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

NCT ID: NCT04515953

Last Updated: 2023-11-09

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-15
• Study Completion Date: 2026-06-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control

Standard practice of pain management for post-TKA

Group Type: ACTIVE_COMPARATOR

IV-PCA

Intervention Type: 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.

ND-340

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

Group Type: EXPERIMENTAL

ND-340

Intervention Type: DRUG

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

Interventions

ND-340

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

Intervention Type: DRUG

IV-PCA

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Subject with age between 20 and 80 (inclusive) years old at the screening visit

2. With physician's order to undergo scheduled primary unilateral TKA

3. Female subject with childbearing potential must have a negative serum pregnancy test at the screening visit

4. 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).

5. Able and willing to comply with all study visits and procedures

6. 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

7. Willing and capable of providing written informed consent

Exclusion Criteria

1. Body weight < 50 kilograms or a morbidly obese (body mass index ≥ 35kg/m2)

2. Subject with American Society of Anesthesiologists (ASA) physical status > 3 at the screening visit

3. Undergoing or is plan to undergo bilateral or revision total knee replacement

4. 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.

5. 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

6. 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)

7. 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

8. Pre-operative renal insufficiency (creatinine clearance < 60 mL/min) at the screening visit

9. Known of active infection with HIV, HBV, or HCV at the screening visit

10. With abnormal ECG at screening and admission, which is not suitable to participate into this study as judged by the investigator before TKA

11. With abnormal results of sensory examination as judged by the investigator before TKA

12. 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

13. Receiving other surgeries within 30 days prior to screening

14. Receiving blood transfusion within 30 days prior to screening

15. With a history of allergy or hypersensitivity to local anesthetics

16. 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)

17. 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

18. Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that could interfere with study assessments or compliance in the opinion of the investigator

19. 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

20. 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

21. With pre-existed psychiatric or neurological deficits, which may compromise the neurological toxicity evaluations in this study by the investigator's judgment

22. With stroke within 1 year prior to screening

23. With bone cancer within 5 years prior to screening

24. Inability to understand or operate the PCA machine

25. Female subject who is breast-feeding, pregnant, or planning to become pregnant

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nang Kuang Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chih-Peng Lin

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Locations

Nang Kuang Pharmaceutical Co., LTD

Tainan City, Taiwan (台灣), Taiwan

Countries

Taiwan

Other Identifiers

QCR19001

Identifier Type: -

Identifier Source: org_study_id