Pilot Phase II Study of AMT-143 for Postsurgical Analgesia After Hernia Repair
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 30
- 主要终点
- Incidence of Treatment-Emergent Adverse Events to evaluate the safety and tolerability of AMT-143
研究概览
简要总结
The study is designed to evaluate the safety, efficacy, and pharmacokinetics (PK) of three ascending doses of AMT-143 to determine the appropriate dose of AMT-143 for the management of postsurgical pain following inguinal hernia repair.
详细描述
This is a Pilot Phase II Study of AMT-143 for Postsurgical Analgesia After Hernia Repair considered Phase IIa. The study is designed to evaluate the safety, efficacy, and pharmacokinetics (PK) of three ascending doses of AMT-143 to determine the appropriate dose of AMT-143 for the management of postsurgical pain following inguinal hernia repair.
This will be a randomized, single blind, placebo and active controlled, dose escalation study performed at one clinical site to determine optimal doses of AMT-143. The study will consist of 30 participants, 10 per dose: 6 participants will receive AMT-143 hydrogel, 2 participants will receive saline placebo, and 2 will receive the active control ropivacaine hydrochloride 1% solution.
The 30 participants will be randomly assigned sequentially to one of 3 treatment cohorts of escalating doses of AMT-143. Participants will receive AMT-143, or saline placebo, or ropivacaine 1% solution. Participants will be blinded to treatment.
Each cohort consists of 10 participants who will be dosed in a sequential manner to evaluate the safety, efficacy, and PK of three ascending doses of AMT-143 hydrogel (concentration 385 mg/mL) at 385, 770, and 1,155 mg ropivacaine. The volume of saline placebo will match the volume of AMT-143 used while the 1% ropivacaine solution active control will be administered at the same volume for each Cohort.
Study drug will be administered via syringe instillation into the surgical site prior to wound closure. Participants will be followed for 28 days, both in-clinic and as outpatients for safety, efficacy, and PK assessments. Safety assessment will include incidence of treatment-emergent adverse events (TEAEs), electrocardiogram (ECG) changes, vital signs, clinical laboratory assessments, and physical examination. Efficacy assessments will include pain intensity assessment using the Numeric Rating Scale (NRS) at rest and with active movement (NRS-A) over 28 days and use of rescue medications. Blood samples will be collected before surgery (pre) and after surgery at 1, 2, 4, 9±1 h and then Days 2, 3, 7, 14, 21 and 28.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The following inclusion criteria apply to all participants scheduled for open inguinal hernia repair in all cohorts.
- •Provides voluntary written informed consent.
- •Participants are ≥18 years of age at screening.
- •Scheduled to undergo unilateral open inguinal hernia repair.
- •Body mass index (BMI) ≤40.0 kg/m
- •Male participants must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control for the duration of the study until at least 1 week after the administration of study medication.
- •Female participants:
- •Not pregnant (female participant of childbearing potential must have a negative urine pregnancy test before surgery).
- •Not lactating.
- •Not planning to become pregnant during the study.
- •Be surgically sterile; or at least two years post-menopausal; or have a monogamous partner who is surgically sterile; or is practicing double-barrier contraception; or practicing abstinence (must agree to use double-barrier contraception in the event of sexual activity); or using an insertable, injectable, transdermal, or combination oral contraceptive approved by Health Canada for greater than 2 months prior to screening visits and commits to the use of an acceptable form of birth control for the duration of the study.
- •In the opinion of the Investigator, is willing and able to understand the study procedures, and agrees to adhere to the requirements of the study protocol, in order to enable accurate and appropriate responses to pain scales.
排除标准
- •The following exclusion criteria apply to all participants in all cohorts.
- •Have chronic pain and have been receiving or have received chronic opioid therapy defined as greater than 15 morphine equivalents units per day for greater than 3 out of 7 days per week over a one-month period within 12 months of study treatment initiation.
- •History of hypersensitivity to any ingredient in the formulation (hyaluronan or methylcellulose).
- •History of hypersensitivity or allergy to amide type local anaesthetics (lidocaine, bupivacaine, or ropivacaine).
- •History of ventricular tachycardia, ventricular fibrillation, or atrioventricular block without a pacemaker.
- •Have a clinically significant abnormal clinical laboratory test value, according to the judgement of the investigator.
- •Have a clinically significant 12-lead ECG abnormality, according to the judgement of the investigator.
- •Have received any medications with a potential for drug interactions with ropivacaine (i.e., amide-type local anaesthetics such as lidocaine, bupivacaine, mepivacaine and prilocaine; antiarrhythmics such as procainamide, disopyramide, tocainide, mexiletine and flecainide; sedative; strong inhibitors of cytochrome P4501A2 such as fluvoxamine enoxacin, theophylline and imipramine for at least 5 half-lives prior to the start of this).
- •Have received any investigational product within 30 days before dosing with study medication.
- •Suspected or known history of substance abuse and/or alcoholism.
研究组 & 干预措施
AMT-143
干预措施: AMT-143 (Drug)
Saline Placebo
干预措施: Saline (NaCl 0,9 %) (placebo) (Other)
Ropivacaine solution
干预措施: ropivacaine (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events to evaluate the safety and tolerability of AMT-143
时间窗: From surgery to Day 28 follow-up
To evaluate the safety and tolerability of AMT-143 for postsurgical pain management following inguinal hernia repair surgery. The safety endpoint of the study will be the incidence of Treatment Emergent Adverse Events (TEAEs). This will include reported Adverse Events as well as all clinically significant abnormalities in clinical laboratory investigations, vital signs, physical examination results, and ECG tracings.
Pharmacokinetics of AMT-143
时间窗: From surgery to Day 28 follow-up
To assess the PK profile of AMT-143. Plasma samples will be analyzed for ropivacaine concentrations using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Incurred sample reanalysis will be performed on approximately 10% of study samples with a minimum of 20 samples for confirmation of results. At least two thirds of the incurred samples analyzed should have a percent difference between re-assay \& original concentrations within ±20%. Plasma concentration-time data for AMT-143 will be analyzed by the noncompartmental method to obtain the PK parameters using validated Phoenix WinNonlin® version 8.3 or higher software (Pharsight Corp).
次要结局
- Analgesic efficacy of AMT-143(From surgery to Day 28 follow-up)