A Study of MDT-10013 in the Treatment of Acute Postoperative Pain Following Bunionectomy
Condition: Postoperative Pain
MeSH terms: Pain, Postoperative
Intervention: MDT-10013; Standard of care for pain
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 192.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the efficacy and safety of MDT-10013 in men and
      women 18 to 80 years of age who are undergoing bunionectomy. The primary objective is to
      determine the analgesic efficacy of MDT-10013 compared with standard of care in the treatment
      of acute postoperative pain after subjects undergo bunionectomy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Is male or female aged 18 to 80 years.

          2. Has a body mass index from 18 kg/m2 to 40 kg/m2.

          3. Is scheduled to undergo primary, unilateral, first metatarsal bunionectomy (osteotomy
             and internal fixation) with no additional collateral procedures.

          4. Is classified by American Society of Anesthesiologists Physical Status Classification
             System as Class I or II.

          5. Must meet the following criteria if female:

               -  Is of non-childbearing potential, defined as any woman who has undergone surgical
                  sterilization or is more than 2 years postmenopausal

               -  If of childbearing potential, may be enrolled on the condition that results of a
                  pregnancy test are negative at baseline (at Screening and before surgery) and
                  that she is routinely using an effective method of birth control with a low
                  failure rate (i.e., hormonal contraception, intrauterine device, condoms in
                  combination with a spermicidal cream, or total sexual abstinence)

          6. Has read, understood, and signed the informed consent prior to study entry.

          7. Is mentally competent, reliable, and cooperative to undergo all visits and procedures
             scheduled in the study protocol and to record the required information.

          8. Has medical history, physical examination, vital signs, laboratory tests, and 12-lead
             electrocardiograms (ECGs) that are normal or without clinically relevant abnormalities
             as per investigator's judgment.

        Exclusion Criteria:

          1. Is a female who is pregnant or breastfeeding.

          2. Is not indicated for surgery because of an inflammatory process or risk of infection
             or delayed wound healing (e.g., autoimmune disorder).

          3. Has a history of allergy or hypersensitivity to the components in the investigational
             product or to the opioid medication (oxycodone).

          4. Before surgery, has current orthostatic hypotension (defined as systolic blood
             pressure decrease of at least 20 mm Hg or a diastolic blood pressure decrease of at
             least 10 mm Hg or an increase in heart rate by 20 beats per minute within 3 minutes of
             sitting up or standing).

          5. Has severe asthma, defined as requiring frequent or ongoing treatment to control
             symptoms. Exercise-induced asthma or mild asthma not requiring ongoing treatment may
             not be exclusionary at the discretion of the investigator.

          6. Has a current gastrointestinal disorder associated with bleeding, a history of such a
             disorder, or gastrointestinal inflammatory diseases as Crohn's disease or ulcerative
             colitis.

          7. Has any clinically significant cardiovascular condition as evidenced by physical
             examination, medical history, and/or baseline ECG.

          8. Has evidence of bradycardia as shown by heart rate of <50 beats per minute via
             screening ECG.

          9. Has a known infection with human immunodeficiency virus, hepatitis B virus, or
             hepatitis C virus.

         10. Has a chronic pain condition that may interfere with the subject's assessment of pain
             postoperatively, as determined by the investigator.

         11. Has any poorly controlled or serious medical conditions, psychiatric illnesses, or
             clinically significant laboratory values that, in the opinion of the investigator,
             could compromise the safety of the subject or the scientific integrity of the study
             (e.g., uncontrolled hypertension, autoimmune disease, or clinically relevant symptoms
             of thyroid dysfunction).

         12. Has presence or history of local or systemic malignant disease in the past 5 years
             (history of basal cell carcinoma will be allowed).

         13. Has impaired renal function (creatinine >1.5 times upper limit of normal).

         14. Has chronic impairment liver function (aspartate aminotransferase or alanine
             aminotransferase >3 times upper limit of normal).

         15. Has insulin-dependent diabetes or uncontrolled diabetes mellitus (glycosylated
             hemoglobin >7%).

         16. Has leukopenia (<3500 leukocytes/μL).

         17. Has current treatment with any of the following medications:

               1. Systemic corticosteroids (intranasal/inhaled steroids are acceptable).

               2. Immunosuppressant therapy to treat autoimmune diseases (e.g., rheumatoid
                  arthritis, multiple sclerosis, myasthenia gravis, systemic lupus erythematosus,
                  sarcoidosis, focal segmental glomerulosclerosis, Crohn's disease, Behcet's
                  Disease, pemphigus, and ulcerative colitis).

               3. Oral or topical products that contain clonidine (e.g., Catapres).

               4. Herbal supplements that contain yohimbine.

               5. Anticoagulant/antiplatelet therapy (prophylactic aspirin at 81 mg/day is
                  acceptable). If applicable, aspirin therapy should be held before and after the
                  study procedure on the basis of the investigator's discretion.

               6. Antiepileptic drugs, antipsychotics, tricyclic antidepressants, monoamine oxidase
                  inhibitors, lithium, and sulfonamides.

               7. Calcium channel blocker, digoxin, or beta-adrenergic blockers.

         18. Has chronic use of opioids (including tramadol), defined as use 20 out of the last 30
             days before study screening.

         19. Has a history of or current diagnosis of epilepsy.

         20. Has a known or suspected history of drug or alcohol abuse (as determined by the
             investigator).

         21. Is judged by the investigator not to be a suitable candidate for study treatment and
             pain relief medication on the basis of medical history, concomitant medication, and
             concurrent systemic disease.

         22. Is not stabilized on the following medications for at least 8 weeks prior to dosing:
             selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake
             inhibitors (SNRIs).

         23. Is unable to refrain from taking nonsteroidal anti inflammatory drugs (NSAIDs) or
             opioids within the 24-hour period prior to surgery.

         24. Has participated in any other clinical trial in the 4 weeks prior to Screening.

         25. Experiences any surgical complication that, in the opinion of the investigator,
             precludes implantation of MDT-10013.