A Safety and Effectiveness Pilot Study of PRF-108 in Healthy Volunteers

This is a clinical study testing PRF-108 (a new extended release 2% gel formulation of ropivacaine) in an experimentally induced pain model in healthy volunteers. PRF-108 is designed to deliver slow release of ropivacaine over 72 hours.

The purpose of this study is to investigate the safety (side effects if any occurs) associated with the single administration of PRF-108 and evaluate its analgesic effect in an experimentally induced pain model compared with ropivacaine Solution 0.5% and Vehicle Gel.

• Drug: PRF-108
  Ropivacaine
• Drug: Placebo
  PRF-108 Placebo
• Drug: Ropivacaine
  Solution

• Experimental: 1
  PRF-108 Gel, 2%
  Intervention: Drug: PRF-108
• Placebo Comparator: 2
  PRF-108 Gel, Vehicle
  Intervention: Drug: Placebo
• Active Comparator: 3
  Ropivacaine Solution 0.5%
  Intervention: Drug: Ropivacaine

Inclusion Criteria:

1. Male subjects between 18-60 years of age;
2. Subjects are within ±10% of ideal body weight/height (based on frame size) as given by the Metropolitan Life Insurance Tables;
3. Subjects are ASA Category I and in normal physical health as judged by physical and laboratory examinations and have a negative urine based screen for drugs of abuse;
4. Subjects must agree to refrain from ingesting any analgesic medication for 3 days or 5 half-lives of the drug prior to and during the study period and alcohol for 1 day prior to and during the study period;
5. Subjects can tolerate a 0.5mL injection of saline in the lower back area.
6. The subject is capable of reading, comprehending, and signing the informed consent form.

Exclusion Criteria:

1. Subjects with a history of any significant hepatic, renal, endocrine, cardiac, neurological, psychiatric, gastrointestinal, pulmonary, hematologic, or metabolic disorders, including glaucoma, diabetes, emphysema, and chronic bronchitis;
2. Subjects with a history of any type of cancer;
3. Subjects with conditions that affect the absorption, metabolism, or passage of drugs out of the body, (e.g., sprue, celiac disease, Crohn's disease, colitis, or liver, kidney, or thyroid conditions);
4. Subjects with any history of alcohol or substance abuse (including a positive drug screen test);
5. Subjects that currently have or have a history of hypertension;
6. Subjects with a known hypersensitivity to any local anesthetic drug;
7. Subjects with a history of benign prostatic hyperplasia or difficulty in urination;
8. Subjects with a hematocrit level below the normal range on the screening laboratory examination;
9. Subjects with any clinically significant abnormal lab result (as judged by the Principal Investigator);
10. An abnormal ECG at screening including PR>200 ms, QRS>110 ms, QTcF<380 or >400 ms, lead II T wave abnormalities. Non-specific T wave abnormalities in leads other than lead II are permissible if not accompanied by any other morphological abnormalities.
11. Subjects with any condition or history felt by the Investigator to place the subject at increased risk;
12. Subjects who have smoked or chewed tobacco-containing substances within 6 months prior to the start of the study;
13. Subjects judged by the Investigator to be unable or unwilling to comply with the requirements of the protocol;
14. Subjects who have used an investigational drug within 30 days prior to entering the study;
15. Subjects who have donated blood within 3 months prior to the start of the study (including blood donation related to the surgical procedure);
16. Subjects who have previously participated in the trial;
17. Subjects who are members of the study site staff directly involved with the study or a relative of the Sponsor or other personnel involved with the study.