Safety, Tolerability, and Pharmacokinetics of Oral EC5026 in Healthy Subjects
Condition: Healthy Adults
Intervention: EC5026 oral capsule; Placebo oral capsule
Intervention description: 5 sequential cohorts of 8 subjects randomly assigned to receive single ascending oral doses of EC5026 (n=6 per cohort) or matching placebo (n=2 per cohort).
Oral doses of EC5026 tested in each cohort: 0.5 mg (Cohort 1), 2 mg (Cohort 2), 8 mg (Cohort 3), 16 mg (Cohort 4), and 24 mg (Cohort 5).
A blinded sentinel group of 2 subjects (1 active and 1 placebo) will be dosed at least 2 days before the remaining 6 subjects (5 active and 1 placebo) will receive blinded doses of active study drug or placebo.; 5 sequential cohorts of 8 subjects randomly assigned to receive single ascending oral doses of EC5026 (n=6 per cohort) or matching placebo (n=2 per cohort)
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This is a first-in-human study with EC5026, a new drug candidate intended to treat
      neuropathic pain. The purpose of the study is to provide initial safety, tolerability, and
      pharmacokinetics data of single ascending oral doses of EC5026 in healthy subjects.
    

Eligibility criteria:

        Inclusion Criteria:

        Each subject must meet all of the following criteria to be enrolled in this study:

          1. The subject is male of female 18 to 65 years, inclusive

          2. The subject is able and willing to provide written informed consent to participate in
             the study.

          3. The subject is considered by the investigator to be in good general health as
             determined by prestudy medical history, physical examination findings, clinical
             laboratory test results, and 12-lead electrocardiogram (ECG) results.

          4. The subject is willing and able to remain in confinement at the study unit from Day -1
             to Day 5 and return to the unit at Days 7 and 14 for additional blood tests and safety
             evaluations.

          5. The subject has a body mass index of 19.0 to 32.0 kg/m2, inclusive, at Screening.

          6. The subject has normal blood pressure (systolic blood pressure 90 to 140 mm Hg,
             diastolic blood pressure 50 to 90 mm Hg), and heart rate (resting heart rate 45 to 90
             beats per minute) without medication.

          7. The subject has a clinical chemistry profile including electrolytes, alkaline
             phosphatase (ALP), lactate dehydrogenase, creatine phosphokinase (CPK), creatinine,
             and urea within the normal range without medication at Screening.

          8. The subject has urinalysis results including urinary creatinine within the normal
             range.

          9. The subject is a nonsmoker or is willing to abstain from smoking starting 2 weeks
             prior to randomization and for the duration of the study.

         10. The subject is able to read, understand, and follow the study instructions.

         11. Male subjects and their female partners must agree to use double-barrier contraception
             during the study and for 2 months after receiving the last dose of study drug or
             provide proof of postmenopausal state (minimum 1 year) or surgical sterility.

         12. Male subjects must not donate sperm during the study and for 12 months after receiving
             the last dose of study drug.

         13. Female subjects must be nonpregnant, nonlactating, and either postmenopausal for at
             least 1 year, or surgically sterile for at least 3 months, or agrees to use double
             barrier contraception from 28 days prior to randomization and/or their last confirmed
             menstrual period prior to study randomization (whichever is longer) until 2 months
             after discharge from the clinic. Female subjects will refrain from using hormonal
             contraceptives for at least 28 days prior to study entry until the end of study (EOS)
             visit (Day 14). All female subjects of childbearing potential must have a negative
             pregnancy test result at Screening and baseline (Day -1).

        Exclusion Criteria:

        Subjects meeting any of the following criteria will be excluded from the study:

          1. The subject has any abnormalities in any of the following: liver function tests, CPK,
             or urinalysis results. Liver function tests, CPK, or urinalysis tests may be repeated
             at the discretion of the investigator, if necessary, to confirm any abnormalities.

          2. The subject has used any nonstudy medication(s), including low-dose aspirin for
             cardiovascular prophylaxis, within 1 week before administration of study drug.

          3. The subject has used chemotherapy agents or has a history of cancer, other than
             nonmetastatic skin cancer that has been completely excised, within 5 years prior to
             screening.

          4. The subject has a history of bacterial, fungal, or viral infection requiring treatment
             with antibiotics, antifungal agents, or antivirals within 1 month prior to
             randomization.

          5. The subject has a presence or history of peripheral edema within the past 5 years.

          6. The subject has a history of congestive heart failure.

          7. The subject has used drugs which are CYP inducers or inhibitors within 30 days of
             randomization (eg, cimetidine, paroxetine, fluoxetine, haloperidol, ketoconazole,
             itraconazole, fluconazole, erythromycin, clarithromycin).

          8. The subject has used any dietary aids, supplements, or foods that are known to
             modulate drug metabolizing enzymes (eg, St. John's wort, grapefruit juice) within 14
             days of administration of study drug.

          9. The subject has difficulty in swallowing oral medications.

         10. The subject has a history of seizure disorder.

         11. The subject has serious psychosocial comorbidities as determined by the principal
             investigator.

         12. The subject has cognitive or psychiatric disorders, or any other condition that could
             interfere with compliance with study procedures and/or confinement in a study unit for
             5.5 days.

         13. The subject has a history of drug or alcohol abuse within 1 year prior to Screening.

         14. The subject has used any other investigational drug within 1 month or 5 half-lives,
             whichever is longer, prior to randomization.

         15. The subject has used prescription drugs within 1 month or 5 half-lives, whichever is
             longer, prior to randomization.

         16. The subject has used over-the-counter medication excluding routine vitamins, but
             including mega-dose vitamin therapy, within 1 week prior to randomization.

         17. The subject has donated and/or received any blood or blood products (more than 450 mL)
             within 3 months prior to randomization.

         18. The subject has a presence or history of active gastrointestinal, renal, hepatic, or
             coagulant disorder within 1 month prior to randomization.

         19. The subject has a presence or history of esophageal or gastroduodenal ulceration
             within 1 month prior to randomization.

         20. The subject has a family history of significant cardiac disease (ie, sudden death in
             first degree relative; myocardial infarction prior to 50 years