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
The drug being tested in this study is called TAK-915. TAK-915 is being tested to find a
safe and well-tolerated dose. This study will look at the pharmacokinetic characteristics
(how the drug acts throughout the body) of the drug and safety and tolerability (lab
results, vital signs, ECG, and side effects) in healthy people (including elderly) who take
The study will enroll a total of approximately 112 patients. This study is designed to
consist of 5 different dosing schedules: single rising dose (SRD), multiple rising dose
(MRD), drug-drug interaction (DDI), bioavailability and food effect (BA/FE), and Elderly
Subject Single Dose (ESSD). The study population for SRD will consist of 48 participants
enrolled into 6 cohorts. Each cohort will have 8 randomized participants, with 6 receiving a
single dose of TAK-915, and 2 receiving matching placebo under fasted conditions. The
starting dose is 30 mg. The dose for Cohorts 2 through 6 will be determined based on data
collected from previous cohorts.
The study population for MRD will consist of 32 participants enrolled into 4 cohorts. Each
cohort will have 8 randomized participants, with 6 receiving one dose of TAK-915 on Day 1
and daily dosing on Days 8-14, and 2 receiving matching placebo under fasted conditions. The
dose for each cohort in Part 2 will be determined based on data collected from completed SRD
cohorts of the study.
The study population for DDI will consist of 12 participants enrolled into 1 cohort. All
participants will receive one dose of TAK-915 on Day 3 and daily dosing on Days 10-16 under
fasted conditions. All participants will also receive a single dose of Midazolam 2 mg on Day
1 and Day 16. The dose of TAK-915 in this cohort will be determined based on data collected
from SRD cohorts and will be the same dose that is administered in MRD Cohort 8.
The study population for BA/FE will consist of 12 participants enrolled into 1 cohort.
TAK-915 will be administered in 3 single-dose regimens in a 3-way crossover design using 50
mg oral dose treatments (Regimen A: TAK915 50 mg oral suspension formulation in fasted
state; Regimen B: TAK-915 50 tablet formulation in fated state; Regimen C: TAK-915 50 tablet
formulation in fated state). TAK-915 dosing will occur on Day 1 of each treatment period
followed by a 14 day washout period.
The study population for ESSD will consist of 8 elderly participants (ages 65-75 years)
enrolled into 1 cohort. All 8 participants will receive a single dose of TAK-915 50 mg
suspension under fasted conditions.
This single-center trial will be conducted in the United States. The overall time to
participate in this study is up to 70 days. Participants will make multiple visits to the
clinic including a period of confinement to the clinic and will be contacted by telephone 12
days after the last dose of study drug for a follow-up assessment.
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).
1. Has received any investigational compound within 30 days prior to the first dose of
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
6. If female, the participant is of childbearing potential (eg. premenopausal, not
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
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
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
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.