- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03838133
A Study to Evaluate Safety, PK, Efficacy of TLC590 for Postsurgical Pain Management Following Bunionectomy
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
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Arizona
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Phoenix, Arizona, United States, 85053
- Arizona Research Center
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California
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Anaheim, California, United States, 92801
- Anaheim Clinical Trials, LLC
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Maryland
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Pasadena, Maryland, United States, 21122-1020
- Chesapeake Research Group
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Texas
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San Antonio, Texas, United States, 78229
- Endeavor Clinical Trials
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Utah
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Draper, Utah, United States, 84020
- JBR Clinical Research
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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/m2.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: SUPPORTIVE_CARE
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: 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.
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TLC590, a sustained-release formulation of the local anesthetics with lipid-based excipients
Other Names:
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EXPERIMENTAL: 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.
|
TLC590, a sustained-release formulation of the local anesthetics with lipid-based excipients
Other Names:
|
EXPERIMENTAL: 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.
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TLC590, a sustained-release formulation of the local anesthetics with lipid-based excipients
Other Names:
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ACTIVE_COMPARATOR: Naropin®
Naronpin injection contains ropivacaine HCl 50 mg (0.5%, 10 mL)
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Local infiltration of Naropin to produce anesthesia for surgery and analgesia in postoperative pain management.
50 mg (0.5%, 10 mL)
Other Names:
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PLACEBO_COMPARATOR: Placebo
Normal Saline (0.9% sodium chloride, 10 mL)
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Normal Saline (0.9% sodium chloride, 10ml)
Other Names:
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ACTIVE_COMPARATOR: Bupivacaine
Bupivacaine HCl 50 mg (0.5%, 10 mL)
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Bupivacaine 50 mg (0.5%, 10 mL)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
AUC of numerical pain rating scale
Time Frame: 0-24 hours, 0-72 hours
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AUC of numerical pain rating scale (NPRS-R) following bunionectomy surgery
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0-24 hours, 0-72 hours
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
PK Cmax
Time Frame: 0-168 hours
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Maximum blood concentration (Cmax)
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0-168 hours
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PK Tmax
Time Frame: 0-168 hours
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Time to reach maximum blood concentration (Tmax)
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0-168 hours
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PK t½
Time Frame: 0-168 hours
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Terminal elimination half-life (t½)
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0-168 hours
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PK AUC
Time Frame: 0-24, 0-48 , 0-72, 0-96 hours
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Area under the blood concentration-time curve (AUC)
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0-24, 0-48 , 0-72, 0-96 hours
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Number of treatment emergent adverse event (TEAE)
Time Frame: Screening through Day 43
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Number of treatment emergent adverse event (TEAE) occurred in the study
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Screening through Day 43
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Electrocardiogram (RR interval, QRS duration, QT duration, PR duration, QTcF interval)
Time Frame: Screening through Day 43
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The 12-lead electrocardiogram (ECG) result will be assessed including RR interval, QRS duration, QT duration, PR duration, and QTcF interval
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Screening through Day 43
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Wound assessment by Numerical Pain Rating Scale (NPRS)
Time Frame: Day 1 through Day 43
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The surgical site will be examined by the investigator using a 5-point numerical pain rating scale as follows:
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Day 1 through Day 43
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AUC of NPRS-R (0-10)
Time Frame: 0-36, 0-48, 0-72, 0-96, 0-120,24-48, 48-72, 72-96, 96-120, and 120-168 hours
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AUC of NPRS-R (0-10)
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0-36, 0-48, 0-72, 0-96, 0-120,24-48, 48-72, 72-96, 96-120, and 120-168 hours
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Proportion of pain-free (NPRS-R of 0 or 1) subjects
Time Frame: at 12, 24, 36, 48, 72, 96, 120, and 168 hours
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Proportion of pain-free (NPRS-R of 0 or 1) subjects
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at 12, 24, 36, 48, 72, 96, 120, and 168 hours
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Proportion of subjects who used no rescue opioid analgesic
Time Frame: through 12, 24, 36, 48, 72, 96, 120, and 168 hours
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Proportion of subjects who used no rescue opioid analgesic
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through 12, 24, 36, 48, 72, 96, 120, and 168 hours
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Time to the first postoperative use of rescue opioid analgesics
Time Frame: Day 1 to Day 43
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Time to the first postoperative use of rescue opioid analgesics
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Day 1 to Day 43
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Total postoperative consumption of rescue opioid analgesics used
Time Frame: through 24, 36, 48, 60, 72, 96, 120, and 168 hours
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Total postoperative consumption of rescue opioid analgesics used
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through 24, 36, 48, 60, 72, 96, 120, and 168 hours
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Postoperative Complications
- Pain
- Neurologic Manifestations
- Musculoskeletal Diseases
- Foot Deformities
- Pain, Postoperative
- Hallux Valgus
- Physiological Effects of Drugs
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Sensory System Agents
- Anesthetics
- Anesthetics, Local
- Bupivacaine
- Ropivacaine
Other Study ID Numbers
- TLC590A1002
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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