A Study of Acetaminophen for Post Surgical Dental Pain
Condition: Pain, Postoperative; Dental Pain
MeSH terms: Toothache; Pain, Postoperative
Intervention: Acetaminophen; Placebo
Intervention description: Acetaminophen is an analgesic and antipyretic; Saline
Intervention MeSH terms: Acetaminophen
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: High Dose Acetaminophen (APAP) versus Placebo, Low Dose APAP versus Placebo
Masking: Double (Participant, Investigator)
Masking description: Double Blind, Placebo controlled
Enrollment: 110.0
Sex: All
Minimum age: 17 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      To assess the safety, tolerability, analgesic, efficacy and pharmacokinetics of high dose
      acetaminophen relative to placebo and low dose acetaminophen relative to placebo over a 24
      hour period in patient experiencing moderate to severe pain following the surgical removal of
      third molar.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients must be capable of reading, comprehending, and signing the informed
             consent/assent form;

          2. Male and female patients between 17-55 years of age;

          3. Body Mass Index (BMI) ≤35.0 kg/m2

          4. Body weight of >50 kg

          5. Patients are American Society of Anaesthesiologists (ASA) Category I or II and are in
             good physical health as judged by a thorough history and physical examination;

          6. Patients without infections in the area of the impacted teeth;

          7. Patients must agree to refrain from ingesting any systemic or applying any topical
             analgesic medication for 3 days or 5 half-lives of the drug prior to and during the
             study;

          8. No alcohol for a minimum of 24 hours prior to the surgery;

          9. Female patients must be of non-child bearing potential, defined as postmenopausal for
             more than 1 year or surgically sterile (hysterectomy, tubal ligation/occlusion) or
             practicing an acceptable method of contraception (hormonal oral, patch, or implant,
             double barrier method, intrauterine device, vasectomized or same sex partner, or
             abstinence). Patients using hormonal birth control must have been on a stable dose of
             treatment for at least 30 days and received at least 1 cycle of treatment prior to
             randomization. At Screening and at the day of surgery, all females of childbearing
             potential must have a negative (serum at screening and urine on day of surgery 1)
             pregnancy test and not be breastfeeding;

         10. Patients must have a negative urine drug screen for drugs of abuse at Screening and on
             the day of surgery. At the discretion of the Principal Investigator, a positive drug
             screen result may be permitted if the patient has been on a stable dose of an allowed
             medication for >30 days;

         11. Patients who are scheduled to undergo the surgical removal of up to 4 third molars of
             which at least two have to be mandibular molars with a difficulty rating of 4 or 5 and
             meeting the following criteria:

               -  two full bony impactions

               -  two partial bony impactions

               -  one full bony impaction in combination with one partial bony impaction (see
                  Appendix 1 for Impaction Difficulty Rating Scale);

         12. Patients able to comprehend and follow the requirements of the study (including
             availability on scheduled visit dates) based upon the research site's judgment.

        Exclusion Criteria:

          1. Patients with a history of any significant medical condition that, in the opinion of
             the Principal Investigator or his designee, would place the patient at increased risk
             such as: hepatic, renal, endocrine, cardiac, neurological, psychiatric,
             gastrointestinal, pulmonary, hematologic, or metabolic disorders, including glaucoma,
             diabetes, emphysema, and chronic bronchitis;

          2. Patients with a history of any type of malignancy within the past 5 years other than
             minor skin related cancers;

          3. Patients with a history of alcohol or substance abuse in the past three years
             according to Diagnostic and Statistical Manual (DSM) V and who do not satisfy
             Inclusion Criteria 10 (including a positive urine drug screen test);

          4. Patients with a known allergy or hypersensitivity to any local anesthetic drug,
             acetaminophen, ibuprofen, or other NSAIDS;

          5. Patients who are taking any concomitant medications that might confound assessments of
             pain relief, such as psychotropic drugs, antidepressants, sedative hypnotics or any
             analgesics taken within three days or five times of their elimination half-lives,
             whichever is longer. Selective serotonin reuptake inhibitors (SSRIs) and selective
             noradrenaline reuptake inhibitors (SNRIs) are permitted if the patient has been on a
             stable dose for at least 30 days prior to screening;

          6. Patients who have smoked or chewed tobacco-containing substances within 48 hours prior
             to the day of surgery;

          7. Patients judged by the Principal Investigator to be unable or unwilling to comply with
             the requirements of the protocol;

          8. Patients who have used an investigational drug within 30 days prior to the screening
             day or have previously participated in any Nevakar trial;

          9. Patients who have donated blood within 3 months prior to the screening day;

         10. Patients who are employees or relatives of employees of JBR Clinical Research or
             Nevakar, Inc.

         11. Patients with liver function tests (ALT, AST) that are above the normal reference
             range.

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