Acute Postoperative PainPhase 1NCT04169256
Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profile of HYR-PB21 in Healthy Volunteers
A Phase 1 study testing HYR-PB21, Liposomal bupivacaine and Normal Saline in people with Acute Postoperative Pain, run by Fruithy Medical Pty Ltd at 1 site in Australia.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Acute Postoperative Pain
- What is being tested?
- HYR-PB21, Liposomal bupivacaine and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteAustralia
- Study dates
- 3 Mar 2020to 30 Jul 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Voluntarily provide written informed consent.
- Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
- Subjects with liver function tests (LFTs) within the reference range, or deemed clinically not significant by the investigator or delegate.
- Male or female (of non-child bearing potential) between 18 and 50 years of age, inclusive.
- 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.
- 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.
Show all 12Show fewer
- Have a body mass index 18-30 kg/m2 (inclusive).
- 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.
- 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.
- Subjects must not donate sperm or egg during study or in 30 days after dosing.
- Be able to understand the study procedures, comply with all study procedures, and agree to participate in the study program.
- Be able to understand and communicate in English.
Who cannot join
- History of hypersensitivity or idiosyncratic reactions to amide-type local anaesthetics.
- History of abnormal bleeding tendencies/clotting disorders.
- History of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
- History of significant neurological, hepatic, renal, endocrine, cardiovascular, cardiac arrhythmias, gastrointestinal, pulmonary, or metabolic disease.
- Regular use of anticoagulants.
- 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.
Show all 12Show fewer
- Currently pregnant or nursing.
- 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.
- The subject has a positive serum hepatitis B surface antigen or positive HCV antibody test at the Screening Visit.
- Subject has a positive HIV test at the Screening Visit.
- 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.
- Any conditions, that according to investigator's best judgment, prevent participation in the trial.
Trial locations and contacts
1 site in 1 country.
About this study
Official 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
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.
- Conditions
- Acute Postoperative Pain
- Being tested
- HYR-PB21, Liposomal bupivacaine, Normal Saline
- Keywords
- pain, postoperative, local anesthesia, long-action
- Medical subject headings
- Pain, Postoperative, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HYR-PB21Drug
HYR-PB21 for injection 100mg, 200mg,or 400mg by single subcutaneous injection on the abdomen
Liposomal bupivacaineDrug
Liposome Bupivacaine Suspension for injection 200mg by single subcutaneous injection on the abdomen
Normal SalineOther
Normal Saline 30ml, or 40mL by single subcutaneous injection on the abdomen
| Study group | Role | What they receive |
|---|---|---|
| HYR-PB21 & Placebo | Experimental | Not described Receives: Drug: HYR-PB21; Other: Normal Saline |
| Liposome Bupivacaine & Placebo | Active comparator | Not described Receives: Drug: Liposomal bupivacaine; Other: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 15 days
The maximum observed plasma bupivacaine concentration obtained directly from the experimental data without interpolation.
Measured: 15 days
The time to maximum plasma concentration (Cmax)
Measured: 15 days
The apparent terminal elimination half-life calculated as 0.693/λz
Measured: 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
Measured: 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.
Measured: 8 days
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Measured: 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.
Measured: 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:
- 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)
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2019
- Study start3 Mar 2020
- Primary completion30 Jul 2020
- Study completion30 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Postoperative PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fruithy Medical Pty Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04169256
- Sponsor's protocol ID
- HYR-PB21-AU-01
- Status last verified
- Feb 2021
- First submitted
- 6 Nov 2019
- Last updated
- 4 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT04169256
- Acronym / sponsor ID
- HYR-PB21-AU-01
- Conditions
- Acute Postoperative Pain
- Keywords
- pain, postoperative, local anesthesia, long-action
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Fruithy Medical Pty LtdIndustry (pharma, biotech, devices)
- Study start
- 3 Mar 2020 (actual)
- Primary completion
- 30 Jul 2020 (actual)
- Study completion
- 30 Jul 2020 (actual)
- First posted
- 19 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HYR-PB21 & Placebo | Experimental | Drug: HYR-PB21, Other: Normal Saline |
| Liposome Bupivacaine & Placebo | Active comparator | Drug: Liposomal bupivacaine, Other: Normal Saline |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Voluntarily provide written informed consent.
- Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
- Subjects with liver function tests (LFTs) within the reference range, or deemed clinically not significant by the investigator or delegate.
- Male or female (of non-child bearing potential) between 18 and 50 years of age, inclusive.
- 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.
Key exclusion criteria (12 listed)
- History of hypersensitivity or idiosyncratic reactions to amide-type local anaesthetics.
- History of abnormal bleeding tendencies/clotting disorders.
- History of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
- History of significant neurological, hepatic, renal, endocrine, cardiovascular, cardiac arrhythmias, gastrointestinal, pulmonary, or metabolic disease.
- Regular use of anticoagulants.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HYR-PB21HYR-PB21 for injection 100mg, 200mg,or 400mg by single subcutaneous injection on the abdomen | Drug | HYR-PB21 & Placebo |
| Liposomal bupivacaineLiposome Bupivacaine Suspension for injection 200mg by single subcutaneous injection on the abdomen | Drug | Liposome Bupivacaine & Placebo |
| Normal SalineNormal Saline 30ml, or 40mL by single subcutaneous injection on the abdomen | Other | HYR-PB21 & Placebo, Liposome Bupivacaine & Placebo |
Primary outcome
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
Time frame: 15 days
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.
The area under the plasma concentration-versus-time curve from the time of administration extrapolated to infinity.
Time frame: 15 days
The residual area from the time of the last quantifiable concentration to infinity is to be calculated using the approximation
The maximum observed plasma bupivacaine concentration obtained directly from the experimental data without interpolation.
Time frame: 15 days
The time to maximum plasma concentration (Cmax)
Time frame: 15 days
The apparent terminal elimination half-life calculated as 0.693/λz
Time frame: 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
Time frame: 15 days
The average Von Frey filament pressure across five test points at each protocol scheduled time-point
Time frame: 8 days
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.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: 15 days
Investigator assessment of the ECG (normal, abnormal - not clinically significant, abnormal - clinically significant)
Time frame: 15 days
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.
Observer's assessment of alertness/sedation(OAA/S) scale
Time frame: 5 days
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2021.
- Individual participant dataSharing planned: No
Related trials for Acute Postoperative Pain
RecruitingPhase 2
REctus Sheath Trial
Acute Pain, Postoperative Pain, Acute
Not yet recruiting
Post-operative Pain and Clinical Outcome After Single-cone Obturation With a Calcium Silicate-based Versus Epoxy Resin Sealer
Post Operative Pain, Acute, Irreversible Pulpitis (Toothache)
Not yet recruiting
Lumbar ESP Block Versus TAP Block for Postoperative Pain Control in Children Undergoing Open Inguinal Hernia Repair
Inguinal Hernia, Postoperative Pain
Recruiting
Ultrasound-Guided Serratus Posterior Superior Intercostal Plane Block for Analgesia in Arthroscopic Shoulder Surgery
Postoperative Pain, Acute, Shoulder Pain
Not yet recruitingPhase 4
Suzetrigine (Journavx) as Multimodal Therapy for Pain Management in Adults Undergoing Surgery for Hip Fracture
Hip Fractures (ICD-10 72.01-72.2), Post Operative Analgesia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HYR-PB21, Liposomal bupivacaine and Normal Saline in people with Acute Postoperative Pain, run by Fruithy Medical Pty Ltd at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 15 days). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2021.