Pharmacokinetic and Safety Study of HYR-PB21 vs Bupivacaine Hydrochloric Acid in Healthy Participants

NCT07717086 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: HYR-PB21-US-01
• Study Type: interventional
• Target: 28
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase I, randomized, single-blind, active-controlled, single-dose, parallel-group study to evaluate the safety and pharmacokinetic (PK) profile of HYR-PB21, a pamoate-formulated bupivacaine injectable, in healthy adult participants. Participants are randomized to receive a single subcutaneous dose of HYR-PB21 at one of three dose levels (100 mg, 200 mg, or 400 mg) or a single 100 mg dose of Bupivacaine hydrochloride injection (as base) as active control. The primary objectives are to characterize the PK profile of HYR-PB21 at the three dose levels compared with Bupivacaine hydrochloride, and to determine the Pharmacokinetics characteristics of the pamoic acid moiety following HYR-PB21 administration. Secondary objectives are to extend cumulative safety and tolerability observations of single subcutaneous doses of HYR-PB21 in healthy adults.

Conditions

Postoperative Analgesia

Outcome Measures

Primary Outcomes (8)

• Maximum observed plasma concentration(Cmax) of bupivacaine

  The maximum observed plasma concentrations of bupivacaine was directly obtained from the observed concentration-time curves. Units: ng/mL. The PK parameters will be analyzed using the non-partial model. For ease of statistical comparison, the Cmax values will be log-transformed.

  Predose; 0.25, 0.5, 1, 2, 4, 8, 12, 18, 24, 30, 36, 48, 60, 72, 96, 120, 144, 168 hours and Day 14 post-dose

• Maximum observed plasma concentration(Cmax) of pamoic acid

  The maximum observed plasma concentrations of pamoic acid was directly obtained from the observed concentration-time curves. Units: ng/mL. The PK parameters will be analyzed using the non-partial model. For ease of statistical comparison, the Cmax values will be log-transformed.

  Predose; 0.25, 0.5, 1, 2, 4, 8, 12, 18, 24, 30, 36, 48, 60, 72, 96, 120, 144, 168 hours and Day 14 post-dose

• Area Under the Curve(AUC0-t) of bupivacaine

  During the period from time zero (the administration time) to Tlast (the last time point when the concentration reaches or exceeds the quantitative lower limit), the area under the plasma concentration-time curve of bupivacaine was calculated according to the mixed logarithmic linear trapezoidal rule. Unit: ng·hour/mL.

  Predose; 0.25, 0.5, 1, 2, 4, 8, 12, 18, 24, 30, 36, 48, 60, 72, 96, 120, 144, 168 hours and Day 14 post-dose

• Area Under the Curve(AUC0-t) of pamoic acid

  During the period from time zero (the administration time) to Tlast (the last time point when the concentration reaches or exceeds the quantitative lower limit), the area under the plasma concentration-time curve of pamoic acid was calculated according to the mixed logarithmic linear trapezoidal rule. Unit: ng·hour/mL.

  Predose; 0.25, 0.5, 1, 2, 4, 8, 12, 18, 24, 30, 36, 48, 60, 72, 96, 120, 144, 168 hours and Day 14 post-dose

• Terminal elimination half-life(t1/2) of bupivacaine

  The apparent terminal half-life of bupivacaine was calculated using the formula ln(2)/λz, where λz is the terminal elimination rate constant determined through linear regression of the logarithm of the final stage concentration (at least 3 data points, along with the R² value). The unit is hour.

  Predose; 0.25, 0.5, 1, 2, 4, 8, 12, 18, 24, 30, 36, 48, 60, 72, 96, 120, 144, 168 hours and Day 14 post-dose

• Terminal elimination half-life(t1/2) of pamoic acid

  The apparent terminal half-life of pamoic acid was calculated using the formula ln(2)/λz, where λz is the terminal elimination rate constant determined through linear regression of the logarithm of the final stage concentration (at least 3 data points, along with the R² value). The unit is hour.

  Predose; 0.25, 0.5, 1, 2, 4, 8, 12, 18, 24, 30, 36, 48, 60, 72, 96, 120, 144, 168 hours and Day 14 post-dose

• Time of maximum observed plasma concentration(Tmax) of bupivacaine

  The time at which bupivacaine reach their maximum plasma concentrations is recorded based on the actual sampling time corresponding to the Cmax value (if there are multiple identical Cmax values, the time of the first occurrence is taken as the reference). Unit: hour

  Predose; 0.25, 0.5, 1, 2, 4, 8, 12, 18, 24, 30, 36, 48, 60, 72, 96, 120, 144, 168 hours and Day 14 post-dose

• Time of maximum observed plasma concentration(Tmax) of pamoic acid

  The time at which pamoic acid reach their maximum plasma concentrations is recorded based on the actual sampling time corresponding to the Cmax value (if there are multiple identical Cmax values, the time of the first occurrence is taken as the reference). Unit: hour

  Predose; 0.25, 0.5, 1, 2, 4, 8, 12, 18, 24, 30, 36, 48, 60, 72, 96, 120, 144, 168 hours and Day 14 post-dose

Secondary Outcomes (1)

• Number of participants with abnormal laboratory tests results, abnormal vital signs,abnormal ECG readings, abnormal physical examination findings

  Baseline through Day 28 (or 30 days post-dose)

Study Arms (4)

HYR-PB21， 100 mg

EXPERIMENTAL

HYR-PB21， 100 mg， administered as a single subcutaneous injection

Drug: HYR-PB21， 100 mg

HYR-PB21， 200 mg

EXPERIMENTAL

HYR-PB21， 200 mg，administered as a single subcutaneous injection

Drug: HYR-PB21， 200 mg

HYR-PB21， 400 mg

EXPERIMENTAL

HYR-PB21， 400 mg， administered as a single subcutaneous injection

Drug: HYR-PB21， 400 mg

Bupivacaine hydrochloride， 100 mg (as base)

ACTIVE COMPARATOR

Bupivacaine hydrochloride， 100 mg， administered as a single subcutaneous injection

Drug: Bupivacaine hydrochloride， 100 mg (as base)

Interventions

HYR-PB21， 400 mg DRUG

HYR-PB21 400 mg, administered as a single subcutaneous injection.

Also known as: Bupivacaine Pamoic acid Injection， 400 mg

HYR-PB21， 400 mg

HYR-PB21， 200 mg DRUG

HYR-PB21 200 mg, administered as a single subcutaneous injection.

Also known as: Bupivacaine Pamoic acid Injection， 200 mg

HYR-PB21， 200 mg

HYR-PB21， 100 mg DRUG

HYR-PB21， 100 mg, administered as a single subcutaneous injection.

Also known as: Bupivacaine Pamoic acid Injection， 100 mg

HYR-PB21， 100 mg

Bupivacaine hydrochloride， 100 mg (as base) DRUG

Bupivacaine Hydrochloric acid injection 100 mg (expressed as bupivacaine base), administered as a single subcutaneous injection. Active comparator.

Also known as: MARCAINE®， 100 mg

Bupivacaine hydrochloride， 100 mg (as base)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female adult participants
• Age 18 to 50 years old (inclusive)
• Body mass index (BMI) of 18.0 to 32.0 kg/m2 and weight ≥50 kg.
• Participant is generally healthy, as determined by the Investigator based on medical history, physical examination, clinical laboratory test results, vital signs, and 12-lead electrocardiogram (ECG) at screening.
• Female participants who engage in heterosexual intercourse must be non-pregnant or non-lactating. Female participants of childbearing potential must agree to use 2 acceptable methods of contraception with their male partner from screening until 6 months after the last dose of the study drug and refrain from donating ovum for this same period. (Refer to contraception section).Females of non-childbearing potential must either be :
• Post menopausal as defined by at least 12 months of consecutive Amenorrhea and Follicle-Stimulating Hormone(FSH) and estradiol confirming Post menopausal status at screening. See Appendix Section 13 for additional details.
• Surgically sterile at least 6 months prior to screening with documentation.
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• Bilateral tubal ligation
• Hysterectomy (partial or total)
• Bilateral salpingectomy
• Bilateral oophorectomy
• Male participants, if sexually active with a female partner of child-bearing potential, must be vasectomized or agree to take appropriate precautions to prevent conception, including practicing an effective method of contraception, and must not donate sperm from screening through 12 weeks following administration of the last dose of study medication.
• Only non-smokers are eligible. For a period of at least six months prior to Screening, all participants must have been free from excessive alcohol intake or regular use of illegal recreational drugs. Participants with any past or current history of marijuana use are not eligible for the study.
• Ability to understand and willingness to sign a written informed consent form (The consent form must be signed by the participant prior to any study-specific procedures.)

You may not qualify if:

• Participants will be excluded if they have
• A history of hypersensitivity or idiosyncratic reactions to amide-type local anesthetics;
• Have a personal or family history of clotting disorder or hematologic abnormality, such as excessive bleeding, joint hematoma, thrombovascular disease, thrombocytopenia, or any chronic condition requiring treatment with transfusions; have a history of recurrent bleeding episodes (eg, epistaxis, bruising or gingival bleeding) within 1 month prior to Screening, or a longstanding history of such bleeding.
• Participants who were detected to have Glucose-6-phosphate dehydrogenase(G6PD) deficiency during the screening period.
• Females who are pregnant, lactating, or have plans to become pregnant during the study
• History and/or recent evidence within six months prior to Screening of alcohol or drug/substance abuse disorder
• History of clinically significant allergies, including drug allergies, or allergic bronchial asthma, or related bronchospastic conditions
• Participants who have a history of unexplained syncope or fainting or a condition that predisposes them to syncope, such as hypotension, orthostatic hypotension, bradycardia, or dehydration.
• Participants who have used P-gp and/or Cytochrome P450 hepatic microsomal enzyme-inducing or inhibiting drugs (e.g., propafenone, voriconazole, fluconazole, cimetidine) within 30 days of first dosing, refer to Appendix 15-16 for detailed list
• Participants with a history or presence of significant cardiovascular, pulmonary, hepatic, gallbladder or biliary tract, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychiatric disease, or active sexually transmitted disease to include:
• Current or history of thrombosis or thromboembolic disorders
• Any history of malignancy, especially breast cancer or other hormone-sensitive cancers
• Undiagnosed abnormal vaginal bleeding unrelated to pregnancy
• Cholestatic jaundice of pregnancy
• Liver tumors, benign or malignant, or active liver disease

Sponsors & Collaborators

• Fruithy Holdings Limited: lead
• Frontage Clinical Services: collaborator

MeSH Terms

Interventions

Bupivacaine; Alkalies

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Inorganic Chemicals

Study Officials

• shanchun zhang, Doctor

  Fruithy Holdings Limited

  STUDY DIRECTOR

Central Study Contacts

Lisa Mulligan, Bachelor

CONTACT

Mulligan; lmulligan@frontagelab.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2026
• First Posted: July 21, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: July 21, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share