Study to Evaluate Analgesic Effect of IV Administration of Kappa Agonist CR845 For Hysterectomy Surgery
Condition: Postoperative Pain
MeSH terms: Pain, Postoperative
Intervention: CR845; Placebo; CR845; Placebo
Intervention description: Single i.v. dose (0.04 mg/kg) administered preoperatively; Single i.v. dose administered preoperatively; Single i.v. dose (0.04 mg/kg) administered postoperatively for pain; Single i.v. dose administered postoperatively for pain
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 203.0
Sex: Female
Minimum age: 21 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: pain; acute pain; visceral pain; kappa agonist; opioid analgesics; peripheral nervous system agents; physiological effects of drugs; surgery; hysterectomy; post-operative; post-operative complications

Summary:

      The primary purpose of this study is to determine if CR845 is effective in treating the pain
      associated with a laparoscopic hysterectomy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Able to provide written informed consent prior to any study procedures;

          -  Able to communicate clearly with the Investigator and staff;

          -  Female between 21 and 65 years of age, inclusive;

          -  Scheduled for elective laparoscopic hysterectomy under general anesthesia;

          -  Negative result on serum pregnancy test at screening and negative urine pregnancy test
             at Baseline (for women of child-bearing potential only) and not currently breast
             feeding, or planning to do so within 30 days of dosing;

          -  Negative urine drug screen for drugs of abuse at Screening and at Baseline;

          -  American Society of Anesthesiologists (ASA) risk class of I to III;

          -  Body mass index (BMI) between 17 and 40 inclusive.

        Exclusion Criteria:

          -  Has known allergies to opioids, or hypersensitivity to other materials (such as
             infusion line) or medications to be used in the study;

          -  Has a known or suspected history of Diagnostic and Statistical Manual of Mental
             Disorders, Fourth Edition (DSM-IV)-diagnosed alcohol, opiate or other drug abuse or
             dependence within 12 months prior to screening;

          -  Is unable to refrain from alcohol consumption for a period beginning 24 hours prior to
             surgery through the end of the Treatment Period;

          -  Is scheduled to undergo a hysterectomy that will utilize any type of robotic
             technology and/or a concomitant surgical procedure that would produce a significantly
             greater degree of surgical trauma than the laparoscopic hysterectomy or laparoscopic
             assisted vaginal hysterectomy alone;

          -  Has taken non-opioid analgesics (including cyclooxygenase-2 [COX-2] inhibitors) or
             nonsteroidal anti-inflammatory drugs (NSAIDs) within 12 hours of the Baseline
             assessments;

          -  Has taken any opioid analgesics or used systemic steroids within 4 days of surgery OR
             has previously used opiates chronically for a period of ≥3 months;

          -  Has used antipsychotics, antiepileptics, sedatives, hypnotics, or antianxiety agents,
             selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants for < 30
             days prior to surgery or had a dose change within the previous 30 days;

          -  Has taken any prescription or over-the-counter medication within 3 days prior to
             surgery that, in the opinion of the Investigator, is expected to confound the
             analgesic response;

          -  Has taken herbal agents or nutraceuticals (i.e., chaparral, comfrey, germander, gin bu
             huan, kava, pennyroyal, skullcap, St. John's wort, or valerian) 7 days prior to
             surgery;

          -  In the opinion of Investigator shows clinical signs of hypovolemia;

          -  Has an oxygen saturation < 92% on room air at Screening or prior to receiving the
             first infusion of study drug;

          -  Has any history of clinically significant cardiovascular disease,

          -  Has a clinically significant abnormal electrocardiogram (ECG) or a history of
             additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia,
             family history of Long QT Syndrome);

          -  Has a history of any serious medical conditions that in the opinion of the
             Investigator would preclude study participation;

          -  Has serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline
             phosphatase, or gamma glutamyl transferase (GGT) >2.5 x the upper limit of normal
             (ULN) at screening;

          -  Has bilirubin, blood urea nitrogen (BUN), or creatinine >1.5 x the reference ULN at
             Screening;

          -  Has abnormally low hemoglobin < 10 mg/dl at Screening;

          -  Has serum sodium levels > 146 mmol/L at Screening;

          -  Has impaired renal function (creatinine clearance [CrCl] < 50 ml/min) at Screening;

          -  Has a positive test for human immunodeficiency virus (HIV) or known history of HIV
             infection;

          -  Has received another investigational drug within 30 days of scheduled surgery;

          -  Has a significant chronic pain condition in areas unrelated to the operative site at
             the time of Screening that in the Investigator's opinion could confound the
             interpretation of study results