Phase I/II Dose-escalation Study to Evaluate Safety, PK and Efficacy of TLC590 for Postsurgical Pain Management

NCT03591146 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: TLC590A1001
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

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®

Conditions

Inguinal Hernia

Keywords

Postsurgical Pain Management

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability: Event of SAE and Treatment-related Severe AE

  Event of serious adverse event (SAE) and treatment-related severe adverse event (TRAE)

  Screening till 30 days post investigational product (IP) administration, up to 58 days

Study Arms (5)

TLC590 190mg

EXPERIMENTAL

TLC590 (Ropivacaine Liposome Injectable Suspension) is a sustained-release liposome formulation of ropivacaine, white aqueous suspension with ropivacaine concentration at approximately 19 mg/mL.

Drug: TLC590

TLC590 380mg

EXPERIMENTAL

TLC590 (Ropivacaine Liposome Injectable Suspension) is a sustained-release liposome formulation of ropivacaine, white aqueous suspension with ropivacaine concentration at approximately 19 mg/mL.

Drug: TLC590

TLC590 570mg

EXPERIMENTAL

TLC590 (Ropivacaine Liposome Injectable Suspension) is a sustained-release liposome formulation of ropivacaine, white aqueous suspension with ropivacaine concentration at approximately 19 mg/mL.

Drug: TLC590

TLC590 475mg

EXPERIMENTAL

TLC590 (Ropivacaine Liposome Injectable Suspension) is a sustained-release liposome formulation of ropivacaine, white aqueous suspension with ropivacaine concentration at approximately 19 mg/mL.

Drug: TLC590

Naropin 150mg

ACTIVE COMPARATOR

Naropin injection contains ropivacaine hydrochloride (HCl). Strength: 150mg/ 30mL (5 mg/mL) Size: 30mL fill, in a 30mL single dose vial

Drug: Naropin

Interventions

TLC590 DRUG

TLC590 lyophilized cake will be reconstituted with the TLC590 reconstitution solution to form the TLC590 ropivacaine liposome injectable suspension

Also known as: TLC590 (Ropivacaine Liposome Injectable Suspension)

TLC590 190mg; TLC590 380mg; TLC590 475mg; TLC590 570mg

Naropin DRUG

Local infiltration of Naropin to produce anesthesia for surgery and analgesia in postoperative pain management. Naropin 150mg \[0.5%, 5mg/mL\] x 30mL

Also known as: Naropin, 0.5% Injectable Solution

Naropin 150mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing to provide a written informed consent.
• Male or female between 18 and 65 years of age.
• Scheduled to undergo a primary, unilateral Lichtenstein inguinal hernia repair with mesh, and be able to use the anesthesia regimen.
• American society of anesthesiologists (ASA) Physical Status Classification of 1 or 2.
• 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.
• 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.
• Body mass index ≤ 35 kg/m2.

You may not qualify if:

• Clinically significant abnormal clinical laboratory test value.
• Evidence of a clinically significant 12-lead ECG.
• History or evidence of orthostatic hypotension, syncope or other syncopal attacks.
• History or clinical manifestations of significant renal, hepatic, gastrointestinal, cardiovascular, metabolic, neurologic, psychiatric, or other condition.
• History of seizures or are currently taking anticonvulsants.
• History of hypersensitivity to ropivacaine, any other amide-type local anesthetic, propofol, hydromorphone or oxycodone (or other opioids).
• Persistent or recurrent nausea and/or vomiting due to other etiologies, including, but not limited to gastric outlet obstruction, hypercalcemia, or active peptic ulcer.
• History of severe or refractory post-operative nausea or vomiting deemed clinically significant.
• Concurrent painful condition that may require analgesic treatment during the study period.
• Have been receiving or have received chronic opioid therapy.
• 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.
• History of alcohol abuse or prescription and/or illicit drug abuse within 2 years.
• Current report of alcohol abuse within 6 months.
• Positive results on the urine drug screen or alcohol breath test indicative of illicit drug or alcohol abuse.

Sponsors & Collaborators

• Taiwan Liposome Company: lead

Study Sites (1)

JBR Clinical Research

Draper, Utah, 84020, United States

Location

MeSH Terms

Conditions

Hernia, Inguinal

Interventions

Ropivacaine

Condition Hierarchy (Ancestors)

Hernia, Abdominal; Hernia; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Results Point of Contact

• Title: Cynthia Lin
• Organization: Taiwan Liposome Company

cynthia_lin@tlcbio.com

+886 2 2655 7377

Study Officials

• Carl Brown, PhD

  Taiwan Liposome Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: SUPPORTIVE CARE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 25, 2018
• First Posted: July 19, 2018
• Study Start: July 31, 2018
• Primary Completion: January 5, 2019
• Study Completion: January 14, 2019
• Last Updated: July 14, 2021
• Results First Posted: July 14, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)