Clinical trial NCT01743625 (phase 3, status: completed)
Conditions: pain, postoperative, bunion
ICD codes: M21.611, M21.612, M21.619, M21.621, M21.622, M21.629
Drugs: cov155, placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria

          -  Voluntarily provide written informed consent

          -  General good health

          -  18 to 75 years of age

          -  Scheduled for primary unilateral first metatarsal bunionectomy (with no collateral
             procedures)

          -  Body mass index ≤33

          -  Female subjects eligible if

               -  Not pregnant or lactating; not planning to become pregnant for duration of study;

               -  Surgically sterile, or have a monogamous partner who is surgically sterile, or at
                  least 2 years postmenopausal, or practicing acceptable birth control for more
                  than 2 months prior to Screening, during the study and for 1 week following last
                  dose of COV155

          -  Male subjects must be sterile (biologically or surgically) or use reliable birth
             control during the study until at least 1 week after the last dose of COV155

          -  Classified as either Physical Status-1 (PS) or PS-2 by the American Society of
             Anesthetists (ASA) Physical Status Classification System.

          -  Willing to complete pain assessments and clinic visits.

          -  Additional inclusion criterion for randomization into the Double-Blind Phase: Subjects
             must experience postoperative pain intensity score ≥5 on a 0 to 10 Numerical Pain
             Rating Score (NPRS) more than 1 hour, and less than 9 hours after discontinuing the
             nerve block, and at least 30 minutes after the last ice pack has been removed (if
             used).

        Exclusion Criteria

          -  Uncontrolled medical condition, serious intercurrent illness, clinically significant
             general health condition, or extenuating circumstance that may significantly decrease
             study compliance or otherwise preclude study participation

          -  Clinically significant abnormal ECG at Screening

          -  Gastric bypass surgery or gastric band

          -  Previous abdominal surgery within the past year or history of abdominal adhesions,
             known or suspected paralytic ileus

          -  History of any medical condition that would alter the absorption, distribution,
             metabolism or excretion of COV155 including but not limited to severe chronic
             diarrhea, chronic constipation, severe irritable bowel syndrome, or unexplained weight
             loss

          -  History of severe bronchial asthma, hypercarbia, hypoxia or sleep apnea

          -  Certain lab abnormalities

          -  Addison's disease, benign prostatic hyperplasia, or kidney disease

          -  Donated blood or blood components within 3 months prior to Screening or during study

          -  Known allergy/hypersensitivity to any opioid analgesics, anesthetics, acetaminophen,
             non steroidal anti-inflammatory drugs (NSAIDs)

          -  History of intolerance to short term opioid use

          -  Unable to discontinue the use of prohibited medications or a history of substance or
             alcohol abuse within 2 years prior to Screening or a positive quantitative urine drug
             test at Screening

          -  Positive for human immunodeficiency virus, hepatitis B or C

          -  Dysphagia and/or cannot swallow study treatment whole

          -  History of migraine or frequent headaches within the previous 2 years, seizures, or
             are currently taking anticonvulsants

          -  Previously received COV155 in a clinical study, or undergone a bunionectomy within the
             last 3 months

          -  Received any investigational drugs or devices within 4 weeks prior to Screening or
             during study

          -  Active malignancy or history of malignancy within 2 years prior to Screening, other
             than completely eradicated cervical squamous cell carcinoma in situ or basal skin
             cancer

          -  Currently taking neuroleptics or stable doses of a benzodiazepine

          -  Other criteria as specified in the protocol

          -  Additional exclusion criterion for randomization into the Double-Blind Phase: Have
             surgical complications that could compromise the safety of the subject or confound the
             results of the study.