A Phase 2 Study to Evaluate Analgesic Effect of IV CR845 For Pain Following Bunionectomy Surgery
Condition: Acute Pain
MeSH terms: Acute Pain
Intervention: CR845; Placebo
Intervention description: CR845 dosage = 0.005 mg/kg per dose, IV bolus. The initial dose was administered upon reaching a qualifying pain intensity score and followed by a supplemental dose, if requested by patient for pain. Additional doses could be administered every 8 hours up to 48 hours.; Matching placebo administered using same dosing algorithm as the active arm
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: pain; acute pain; kappa agonis; opioid analgesia; bunionectomy; peripheral nervous system agents; physiological effects of drugs; surgery; post-operative; post-operative complications

Summary:

      This is a single-center, randomized, double blind, placebo controlled, parallel group proof
      of concept study to evaluate the analgesic efficacy as well as the safety, tolerability and
      pharmacokinetic profile of CR845 in patients with pain following bunionectomy surgery.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Able to provide written informed consent prior to any study procedures;

          2. Able to communicate clearly with the Investigator and staff;

          3. Males and females aged 18 years or older;

          4. Scheduled for elective primary unilateral first metatarsal bunionectomy surgery
             (osteotomy and internal fixation) with no collateral procedures;

          5. Females physically incapable of childbearing potential (postmenopausal for more than 1
             year or surgically sterile) or practicing an acceptable method of contraception
             (hormonal, barrier with spermicide, intrauterine device, vasectomized partner, or
             abstinence). Subjects using hormonal birth control must have received at least 1 cycle
             of treatment prior to randomization. All females of childbearing potential must have a
             negative pregnancy test and not be breast feeding at Baseline;

          6. Negative urine drug screen for drugs of abuse at Screening and at Baseline; a positive
             drug screen result may be permitted if the patient has been on a stable dose of an
             allowed medication for >30 days (antipsychotics, antiepileptics, sedatives, hypnotics,
             or antianxiety agents, selective serotonin reuptake inhibitors [SSRIs], tricyclic
             antidepressants) or >3 months (opioid analgesics or systemic steroids);

          7. American Society of Anesthesiologists (ASA) risk class of I to II;

          8. Body weight <170 kg

        Exclusion Criteria:

          1. Has known allergies to opioids, unless has subsequently tolerated other opioids and in
             the opinion of the PI could tolerate study drug;

          2. 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;

          3. Is unable to refrain from alcohol consumption for a period beginning 24 hours prior to
             surgery through the end of the Treatment Period;

          4. Has taken non-opioid analgesics (including cyclooxygenase-2 [COX-2] inhibitors) or
             nonsteroidal anti-inflammatory drugs (NSAIDs) within 12 hours of the Baseline
             assessments;

          5. Has taken any opioid analgesics or used systemic steroids within 4 days of surgery OR
             has been using opiates chronically for a period of < 3 months; (Note: Patients on
             stable chronic opioids for ≥ 3 months will need to discontinue them for 4 days prior
             to surgery);

          6. 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;

          7. Has taken any prescription or over-the-counter medication within 4 days prior to
             surgery that, in the opinion of the Investigator, is expected to confound the
             analgesic response;

          8. Has taken herbal agents or nutraceuticals (i.e., chaparral, comfrey, germander, jin bu
             huan, kava, pennyroyal, skullcap, St. John's wort, or valerian) during any of the 7
             days prior to surgery;

          9. Has any clinically significant condition or a significant laboratory abnormality that
             would, in the Investigator's or designee's opinion, preclude study participation

         10. Has received another investigational drug within 30 days of scheduled surgery.