Safety, Tolerability and Pharmacokinetics of Escalating Single Doses of ENV8058 (TAK-058) in Healthy Participants
Condition: Dose Finding Study
Intervention: TAK-058 (ENV8058); Placebo
Intervention description: TAK-058 (ENV8058) oral solution; TAK-058 (ENV8058) placebo-matching oral solution
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Drug therapy

Summary:

      The purpose of this study is to characterize the safety and tolerability profile of
      escalating dose levels of ENV8058 (TAK-058) solution when administered as a single oral dose
      in healthy adults.
    

Eligibility criteria:

        Inclusion Criteria:

          1. In the opinion of the investigator, the participant is capable of understanding and
             complying with protocol requirements.

          2. The participant or, when applicable, the participant's legally acceptable
             representative signs and dates a written, informed consent form and any required
             privacy authorization prior to the initiation of any study procedures including
             requesting that a participant fast for any laboratory evaluations.

          3. Is a healthy male or female adult who is 18 to 55 years of age inclusive at the time
             of informed consent and study drug dosing.

          4. Weighs at least 45 kg (99 lbs) and has a body mass index (BMI) between 18.0 and 30.0
             kg/m^2, inclusive at Screening.

          5. A male participant who is nonsterilized and sexually active with a female partner of
             childbearing potential agrees to use adequate contraception from signing of informed
             consent throughout the duration of the study and for 12 weeks after last dose.

          6. A female participant with no childbearing potential, defined as the participant has
             been surgically sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or
             who are postmenopausal (defined as continuous amenorrhea of at least 2 years and
             follicle-stimulating hormone (FSH)>40 IU/L).

        Exclusion Criteria:

          1. Has received any investigational compound within 30 days prior to the first dose of
             study medication.

          2. Is an immediate family member, study site employee, or is in a dependant relationship
             with a study site employee who is involved in the conduct of this study (eg, spouse,
             parent, child, sibling) or may consent under duress.

          3. Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary,
             hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease,
             or psychiatric disorder, or other abnormality, which may impact the ability of the
             participant to participate or potentially confound the study results.

          4. Has a known hypersensitivity to any component of the formulation of ENV8058 (TAK-058).

          5. Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -1).

          6. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol
             abuse within 1 year prior to the Screening Visit or is unwilling to agree to abstain
             from alcohol and drugs throughout the study.

          7. Has taken any excluded medication, supplements, or food products listed in the
             Excluded Medications and Dietary Products table.

          8. If female, the participant is of childbearing potential (e.g premenopausal, not
             sterilized).

          9. If male, the participant intends to donate sperm during the course of this study or
             for 12 weeks thereafter.

         10. Has evidence of current cardiovascular, central nervous system, hepatic, hematopoietic
             disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy,
             asthma hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding
             in the participant's medical history, physical examination, or safety laboratory tests
             giving reasonable suspicion of a disease that would contraindicate taking ENV8058
             (TAK-058), or a similar drug in the same class, or that might interfere with the
             conduct of the study. This includes, but is not limited to seizure disorders and
             cardiac arrhythmias.

         11. Has previously had a seizure or convulsion (lifetime), including absence seizure and
             febrile convulsion.

         12. Has current or recent (within 6 months) gastrointestinal disease that would be
             expected to influence the absorption of drugs (ie, a history of malabsorption, any
             surgical intervention known to impact absorption [eg, bariatric surgery or bowel
             resection], esophageal reflux, peptic ulcer disease, erosive esophagitis, or frequent
             [more than once per week] occurrence of heartburn).

         13. Has a history of cancer or other malignancy, except basal cell carcinoma that has been
             in remission for at least 5 years prior to Day 1.

         14. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus
             (HCV) antibody or a known history of human immunodeficiency virus infection at
             Screening.

         15. Has used nicotine-containing products (including but not limited to cigarettes,
             electronic cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum)
             within 28 days prior to Check-in (Day -1). Cotinine test is positive at Screening or
             Check-in (Day -1).

         16. Has poor peripheral venous access.

         17. Has donated or lost 450 mL or more of his or her blood volume (including
             plasmapheresis), or had a transfusion of any blood product within 45 days prior to Day
             1.

         18. Has a Screening or Check-in (Day -1) abnormal (clinically significant)
             electrocardiogram (ECG). Entry of any participant with an abnormal (not clinically
             significant) ECG must be approved and documented by signature by the principal
             investigator or medically qualified subinvestigator.

         19. Subject had a supine blood pressure outside the ranges of 90 to 140 mm Hg for systolic
             and 60 to 90 mm Hg (males) and 50 to 90 mm Hg (females) for diastolic, confirmed with
             1repeat testing, at the Screening Visit or Check-in (Day -1).

         20. Has a resting heart rate outside the range 40 to 90 bpm, confirmed with one repeat
             testing, at the Screening Visit or Check-in (Day -1).

         21. Has a QT interval with Fridericia's correction method (QTcF) >430 ms (males) or >450
             ms (females) or PR outside the range of 120 to 220 ms, confirmed with one repeat
             testing, at the Screening Visit or Check-in (Day -1) Visit.

         22. Has abnormal Screening or Check-in (Day -1) laboratory values that suggest a
             clinically significant underlying disease or participant with the following lab
             abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)
             >1.5 the upper limits of normal.

         23. Has a risk of suicide according to the Investigator's clinical judgment (eg, per
             Columbia-Suicide Severity Rating Scale [CSSRS] or has made a suicide attempt in the
             previous 6 months.