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

NCT04515953 | Suspended Phase 1

• 1 other identifier: QCR19001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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 effect of pain relief after surgery.

Conditions

Pain, Postoperative

Outcome Measures

Primary Outcomes (10)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  The AEs of special interest, including any symptom of local anesthetic systemic toxicity (LAST), cardiac events, neurologic events, and falls, will be analyzed by cohort.

  up to 3 months

• Cmax

  Maximum Plasma Concentration of ND-340

  0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour

• Tmax

  Time of peak concentration of ND-340

  0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour

• AUC 0-t

  Area under the plasma concentration versus time curve from zero to t of ND-340

  0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour

• AUC 0-∞

  Area under the plasma concentration versus time curve from zero to infinity of ND-340

  0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour

• T1/2

  Terminal half life of ND-340

  0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour

• CL/F

  Clearance/Bioavailability of ND-340

  0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour

• λz

  Terminal elimination rate constant

  0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour

• Vz/F

  Apparent volume of distribution during terminal phase after non-intravenous administration

  0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour

• MRT 0-∞

  Mean residence time

  0(Pre-dose), 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140,164 hour

Secondary Outcomes (5)

• Pain intensity

  up to 1 week

• The requirement for rescue pain medication

  up to 1 week

• The ambulation distance

  up to 3 months

• Range of motion of knee

  up to 3 months

• WOMAC

  up to 3 months

Study Arms (2)

Control

ACTIVE COMPARATOR

Standard practice of pain management for post-TKA

Drug: IV-PCA

ND-340

EXPERIMENTAL

ND-340 90mg\~320mg at dose escalations

Drug: ND-340

Interventions

ND-340 DRUG

ND-340: Subjects will receive a single administration of ND-340 at the specified dose in each arm after TKA.

ND-340

IV-PCA DRUG

IV-PCA: Intravenous patient-controlled analgesia (IV-PCA), morphine, will be administered in subjects of control group after TKA for postoperative pain management as standard practice.

Control

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nang Kuang Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Nang Kuang Pharmaceutical Co., LTD

Tainan, Taiwan (台灣), 712, Taiwan

Location

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Analgesia, Patient-Controlled

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Analgesia; Anesthesia and Analgesia

Study Officials

• Chih-Peng Lin

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The first two arms of the placebo control and the 1st dose level ND-340 were randomly paralleled and then subsequently arms for ND-340 dose escalations.

Study Record Dates

• First Submitted: July 8, 2020
• First Posted: August 17, 2020
• Study Start: October 15, 2020
• Primary Completion: December 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: November 9, 2023

Record last verified: 2023-10

Locations

TW (1)