A Phase II, Dose-escalating, Randomized, Double-blind, Multicenter Study to Evaluate the Efficacy, Safety and Pharmacokinetic Profile of MDT-10013 Versus Standard of Care in the Treatment of Acute Postoperative Pain Following Bunionectomy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 192
- 试验地点
- 1
- 主要终点
- Summed Pain Intensity Over 1- 48hrs (SPI-48) From Cohort 1 to 3
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of MDT-10013 in men and women 18 to 80 years of age who are undergoing bunionectomy. The primary objective is to determine the analgesic efficacy of MDT-10013 compared with standard of care in the treatment of acute postoperative pain after subjects undergo bunionectomy.
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, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is male or female aged 18 to 80 years.
- •Has a body mass index from 18 kg/m2 to 40 kg/m
- •Is scheduled to undergo primary, unilateral, first metatarsal bunionectomy (osteotomy and internal fixation) with no additional collateral procedures.
- •Is classified by American Society of Anesthesiologists Physical Status Classification System as Class I or II.
- •Must meet the following criteria if female:
- •Is of non-childbearing potential, defined as any woman who has undergone surgical sterilization or is more than 2 years postmenopausal
- •If of childbearing potential, may be enrolled on the condition that results of a pregnancy test are negative at baseline (at Screening and before surgery) and that she is routinely using an effective method of birth control with a low failure rate (i.e., hormonal contraception, intrauterine device, condoms in combination with a spermicidal cream, or total sexual abstinence)
- •Has read, understood, and signed the informed consent prior to study entry.
- •Is mentally competent, reliable, and cooperative to undergo all visits and procedures scheduled in the study protocol and to record the required information.
- •Has medical history, physical examination, vital signs, laboratory tests, and 12-lead electrocardiograms (ECGs) that are normal or without clinically relevant abnormalities as per investigator's judgment.
排除标准
- •Is a female who is pregnant or breastfeeding.
- •Is not indicated for surgery because of an inflammatory process or risk of infection or delayed wound healing (e.g., autoimmune disorder).
- •Has a history of allergy or hypersensitivity to the components in the investigational product or to the opioid medication (oxycodone).
- •Before surgery, has current orthostatic hypotension (defined as systolic blood pressure decrease of at least 20 mm Hg or a diastolic blood pressure decrease of at least 10 mm Hg or an increase in heart rate by 20 beats per minute within 3 minutes of sitting up or standing).
- •Has severe asthma, defined as requiring frequent or ongoing treatment to control symptoms. Exercise-induced asthma or mild asthma not requiring ongoing treatment may not be exclusionary at the discretion of the investigator.
- •Has a current gastrointestinal disorder associated with bleeding, a history of such a disorder, or gastrointestinal inflammatory diseases as Crohn's disease or ulcerative colitis.
- •Has any clinically significant cardiovascular condition as evidenced by physical examination, medical history, and/or baseline ECG.
- •Has evidence of bradycardia as shown by heart rate of <50 beats per minute via screening ECG.
- •Has a known infection with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus.
- •Has a chronic pain condition that may interfere with the subject's assessment of pain postoperatively, as determined by the investigator.
- •Has any poorly controlled or serious medical conditions, psychiatric illnesses, or clinically significant laboratory values that, in the opinion of the investigator, could compromise the safety of the subject or the scientific integrity of the study (e.g., uncontrolled hypertension, autoimmune disease, or clinically relevant symptoms of thyroid dysfunction).
- •Has presence or history of local or systemic malignant disease in the past 5 years (history of basal cell carcinoma will be allowed).
- •Has impaired renal function (creatinine >1.5 times upper limit of normal).
- •Has chronic impairment liver function (aspartate aminotransferase or alanine aminotransferase >3 times upper limit of normal).
- •Has insulin-dependent diabetes or uncontrolled diabetes mellitus (glycosylated hemoglobin >7%).
- •Has leukopenia (<3500 leukocytes/μL).
- •Has current treatment with any of the following medications:
- •Systemic corticosteroids (intranasal/inhaled steroids are acceptable).
- •Immunosuppressant therapy to treat autoimmune diseases (e.g., rheumatoid arthritis, multiple sclerosis, myasthenia gravis, systemic lupus erythematosus, sarcoidosis, focal segmental glomerulosclerosis, Crohn's disease, Behcet's Disease, pemphigus, and ulcerative colitis).
- •Oral or topical products that contain clonidine (e.g., Catapres).
- •Herbal supplements that contain yohimbine.
- •Anticoagulant/antiplatelet therapy (prophylactic aspirin at 81 mg/day is acceptable). If applicable, aspirin therapy should be held before and after the study procedure on the basis of the investigator's discretion.
- •Antiepileptic drugs, antipsychotics, tricyclic antidepressants, monoamine oxidase inhibitors, lithium, and sulfonamides.
- •Calcium channel blocker, digoxin, or beta-adrenergic blockers.
- •Has chronic use of opioids (including tramadol), defined as use 20 out of the last 30 days before study screening.
- •Has a history of or current diagnosis of epilepsy.
- •Has a known or suspected history of drug or alcohol abuse (as determined by the investigator).
- •Is judged by the investigator not to be a suitable candidate for study treatment and pain relief medication on the basis of medical history, concomitant medication, and concurrent systemic disease.
- •Is not stabilized on the following medications for at least 8 weeks prior to dosing: selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).
- •Is unable to refrain from taking nonsteroidal anti inflammatory drugs (NSAIDs) or opioids within the 24-hour period prior to surgery.
- •Has participated in any other clinical trial in the 4 weeks prior to Screening.
- •Experiences any surgical complication that, in the opinion of the investigator, precludes implantation of MDT-10013.
研究组 & 干预措施
MDT-10013
Subjects will receive MDT-10013.
干预措施: MDT-10013 (Drug)
Standard of Care
Subjects will receive standard of care.
干预措施: Standard of care for pain (Drug)
结局指标
主要结局
Summed Pain Intensity Over 1- 48hrs (SPI-48) From Cohort 1 to 3
时间窗: over 1 to 48hrs
Summed pain intensity is a time-weighted average pain score in numeric rating scale (NRS) over 1 to 48hrs (SPI-48). Summed pain intensity is calculated as area under the curve, using the trapezoidal rule to bridge adjacent time points. Specifically, NRS scores for two adjacent time points are averaged and then multiplied by the time span between points (in hours). The theoretical range for SPI-48 is 0 to 470, with lower scores indicative of less pain over this time period (i.e., lower scores are consistent with better analgesia). Time 0 was defined as the time the capsule was closed.
Summed Pain Intensity Over 1- 48hrs (SPI-48)--Sensitivity Analysis Using Windowed Worst Observation Carried Forward (WOCF)
时间窗: over 1 to 48hrs
Similar to SPI-48, the theoretical range for this WOCF adjustment for rescue medication is 0-470, with lower scores indicative of less pain over this time period (i.e., lower scores are consistent with better analgesia). The calculation is identical in terms of area-under the curve using the trapezoidal rule. However, the NRS score at the final assessment prior to each instance of rescue medication is carried forward through for a window based on the approximate half-life of the drug, replacing the raw NRS scores post-rescue for each patient until the end of the pharmacological activity window, at which point calculations revert to raw NRS as applicable. Note that WOCF SPI-48 may include multiple adjustment windows for each patient, depending on the number or rescue events and the active life of the medication selected.
Summed Pain Intensity Over 1- 48hrs (SPI-48)--Sensitivity Analysis Using Last Observation Carried Forward (LOCF)
时间窗: over 1 to 48hrs
Similar to SPI-48, the theoretical range for this LOCF adjustment for rescue medication is 0-470, with lower scores indicative of less pain over this time period (i.e., lower scores are consistent with better analgesia). The calculation is identical to SPI-48 in terms of area-under the curve using the trapezoidal rule. However, the NRS score at the final assessment prior to rescue is carried forward through 48 hours, replacing the raw NRS scores post-rescue for each patient as applicable.
Integrated Summed Pain Intensity Over 1- 48hrs (SPI-48) and Total Opioid Intake in First 48hrs --Sensitivity Analysis Using Silverman Method
时间窗: over 1 to 48hrs
This sensitivity analysis is an integrated assessment of summed pain intensity over 1 to 48hrs (SPI-48) and total opioid intake (ME0-48) in first 48hrs. Briefly, subjects were ranked according to SPI-48 regardless of the treatment received (including Standard of Care, SOC). The mean of all the ranks for this variable was calculated. Then, the percent difference for each individual rank from the pooled mean rank was computed. This process was repeated for total opioid intake in the first 48hrs (ME0-48). The integrated endpoint for each subject was the sum of the rank order percent differences for SPI-48 and ME0-48. The theoretical minimum and maximum on the integrated endpoint are -197% and +197% in this study. Lower scores are better, indicative of less pain and/or less opioid intake.
次要结局
- Total Use of Opioid Analgesia Over 0 to 24hrs, 0 to 48hrs, 0 to 72hrs, and 0 to 96hrs.(over 0 to 24hrs, 0 to 48hrs, 0 to 72hrs, and 0 to 96hrs)
- Time to First Use of Opioid Analgesia(up to 96hrs)
- Summed Pain Intensity Scores Over 1- 24hrs (SPI-24), 1- 72hrs (SPI-72) and 1- 96hrs (SPI-96)(over 1 to 24hrs, 1 to 72hrs, and 1 to 96hrs)
- Subject's Satisfaction With Study Treatment(up to 72hrs)