Postsurgical Analgesia After Hernia Repair

Pilot Phase II Study of AMT-143 for Postsurgical Analgesia After Hernia Repair

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.

Study Overview

• Status: Withdrawn
• Conditions: Hernia, Inguinal; Hernia Inguinal; Hernia Surgery; Hernia, Inguinal/Surgery; Hernia Repair
• Intervention / Treatment: Drug: AMT-143; Other: Saline (NaCl 0,9 %) (placebo); Drug: ropivacaine

Detailed Description

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.

All assessments up to 4 h will be performed in the hospital clinic setting. Post discharge follow-up for the study will be handled on an outpatient basis and will be conducted by a home nurse up to Day 21. The participant will return to the clinical site for a final End of Study visit on Day 28.

All postsurgical assessments will be timed from the start of study drug instillation (Time 0) in the surgical site, prior to suturing. Participants will be discharged from the hospital on the same day as the surgery and study procedures will be performed on a home basis for safety and efficacy assessments of AMT-143 hydrogel and additional PK blood draws up to Day 21 as required. An end of study visit is planned for Day 28.

Data will be reviewed by the Safety Evaluation Committee (SEC) after each Cohort to determine if it is safe to move forward to the next dose level.

Participants undergoing primary open hernia repair, will be randomized to one of three treatment cohorts of escalating doses of AMT-143 hydrogel. Saline Placebo will match the volume of AMT-143 hydrogel in each of the 3 cohorts. Ropivacaine 1% solution will remain constant for each cohort.

Cohort 1:

• 6 participants: 1 mL AMT-143 hydrogel containing 385 mg ropivacaine
• 2 participants: 1 mL Saline Placebo
• 2 participants: 5 mL Ropivacaine 10 mg 1% solution

Cohort 2:

• 6 participants: 2 mL AMT-143 hydrogel containing 770 mg ropivacaine
• 2 participants: 2 mL Saline Placebo
• 2 participants: 5 mL Ropivacaine 10 mg/mL (1%) solution

Cohort 3:

• 6 participants: 3 mL AMT-143 hydrogel containing 1,155 mg ropivacaine
• 2 participants: 3 mL Saline Placebo
• 2 participants: 5 mL Ropivacaine 10 mg/mL (1%) solution Study drug will be administered locally (from a syringe) into the surgical site prior to wound closure.

The SEC will monitor safety, efficacy and PK data from each cohort to determine if it is safe to move to the next cohort.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
      • McMaster University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

The following inclusion criteria apply to all participants scheduled for open inguinal hernia repair in all cohorts.

1. Provides voluntary written informed consent.
2. Participants are ≥18 years of age at screening.
3. Scheduled to undergo unilateral open inguinal hernia repair.
4. Body mass index (BMI) ≤40.0 kg/m2.
5. 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.

6. 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.
7. 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.

Exclusion Criteria:

The following exclusion criteria apply to all participants in all cohorts.

1. 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.
2. History of hypersensitivity to any ingredient in the formulation (hyaluronan or methylcellulose).
3. History of hypersensitivity or allergy to amide type local anaesthetics (lidocaine, bupivacaine, or ropivacaine).
4. History of ventricular tachycardia, ventricular fibrillation, or atrioventricular block without a pacemaker.
5. Have a clinically significant abnormal clinical laboratory test value, according to the judgement of the investigator.
6. Have a clinically significant 12-lead ECG abnormality, according to the judgement of the investigator.
7. 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).
8. Have received any investigational product within 30 days before dosing with study medication.
9. Suspected or known history of substance abuse and/or alcoholism.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline Placebo	Other: Saline (NaCl 0,9 %) (placebo); Saline placebo will consist of 0.9% sodium chloride injection USP and will be administered in an amount matching the volume of AMT-143 to be used in each of the Cohorts 1 to 3.
Experimental: AMT-143	Drug: AMT-143; AMT-143 is provided as a hydrogel containing 385 mg/mL ropivacaine (on a ropivacaine hydrochloride equivalence basis). Participants undergoing primary open hernia repair, will be randomized to one of three treatment cohorts of escalating doses of AMT-143 hydrogel: Cohort 1: 1 mL AMT-143 hydrogel; Cohort 2: 2 mL AMT-143 hydrogel; Cohort 3: 3 mL AMT-143 hydrogel
Active Comparator: Ropivacaine solution	Drug: ropivacaine; The active comparator, ropivacaine hydrochloride 1% solution will be administered at a volume of 5 mL (50 mg) for all 3 cohorts.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events to evaluate the safety and tolerability of AMT-143	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.	From surgery to Day 28 follow-up
Pharmacokinetics of AMT-143	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).	From surgery to Day 28 follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analgesic efficacy of AMT-143	To evaluate analgesic efficacy of AMT-143 for postsurgical pain management following inguinal hernia repair surgery utilizing the Numeric Rating Scale (NRS). The NRS runs from 0 (no pain) to 10 (worst pain).	From surgery to Day 28 follow-up

Collaborators and Investigators

• Sponsor: AmacaThera Inc.
• Investigators: Principal Investigator: James Paul, MD, McMaster University

Study record dates

Study Major Dates

• Study Start (Estimated): January 27, 2025
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: October 31, 2024
• First Submitted That Met QC Criteria: November 25, 2024
• First Posted (Actual): November 29, 2024

Study Record Updates

• Last Update Posted (Actual): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 18, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Pain Control; Abdominal hernia
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Hernia, Abdominal; Pathological Conditions, Signs and Symptoms; Hernia; Hernia, Inguinal; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Ropivacaine; Sodium Chloride
• Other Study ID Numbers: AMT-143-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pilot study with limited enrollment.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No