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A Study to Evaluate Safety, PK, Efficacy of TLC590 for Postsurgical Pain Management Following Bunionectomy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03838133
Recruitment Status : Active, not recruiting
First Posted : February 12, 2019
Last Update Posted : June 17, 2019
Sponsor:
Information provided by (Responsible Party):
Taiwan Liposome Company

Brief Summary:
This is a Phase 2, randomized, double-blind, comparator- and placebo-controlled study to evaluate the safety, PK, and efficacy of TLC590 compared with Naropin® and Placebo via a single infiltrative local administration in adult subjects following bunionectomy.

Condition or disease Intervention/treatment Phase
Hallux Valgus Drug: TLC590 Drug: Naropin® Drug: Normal Saline Phase 2

Detailed Description:

This is a Phase 2, randomized, double-blind, comparator- and placebo-controlled study to evaluate the safety, PK, and efficacy of TLC590 compared with Naropin® and Placebo 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 Two Doses of TLC590 versus Naropin® and Placebo. Part 2 of the study will randomize approximately 175 evaluable subjects who meet all entry criteria.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 223 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: 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
Actual Study Start Date : March 5, 2019
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : March 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TLC590 dose 1
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 lyophilized cake will be reconstituted with the TLC590 reconstitution solution to form the TLC590 ropivacaine liposome injectable suspension
Other Name: TLC590 (Ropivacaine Liposome Injectable Suspension)

Experimental: TLC590 dose 2
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 lyophilized cake will be reconstituted with the TLC590 reconstitution solution to form the TLC590 ropivacaine liposome injectable suspension
Other Name: TLC590 (Ropivacaine Liposome Injectable Suspension)

Experimental: TLC590 dose 3
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 lyophilized cake will be reconstituted with the TLC590 reconstitution solution to form the TLC590 ropivacaine liposome injectable suspension
Other Name: TLC590 (Ropivacaine Liposome Injectable Suspension)

Active Comparator: Naropin®
Naronpin injection contains ropivacaine HCl. 50 mg (0.5%, 10 mL)
Drug: Naropin®
Local infiltration of Naropin to produce anesthesia for surgery and analgesia in postoperative pain management. 50 mg (0.5%, 10 mL)
Other Name: Naropin, 0.5% Injectable Solution

Placebo Comparator: Placebo
Normal Saline (0.9% sodium chloride, 10 mL)
Drug: Normal Saline
Normal Saline (0.9% sodium chloride, 10ml)
Other Name: Saline




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. PK Cmax [ Time Frame: 0-168 hours ]
    Maximum blood concentration (Cmax)

  2. PK Tmax [ Time Frame: 0-168 hours ]
    Time to reach maximum blood concentration (Tmax)

  3. PK t½ [ Time Frame: 0-168 hours ]
    Terminal elimination half-life (t½)

  4. PK AUC [ Time Frame: 0-24, 0-48 , 0-72, 0-96 hours ]
    Area under the blood concentration-time curve (AUC)

  5. Number of treatment emergent adverse event (TEAE) [ Time Frame: Screening through Day 43 ]
    Number of treatment emergent adverse event (TEAE) occurred in the study

  6. Electrocardiogram (RR interval, QRS duration, QT duration, PR duration, QTcF interval) [ Time Frame: Screening through Day 43 ]
    The 12-lead electrocardiogram (ECG) result will be assessed including RR interval, QRS duration, QT duration, PR duration, and QTcF interval

  7. Wound assessment by Numerical Pain Rating Scale (NPRS) [ Time Frame: Day 1 through Day 43 ]

    The surgical site will be examined by the investigator using a 5-point numerical pain rating scale as follows:

    1. Normal healing
    2. Bruising, erythema, edema
    3. Clear or hemoserous drainage
    4. Evidence of cellulitis such as heat, spreading erythema, purulent discharge
    5. Tissue breakdown, wound dehiscence, hematoma requiring aspiration

  8. 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 ]
    AUC of NPRS-R (0-10)

  9. Proportion of pain-free (NPRS-R of 0 or 1) subjects [ Time Frame: at 12, 24, 36, 48, 72, 96, 120, and 168 hours ]
    Proportion of pain-free (NPRS-R of 0 or 1) subjects

  10. Proportion of subjects who used no rescue opioid analgesic [ Time Frame: through 12, 24, 36, 48, 72, 96, 120, and 168 hours ]
    Proportion of subjects who used no rescue opioid analgesic

  11. Time to the first postoperative use of rescue opioid analgesics [ Time Frame: Day 1 to Day 43 ]
    Time to the first postoperative use of rescue opioid analgesics

  12. Total postoperative consumption of rescue opioid analgesics used [ Time Frame: through 24, 36, 48, 60, 72, 96, 120, and 168 hours ]
    Total postoperative consumption of rescue opioid analgesics used



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Able and willing to provide a written informed consent.
  2. Male or female between 18 and 65 years of age.
  3. Body mass index ≤ 35 kg/m2.
  4. Mild to moderate hallux valgus deformity.
  5. Scheduled to undergo a primary, unilateral first metatarsal bunionectomy repair under local anesthesia.
  6. American Society of Anesthesiology Physical Status Classification of 1 or 2 at screening.
  7. 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.
  8. 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:

  1. Clinically significant abnormal clinical laboratory test value.
  2. Evidence of a clinically significant 12-lead ECG abnormality.
  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 that would preclude participation in the study.
  5. History of migraine or seizures or currently taking anticonvulsants.
  6. History of hypersensitivity to ropivacaine, any other amide-type local anesthetic, propofol, lidocaine, midazolam, acetaminophen, naproxen, morphine or oxycodone (or other opioids).
  7. Concurrent painful physical condition that may confound post-operative pain assessments.
  8. Persistent or recurrent nausea and/or vomiting due to other etiologies.
  9. History of severe or refractory post-operative nausea or vomiting (PONV) deemed clinically significant.
  10. History of alcohol abuse or prescription/illicit drug abuse within 2 years.
  11. Current evidence of alcohol abuse within 6 months.
  12. Received opioid therapy for longer than 4 days per week within 2 months or opioid use within 2 weeks.
  13. Use of concurrent therapy that could interfere with the evaluation of efficacy or safety.
  14. 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.
  15. 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.
  16. Positive results on the urine drug screen or alcohol breath test indicative of illicit drug or alcohol abuse.
  17. History or positive test results for HIV; active Hepatitis B or C.
  18. Contralateral foot bunionectomy in the last 3 months or have collateral procedures.
  19. 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.
  20. History of rheumatoid disease, Type 1 or Type 2 diabetes or peripheral circulatory disorders.
  21. Documented sleep apnea or are on home continuous positive airway pressure.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03838133


Locations
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United States, California
Anaheim Clinical Trials
Anaheim, California, United States, 92801
United States, Utah
JBR clinical research
Draper, Utah, United States, 84020
Sponsors and Collaborators
Taiwan Liposome Company
Investigators
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Study Director: Carl Brown, PhD Taiwan Liposome Company

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Responsible Party: Taiwan Liposome Company
ClinicalTrials.gov Identifier: NCT03838133     History of Changes
Other Study ID Numbers: TLC590A1002
First Posted: February 12, 2019    Key Record Dates
Last Update Posted: June 17, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Hallux Valgus
Foot Deformities
Musculoskeletal Diseases
Ropivacaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents