A Phase 2 Study to Evaluate Pregabalin and Acetaminophen Compared to Acetaminophen and Placebo in Subjects Undergoing Bunionectomy
Condition: Postoperative Pain
MeSH terms: Pain, Postoperative
Intervention: Pregabalin; Acetaminophen; Placebo 1; Placebo 2
Intervention description: Pregabalin is a structural derivative of the inhibitory neurotransmitter gamma aminobutyric acid with anticonvulsant, anxiolytic and sleep-modulating properties.; Acetaminophen is a non-salicylate antipyretic and non-opioid analgesic agent.; Placebo for APAP; Placebo for combination
Intervention MeSH terms: Acetaminophen; Pregabalin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Up to 80 subjects will be randomized (32 in each active treatment group, 16 placebo).
Eligible subjects will be randomized on Day 1 in a 2:2:1 ratio to receive either a combination of PGB and APAP administered (Group A), APAP (Group B), or placebo (Group C).
Enrollment: 87.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      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
    

Eligibility criteria:

        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:

               1. 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.

               2. Hypertension (uncontrolled), cardiovascular disease, or history of
                  cerebrovascular events. Hypertension must be controlled without known end organ
                  damage.

               3. Concurrent painful conditions that may require analgesic treatment during the
                  study period.

               4. History of significantly reduced hepatic or renal function, angle closure
                  glaucoma, or convulsive disorder.

               5. Recent history of urinary retention.

               6. 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.

               7. Active cutaneous disease, or other disease, at the surgical site.

               8. Peripheral vascular disease, sickle cell disease, vascular grafts, or vasospastic
                  disorders.

               9. Known bleeding disorder or is taking agents affecting coagulation preoperatively.

                  Deep venous thrombosis (DVT) prophylaxis of the surgeon's choice is permitted
                  postoperatively.

              10. Diabetes mellitus (uncontrolled). Diabetes mellitus must be controlled without
                  known end organ damage.

              11. History of malignancy in the past 2 years with the exception of squamous cell
                  carcinoma or basal cell carcinoma.

              12. 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:

               1. Pain medication (opioids, NSAIDs, cyclooxygenase (COX)-2 inhibitors, tramadol,
                  ketamine, clonidine, gabapentin, pregabalin, or cannabinoids) within 2 days prior
                  to Day 1.

               2. 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.

               3. Use of parenteral or oral corticosteroid(s) within 14 days prior to Day 1.

               4. 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.

               5. 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.