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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04169256




Registration number
NCT04169256
Ethics application status
Date submitted
6/11/2019
Date registered
19/11/2019
Date last updated
7/07/2020

Titles & IDs
Public title
Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profile of HYR-PB21 in Healthy Volunteers
Scientific title
A Phase I, Single Centre, Randomized, Double-blinded, Placebo-controlled, Single Ascending Dose-Escalation, Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profile of HYR-PB21 and Liposome Bupivacaine in Healthy Volunteers
Secondary ID [1] 0 0
HYR-PB21-AU-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Postoperative Pain 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - HYR-PB21
Treatment: Drugs - Liposomal bupivacaine
Other interventions - Normal Saline

Experimental: HYR-PB21 & Placebo -

Active Comparator: Liposome Bupivacaine & Placebo -


Treatment: Drugs: HYR-PB21
HYR-PB21 for injection 100mg, 200mg,or 400mg by single subcutaneous injection on the abdomen

Treatment: Drugs: Liposomal bupivacaine
Liposome Bupivacaine Suspension for injection 200mg by single subcutaneous injection on the abdomen

Other interventions: Normal Saline
Normal Saline 30ml, or 40mL by single subcutaneous injection on the abdomen

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
15 days
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
15 days
Primary outcome [3] 0 0
The maximum observed plasma bupivacaine concentration obtained directly from the experimental data without interpolation.
Timepoint [3] 0 0
15 days
Primary outcome [4] 0 0
The time to maximum plasma concentration (Cmax)
Timepoint [4] 0 0
15 days
Primary outcome [5] 0 0
The apparent terminal elimination half-life calculated as 0.693/?z
Timepoint [5] 0 0
15 days
Primary outcome [6] 0 0
The apparent terminal elimination rate constant determined by log-linear regression of the terminal log-linear segment of the plasma concentration-versus-time curve
Timepoint [6] 0 0
15 days
Primary outcome [7] 0 0
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.
Timepoint [7] 0 0
8 days
Primary outcome [8] 0 0
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Timepoint [8] 0 0
15 days
Primary outcome [9] 0 0
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.
Timepoint [9] 0 0
15 days
Primary outcome [10] 0 0
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:
Responds readily to name spoken in normal tone (5 scores)
Responds lethargically to name spoken in normal tone (4 scores)
Responds only after name is called loudly, repeatedly, or both (3 scores)
Responds only after mild prodding or shaking (2 scores)
Responds only after painful trapezius squeeze (1 score)
Does not respond to painful trapezius squeeze (0 score)
Timepoint [10] 0 0
5 days

Eligibility
Key inclusion criteria
1. Voluntarily provide written informed consent.

2. Subjects who are overtly healthy as determined by medical evaluation including medical
history, physical examination, laboratory tests, and cardiac monitoring.

3. Subjects with liver function tests (LFTs) within the reference range, or deemed
clinically not significant by the investigator or delegate.

4. Male or female (of non-child bearing potential) between 18 and 50 years of age,
inclusive.

5. If female, be of non-childbearing potential: e.g. post-menopausal for =12 consecutive
months with follicle stimulating hormone (FSH) =40 mIU/mL at Screening; or surgical
sterilization for at least 90 days prior to screening e.g., tubal ligation or
hysterectomy. Note: Provision of documentation is not required for female
sterilization, verbal confirmation is adequate.

6. Male patients must be surgically sterile (biologically or surgically) or commit to the
use of a reliable method of birth control for the duration of the study until at least
30 days after the administration of study medication.

7. Have a body mass index 18-30 kg/m2 (inclusive).

8. Blood pressure < 140/90 mmHg at screening and heart rate <100 bpm. One repeat
assessment is permitted. Screening laboratory tests that are deemed to be
non-clinically significant by the investigator.

9. Subjects must not have donated or lost more than 400 mL of blood within 12 weeks of
dosing, more than 200mL of blood within 4 weeks of dosing or donated any blood within
2 weeks of dosing.

10. Subjects must not donate sperm or egg during study or in 30 days after dosing.

11. Be able to understand the study procedures, comply with all study procedures, and
agree to participate in the study program.

12. Be able to understand and communicate in English.
Minimum age
18 Years
Maximum age
50 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History of hypersensitivity or idiosyncratic reactions to amide-type local
anaesthetics.

2. History of abnormal bleeding tendencies/clotting disorders.

3. History of glucose-6-phosphate dehydrogenase (G6PD) deficiency.

4. History of significant neurological, hepatic, renal, endocrine, cardiovascular,
cardiac arrhythmias, gastrointestinal, pulmonary, or metabolic disease.

5. Regular use of anticoagulants.

6. Received any investigational drug within 30 days or 5 half-lives of the
investigational drug prior to study drug administration, and/or has planned
administration of another investigational product or procedure during his/her
participation in this study.

7. Currently pregnant or nursing.

8. The subject has a history of substance abuse or smoking, a positive ethanol breath
test, urine cotinine, or urine drug screen at screening or at check-in. One repeat
test is allowable if a false positive is suspected at the investigator's discretion.

9. The subject has a positive serum hepatitis B surface antigen or positive HCV antibody
test at the Screening Visit.

10. Subject has a positive HIV test at the Screening Visit.

11. Received bupivacaine, other local anaesthetic, prescription or OTC medications, herbal
remedies or supplements per standard practice within 14 days of first study drug
administration. Received caffeine and alcohol consumption within 48 h prior to drug
administration.

12. Any conditions, that according to investigator's best judgment, prevent participation
in the trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Fruithy Medical Pty Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04169256
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Jane Kelly
Address 0 0
Country 0 0
Phone 0 0
+61870887900
Fax 0 0
Email 0 0
cmax@cmax.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04169256