A Phase 2, Randomized, Double-blind, Comparator- and Placebo-controlled Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of TLC590 for Postsurgical Pain Management Following Bunionectomy
Overview
- Phase
- Phase 2
- Intervention
- TLC590
- Conditions
- Hallux Valgus
- Sponsor
- Taiwan Liposome Company
- Enrollment
- 150
- Locations
- 5
- Primary Endpoint
- AUC of numerical pain rating scale
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This is a Phase 2, randomized, double-blind, 2-part comparator- and placebo-controlled study to evaluate the safety, PK, and efficacy of TLC590 via a single infiltrative local administration in adult subjects following bunionectomy.
Detailed Description
This is a Phase 2, randomized, double-blind, 2-part comparator- and placebo-controlled study to evaluate the safety, PK, and efficacy of TLC590 via a single infiltrative local administration in adult subjects following bunionectomy. The primary objective of this study is to evaluate the analgesic efficacy of TLC590 for post-surgical pain management in subjects following bunionectomy. The secondary objectives of this study are: * To evaluate the pharmacokinetic (PK) profile and dose-exposure relationship of TLC590, as well as the bioavailability as compared with Naropin®. * To evaluate the safety and tolerability of TLC590 for post-surgical pain management in subjects following bunionectomy. * To evaluate the exposure-response relationship between PK parameters and pain intensity. The study will be divided into two parts: Part 1: Blinded Pharmacokinetics of TLC590 and Naropin®. Approximately 48 subjects will be randomized to treatments. Part 2: Efficacy and Safety of TLC590 versus bupivacaine and Placebo. Part 2 of the study will randomize approximately 150 evaluable subjects who meet all entry criteria.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Able and willing to provide a written informed consent.
- •Male or female between 18 and 65 years of age.
- •Body mass index ≤ 35 kg/m
- •Mild to moderate hallux valgus deformity.
- •Scheduled to undergo a primary, unilateral first metatarsal bunionectomy repair under local anesthesia.
- •American Society of Anesthesiology Physical Status Classification of 1 or 2 at screening.
- •Female subjects are eligible only if all of the following apply:
- •Not pregnant;
- •Not lactating;
- •Not planning to become pregnant during the study;
Exclusion Criteria
- •Clinically significant abnormal clinical laboratory test value.
- •Evidence of a clinically significant 12-lead ECG abnormality.
- •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 that would preclude participation in the study.
- •A history of seizure disorder or currently taking anticonvulsants.
- •History of hypersensitivity to ropivacaine, any other amide-type local anesthetic, propofol, lidocaine, midazolam, acetaminophen, naproxen, morphine or oxycodone (or other opioids).
- •Concurrent painful physical condition that may confound post-operative pain assessments.
- •Persistent or recurrent nausea and/or vomiting due to other etiologies.
- •History of severe or refractory post-operative nausea or vomiting (PONV) deemed clinically significant.
- •History of alcohol abuse or prescription/illicit drug abuse within 2 years.
Arms & Interventions
TLC590 dose 1 (152 mg)
TLC590 (Ropivacaine Liposome Injectable Suspension) is a sustained-release liposome formulation of ropivacaine, white aqueous suspension with ropivacaine concentration at approximately 19 mg/mL.
Intervention: TLC590
TLC590 dose 2 (190 mg)
TLC590 (Ropivacaine Liposome Injectable Suspension) is a sustained-release liposome formulation of ropivacaine, white aqueous suspension with ropivacaine concentration at approximately 19 mg/mL.
Intervention: TLC590
TLC590 dose 3 (228 mg)
TLC590 (Ropivacaine Liposome Injectable Suspension) is a sustained-release liposome formulation of ropivacaine, white aqueous suspension with ropivacaine concentration at approximately 19 mg/mL.
Intervention: TLC590
Naropin®
Naronpin injection contains ropivacaine HCl 50 mg (0.5%, 10 mL)
Intervention: Naropin®
Placebo
Normal Saline (0.9% sodium chloride, 10 mL)
Intervention: Normal Saline
Bupivacaine
Bupivacaine HCl 50 mg (0.5%, 10 mL)
Intervention: Bupivacaine
Outcomes
Primary Outcomes
AUC of numerical pain rating scale
Time Frame: 0-24 hours, 0-72 hours
AUC of numerical pain rating scale (NPRS-R) following bunionectomy surgery
Secondary Outcomes
- PK Tmax(0-168 hours)
- PK Cmax(0-168 hours)
- PK AUC(0-24, 0-48 , 0-72, 0-96 hours)
- Electrocardiogram (RR interval, QRS duration, QT duration, PR duration, QTcF interval)(Screening through Day 43)
- Wound assessment by Numerical Pain Rating Scale (NPRS)(Day 1 through Day 43)
- Proportion of subjects who used no rescue opioid analgesic(through 12, 24, 36, 48, 72, 96, 120, and 168 hours)
- Time to the first postoperative use of rescue opioid analgesics(Day 1 to Day 43)
- PK t½(0-168 hours)
- Number of treatment emergent adverse event (TEAE)(Screening through Day 43)
- AUC of NPRS-R (0-10)(0-36, 0-48, 0-72, 0-96, 0-120,24-48, 48-72, 72-96, 96-120, and 120-168 hours)
- Proportion of pain-free (NPRS-R of 0 or 1) subjects(at 12, 24, 36, 48, 72, 96, 120, and 168 hours)
- Total postoperative consumption of rescue opioid analgesics used(through 24, 36, 48, 60, 72, 96, 120, and 168 hours)