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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 150
- Locations
- 5
- Primary Endpoint
- AUC of numerical pain rating scale
Study 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:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Supportive Care
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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;
- •Commits to the use of an acceptable form of birth control for the duration of the study and for 42 days from administration of study drug.
- •Male subjects must be surgically 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.
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.
- •Current evidence of alcohol abuse within 6 months.
- •Received opioid therapy for longer than 4 days per week within 2 months or opioid use within 2 weeks.
- •Use of concurrent therapy that could interfere with the evaluation of efficacy or safety.
- •Unable to discontinue medications that have not been at a stable dose for at least 14 days prior to the study surgical procedure, within 5 half-lives of the specific prior medication.
- •Use of any of the following medications within 5 half-lives or as specified prior to the study surgical procedure:
- •Low-dose aspirin therapy for cardiovascular protection
- •Class III antiarrhythmic drugs
- •Strong CYP1A2 inhibitors
- •CYP1A2 substrates
- •Strong CYP3A4 inhibitors
- •Corticosteroids, either systemically, inhaled either intranasally or orally, or by intra-articular injection, or NSAIDs within 14 days
- •Any investigational product within 30 days.
- •Positive results on the urine drug screen or alcohol breath test indicative of illicit drug or alcohol abuse.
- •History or positive test results for HIV; active Hepatitis B or C.
- •Contralateral foot bunionectomy in the last 3 months or have collateral procedures.
- •Malignancy in the last 2 years, with the exception of non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
- •History of rheumatoid disease, Type 1 or Type 2 diabetes or peripheral circulatory disorders.
- •Documented sleep apnea or are on home continuous positive airway pressure.
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 (Drug)
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 (Drug)
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 (Drug)
Naropin®
Naronpin injection contains ropivacaine HCl 50 mg (0.5%, 10 mL)
Intervention: Naropin® (Drug)
Placebo
Normal Saline (0.9% sodium chloride, 10 mL)
Intervention: Normal Saline (Drug)
Bupivacaine
Bupivacaine HCl 50 mg (0.5%, 10 mL)
Intervention: Bupivacaine (Drug)
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)