A Phase 2 Study to Evaluate Pregabalin and Acetaminophen Compared to Acetaminophen and Placebo in Subjects Undergoing Bunionectomy

A Phase 2, Randomized, Double-Blind, Placebo- and Comparator-Controlled Trial to Evaluate the Safety and Efficacy of Combination Pregabalin and Acetaminophen Compared to Acetaminophen and Placebo in Subjects Undergoing Bunionectomy

Up to 80 subjects will be randomized (32 in each active treatment group, 16 placebo).

To evaluate the efficacy of combination pregabalin (PGB) and acetaminophen (APAP) administered vs. placebo for pain control in subjects undergoing bunionectomy.

The placebo will be the saline solution.

Inclusion criteria

• Provide informed consent by signing the informed consent form (ICF) approved by the Institutional Review Board (IRB);
• Be male or female aged 18-65 years;
• Be scheduled to undergo unilateral first metatarsal bunionectomy;
• Be in good health and capable of undergoing a bunionectomy under anesthesia as described in the study surgical and anesthetic protocol;
• Weigh between 50 and 100 kg (body mass index [BMI] <32 kg/m2);
• Have no additional planned surgeries other than bunionectomy during the course of the study;
• Have negative urine drug screen for drugs indicative of illicit drug use (unless results can be explained by a current prescription or acceptable over-the-counter medication at screening as determined by the investigator) and no detectable results on the alcohol test (breath or saliva) indicative of alcohol abuse at screening, and/or prior to surgery (may be repeated if the Investigator suspects a false-positive result). Note: For those subjects who test positive for tetrahydrocannabinol (THC), if they are willing to abstain from use or consumption of THC-containing products from screening through end of the subject's participation in the study, they may be allowed to participate in the study.
• Biological female subjects must be non-lactating, sterile (bilateral tubal ligation, bilateral salpingectomy, or hysterectomy), post-menopausal for at least 2 years, have a partner that is sterile, be abstinent, use a highly effective double- contraception method (hormonal protection is insufficient), or use an FDA-approved contraceptive for greater than 2 months prior to the screening visit and commit to an acceptable form of birth control for the duration of the study and for 30 days after completion of the study;
• Be willing and able to complete the study procedures and pain scales and communicate meaningfully in English with study personnel.

Exclusion criteria

• Have a medical condition or history that in the Investigator's opinion could adversely impact the subject's participation or safety or the conduct of the study, or interfere with the pain assessments, including the following:

• Serious breathing difficulties or respiratory risk factors (including use of opioid pain medicines and other drugs that depress the central nervous system), and conditions such as chronic obstructive pulmonary disease that reduce lung function.
• Hypertension (uncontrolled), cardiovascular disease, or history of cerebrovascular events. Hypertension must be controlled without known end organ damage.
• Concurrent painful conditions that may require analgesic treatment during the study period.
• History of significantly reduced hepatic or renal function, angle closure glaucoma, or convulsive disorder.
• Recent history of urinary retention.
• Opioid tolerant, i.e., the subject is currently taking or has taken a chronic opioid at a dose greater than or equal to 20 mg morphine milligram equivalents (MME) per day (more than 30 consecutive days of daily use) for pain in the 2 months prior to surgery.
• Active cutaneous disease, or other disease, at the surgical site.
• Peripheral vascular disease, sickle cell disease, vascular grafts, or vasospastic disorders.
• Known bleeding disorder or is taking agents affecting coagulation preoperatively.

Deep venous thrombosis (DVT) prophylaxis of the surgeon's choice is permitted postoperatively.

• Diabetes mellitus (uncontrolled). Diabetes mellitus must be controlled without known end organ damage.
• History of malignancy in the past 2 years with the exception of squamous cell carcinoma or basal cell carcinoma.
• Prior bunionectomy on the index foot or other foot surgery on the index foot that could impact the surgery or data collection endpoints.
• Use of disallowed medications including the following:

• Pain medication (opioids, NSAIDs, cyclooxygenase (COX)-2 inhibitors, tramadol, ketamine, clonidine, gabapentin, pregabalin, or cannabinoids) within 2 days prior to Day 1.
• Central nervous system (CNS) active drugs such as benzodiazepines, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors (SNRIs), or selective serotonin reuptake inhibitors (SSRIs) for pain within seven days prior to Day 1. These drugs are permitted for non-pain indications if the dose has been stable for at least 30 days prior to Day 1 and is planned to remain stable throughout the study. The use of lorazepam and other sleep medications, except those containing analgesic properties, is permitted.
• Use of parenteral or oral corticosteroid(s) within 14 days prior to Day 1.
• Antihypertensive agent or diabetic regimen at a dose that has not been stable for at least 30 days, or which is not expected to remain stable throughout the study.
• Digoxin, warfarin (see exception below), lithium, theophylline preparations, aminoglycosides, and all antiarrhythmics except beta-blockers, and use of anticonvulsants except benzodiazepines within 7 days prior to Day 1 and throughout the study.
• Use of warfarin is allowed, at the investigator's discretion, for DVT prophylaxis after the surgery.
• Significant history of allergic reactions or known intolerance to pregabalin or any gabapentinoid, to APAP, to any rescue medication used in the study, or any medication used in the surgical and anesthetic protocol.
• Female subjects (biological females only) who are pregnant or lactating, who plan to get pregnant, or who have a positive serum pregnancy test at Screening or a positive urine pregnancy test at either Day -1 or Day 1 prior to surgery.
• Participated in another clinical trial within 30 days, or previously participated in a clinical study with a similar investigational product.