Maxigesic IV Bunionectomy Study- A Phase 3, Randomized, Double-Blind, Multiple-Dose, Parallel-Group and Placebo-Controlled Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 276
- 试验地点
- 2
- 主要终点
- 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).
研究概览
简要总结
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
详细描述
AFT Pharmaceuticals Ltd. has been developing a fixed-dose combination of acetaminophen 1000mg and ibuprofen 300mg/100mL solution for infusion (Maxigesic IV) for the temporary relief of postoperative pain, when administration by intravenous route is clinically justified by an urgent need to treat pain or hyperthermia and/or when other routes of administration not possible.
A phase 3 efficacy study (AFT-MXIV-07) is proposed to determine the analgesic effects of the fixed dose combination product Maxigesic IV versus its individual components (acetaminophen IV and ibuprofen IV) and placebo in participants with acute post-operative pain after bunionectomy.
The primary efficacy objective is to determine the efficacy of Maxigesic IV, acetaminophen IV, Ibuprofen IV versus placebo IV as measured by the summed pain intensity difference (SPID) (calculated as a time-weighted average) over 0-48 hours (SPID-48) after time 0.
Other secondary efficacy endpoints are:
VAS Pain intensity difference (PID) at each scheduled assessment time point after Time 0 VAS Pain intensity score at each scheduled assessment time point 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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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/m
- •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.
排除标准
- •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.
- •Has been treated with agents that could affect the analgesic response (such as central alpha agents [clonidine and tizanidine], neuroleptic agents, and other antipsychotic agents) within 2 weeks before dosing with study drug.
- •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], and lactate dehydrogenase, 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.
- •Has significant difficulties swallowing capsules or is unable to tolerate oral medication.
- •Previously participated in another clinical study of Maxigesic® IV or received any investigational drug or device or investigational therapy within 30 days before Screening.
研究组 & 干预措施
Maxigesic IV
intravenous acetaminophen1000 mg + intravenous ibuprofen 300 mg/100 ml solution for infusion, 100 mL, every 6 hours for 48 hours
干预措施: Maxigesic IV (Drug)
IV Acetaminophen
IV Acetaminophen 1000 mg/100 mL solution for infusion, 100mL. every 6 hours for 48 hours
干预措施: IV Acetaminophen (Drug)
IV Ibuprofen
IV Ibuprofen 300 mg/100 mL solution for infusion, 100mL every 6 hours for 48 hours
干预措施: IV Ibuprofen (Drug)
Placebo IV
Placebo IV- 100 mL saline for infusion, 100mL every 6 hours for 48 hours
干预措施: Placebo IV (Drug)
结局指标
主要结局
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).
时间窗: 48 hours after the first dose
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).
次要结局
- 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)
- 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)
- Percentage of Subjects Using Rescue Medication(48 hrs 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)
- 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)
- The Percentage of Participants Who Evaluated Their Study Drug as " Excellent" on a 5-point Categorical Scale Global Evaluation of Study Drug(48 hrs after the first dose)
- Percentage of Participants With Complete Pain Relief(48 hours after the first dose)
- Percentage of Participants Who Obtained a Peak Pain Relief -Value of 3 ('A Lot of Relief') or 4 ('Complete Relief') Prior to the First Dose of Rescue(48 hours after the first dose)
- Time to Peak Pain Relief(48 hrs after the first dose)
- Time to the First Dose of Rescue Medication(48 hrs)
- Total Use of Rescue Medication(24, 48 hrs after the first dose)
- Number of Participants With Treatment Emergent Adverse Events (AEs)(Day 7)