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

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ClinicalTrials.gov Identifier: NCT03591146
Recruitment Status : Completed
First Posted : July 19, 2018
Last Update Posted : April 12, 2019
Sponsor:
Information provided by (Responsible Party):
Taiwan Liposome Company

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®

Condition or disease Intervention/treatment Phase
Inguinal Hernia Drug: TLC590 Drug: Naropin Phase 1 Phase 2

Detailed Description:

A 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® via a single infiltrative local administration in adult subjects following inguinal hernia repair surgery.

Approximately 64 evaluable subjects across 4 cohorts. Dose escalation of a single postsurgical administration of TLC590 or Naropin® will be performed. Dose escalation will be determined by review of treatment-related adverse events and all serious AEs by a safety monitoring committee.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Supportive Care
Official Title: A Phase I/II, Randomized, Double-blind, Comparator-controlled, Dose-escalation Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of TLC590 for Postsurgical Pain Management Following Inguinal Hernia Repair
Actual Study Start Date : July 31, 2018
Actual Primary Completion Date : January 5, 2019
Actual Study Completion Date : January 14, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TLC590
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. Strength: 150mg/ 30mL (5 mg/mL) Size: 30mL fill, in a 30mL single dose vial
Drug: Naropin
Local infiltration of Naropin to produce anesthesia for surgery and analgesia in postoperative pain management. Naropin 150mg [0.5%, 5mg/mL] x 30mL
Other Name: Naropin, 0.5% Injectable Solution




Primary Outcome Measures :
  1. Safety and tolerability: Number of SAEs and treatment-related severe AEs [ Time Frame: Screening till 30 days post IP administration ]
    Number of SAEs and treatment-related severe AEs


Secondary Outcome Measures :
  1. Pain intensity assessed using an 11-point NPRS ranging [ Time Frame: Baseline till 168 hours post IP administration ]
    11-point NPRS ranging from a score of 0 to 10

  2. Patient Global Assessment of the method of pain control [ Time Frame: 24 hours post IP administration till 168 hours post IP administration ]
    Patient Global Assessment: poor, fair, good, or excellent

  3. AUC of NPRS [ Time Frame: For time periods 0-12, 0-24, 0-36, 0-48, 0-72, and 0-96 hours ]
    AUC of NPRS for time periods 0-12, 0-24, 0-36, 0-48, 0-72, and 0-96 hours

  4. Cumulative proportion of pain-free subjects at scheduled timepoints [ Time Frame: Baseline till 168 hours post IP administration ]
    Pain-free defined as an NPRS of 0 or 1

  5. Proportion of pain-free subjects at scheduled timepoints. [ Time Frame: Baseline till 168 hours post IP administration ]
    Pain-free defined as an NPRS of 0 or 1

  6. Cumulative proportion of subjects who used no rescue analgesic [ Time Frame: Baseline till 30 days post IP administration ]
    Cumulative proportion of subjects who used no rescue analgesic through 12, 24, 36, 48, 72, and 96 hours

  7. Time to the first postoperative use of rescue analgesics. Total postoperative consumption of rescue analgesics through 12, 24, 36, 48, 72, and 96 hours [ Time Frame: Baseline till 30 days post IP administration ]
    Time to the first postoperative use of rescue analgesics. Total postoperative consumption of rescue analgesics through 12, 24, 36, 48, 72, and 96 hours

  8. Average daily rescue analgesic consumption [ Time Frame: Baseline till 30 days post IP administration ]
    Average daily rescue analgesic consumption through 24, 48, 72 and 96 hours

  9. Integrated analgesic score using NPRS score and rescue analgesic consumption [ Time Frame: Baseline till 30 days post IP administration ]
    Integrated analgesic score using NPRS score and rescue analgesic consumption

  10. Cumulative proportion of subjects who used no postoperative antiemetic therapy [ Time Frame: Baseline till 30 days post IP administration ]
    Cumulative proportion of subjects who used no postoperative antiemetic therapy through 12, 24, 36, 48, 72, and 96 hours

  11. Incidence of all adverse events by severity and relatedness [ Time Frame: Screening till 30 days post IP administration ]
    Incidence of all adverse events by severity and relatedness

  12. Exposure-response relationship between PK parameters and NPRS scores [ Time Frame: Baseline till 168 hours post IP administration ]
    Exposure-response relationship between PK parameters and NPRS scores



Information from the National Library of Medicine

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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. Scheduled to undergo a primary, unilateral Lichtenstein inguinal hernia repair with mesh, and be able to use the anesthesia regimen.
  4. ASA Physical Status Classification of 1 or 2.
  5. 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.
  6. 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.
  7. Body mass index ≤ 35 kg/m2.

Exclusion Criteria:

  1. Clinically significant abnormal clinical laboratory test value.
  2. Evidence of a clinically significant 12-lead ECG.
  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.
  5. History of seizures or are currently taking anticonvulsants.
  6. History of hypersensitivity to ropivacaine, any other amide-type local anesthetic, propofol, hydromorphone or oxycodone (or other opioids).
  7. Persistent or recurrent nausea and/or vomiting due to other etiologies, including, but not limited to gastric outlet obstruction, hypercalcemia, or active peptic ulcer.
  8. History of severe or refractory post-operative nausea or vomiting deemed clinically significant.
  9. Concurrent painful condition that may require analgesic treatment during the study period.
  10. Have been receiving or have received chronic opioid therapy.
  11. 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.

  12. History of alcohol abuse or prescription and/or illicit drug abuse within 2 years.
  13. Current report of alcohol abuse within 6 months.
  14. Positive results on the urine drug screen or alcohol breath test indicative of illicit drug or alcohol abuse.
  15. History of human immunodeficiency virus (HIV), hepatitis C, or hepatitis B.
  16. Have had an inguinal hernia repair in the last 3 months before the study surgical procedure or presents with bilateral or recurrent inguinal hernia, other hernia presentations, or hernias with a large scrotal component that would be difficult to reduce surgically.

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): NCT03591146


Locations
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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: NCT03591146     History of Changes
Other Study ID Numbers: TLC590A1001
First Posted: July 19, 2018    Key Record Dates
Last Update Posted: April 12, 2019
Last Verified: April 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
Keywords provided by Taiwan Liposome Company:
Postsurgical Pain Management
Additional relevant MeSH terms:
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Hernia
Hernia, Inguinal
Pathological Conditions, Anatomical
Hernia, Abdominal
Ropivacaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents