A Phase I Study to Evaluate the Safety and PK of ND-340 in Healthy Volunteers

NCT05588557 | Completed Phase 1 DMC

• 1 other identifier: NKC340-202101
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study focuses on ND-340 extended release injection suspension for healthy volunteers with a one-time nerve blockade to determine the safety, tolerability, and pharmacokinetic profile.

Conditions

Pain, Postoperative

Keywords

Bupivacaine; Pharmacokinetics; Analgesics

Outcome Measures

Primary Outcomes (17)

• Adverse events as assessed by CTCAE v 5.0

  Treatment-related adverse events will be analyzed by cohort

  From administration of ND-340 to 140 hours

• Changes in 12-lead ECG and Holter monitor

  To definition safety profile in cardiac events, vent. rate, PR interval, QRS duration, QT interval, QTc interval

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

• Changes in Laboratory test - hematology

  Hemoglobin, Hct, RBC count, WBC count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelet count

  Pre-dose, 140 hour

• Changes in Laboratory tests - biochemistry

  Albumin, Total protein, ALT, AST, ALP, Total bilirubin, BUN, Serum creatinine, K, Na, Mg, Ca, P, Uric acid, Total cholesterol, HbA1c

  Pre-dose, 140 hour

• Changes in Laboratory tests - urinalysis

  pH, Specific gravity, Leukocyte, Erythrocyte, Protein, Glucose

  Pre-dose, 140 hour

• Changes in vital signs

  To definition safety profile including body temperature,blood pressure, respiratory rate, pulse rate

  Screening visit, day 0 (Pre-dose, 60 mins), Day 1, Day 2, Day 3, Day 4, Day 5, Day 6

• Changes in physical examination

  To definition safety profile including general appearance, HEENT, neck, Lymph nodes, skin, cardiovascular, pulmonary, abdomen, neurological system, musculoskeletal/joints

  Screening visit, day -1, Day 6

• The tolerability and maximal tolerated dose (MTD) of ND-340 by dose-limiting toxicities (DLTs)

  The incidence of DLT will be summarized by each cohort. The number of subject who has DLT will be summarized by cohorts. and the determination of MTD in this study will be provided.

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

• Cmax

  Maximum Plasma Concentration of ND-340

  Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140 hours

• Tmax

  Time of peak concentration of ND-340

  Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140 hours

• AUC 0-t

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

  Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140 hours

• AUC 0-∞

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

  Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140 hours

• T1/2

  Terminal half life of ND-340

  Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140 hours

• CL/F

  Clearance/Bioavailability of ND-340

  Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140 hours

• λz

  Terminal elimination rate constant

  Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140 hours

• Vz/F

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

  Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140 hours

• MRT 0-∞

  Mean residence time from zero to infinity of ND-340

  Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140 hours

Secondary Outcomes (2)

• Range of motion of knee

  Pre-dose, 1, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140 hours

• The ambulation distance

  Once a day on Pre-dose, Day 1 and Day 2

Study Arms (2)

Marcaine® 100mg/20mL (0.5%) bupivacaine solution for Injection

ACTIVE COMPARATOR

Marcaine® at 150 mg in each cohort.

Drug: Marcaine® 100mg/20mL (0.5%) bupivacaine solution for Injection

ND-340 (Bupivacaine Microsphere), 300 mg/vial bupivacaine for extended-release injectable suspension

EXPERIMENTAL

ND-340(90-320 mg) at dose escalations

Drug: ND-340 (Bupivacaine Microsphere), 300 mg/vial bupivacaine for extended-release injectable suspension

Interventions

Marcaine® 100mg/20mL (0.5%) bupivacaine solution for Injection DRUG

Subjects in this arm will receive a single administration of Marcaine® at the 150 mg. Marcaine® will be administered under ultrasound guidance with a total volume of 40 mL, of which 20 mL will be used via adductor canal block (ACB) and the other 20 mL will be used as IPACK block (interspace between the popliteal artery and the capsule of the posterior knee).

Marcaine® 100mg/20mL (0.5%) bupivacaine solution for Injection

ND-340 (Bupivacaine Microsphere), 300 mg/vial bupivacaine for extended-release injectable suspension DRUG

Subjects in this arm will receive a single administration of ND-340 at the specified dose (90-320 mg). ND-340 will be administered under ultrasound guidance with a total volume of 40 mL, of which 20 mL will be used via adductor canal block (ACB) and the other 20 mL will be used as IPACK block (interspace between the popliteal artery and the capsule of the posterior knee).

ND-340 (Bupivacaine Microsphere), 300 mg/vial bupivacaine for extended-release injectable suspension

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• year-old healthy male subjects or female subjects who are in non-lactating and non-pregnant status.
• Subjects must have a Body Mass Index (BMI) of 18.5 to 30.0 Kg/m², inclusive. For male subjects, body weight must be above 50 kg; for female subjects, body weight must be above 45 kg. BMI = Weight (kg)/Height (m2).
• Female subject with childbearing potential must have a negative serum pregnancy test at the screening visit.
• Able and willing to comply with all study visits and procedures.
• The informed consent form has been read, signed and dated by the subject.
• Able to communicate well with the investigator, comply with study questionnaires, and other instruments used for collecting subject-reported outcomes.

You may not qualify if:

• Subject has a sitting pulse rate outside the reference range of 50 to 90 beats per minute or an ear temperature outside the reference range of 35.0 to 37.5°C or a sitting blood pressure less than 90/50 mmHg or more than 140/90 mmHg at screening visit.
• Subject has clinically significant results of physical examination, laboratory tests, electrocardiogram, or chest X-ray as judged by the investigator at the screening visit.
• With abnormal results of sensory and neurological assessment as judged by the investigator at the screening visit.
• Presence of liver disease or liver injury as indicated by an abnormal liver function profile such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkalinephosphatase (ALP), or total bilirubin, if any one of them is out of the reference range.
• Presence of impaired renal function as indicated by abnormal creatinine or blood urea nitrogen values or abnormal urinary constituents, if any one of them is out of the reference range.
• Known of active infection with HIV, HBV, or HCV as defined by blood tests at the screening visit.
• Presence of clinically significant illness, such as cardiovascular disease, cerebrovascular disease, metabolic disease, respiratory disease, neurological disease, psychiatric disease, cancers or immunological disease, may increase the risk of study as judged by the investigator at the screening visit.
• Subject does not agree not to take any prescription, over-the-counter medication, herbal medicine and dietary supplement (including multivitamins) within two weeks before hospital admission and until the end of the study.
• Subject does not agree not to consume any beverage or food that might affect the drug metabolism, such as pomelo, grapefruit or related products within one week before hospital admission and until the end of the study.
• Subject does not agree not to consume any caffeine-containing product (e.g., tea, coffee, coke, or chocolate) 3 days prior to hospital admission and until the end of the study.
• Subject does not agree not to consume any product containing tobacco, nicotine (such as e-cigarettes, nicotine gum), and alcohol 3 days prior to hospital admission and until the end of the study.
• Administration of an investigational drug within 2 months 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.
• Donation or loss of more than 500 mL and 250 mL of blood within 3 months and 2 months before the screening visit, respectively.
• Known with a history of allergy or hypersensitivity to medicine as judged by the investigator at the screening visit.
• Female subject who is breast-feeding, pregnant, or planning to become pregnant.

Sponsors & Collaborators

• Nang Kuang Pharmaceutical Co., Ltd.: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, 100229, Taiwan

Location

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Bupivacaine; Injections

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Chih-Peng Lin, MD, PhD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The subjects of each cohort will be randomly arranged to receive ND-340 or control drug (Marcaine® Injection 0.5%, equal to bupivacaine base 5 mg/mL) in the ratio of 3:1.

Study Record Dates

• First Submitted: July 4, 2022
• First Posted: October 20, 2022
• Study Start: July 8, 2022
• Primary Completion: March 19, 2024
• Study Completion: March 19, 2024
• Last Updated: November 27, 2024

Record last verified: 2024-11

Locations

TW (1)