Phase 1, TAK-915-1001, Single-Rising Dose, Multiple-Rising Dose, Drug-Drug Interaction, Relative Bioavailability, Food Effect, and Effect on Elderly Participants Study
Condition: Healthy Volunteers
Intervention: TAK-915 suspension; Midazolam; Placebo; TAK-915 tablet
Intervention description: TAK-915 oral suspension; Midazolam oral solution; Placebo-matching TAK-915 suspension; TAK-915 tablet
Intervention MeSH terms: Midazolam
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 88.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Drug therapy

Summary:

      The purpose of this study is to characterize the safety, tolerability and plasma
      pharmacokinetic (PK) profile of TAK-915 when administered as single and multiple oral
      suspension doses at escalating dose levels in healthy participants, including elderly
      participants.
    

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 man or woman, aged 18 to 55 years, inclusive at the time of informed
             consent and first study medication dose for all cohorts will be included. Note that
             Cohort 12 will enroll healthy, elderly men and women, aged 65 to 75 years, inclusive.

          4. Weighs at least 50 kg and has a body mass index (BMI) from 18.0 to 35.0 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 y ears 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. Has received TAK-915 in a previous clinical study or as a therapeutic agent.

          3. Is an immediate family member, study site employee, or is in a dependent 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.

          4. 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.

          5. Has a known hypersensitivity to any component of the formulation of TAK-915 and/or
             midazolam.

          6. If female, the participant is of childbearing potential (eg. premenopausal, not
             sterilized).

          7. Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day 1).

          8. 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. One unit is equivalent to a half-pint of
             beer or 1 measure of spirits or 1 glass of wine.

          9. Has taken any excluded medication, supplements, or food products during the time
             periods listed in the Excluded Medications and Dietary Products table.

         10. Is pregnant or lactating or intending to become pregnant before, during, or within 12
             weeks after participating in this study ; or intending to donate ova during such time
             period.

         11. If male, the participant intends to donate sperm during the course of this study or
             for 12 weeks after the last dose of study medication.

         12. 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 TAK-915, 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, peptic ulcer disease, seizure disorders,
             and cardiac arrhythmias.

         13. Has mental retardation or medical condition that can cause cognitive impairment.

         14. 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).

         15. Has a history of cancer, except basal cell carcinoma which has been in remission for
             at least 5 years prior to Check-in (Day -1).

         16. Has a positive test result for hepatitis B surface antigen (HBsAg), antibody to
             hepatitis C (anti -HCV) or a known history of human immunodeficiency virus infection
             at Screening.

         17. Has used nicotine-containing products (including but not limited to cigarettes, pipes,
             cigars, electronic cigarettes, 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).

         18. 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 the
             first dose of study medication.

         19. 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.

         20. Has a supine blood pressure outside the ranges of 90 to 140 mmHg for systolic and 60
             to 90 mmHg for diastolic, confirmed on repeat testing within a maximum of 30 minutes,
             at the Screening Visit or Check-in (Day -1).

         21. Has a resting heart rate outside the range 40 to 100 bpm, confirmed on repeat testing
             within a maximum of 30 minutes, at the Screening Visit or Check-in (Day -1).

         22. Has a QT interval with Fridericia correction method (QTcF) >430 ms (males) or >450 ms
             (females) or PR outside the range 120 to 220 ms, confirmed on repeat testing within a
             maximum of 30 minutes, at the Screening Visit or Check-in (Day -1).

         23. 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.

         24. Has a risk of suicide according to the Investigator's clinical judgment (eg, per
             Columbia-Suicide Severity Rating Scale [C-SSRS] or has made a suicide attempt in the
             previous 6 months).

         25. Has poor peripheral venous access.