Evaluation of the Safety and Efficacy of a Single Dose of SKY0402 in Subjects Undergoing Augmentation Mammoplasty

This was a Phase 2, parallel-group, active-control, randomized, double-blind study conducted to evaluate a single local administration of low dose or high dose of SKY0402 compared with 75 mg of bupivacaine HCl (i.e., Marcaine® 0.5%) in women undergoing bilateral, cosmetic, sub-muscular, augmentation mammoplasty under general anesthesia. Each subject was to serve as her own control.

A total of 40 subjects were randomized in a 1:1 ratio to receive one of the following regimens:

• Low-dose SKY0402 in one side and Marcaine 75 mg in the contralateral side.
• Mid-dose SKY0402 in one side and Marcaine 75 mg in the contralateral side.

Study drug was administered locally into the breast implant pocket at the end of surgery. After surgery, subjects were to receive standard treatment with acetaminophen 1000 mg three times daily and rescue analgesia with immediate-release oxycodone, as needed, for breakthrough pain.

Assessments of postoperative pain were conducted through 96 hours. Safety assessments were conducted including monitoring of local and systemic adverse events (AEs).

Inclusion criteria

Subjects who met all of the following criteria were eligible for inclusion in the study:

• Women, 18-40 years of age at the Screening Visit.
• Postmenopausal, surgically sterile, or willing to use an acceptable means of contraception for at least 30 days after surgery including any of the following: hormonal contraceptives (e.g., oral, injectable, implantable starting at least 30 days before study drug administration), effective double-barrier methods (e.g., condoms with spermicide), intrauterine device, lifestyle with a personal choice of abstinence, nonheterosexual lifestyle, or a strictly monogamous relationship with a partner who has had a vasectomy.
• Scheduled to undergo primary, bilateral, sub-muscular, augmentation mammoplasty under general anesthesia.
• American Society of Anesthesiology (ASA) Physical Class 1-3.
• Able and willing to comply with all study visits and procedures.
• Able to speak, read, and understand the language of the ICF, study questionnaires, and other instruments used for collecting subject-reported outcomes, in order to enable accurate and appropriate responses to pain scales and other required study assessments.
• Willing and capable of providing written informed consent.

Exclusion criteria

• Subjects were not eligible for the study if they met any of the following criteria:

• Pregnancy, nursing, or planning to become pregnant during the study or within one month after study drug administration.
• Body weight less than 50 kilograms.
• History of hypersensitivity or idiosyncratic reaction to amide-type local anesthetics or to opioid medication.
• Administration of an investigational product within 30 days or 5 elimination half-lives of such investigational product, whichever was longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study.
• History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.
• Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the Investigator, may interfere with study assessments or compliance.
• Significant medical conditions or laboratory results that, in the opinion of the Investigator, indicated an increased vulnerability to study drugs and procedures, and exposed the subject to an unreasonable risk as a result of participating in this clinical trial (e.g., severe hepatic insufficiency, hypotension, heart block, or severely impaired cardiac function).

In addition, the subject was ineligible to receive study drug if she met the following criterion during surgery:

• Any clinically significant event or condition uncovered during the surgery (e.g., excessive bleeding, acute sepsis) that might render the subject medically unstable or complicate the subject's postoperative course.