A Phase 1 Study of Intraoperative Administration of CA-008 for the Correction of Hallux Valgus Deformity
Condition: Hallux Valgus Deformity
MeSH terms: Hallux Valgus; Bunion; Congenital Abnormalities
Intervention: CA-008; Placebo
Intervention description: Local administration during surgery; Local administration during surgery
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Double (Participant, Investigator)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Unilateral Transpositional First Metatarsal Osteotomy

Summary:

      This is a single-center, randomized, double-blind, placebo-controlled, single ascending dose,
      sequential-group Phase 1 study. The study will be conducted utilizing a cohort design, with
      sequential groups of 8 subjects. Within each dose cohort, 6 subjects will be randomized to
      active, and 2 will be randomized to placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female aged 18 - 65 years old, inclusive.

          2. Planning to undergo a primary unilateral first metatarsal bunionectomy repair, without
             collateral procedures.

          3. Be American Society of Anesthesiology (ASA) physical Class 1 or 2.

          4. In good health and capable of undergoing a bunionectomy under regional anesthesia.

          5. No additional planned surgeries other than a bunionectomy during the course of the
             study.

          6. Male subjects must be either sterile (surgically or biologically), or commit to an
             acceptable method of birth control while participating in the study.

          7. Female subjects are eligible only if all of the following apply:

               1. Not pregnant (female subject of child bearing potential must have a negative
                  serum pregnancy tests at screening and negative urine pregnancy test before
                  surgery);

               2. Not lactating;

               3. Not planning to become pregnant during the study;

               4. Be surgically sterile; or at least two years post-menopausal; or have a
                  monogamous partner who is surgically sterile; or is practicing double-barrier
                  contraception; or practicing abstinence (must agree to use double-barrier
                  contraception in the event of sexual activity); or using an insertable,
                  injectable, transdermal, or combination oral contraceptive approved by the FDA
                  for greater than 2 months prior to screening visits and commits to the use of an
                  acceptable form of birth control for the duration of the study and for 30 days
                  from completion of the study.

          8. Have a body mass index ≤ 35 kg/m2.

          9. Willing and able to sign the informed consent form (ICF) approved by the Institutional
             Review Board (IRB).

         10. Willing and able to complete the study procedures and pain scales, and to communicate
             meaningfully in English with study personnel.

        Exclusion Criteria:

          1. Subjects with a history of hypertension, cardiovascular disease and a history of
             cerebrovascular events.

          2. Subjects with concurrent painful conditions that may require analgesic treatment
             during the study period, or, in the opinion of the Investigator, may confound
             post-operative pain assessments.

          3. Have been receiving or have received chronic opioid therapy defined as greater than 15
             morphine equivalents units per day for greater than 3 out of 7 days per week over a
             one-month period within 12 months of study treatment initiation.

          4. Have a known allergy or intolerance to the following medications or related
             substances: capsaicin, chili peppers, propofol, bupivacaine, benzodiazepines,
             midazolam, oxycodone, or ondansetron.

          5. Have a clinically significant abnormal clinical laboratory test value according to the
             judgment of the investigator.

          6. Have, as determined by the investigator or the study's medical monitor, a history or
             clinical manifestations of significant renal, hepatic, cardiovascular, metabolic,
             neurologic, psychiatric, or other condition that would preclude participation in the
             study.

          7. Use concurrent therapy that could interfere with the evaluation of efficacy or safety,
             such as any drugs which, in the investigator's opinion, may exert significant
             analgesic properties or act synergistically with CA-008.

          8. Use of disallowed pain medications within 2 days prior to Day 1 (NSAIDs, COX-2
             inhibitors, tramadol, ketamine, clonidine, gabapentin, pregabalin, or cannabinoids).

          9. Use of central nervous system (CNS) active drugs such as benzodiazepines, tricyclic
             antidepressants, SNRIs, or SSRIs for pain within seven days prior to Day 1. These
             drugs are permitted for non-pain indications if the dose has been stable for at least
             30 days prior to Day 1 and is planned to remain stable throughout the study. The use
             of lorazepam and other sleep medications, except those containing analgesic
             properties, is permitted.

         10. Have evidence of a clinically significant 12-lead ECG abnormality according to the
             judgment of the investigator, including QTcF >450 for men and >470 for women.

         11. Use of dietary supplements or over-the-counter (OTC) medications containing
             significant amounts of capsaicin within 1 day prior to Day 1, and throughout the
             hospitalization period.

         12. Subjects with active cutaneous disease, or other disease, at the anticipated site of
             surgery.

         13. History of peripheral vascular disease, sickle cell disease, vascular grafts, or
             vasospastic disorders.

         14. Use of parenteral or oral corticosteroid(s) within 14 days prior to Day 1.

         15. Known bleeding disorder or is taking agents affecting coagulation preoperatively. Deep
             venous thrombosis (DVT) prophylaxis of the surgeon's choice is permitted
             postoperatively.

         16. A medical condition that in the investigator's opinion could adversely impact the
             subject's participation or safety, conduct of the study, or interfere with the pain
             assessments.

         17. Diabetes mellitus.

         18. Use of antihypertensive agent or diabetic regimen at a dose that has not been stable
             for at least 30 days, or which is not expected to remain stable throughout the study.

         19. Use of digoxin, warfarin (see exception below), lithium, theophylline preparations,
             aminoglycosides, and all antiarrhythmics except beta-blockers, and use of
             anticonvulsants except benzodiazepines within 7 days prior to Day 1 and throughout the
             study. (Use of warfarin is allowed, at the investigator's discretion, for DVT
             prophylaxis after the surgery).

         20. History of illicit drug use, or prescription medicine or alcohol abuse (regularly
             drinks > 4 units of alcohol per day; 8 oz. beer, 3 oz. wine, 1 oz. spirits) within the
             past 2 years, in the opinion of the Investigator.

         21. Have positive results on the alcohol breath test indicative of alcohol abuse or urine
             drug screen indicative of illicit drug use (unless results can be explained by a
             current prescription or acceptable over-the-counter medication at screening as
             determined by the investigator) at screening, and/or prior to surgery.

         22. Stable medication regimen for at least 14 days prior to the scheduled bunionectomy
             procedure, within 5 half-lives of the specific prior medication (or, if half-life is
             not known, within 48 hours) before dosing with study medication.

         23. Participated in another clinical trial or used an investigational product within 30
             days or five half-lives (whichever is longer) prior to the planned bunionectomy
             surgery, or is scheduled to receive an investigational product other than CA-008 while
             participating in the study.

         24. Previously participated in a clinical study with CA-008 or capsaicin.

         25. Subjects with peripheral neuropathies which would potentially confound the planned
             neurosensory testing.

         26. Any past or current medical condition that in opinion of investigator, puts subject at
             undue safety risk for surgical complications or for use of the investigational
             product.

         27. Subjects who donated blood or plasma within the 30 days prior to screening.