain Intensity Differences \[SPID\]). SPID48 scores were adjusted by the time interval from baseline to the final VAS score used in the SPID, using the following formula: Time-adjusted SPID48 (mm) = SPID (mm\*hr) / Time (hr) In the event that a patient required rescue medication, the SPID was calculated up until the first Pre-Rescue VAS pain assessment (inclusive).

  48 hours after the first dose

Secondary Outcomes (13)

• VAS Pain Intensity Difference (PID)-Calculated From the Pain Intensity Scores Recorded on a 100mm Long VAS Scale With Anchors for "no Pain" (0 mm) and "Worst Pain Imaginable" (100 mm).

  48 hours after the first dose

• VAS Pain Intensity Score-marking on a 100 mm VAS Scale With Anchors for "no Pain" (0 mm) and "Worst Pain Imaginable" (100 mm). A High VAS Score Indicates a More Intensive Pain Level Experienced.

  48 hours after the first dose

• SPID-6, SPID-12, SPID-24-VAS SPID Over 0 to 6 Hours (SPID-6), Over 0 to 12 Hours (SPID-12), and Over 0 to 24 Hours (SPID-24) After Time 0 (=the First Dose)

  6, 12, 24 hours after the first dose

• TOTPAR-6, TOTPAR-12, TOTPAR-24, TOTPAR-48

  6, 12, 24, 48 hours after the first dose

• Time to the Onset of Analgesia-Time to Onset of Analgesia (Measured as Time to Perceptible Pain Relief Confirmed by Meaningful Pain Relief) Using the Two-stopwatch Method

  6 hours

Study Arms (4)

Maxigesic IV

EXPERIMENTAL

intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours

Drug: Maxigesic IV

IV Acetaminophen

ACTIVE COMPARATOR

IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours

Drug: IV Acetaminophen

IV Ibuprofen

ACTIVE COMPARATOR

IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours

Drug: IV Ibuprofen

Placebo IV

PLACEBO COMPARATOR

Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours

Drug: Placebo IV

Interventions

Maxigesic IV DRUG

IV acetaminophen 1000 mg and IV ibuprofen 300 mg /100 mL solution for infusion, 100mL, every 6 hours for 48 hours

Also known as: Maxigesic

Maxigesic IV

IV Acetaminophen DRUG

IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours

Also known as: Acetaminophen

IV Acetaminophen

IV Ibuprofen DRUG

IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL, every 6 hours for 48 hours

Also known as: Ibuprofen

IV Ibuprofen

Placebo IV DRUG

Placebo IV- 100 mL intravenous saline for infusion, 100mL, every 6 hours for 48 hours

Also known as: Placebo

Placebo IV

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is male or female ≥ 18 and ≤ 65 years of age.
• Is classified by the anesthesiologist as P1 to P2 in the American Society of Anesthesiologists (ASA) Physical Status Classification System.
• Has undergone primary, unilateral, distal, first metatarsal bunionectomy (osteotomy and internal fixation) with no additional collateral procedures.
• Experiences a pain intensity rating of ≥ 40 mm on a 100-mm Visual Analogue Scale (VAS) during the 9-hour period after discontinuation of the anesthetic block.
• Has a body weight ≥ 45 kg and a body mass index (BMI) ≤ 40 kg/m2.
• If female and of childbearing potential, is nonlactating and nonpregnant (has negative pregnancy test results at Screening \[urine\] and on the day of surgery prior to surgery \[urine\]).
• 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:
• 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.
• Total abstinence from sexual intercourse since the last menses before study drug administration through completion of final study visit.
• Intrauterine device (IUD). 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 comply with study requirements (including diet, alcohol, and smoking restrictions), complete the pain evaluations, remain at the study site for approximately 72 hours, and return for follow-up 7 ± 2 days after surgery.

You may not qualify if:

• 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 continues into randomized treatment period or could confound the results of the study.
• Has 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 any ongoing condition, other than a condition associated with the current primary, unilateral, first metatarsal bunionectomy that could generate levels of pain sufficient to confound the results of the study (eg, gout, severe osteoarthritis of the target joint or extremity).
• 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 at Screening only 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 (including, but not limited to, the risks described as precautions, warnings, and contraindications in the current version of the Investigator's Brochure for IV Maxigesic®), 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 (eg, 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 received or will require any analgesic medication within 5 half-lives (or, if half-life is unknown, within 48 hours) before surgery.
• 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.

Sponsors & Collaborators

• AFT Pharmaceuticals, Ltd.: lead

Study Sites (2)

Chesapeake Reserach Group

Pasadena, Maryland, 21122, United States

Location

Optimal Research

Austin, Texas, 78705, United States

Location

Related Publications (2)

• Ferguson MC, Schumann R, Gallagher S, McNicol ED. Single-dose intravenous ibuprofen for acute postoperative pain in adults. Cochrane Database Syst Rev. 2021 Sep 9;9(9):CD013264. doi: 10.1002/14651858.CD013264.pub2.

  PMID: 34499349 DERIVED

• Daniels SE, Playne R, Stanescu I, Zhang J, Gottlieb IJ, Atkinson HC. Efficacy and Safety of an Intravenous Acetaminophen/Ibuprofen Fixed-dose Combination After Bunionectomy: a Randomized, Double-blind, Factorial, Placebo-controlled Trial. Clin Ther. 2019 Oct;41(10):1982-1995.e8. doi: 10.1016/j.clinthera.2019.07.008. Epub 2019 Aug 22.

  PMID: 31447129 DERIVED

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Acetaminophen; Ibuprofen

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids

Results Point of Contact

• Title: Jennifer Zhang -Project Manager
• Organization: AFT Pharmaceuticals

jenniferz@aftpharm.com

+ 64 9 488 0232

Study Officials

• Stephen E Daniels, DO

  Optimal Research LLC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2016
• First Posted: February 23, 2016
• Study Start: October 26, 2016
• Primary Completion: June 30, 2017
• Study Completion: September 15, 2017
• Last Updated: July 6, 2021
• Results First Posted: July 6, 2021

Record last verified: 2016-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)