A Study to Evaluate the Effects of E2609 on QTc Interval in Healthy Subjects

NCT02222324 | Completed Phase 1

• 1 other identifier: E2609-A001-004
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This thorough QT (TQT) study will take place in healthy subjects administered single doses of study drug. It will be a randomized, double-blind, placebo and active-controlled, 4-treatment crossover study. Subjects will be randomized in an equal ratio to one of 12 possible treatment sequences. Each treatment sequence will comprise all 4 treatments.

Conditions

Healthy Subjects

Keywords

QTc Interval; Healthy Subjects

Outcome Measures

Primary Outcomes (1)

• Change from baseline in QTcF obtained from ECGs extracted from the Holter recordings

  Holter recordings are taken from a portable device for continuously monitoring various electrical activity of the cardiovascular system for at least 24 hours. Baseline is defined as the mean of predose QTcF values obtained from ECGs extracted from Holter recordings before dosing during each treatment period.

  Up to 24 hours postdose during each treatment period

Secondary Outcomes (13)

• Change from baseline in ECG recordings: PR interval

  Predose and then up to 24 hours postdose in each treatment period

• Change from baseline in ECG recordings: QRS interval

  Predose and then up to 24 hours postdose in each treatment period

• Change from baseline in ECG recordings: HR

  Predose and then up 24 hours postdose in each treatment period

• Change from baseline in ECG recordings: RR interval

  Predose and then at up to 24 hours postdose in each treatment period

• Change from baseline in ECG recordings: T wave morphology

  Predose and then at up to 24 hours postdose in each treatment period

Study Arms (4)

Treatment A

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Treatment B

EXPERIMENTAL

E2609 Low dose

Drug: E2609

Treatment C

EXPERIMENTAL

E2609 High dose

Drug: E2609

Treatment D

ACTIVE COMPARATOR

Moxifloxacin

Drug: Moxifloxacin

Interventions

Placebo DRUG

8 placebo tablets matching E2609

Treatment A

E2609 DRUG

E2609 will be administered as 8 tablets

Treatment B; Treatment C

Moxifloxacin DRUG

Administered as 1 tablet with 7 tablets of placebo matching E2609

Treatment D

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must meet all of the following criteria to be included in this study:
• Healthy, non-smoking, male or female subjects ages greater than or equal to 18 years to less than or equal to 55 years old at the time of informed consent
• Body mass index (BMI) of greater than or equal to 18 to less than or equal to 30 kg/m2 at Screening
• Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative betahuman chorionic gonadotropin \[B-hCG\]). 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.
• Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use a highly effective method of contraception (eg, total abstinence, an intrauterine device, a double-barrier method \[such as condom plus diaphragm with spermicide\], or have a vasectomized partner with confirmed azoospermia, but not oral contraceptive or contraceptive implant) throughout the entire study period and for 30 days after study drug discontinuation. If currently abstinent, the subject must agree to use a double barrier method as described above if she becomes sexually active during the study period or for 30 days after study drug discontinuation. Hormonal contraceptives (oral or implant) are not permitted forms of contraception in this study. 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 (ie, bilateral tubal ligation, total hysterectomy or bilateral oophorectomy, all with surgery at least one month before dosing).
• Male subjects must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception throughout the study period and for 30 days after study drug discontinuation). No sperm donation is allowed during the study period and for 90 days after study drug discontinuation.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from this study:
• Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks before dosing
• Evidence of disease that may influence the outcome of the study within 4 weeks before dosing (eg, psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or subjects who have a congenital abnormality in metabolism)
• Any history of gastrointestinal surgery that may affect PK profiles of study drugs (eg, hepatectomy, nephrectomy, or digestive organ resection)
• Any clinically abnormal symptom or organ impairment found by medical history, physical examinations, vital signs, ECG finding, or laboratory test results that requires medical treatment at Screening or Baseline Periods
• History of any medical condition which, in the opinion of the investigator, may interfere with study procedures or compromise subject safety
• A prolonged QT/corrected QT interval (QTc) interval (QTc greater than 450 msec) as demonstrated by the mean of triplicate ECGs at Screening or Baseline Periods
• History of risk factors for torsade de pointes or the use of concomitant medications that prolonged the QT/QTc interval
• Persistent systolic blood pressure (BP) greater than 130 mmHg or less than 90 mmHg and diastolic BP greater than 85 mmHg or less than 60 mmHg at Screening or Baseline Periods
• Heart rate less than 50 or greater than 100 beats/minute at Screening or Baseline Periods
• History of prolonged QT/QTc interval
• Left bundle branch block at Screening or Baseline Periods
• History of myocardial infarction or active ischemic heart disease
• History of clinically significant arrhythmia or uncontrolled arrhythmia
• Any other clinically significant ECG abnormalities at Screening or Baseline Periods

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (1)

Unknown Facility

San Antonio, Texas, United States

Location

MeSH Terms

Interventions

Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2014
• First Posted: August 21, 2014
• Study Start: August 1, 2014
• Primary Completion: October 1, 2014
• Study Completion: December 1, 2014
• Last Updated: November 3, 2015

Record last verified: 2015-11

Locations

US (1)