Clinical trial: A Study to Assess the Safety and Tolerability of E2730 After Multiple Dose and the Food Effect After Single Dose in Healthy Participants (NCT04676685)

Eligibility criteria:
Inclusion Criteria:

          1. Non-smoking, healthy male or female, age greater than or equal to (>=) 18 years and
             <55 years old at the time of informed consent. To be considered non-smokers,
             Participants must have discontinued smoking for at least 4 weeks before dosing

          2. Japanese Participants must have been born in Japan of Japanese parents and Japanese
             grandparents, must have lived no more than 5 years outside of Japan, and must not have
             changed their life style or habits, including diet, while living outside of Japan

          3. Body mass index (BMI) >=18 and <30 kilograms per meter square (kg/m^2) at Screening

        Exclusion Criteria:

          1. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a
             positive beta-human chorionic gonadotropin [β-hCG] test). A separate baseline
             assessment is required if a negative screening pregnancy test was obtained more than
             72 hours before the first dose of study drug

          2. Females of childbearing potential who:

               -  Within 28 days before study entry, did not use a highly effective method of
                  contraception, which includes any of the following:

               -  Total abstinence (if it is their preferred and usual lifestyle)

               -  An intrauterine device or intrauterine hormone-releasing system (IUS)

               -  A contraceptive implant

               -  An oral contraceptive (Participant must have been on a stable dose of the same
                  oral contraceptive product for at least 28 days before dosing and must agree to
                  stay on the same dose of the oral contraceptive throughout the study and for 28
                  days after study drug discontinuation)

               -  Have a vasectomized partner with confirmed azoospermia

               -  Do not agree to use a highly effective method of contraception throughout the
                  entire study period and for 28 days after study drug discontinuation

          3. Males who have not had a successful vasectomy (confirmed azoospermia) if their female
             partners meet the exclusion criteria above (that is, the female partners are of
             childbearing potential and are not willing to use a highly effective contraceptive
             method throughout the study period and for 5 times the half-life of the study drug
             plus 90 days after study drug discontinuation)

          4. Clinically significant illness that requires medical treatment within 8 weeks or a
             clinically significant infection that requires medical treatment within 4 weeks of
             dosing

          5. Evidence of disease that may influence the outcome of the study within 4 weeks before
             dosing; example, psychiatric disorders and disorders of the gastrointestinal tract,
             liver, kidney, respiratory system, endocrine system, hematological system,
             neurological system, or cardiovascular system, or participants who have a congenital
             abnormality in metabolism

          6. Any history of gastrointestinal surgery that may affect PK profiles of E2730, example,
             hepatectomy, nephrectomy, and digestive organ resection

          7. Any clinically abnormal symptom or organ impairment found by medical history, physical
             examinations, vital signs, ECG finding, or laboratory test results that require
             medical treatment at Screening

          8. A prolonged QT interval of the ECG/Corrected QT interval (QT/QTc) (QTcF greater than
             [>] 450 milliseconds [ms]) demonstrated by a repeated ECG at Screening or Baseline
             (based on average of triplicate ECGs). A history of risk factors for torsade de
             pointes (example, heart failure, hypokalemia, family history of long QT Syndrome) or
             the use of concomitant medications that prolonged the QT/QTc interval

          9. Persistent systolic BP >139 or <90 millimeter of mercury (mmHg) or diastolic BP >89 or
             <50 mmHg at Screening or Baseline

         10. Heart rate <45 beats/minute or >100 beats/minute at Screening or Baseline

         11. Any lifetime history of suicidal ideation or any lifetime history of suicidal behavior
             as indicated by the Columbia-Suicide Severity Rating Scale (C-SSRS) or equivalent
             scale or via interview with a psychiatrist

         12. Any lifetime history of psychiatric disease (including but not limited to depression
             or other mood disorders, bipolar disorder, psychotic disorders, including
             schizophrenia, panic attacks, anxiety disorders ). The absence of a history of
             psychiatric disease should be documented by a checklist in the electronic case report
             form (eCRF)

         13. Any current psychiatric symptoms as indicated by a standard screening tool

         14. Any suicidal ideation with intent with or without a plan at Screening or within 6
             months of Screening (that is, answering "Yes" to questions 4 or 5 on the Suicidal
             Ideation section of the C-SSRS)

         15. Any lifetime suicidal behavior (per the Suicidal Behavior Section of the C-SSRS)

         16. Known history of clinically significant drug allergy at Screening

         17. Known history of food allergies or presently experiencing significant seasonal or
             perennial allergy at Screening

         18. Known to be human immunodeficiency virus (HIV) positive at Screening

         19. Active viral hepatitis (A, B, or C) and syphilis as demonstrated by positive serology
             at Screening

         20. History of drug or alcohol dependency or abuse, or those who have a positive drug test
             at Screening or Baseline

         21. Exposure within the last 14 days to an individual with confirmed or probable corona
             virus disease 2019 (COVID-19) or symptoms within the last 14 days that are on the most
             recent Centers for Disease Control and Prevention (CDC) list of COVID symptoms or any
             other reason to consider the participants at potential risk for an acute COVID-19
             infection

         22. Currently enrolled in another clinical study or used any investigational drug or
             device within 28 days or 5 half-lives, whichever is longer, preceding informed consent

         23. Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or
             donation of plasma within 1 week of dosing

         24. Any personal or family history of seizures (including febrile seizures) or epilepsy or
             episode of unexplained loss of consciousness

         25. Any history of neurological or other medical conditions which in the opinion of the
             investigator has the potential to reduce seizure threshold (example, history of head
             concussion, traumatic brain injury, alcohol abuse, substance abuse, developmental
             abnormalities in the brain)

         26. Any epileptiform discharges on resting EEG (including during hyperventilation and
             photo-stimulation)
No condition on gender to be admitted to the trial.
Accepts Healthy Volunteers
Subject must be at least 18 Years old.
Subject must be at most 55 Years

Patient description (medical language): A 30-year-old man who is a computer scientist came to the clinic with the lab result stating azoospermia.  The patient is sexually active with his wife and does not use any contraception methods.  They have been trying to conceive for the past year with no success.  The patient has a past medical history of recurrent pneumonia, shortness of breath, and  persistent cough that produces large amounts of thick sputum. The patient had multiple lung infections during childhood. He does not smoke, use illicit drugs or alcohol.  The patient has no history of other medical conditions including allergies or any kind of surgery.  On physical examination, the digits show clubbing.  An ultrasound shows bilateral absence of the vas deferens, and FEV1 was 75% on the respiratory function test.

Patient description (patient's own words): I'm a 30-year-old computer scientist. I did some lab tests that came back quite alarming, stating that I have azoospermia?! I'm sexually active with my wife and we don't use contraception. We've been trying to have a child for the past year. I have a medical history of pneumonia and shortness of breath and regular wet cough. I had several lung infections when I was a kid. That's why I'm very careful and don't smoke, do drugs, or drink. I don't have other medical conditions including allergies or any kind of surgery. The doctor did the clubbing test on my fingers, which was positive. I also did an ultrasound and it showed that I'm missing the tubes that carry sperm around. I also had a 75% for my respiratory function test.

Does the patient match the trial criteria? Contradiction