Clinical trial NCT05588557: A Phase I Study to Evaluate the Safety and PK of ND-340 in Healthy Volunteers
Official title: A Phase I Dose-escalation Study, Randomized Comparison with Active Control to Evaluate the Safety and Pharmacokinetics of a Single Administration of ND-340 Via Adductor Canal Block (ACB) and IPACK Block in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pain, Postoperative
Keywords: Bupivacaine
Pharmacokinetics
Analgesics
Lead sponsor: Nang Kuang Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-10-20
Enrollment: 24
Sex: ALL
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Detailed description: The current investigational product, ND-340, is a bupivacaine microsphere injection with an extended release profiling. Lipid microsphere, or liposphere, has been proposed as new type of lipid-based encapsulation system for drug delivery of bioactive compounds especially lipophilic compound.

ND-340 has not been studied in human before. However, MARCAINE® and EXPAREL® are both FDA-approved drugs, which contain the same active pharmaceutical ingredient (API) as ND-340, which is bupivacaine. MARCAINE® is indicated for the production of local or regional anesthesia or analgesia for surgery, dental and oral surgery procedures, diagnostic and therapeutic procedures, and for obstetrical procedures.

In this study, Investigators will focus on determining the safety, tolerability, and pharmacokinetic profile of ND-340.

Eligibility criteria: Inclusion Criteria:

1. 20 - 45 year-old healthy male subjects or female subjects who are in non-lactating and non-pregnant status.
2. 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).
3. Female subject with childbearing potential must have a negative serum pregnancy test at the screening visit.
4. Able and willing to comply with all study visits and procedures.
5. The informed consent form has been read, signed and dated by the subject.
6. Able to communicate well with the investigator, comply with study questionnaires, and other instruments used for collecting subject-reported outcomes.

Exclusion Criteria:

1. 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.
2. Subject has clinically significant results of physical examination, laboratory tests, electrocardiogram, or chest X-ray as judged by the investigator at the screening visit.
3. With abnormal results of sensory and neurological assessment as judged by the investigator at the screening visit.
4. 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.
5. 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.
6. Known of active infection with HIV, HBV, or HCV as defined by blood tests at the screening visit.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. Donation or loss of more than 500 mL and 250 mL of blood within 3 months and 2 months before the screening visit, respectively.
14. Known with a history of allergy or hypersensitivity to medicine as judged by the investigator at the screening visit.
15. Female subject who is breast-feeding, pregnant, or planning to become pregnant.
16. Subject does not agree to use effective non-hormonal contraception method to prevent from pregnancy ('double barrier method': condoms used concomitantly with vaginal sponge, diaphragm or intra-uterine contraceptive device) or abstain from sexual behavior with his/her partner from screening until the end of the study.
17. Individual is not eligible to be a subject for other reasons based on the judgment of investigator.

Primary outcomes:
measure: Adverse events as assessed by CTCAE v 5.0
timeFrame: From administration of ND-340 to 140 hours
measure: Changes in 12-lead ECG and Holter monitor
timeFrame: 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
measure: Changes in Laboratory test - hematology
timeFrame: Pre-dose, 140 hour
measure: Changes in Laboratory tests - biochemistry
timeFrame: Pre-dose, 140 hour
measure: Changes in Laboratory tests - urinalysis
timeFrame: Pre-dose, 140 hour
measure: Changes in vital signs
timeFrame: Screening visit, day 0 (Pre-dose, 60 mins), Day 1, Day 2, Day 3, Day 4, Day 5, Day 6
measure: Changes in physical examination
timeFrame: Screening visit, day -1, Day 6
measure: The tolerability and maximal tolerated dose (MTD) of ND-340 by dose-limiting toxicities (DLTs)
timeFrame: 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
measure: Cmax
timeFrame: 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
measure: Tmax
timeFrame: 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
measure: AUC 0-t
timeFrame: 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
measure: AUC 0-∞
timeFrame: 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
measure: T1/2
timeFrame: 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
measure: CL/F
timeFrame: 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
measure: λz
timeFrame: 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
measure: Vz/F
timeFrame: 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
measure: MRT 0-∞
timeFrame: 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:
measure: Range of motion of knee
timeFrame: Pre-dose, 1, 2, 4, 8, 18, 24, 32, 44, 56, 68, 80, 92,104,116,128,140 hours
measure: The ambulation distance
timeFrame: Once a day on Pre-dose, Day 1 and Day 2
Other outcomes:
Locations:
city: Taipei city
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Chih-Peng Lin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: