Hernia Inguinal, Hernia, Inguinal, Hernia, Inguinal/Surgery, Hernia Repair, Hernia Surgery
Conditions
Brief summary
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.
Interventions
DRUGAMT-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
OTHERSaline (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.
DRUGropivacaine
The active comparator, ropivacaine hydrochloride 1% solution will be administered at a volume of 5 mL (50 mg) for all 3 cohorts.
Sponsors
AmacaThera Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events to evaluate the safety and tolerability of AMT-143 | 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 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Analgesic efficacy of AMT-143 | From surgery to Day 28 follow-up | 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). |
Outcome results
None listed