Status:

SUSPENDED

A Phase I Dose-escalation Study of a Single Administration of Extended-Release Injectable Suspension (ND-340)

Lead Sponsor:

Nang Kuang Pharmaceutical Co., Ltd.

Conditions:

Pain, Postoperative

Eligibility:

All Genders

20-80 years

Phase:

PHASE1

Brief Summary

This study focused on ND-340 extended release injection suspension for patients undergoing total knee arthroplasty with a one-time nerve blockade to assess drug side effects, pharmacokinetics and the ...

Eligibility Criteria

Inclusion

  • Subject with age between 20 and 80 (inclusive) years old at the screening visit
  • With physician's order to undergo scheduled primary unilateral TKA
  • Female subject with childbearing potential must have a negative serum pregnancy test at the screening visit
  • Both male and female subjects with childbearing potential must agree to use 2 medically accepted methods of contraception (e.g., barrier contraceptives \[male condom, female condom, or diaphragm with a spermicidal gel\], hormonal contraceptives \[implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings\], and intrauterine devices) during the course of the study with their partners (excluding women who are not of childbearing potential and men who have been sterilized).
  • Able and willing to comply with all study visits and procedures
  • Able to speak, read, and understand the language of the informed consent form (ICF), study questionnaires, and other instruments used for collecting subject-reported outcomes, in order to enable accurate and appropriate responses to pain scales and other required study assessments
  • Willing and capable of providing written informed consent

Exclusion

  • Body weight \< 50 kilograms or a morbidly obese (body mass index ≥ 35kg/m2)
  • Subject with American Society of Anesthesiologists (ASA) physical status \> 3 at the screening visit
  • Undergoing or is plan to undergo bilateral or revision total knee replacement
  • Previous contralateral TKA or open knee surgery on the knee being considered for TKA in this study within 1 year prior to screening. Prior arthroscopy at least 1 week prior to TKA is permitted.
  • Use of any of the following medications within the time specified before TKA
  • Use of any opioid within 24 hours or long-acting opioid within 3 days
  • Use of any NSAID including selective COX-2 inhibitor within 3 days
  • Use of any selective serotonin reuptake inhibitors (SSRIs), gabapentin, pregabalin (LYRICA®), or duloxetine (CYMBALTA®) within 3 days
  • Use of monoamine oxidase inhibitors (MAOIs) within 14 days
  • Concurrent painful physical condition, diseases or concurrent surgery that may require analgesic treatment (such as NSAIDs or opioids) in the post-operative period for pain that is not strictly related to the surgery, and which may confound the post-operative assessments (e.g., significant pain from other joints including the non-index knee joint, chronic neuropathic pain, concurrent or prior contralateral TKA, concurrent foot surgery)
  • Pre-operative liver insufficiency as defined by liver function tests \[i.e. alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or total bilirubin\] ≥ 1.5 times the upper limit of normal (ULN) at the screening visit
  • Pre-operative renal insufficiency (creatinine clearance \< 60 mL/min) at the screening visit
  • Known of active infection with HIV, HBV, or HCV at the screening visit
  • With abnormal ECG at screening and admission, which is not suitable to participate into this study as judged by the investigator before TKA
  • With abnormal results of sensory examination as judged by the investigator before TKA
  • Administration of an investigational drug within 30 days or 5 elimination half- lives of such investigational drug, whichever is longer, prior to study drug administration; or planned administration of another investigational product or procedure during the study period
  • Receiving other surgeries within 30 days prior to screening
  • Receiving blood transfusion within 30 days prior to screening
  • With a history of allergy or hypersensitivity to local anesthetics
  • Previous hypersensitivity to or contraindication to any of the pain-control agents planned for surgical or post-operative use in this study (i.e., morphine, bupivacaine, tramadol, and acetaminophen)
  • History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years prior to screening
  • Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that could interfere with study assessments or compliance in the opinion of the investigator
  • Current or historical evidence of any clinically significant disease or condition, especially terminal stage cancer, poorly controlled diabetic mellitus (i.e., HbA1c \> 8%), or neurological disease that, in the opinion of the investigator, may increase the risk of study treatment and TKA, or complicate the subject's post-operative course or interfere with the determination of pain intensity related solely to the TKA
  • Subject with severe heart diseases (NYHA class-III and IV), with ischemic heart diseases (angina pectoris and myocardial infarction) and subject who underwent percutaneous transluminal coronary angioplasty (PTCA) or had treatments for coronary artery bypass graft within 6 months prior to screening
  • With pre-existed psychiatric or neurological deficits, which may compromise the neurological toxicity evaluations in this study by the investigator's judgment
  • With stroke within 1 year prior to screening
  • With bone cancer within 5 years prior to screening
  • Inability to understand or operate the PCA machine
  • Female subject who is breast-feeding, pregnant, or planning to become pregnant

Key Trial Info

Start Date :

October 15 2020

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

June 1 2026

Estimated Enrollment :

36 Patients enrolled

Trial Details

Trial ID

NCT04515953

Start Date

October 15 2020

End Date

June 1 2026

Last Update

November 9 2023

Active Locations (1)

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Nang Kuang Pharmaceutical Co., LTD

Tainan, Taiwan (台灣), Taiwan, 712