A Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of PRF110 in Bunionectomy Surgery

Study Overview
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Brief Summary
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PRF110 is new extended release oily solution formulation of ropivacaine that is intended for local infiltration into surgical wounds. The purpose of this study is to determine the safety and early efficacy of PRF110 in bunionectomy surgery, to measure the pharmacokinetic profile of PRF110 over 72 hours and evaluate the duration of analgesia witnessed in the surgical setting.

Detailed Description
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PRF110 is new extended release oily solution formulation of ropivacaine that is intended for local infiltration into surgical wounds. The formulation is designed to slowly release the ropivacaine over 36-72 hours. By providing local analgesia over a long time span, the need for systemic analgesics is expected to be reduced. The purpose of this study is to determine the safety and early efficacy of PRF110 in bunionectomy surgery, to measure the pharmacokinetic profile of PRF110 over 72 hours and evaluate the duration of analgesia witnessed in the surgical setting.

Official Title
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A Single-Dose, Open-Label, Multi-Center Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of PRF110 in Bunionectomy Surgery

Conditions
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Post Operative Pain

Intervention / Treatment
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* Drug: PRF110


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide written informed consent prior to any study procedures; Able to communicate clearly with the Investigators and study staff; Males and females aged between 18 - 85 years of age; Scheduled for elective primary unilateral first metatarsal bunionectomy surgery (osteotomy and internal fixation) with no collateral procedures; Females must be physically incapable of childbearing potential (postmenopausal for more than at least 2 years or surgically sterile) or practicing an acceptable method of contraception (hormonal, barrier with spermicide, intrauterine device, vasectomized partner, or abstinence). Subjects using hormonal birth control must have received at least 1 cycle of treatment prior to study drug administration. At Baseline, all females of childbearing potential must have a negative pregnancy test and not be breast feeding; Negative urine drug screen for drugs of abuse at Screening and on Day 1 prior to surgery; a positive drug screen result may be permitted if the subject has been on a stable dose of an allowed medication for >30 days (antipsychotics, antiepileptics, sedatives, hypnotics, antianxiety agents, or antidepressants); American Society of Anesthesiologists (ASA) risk class of I to II; Body Mass Index ≤32. Exclusion Criteria: Has known allergies to an opioid, unless has subsequently tolerated other opioids and, in the opinion of the Investigator, could tolerate a rescue drug containing fentanyl; Has a known or suspected allergy to paracetamol, ibuprofen or dipyrone; Has a known or suspected allergy to any local anesthetic; Has atrial fibrillation/flutter, an inserted pacemaker, or complete left bundle branch block (LBBB) on ECG; or myocardial infarction within 6 months prior to surgery; Has a clinically significant abnormal ECG at screening; Has a known or suspected history of diagnosed alcohol, opiate or other substance abuse within 12 months prior to screening; Is unable to refrain from alcohol consumption for a period beginning 24 hours prior to surgery through the end of the 72 hour evaluation period; Has taken any analgesic within 12 hours or any aspirin-containing product within 7 days of the Baseline assessments; Has taken any opioid analgesics or used systemic steroids within 4 days of surgery; Has been using opiates or any non-steroidal anti-inflammatory drug chronically (more than 10 consecutive days) anytime over the past 3 months; Has used antipsychotics, antiepileptics, sedatives, hypnotics, antianxiety agents or antidepressants for < 30 days prior to surgery or had a dose change within the previous 30 days; Has taken any prescription or over-the-counter medication within 4 days prior to surgery that, in the opinion of the Investigator, could potentially confound the analgesic response; Has taken herbal agents or nutraceuticals during any of the 7 days prior to surgery that, in the opinion of the Investigator, could potentially confound the analgesic response; Has any clinically significant condition or a significant laboratory abnormality that would, in the opinion of the Investigator, preclude study participation; Unable or unwilling, in the opinion of the Investigator to comply with the requirements of the protocol; Has received another investigational drug within 30 days of scheduled surgery; Has donated blood within three months prior to start of the study; Employees of the Investigator and study site or the sponsor, as well as family members of the employees or the investigator or the sponsor.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRF110- oily solution<br>Post-operative application of new extended release PRF110- oily solution (Ropivacaine) | Drug: PRF110<br> <br> * Other names: Ropivacaine oily solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events | All adverse events (AE) reported by the subjects will be recorded throughout the trial period | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first rescue medication | Time to first rescue medication | 72 hours | 
| Total amount of rescue medication used during the study | Total amount of rescue medication used during the study | 10 days | 
| Pain intensity recorded at rest | Pain intensity which will be recorded at rest at Hours 1, 2, 4, 6, 8, 10, 12, 18 (optional) 24, 28, 32, 36, 48, 52, 56, 60 and 72. | 72 hours | 
| Subject global assessment of PRF110 | Subject global assessment which will be recorded at Hours 24, 48 and 72. | 72 hours |