Inguinal Hernia
Conditions
Keywords
Postsurgical Pain Management
Brief summary
Phase I/II, randomized, double-blind, comparator-controlled, dose-escalation study to assess the safety, PK, and efficacy of single postsurgical application of TLC590 compared with Naropin®
Detailed description
A Phase I/II, randomized, double-blind, comparator-controlled, dose-escalation study to assess the safety, PK, and efficacy of single postsurgical application of TLC590 compared with Naropin® via a single infiltrative local administration in adult subjects following inguinal hernia repair surgery. Approximately 64 evaluable subjects across 4 cohorts. Dose escalation of a single postsurgical administration of TLC590 or Naropin® will be performed. Dose escalation will be determined by review of treatment-related adverse events and all serious adverse events (AEs) by a safety monitoring committee.
Interventions
DRUGTLC590
TLC590 lyophilized cake will be reconstituted with the TLC590 reconstitution solution to form the TLC590 ropivacaine liposome injectable suspension
DRUGNaropin
Local infiltration of Naropin to produce anesthesia for surgery and analgesia in postoperative pain management. Naropin 150mg \[0.5%, 5mg/mL\] x 30mL
Sponsors
Taiwan Liposome Company
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
To maintain objectiveness, the study drug will be managed and administered by an independent unblinded team. Subjects, investigators, and all other site staff who directly interact with subjects, evaluate safety and efficacy, and collect subject data, will remain blinded and must not communicate or discuss any study information with the unblinded team.
Intervention model description
Subjects will be enrolled to each cohort in a 3:1 ratio. Each cohort will comprise subjects receiving a dose of TLC590 and active comparator drug (Naropin® 150 mg) in accordance with the randomization schedule and dose-escalation scheme.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Able and willing to provide a written informed consent. 2. Male or female between 18 and 65 years of age. 3. Scheduled to undergo a primary, unilateral Lichtenstein inguinal hernia repair with mesh, and be able to use the anesthesia regimen. 4. American society of anesthesiologists (ASA) Physical Status Classification of 1 or 2. 5. Female subjects are eligible only if: not pregnant; not lactating; not planning to become pregnant during the study; commits to the use of an acceptable form of birth control. 6. Male subjects must be sterile 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 blinded study medication. 7. Body mass index ≤ 35 kg/m2.
Exclusion criteria
1. Clinically significant abnormal clinical laboratory test value. 2. Evidence of a clinically significant 12-lead ECG. 3. History or evidence of orthostatic hypotension, syncope or other syncopal attacks. 4. History or clinical manifestations of significant renal, hepatic, gastrointestinal, cardiovascular, metabolic, neurologic, psychiatric, or other condition. 5. History of seizures or are currently taking anticonvulsants. 6. History of hypersensitivity to ropivacaine, any other amide-type local anesthetic, propofol, hydromorphone or oxycodone (or other opioids). 7. Persistent or recurrent nausea and/or vomiting due to other etiologies, including, but not limited to gastric outlet obstruction, hypercalcemia, or active peptic ulcer. 8. History of severe or refractory post-operative nausea or vomiting deemed clinically significant. 9. Concurrent painful condition that may require analgesic treatment during the study period. 10. Have been receiving or have received chronic opioid therapy. 11. Use of any of the following medications within 5 half-lives or as specified prior to the study surgical procedure: Anti-platelet agents such as aspirin therapy within 7 days; clopidogrel within 5 days; Anticoagulants such as warfarin within 5 days; dabigatran etexilate mesylate within 2 days; factor Xa inhibitor within 24 hours; Class III antiarrhythmic drugs (e.g., amiodarone); Strong CYP1A2 inhibitors, such as cimetidine, ciprofloxacin, enoxacin, and fluvoxamine; CYP1A2 substrates, such as theophylline or imipramine; Strong CYP3A4 inhibitors such as voriconazole, erythromycin, ketoconazole, or ritonavir; CYP3A4 substrates, such as atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, or tipranavir; Corticosteroids, either systemically, inhaled, intranasally, orally, or by intra-articular injection within 14 days before the study surgical procedure (topical corticosteroid is allowed); Non-steroidal anti-inflammatory drugs (NSAIDs) within 14 days prior to the study surgical procedure; Any investigational product within 30 days prior to administration of blinded study medication. 12. History of alcohol abuse or prescription and/or illicit drug abuse within 2 years. 13. Current report of alcohol abuse within 6 months. 14. Positive results on the urine drug screen or alcohol breath test indicative of illicit drug or alcohol abuse. 15. History of human immunodeficiency virus (HIV), hepatitis C, or hepatitis B. 16. Have had an inguinal hernia repair in the last 3 months before the study surgical procedure or presents with bilateral or recurrent inguinal hernia, other hernia presentations, or hernias with a large scrotal component that would be difficult to reduce surgically.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability: Event of SAE and Treatment-related Severe AE | Screening till 30 days post investigational product (IP) administration, up to 58 days | Event of serious adverse event (SAE) and treatment-related severe adverse event (TRAE) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TLC590 190mg TLC590 (Ropivacaine Liposome Injectable Suspension) is a sustained-release liposome formulation of ropivacaine, white aqueous suspension with ropivacaine concentration at approximately 19 mg/mL.
TLC590: TLC590 lyophilized cake will be reconstituted with the TLC590 reconstitution solution to form the TLC590 ropivacaine liposome injectable suspension | 12 |
| TLC590 380mg TLC590 (Ropivacaine Liposome Injectable Suspension) is a sustained-release liposome formulation of ropivacaine, white aqueous suspension with ropivacaine concentration at approximately 19 mg/mL.
TLC590: TLC590 lyophilized cake will be reconstituted with the TLC590 reconstitution solution to form the TLC590 ropivacaine liposome injectable suspension | 12 |
| TLC590 570mg TLC590 (Ropivacaine Liposome Injectable Suspension) is a sustained-release liposome formulation of ropivacaine, white aqueous suspension with ropivacaine concentration at approximately 19 mg/mL.
TLC590: TLC590 lyophilized cake will be reconstituted with the TLC590 reconstitution solution to form the TLC590 ropivacaine liposome injectable suspension | 12 |
| TLC590 475mg TLC590 (Ropivacaine Liposome Injectable Suspension) is a sustained-release liposome formulation of ropivacaine, white aqueous suspension with ropivacaine concentration at approximately 19 mg/mL.
TLC590: TLC590 lyophilized cake will be reconstituted with the TLC590 reconstitution solution to form the TLC590 ropivacaine liposome injectable suspension | 12 |
| Naropin 150mg Naropin injection contains ropivacaine HCl. Strength: 150mg/ 30mL (5 mg/mL) Size: 30mL fill, in a 30mL single dose vial
Naropin: Local infiltration of Naropin to produce anesthesia for surgery and analgesia in postoperative pain management. Naropin 150mg \[0.5%, 5mg/mL\] x 30mL | 16 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| TLC590 190mg and Naropin 150mg | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 |
| TLC590 380mg and Naropin 150mg | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| TLC590 380mg and Naropin 150mg | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 |
| TLC590 570mg and Naropin 150mg | Lost to Follow-up | 0 | 0 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | TLC590 190mg | TLC590 380mg | TLC590 570mg | TLC590 475mg | Naropin 150mg | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 12 Participants | 12 Participants | 12 Participants | 16 Participants | 64 Participants |
| Body Mass Index (BMI) BMI <=35 kg/m2 | 12 Participants | 12 Participants | 12 Participants | 12 Participants | 16 Participants | 64 Participants |
| Body Mass Index (BMI) BMI > 35 kg/m2 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 12 Participants | 12 Participants | 12 Participants | 16 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 12 Participants | 12 Participants | 12 Participants | 12 Participants | 16 Participants | 64 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 12 Participants | 11 Participants | 12 Participants | 10 Participants | 15 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 16 |
| other Total, other adverse events | 11 / 12 | 8 / 12 | 7 / 12 | 10 / 12 | 13 / 16 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 16 |
Outcome results
Primary
Safety and Tolerability: Event of SAE and Treatment-related Severe AE
Event of serious adverse event (SAE) and treatment-related severe adverse event (TRAE)
Time frame: Screening till 30 days post investigational product (IP) administration, up to 58 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TLC590 190mg | Safety and Tolerability: Event of SAE and Treatment-related Severe AE | 2 Event |
| TLC590 380mg | Safety and Tolerability: Event of SAE and Treatment-related Severe AE | 1 Event |
| TLC570mg | Safety and Tolerability: Event of SAE and Treatment-related Severe AE | 2 Event |
| TLC590 475mg | Safety and Tolerability: Event of SAE and Treatment-related Severe AE | 2 Event |
| Naropin | Safety and Tolerability: Event of SAE and Treatment-related Severe AE | 2 Event |