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This study is the first time into human study (FTIH) for HYR-PB21 for injection. The study will evaluate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending and single subcutaneous dose of HYR-PB21 for injection in healthy adult volunteers.The results of this study are intended to be used to identify appropriate and well tolerated doses of HYR-PB21 for injection to be used in further studies. A comparison of PK/PD characteristics between HYR-PB21 for injection and EXPAREL will also be included in this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HYR-PB21 & Placebo | Experimental |
| |
| Liposome Bupivacaine & Placebo | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HYR-PB21 | Drug | HYR-PB21 for injection 100mg, 200mg,or 400mg by single subcutaneous injection on the abdomen |
|
| Measure | Description | Time Frame |
|---|---|---|
| The area under the plasma concentration-versus-time curve from the time of administration to the time of the last quantifiable concentration calculated using the log-linear trapezoidal rule | Pharmacokinetic parameters will be estimated from plasma bupivacaine measurements using non-compartmental analysis, based on the sampling schedule at predose (on Day 1 prior to study drug administration); 0.25, 0.5, 1, 2, 4, 8, 12, 18, 24, 30, 36, 48, 60, 72, 96, 120, 144, 168 hours and 14 days post-dose. | 15 days |
| The area under the plasma concentration-versus-time curve from the time of administration extrapolated to infinity. | The residual area from the time of the last quantifiable concentration to infinity is to be calculated using the approximation | 15 days |
| The maximum observed plasma bupivacaine concentration obtained directly from the experimental data without interpolation. | 15 days | |
| The time to maximum plasma concentration (Cmax) | 15 days | |
| The apparent terminal elimination half-life calculated as 0.693/λz | 15 days | |
| The apparent terminal elimination rate constant determined by log-linear regression of the terminal log-linear segment of the plasma concentration-versus-time curve | 15 days | |
| The average Von Frey filament pressure across five test points at each protocol scheduled time-point | Detection of the loss of feeling at injection site (at selected five representative test points) by Von Frey filaments in different pressures will be estimated at 15-45 min pre-dose; 0.25, 0.5 , 1, 2, 4, 8, 12, 18, 24, 30, 36, 48, 60, 72, 96, 120, 144, and 168 hour post-dose. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CMAX Clinical Research Pty Ltd | Adelaide | Southwest | 5000 | Australia |
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| ID | Term |
|---|---|
| D010149 | Pain, Postoperative |
| D010146 | Pain |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009461 | Neurologic Manifestations |
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| ID | Term |
|---|---|
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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| Liposomal bupivacaine | Drug | Liposome Bupivacaine Suspension for injection 200mg by single subcutaneous injection on the abdomen |
|
| Normal Saline | Other | Normal Saline 30ml, or 40mL by single subcutaneous injection on the abdomen |
|
| 8 days |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | 15 days |
| Investigator assessment of the ECG (normal, abnormal - not clinically significant, abnormal - clinically significant) | 12-lead ECG will be obtained at screening, check-in,15-45 min pre-dose;0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 168 hours,and 14 days post-dose using an ECG machine for measurements of PR, QRS, QT, QTcF intervals,and heart rate. | 15 days |
| Observer's assessment of alertness/sedation(OAA/S) scale | Six categories of responsiveness scores were characterized by the following responses for the OAA/S assessment:
| 5 days |
| D012816 | Signs and Symptoms |