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A Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study to Evaluate the Analgesic Efficacy and Safety of VVZ-149 Injection for Post-operative Pain following Total Hip Arthroplasty

Status Approved

  • First Submitted Date

    2017/11/24

  • Registered Date

    2018/01/09

  • Last Updated Date

    2021/10/05

CRIS Required

WHO ICTRP (International Clinical Trial Registry Platform) Required

  • 1. Background

    Background - CRIS Registration Number, Unique Protocol ID, Public/Brief Title, Scientific Title, Acronym, MFDS Regulated Study, IND/IDE Protocol, Registered at Other Registry, Name of Registry/Registration Number
    CRIS
    Registration Number
    KCT0002653
    Unique Protocol ID PT-VVZ149-06
    Public/Brief Title A Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study to Evaluate the Analgesic Efficacy and Safety of VVZ-149 Injection for Post-operative pain following Total Hip Arthroplasty
    Scientific Title A Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study to Evaluate the Analgesic Efficacy and Safety of VVZ-149 Injection for Post-operative Pain following Total Hip Arthroplasty
    Acronym
    MFDS Regulated Study Yes
    IND/IDE Protocol Yes
    Registered at Other Registry Yes
    Name of Registry / Registration Number ClinicalTrials.gov-NCT03347266
    Healthcare Benefit Approval Status Not applicable
  • 2. Institutional Review Board / Ethics Committee

    Institutional Review Board Information
    Board Approval Status Submitted approval
    Board Approval Number 4-2017-0775
    Approval Date 2017-09-29
    Institutional Review Board Name Yonsei University Health System, Severance Hospital, Institutional Review Board
    Institutional Review Board Address 50-1, Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea
    Institutional Review Board Telephone 02-2227-7889
    Data Monitoring Committee No
  • 3. Contact Details

    Contact Details Information - Contact Person for Principal Investigator / Scientific Queries, Contact Person for Public Queries, Contact Person for Updating Information의 Name, Title, Email, Telephone, Cellular Phone, Affiliation, Address
    Contact Person for Principal Investigator / Scientific Queries
    Name Sun Joon Bai
    Title MD, PhD
    Telephone +82-2-2227-3834
    Affiliation Yonsei University Health System, Severance Hospital
    Address 50-1 Yonse-ro, Seodaemun-gu, Seoul, 03722, Korea
    Contact Person for Public Queries
    Name Na Young Kim
    Title MD, PhD
    Telephone +82-2-2227-3549
    Affiliation Yonsei University Health System, Severance Hospital
    Address 50-1 Yonse-ro, Seodaemun-gu, Seoul, 03722, Korea
    Contact Person for Updating Information
    Name Jina Kim
    Title MS
    Telephone +82-2-916-1004
    Affiliation Vivozon
    Address 357, Guseong-ro, Giheung-gu, Yongin-si, Gyeonggi-do, Republic of Korea
  • 4. Status

    Status Information - Study Site, Overall Recruitment Status, Date of First Enrollment, Status of First Enrollment, Target Number of Participant, Primary Completion Date, Recruitment Status by Participating Study Site, Name of Study Site, Recruitment Status, Date of First Enrollment, Status of First Enrollemnt
    Study Site Single
    Overall Recruitment Status Terminated
    Date of First Enrollment 2017-12-20 Actual
    Target Number of Participant 20
    Primary Completion Date 2018-07-19 , Actual
    Study Completion Date 2018-07-19 , Actual
    Recruitment Status by Participating Study Site 1
    Name of Study Yonsei University Health System, Severance Hospital
    Recruitment Status Terminated Terminated Reason : 모집중단
    Date of First Enrollment 2017-12-20 ,
  • 5. Source of Monetary / Material Support

    Source of Monetary / Material Support Information - Organization Name, Organization Type, Project ID
    1. Source of Monetary/Material Support
    Organization Name Vivozon
    Organization Type Pharmaceutical Company
    Project ID
  • 6. Sponsor Organization

    Sponsor Organization Information - Organization Name, Organization Type
    1. Sponsor Organization
    Organization Name Vivozon
    Organization Type Pharmaceutical Company
  • 7. Study Summary

    Study Summary Information
    Lay Summary
    VVZ-149 is a dual antagonist of GlyT2 and 5HT2A. GlyT2 blockage increases inhibitory synaptic transmission by glycine in the spinal cord, resulting in a reduction of pain transmissions to the brain. 5HT2A blockage decreases descending serotonergic facilitatory modulation on pain transmission by the brain and reduces nociceptor activation in peripheral nerves, which are primary sources of pain in post-surgical pain. VVZ-149 has been shown to have comparable efficacy to morphine in well-controlled (blind, complete randomization with a positive control) animal studies using rat models of post-operative pain and formalin-induced pain. The Pharmacokinetics/Pharmacodynamics study in animals indicates that therapeutic plasma concentration in human subjects will be 600-1,900 ng/ml. A clinical Phase 1 study performed in healthy subjects has shown no clinically significant adverse events up to a plasma concentration level of 3,261 ng/ml other than brief symptoms of mild nausea or dizziness, and mild somnolence when the plasma exposure level is more than 2,000 ng/ml.
    Phase 2 was designed as a randomized, double-blind, parallel-group, placebo-controlled trial to evaluate the efficacy and safety of the analgesic drug VVZ-149 injection. 
    The interim analysis of phase 2 study showed that the protocol is appropriate to evaluate the efficacy.
    
    The new phase 2 study tries to determine the direction of the clinical trial by verifying that the pain resulting from the hip bone muscle is beneficial to the bone muscle.
    The drug is administered when they arrive in the operating room.
    
    <A Primary objective> 
    Assessment of the efficacy of VVZ-149 for postoperative pain 
    (1,000 mg IV infusion for 10 hrs)
    
    <A Secondary objective> 
    Pharmacokinetics/Pharmacodynamics correlation evaluation 
    Safety evaluation of VVZ-149  
  • 8. Study Design

    Study Design Information - Study Type, Study Purpose, Phase, Intervention Model, Blinding/Masking, Blinded Subject, Allocation, Intervention Type, Intervention Description, Number of Arms, Arm Label, Target Number of Participant, Arm Type, Arm Description
    Study Type Interventional Study
    Study Purpose
    Treatment
    Phase Phase2
    Intervention Model Parallel  
    Blinding/Masking Double
    Blinded Subject Subject, Investigator, Caregiver
    Allocation RCT
    Intervention Type Drug  
    Intervention Description
    VVZ-149 injections 
    VVZ-149 injections will be mixed with saline, then intravenous infusion for 10hr. The drug product will be administrated with a 1000mg for 10 hours
    
    Placebo 
    Placebo group will receive an water for injection the same volume and period of experimental group.
    
    Number of Arms 2
    Arm 1

    Arm Label

    VVZ-149 Injections

    Target Number of Participant

    10

    Arm Type

    Experimental

    Arm Description

    VVZ-149 injections 
    VVZ-149 injections will be mixed with saline, then intravenous infusion for 10hr. The drug product will be administrated with a 1000mg for 10 hours, In addition, administer remedies to patients according to the needs of the patient for adequate pain control, or inject them with a plasma injection (PCA, Fentanyl IV bolus, 6 minutes).
    Arm 2

    Arm Label

    Placebo

    Target Number of Participant

    10

    Arm Type

    Placebo comparator

    Arm Description

    Placebo group will receive an water for injection the same volume and period of experimental group
    In addition, administer remedies to patients according to the needs of the patient for adequate pain control, or inject them with a plasma injection (PCA, Fentanyl IV bolus, 6 minutes)..
  • 9. Subject Eligibility

    Subject Eligibility Information
    Condition(s)/Problem(s) * (M00-M99)Diseases of the musculoskeletal system and connective tissue 
       (M16.9)Coxarthrosis, unspecified 

    Arthroplasty, Replacement, Hip Pain, Postoperative
    Rare Disease No
    Inclusion Criteria

    Gender

    Both

    Age

    25Year~65Year

    Description

    1.Patient between the ages of 25 and 65 years old
    2.Male patient, in the case of female patient, postmenopausal women, or women physically incapable of childbearing
    3.Subject who underwent surgery specially for the clinical study
    4.Ability to provide written informed consent prior to any study procedures.
    5.Ability to understand study procedures and communicate clearly with the investigator and staff.
    6.Subjects with body weight under 100kg and body mass index (BMI) level lower than 35 kg/m2, inclusive
    7.Single-side surgery patient
    
    Exclusion Criteria
    1.Emergency or unplanned surgery.
    2.Repeat operation
    < Subject Characteristics >
    3.Women with childbearing potential, Women who are pregnant or breastfeeding.
    4.Unstable or poorly controlled psychiatric condition (e.g., untreated Post traumatic stress disorder, anxiety, or depression). Subjects who take stable doses of antidepressants and anti-anxiety drugs may be included.
    5.Unstable or acute medical condition (e.g., unstable angina, congestive heart failure, renal failure, hepatic failure, AIDS).
    
    6.Subjects who have long  Q wave, R wave and S wave (>200msec) or prolonged Corrected QT Interval (> 450msec in male, >470msec in female) at Screening
    
    < Drug, Alcohol, and Pharmacological Considerations >
    
    7.History of alcohol, opiate or other drug abuse or dependence within 12 months prior to Screening .
    8.Ongoing or recent (within 6 hour prior to surgery) use of steroids, opioids, or antipsychotics.
    9.Alcohol consumption within 24 hours of surgery.
    10.Use of nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen within 6 hours of surgery.
    11.Use of herbal agents or nutraceuticals (i.e., chaparral, comfrey, germander, jin bu huan, kava, pennyroyal, skullcap, St. John's wort, or valerian) within 7 days prior to surgery.
    < Anesthetic and Other Exclusion Considerations >
    12.Use of neuraxial or regional anesthesia related to the surgery.
    13.Use of ketamine, gabapentin, pregabalin, or lidocaine (>1 mg/kg) intra or peri-operatively, or within 24 hours of surgery.
    14.Subject with known allergies to hydromorphone.
    15.Subjects who received another investigational drug within 30 days of scheduled surgery
    
    Healthy Volunteers No
  • 10. Outcome Measure(s)

    Outcome Measure(s) Information - Type of Primary Outcome, Primary Outcome, Outcome, Timepoint, Secondary Outcome, Outcome, Timepoint
    Type of Primary Outcome Efficacy
    Primary Outcome(s) 1
    Outcome
    Pain Intensity (Numerical Rating Scale, 0-10, NRS at rest)
    Timepoint
    after onset of PCA, 0, 1, 2, 4, 6, 8, 10, 24 hours
    Secondary Outcome(s) 1
    Outcome
    Amount of Fentanyl consumption after administration of investigational drug
    Timepoint
    0-24 hours, 2 hours interval
    Secondary Outcome(s) 2
    Outcome
    Amount of relief medication consumed of investigational drug number of requests
    Timepoint
    0-24 hours, 2 hours interval
    Secondary Outcome(s) 3
    Outcome
    Total Amount of Fentanyl consumption and rescue dose
    Timepoint
    0-24 hours, 2 hours interval
    Secondary Outcome(s) 4
    Outcome
    Pain Intensity Difference and Sum Pain Intensity Difference
    Timepoint
    after onset of PCA, 0-1, 1-2, 2-4, 4-6, 6-8, 8-10, 10-24 hours
    Secondary Outcome(s) 5
    Outcome
    global measurement of patient satisfaction 
    Timepoint
    8, 24 hours after onset of PCA
    Secondary Outcome(s) 6
    Outcome
    Pharmacokinetics/Pharmacodynamics correlation
    Timepoint
    0, 4 ,6 hours after onset of PCA
  • 11. Study Results and Publication

    Study Results and Publication Information - Result Registered, Final Enrollment Number, Number of Publication, Publications, Results Upload, Date of Posting Results, Protocol URL or File Upload, Brief Summary
    Result Registered No
  • 12. Sharing of Study Data(Deidentified Individual-Patient Data, IPD)

    Sharing of Study Data Information - Sharing Statement, Time of Sharing, Way of Sharing
    Sharing Statement No
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