Study to Evaluate the Effect of Diltiazem Extended Release on the Pharmacokinetics of E2027 in Healthy Subjects



Status:Completed
Conditions:Healthy Studies
Therapuetic Areas:Other
Healthy:No
Age Range:18 - 50
Updated:3/8/2017
Start Date:October 2016
End Date:January 2017

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An Open-label, Single-Sequence, Drug-Drug Interaction Study to Evaluate the Effect of Diltiazem Extended Release on the Pharmacokinetics of E2027 in Healthy Subjects

This Phase 1, open-label, single-sequence, drug-drug Interaction study is conducted to
evaluate the effect of diltiazem extended release (ER) (a moderate CYP3A inhibitor and P
glycoprotein [Pgp] inhibitor) on the pharmacokinetics (PK) of a single oral dose of E2027 in
healthy participants.


Inclusion Criteria:

- Non-smoking, male or female participants, ≥18 years old and ≤50 years old at the time
of informed consent

- Body mass index of 18 to 32 kilograms per meters squared (kg/m^2) at Screening

Exclusion Criteria:

- Clinically significant illness that requires medical treatment within 8 weeks or a
clinically significant infection that requires medical treatment within 4 weeks prior
to the first dose

- Females who are: (a) breastfeeding; or (b) pregnant at Screening or Baseline
(documented by a negative beta human chorionic gonadotropin [β-hCG] (or human
chorionic gonadotropin [hCG]) test with a sensitivity of at least 25 International
Units per Liter (IU/L) or equivalent units of β-hCG [or hCG]). Note: A negative urine
pregnancy test is required before the administration of the first dose.

- Females of childbearing potential who:

- Had unprotected sexual intercourse within 30 days before study entry and do not
agree to use a highly effective method of contraception (e.g., total abstinence,
an intrauterine device, a double barrier method [such as condom plus diaphragm
with spermicide] or have a vasectomized partner with confirmed azoospermia)
throughout the entire study period and for 28 days after study drug
discontinuation. Note: Hormonal contraceptives are not allowed.

- Are currently (for at least 30 days) abstinent, and do not agree to use a double
barrier method (as described above) or refrain from sexual activity during the
study period or for 28 days after study drug discontinuation NOTE: All females
will be considered to be of childbearing potential unless they are
postmenopausal (amenorrheic for at least 12 consecutive months, in the
appropriate age group, and without other known or suspected cause) or have been
sterilized surgically (i.e., bilateral tubal ligation, hysterectomy, or
bilateral oophorectomy, all with surgery at least 1 month prior to first dose).

- Males who have not had a successful vasectomy (confirmed azoospermia) or they and
their female partners do not meet the criteria above (i.e., not of childbearing
potential or practicing highly effective contraception throughout the study period or
for 28 days after study drug discontinuation). No sperm donation is allowed during
the study period or for 28 days after study drug discontinuation.

- Evidence of disease that may influence the outcome of the study within 4 weeks prior
to the first dose (e.g., 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)

- Any history of abdominal surgery that may affect pharmacokinetic profiles of E2027
(e.g., hepatectomy, nephrectomy, digestive organ resection). Participants with a
history cholecystectomy or appendectomy are not excluded.

- Any other clinically abnormal symptom or organ impairment found by medical history,
physical examinations, vital signs, electrocardiogram (ECG) finding (including a PR
greater than 210 milliseconds (msec), a QRS greater than 110 msec), or laboratory
test results that requires medical treatment at Screening or Baseline as determined
by the Principal Investigator or designee

- A prolonged QT/QTc interval (QTc greater than 450 msec) demonstrated on ECG at
Screening or Baseline (based on average of triplicate ECGs). A history of risk
factors for torsade de pointes (e.g., heart failure, hypokalemia, family history of
long QT Syndrome) or the use of concomitant medications that prolonged the QT/QTc
interval

- Left bundle branch block at Screening or Baseline

- Persistent systolic blood pressure (BP) greater than 160 or less than 100 millimeters
of mercury (mmHg) or diastolic BP greater than 100 or less than 50 mmHg at Screening
or Baseline

- Persistent pulse rate less than 50 beats/minute (min) or more than 90 beats/min at
Screening or Baseline

- History of myocardial infarction, ischemic heart disease, or cardiac failure at
Screening

- History of clinically significant arrhythmia or uncontrolled arrhythmia

- Known history of clinically significant drug allergy at Screening or Baseline

- Participants with any contraindications to diltiazem Extended Release

- Known history of food allergies or presently experiencing significant seasonal or
perennial allergy at Screening or Baseline

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

- Active viral hepatitis (A, B, or C) as demonstrated by positive serology at Screening

- History of drug or alcohol dependency or abuse within the 2 years before Screening,
or those who have a positive urine drug or alcohol test at Screening or Baseline

- Participants who smoke or have used tobacco or nicotine-containing products within 4
weeks prior to first dose

- A Columbia Suicide Severity Rating Scale (C-SSRS) suicidal ideation score of 4 or 5
at Screening or Baseline, or for the period within 6 months before Screening or
Baseline, or any lifetime suicidal behavior

- Currently enrolled in another clinical trial or used any investigational drug or
device within 30 days (or 5 half-lives, whichever is longer) preceding informed
consent

- Engagement in strenuous exercise within 2 weeks prior to first dose (e.g., marathon
runners, weight lifters)

- Intake of caffeinated beverages or caffeinated food within 72 hours prior to first
dose

- Intake of nutritional supplements, juice, and herbal preparations or other foods or
beverages that may affect the various drug metabolizing enzymes and transporters
(e.g., alcohol, grapefruit, grapefruit juice, grapefruit-containing beverages, apple
or orange juice, vegetables from the mustard green family [e.g., kale, broccoli,
watercress, collard greens, kohlrabi, Brussels sprouts, mustard], and charbroiled
meats) within 1 week prior to first dose

- Intake of herbal preparations containing St. John's Wort within 4 weeks prior to
first dose

- Intake of over-the-counter (OTC) medications within 14 days (or 5 half-lives,
whichever is longer) before dosing unless the Principal Investigator and sponsor
medical monitor consider that they do not compromise participant safety or study
assessments

- Use of any prescription drugs within 4 weeks prior to first dose
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