- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01261156
A Study to Evaluate the Effects of Diltiazem, a Moderate CYP3A4/A5 Inhibitor, on the Pharmacokinetics and Pharmacodynamics of E5555 and Its Metabolites in Healthy Subjects
July 10, 2014 updated by: Eisai Inc.
An Open-label, Single-Sequence Study to Evaluate the Effects of Diltiazem, a Moderate CYP3A4/A5 Inhibitor, on the Pharmacokinetics and Pharmacodynamics of E5555 and Its Metabolites in Healthy Subjects
The purpose of this study is to evaluate the effects of diltiazem on the pharmacokinetics (PK) and pharmacodynamics (PD) of E5555 and its metabolites in healthy subjects.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This is an open-label, 2-arm study to evaluate the effects of diltiazem given in conjunction with E5555 on the PK of diltiazem and its metabolites.
This is a Phase 1 study of 24 healthy male and female subjects that will be conducted at a single site.
The planned duration of treatment for each subject is approximately 15 days including 1 day in Treatment Period 1 and 14 days in Treatment Period 2.
Study Type
Interventional
Enrollment (Actual)
24
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
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Zuidlaren, Netherlands, 9471
- PRA International
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 55 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion:
- Provide written informed consent
- Healthy, non-smoking, male or female subjects aged greater than or equal to 18 years to 55 years
- Body mass index (BMI) greater than or equal to 18 and less than or equal to 32 kg/m2 at Screening
- All females must have a negative serum beta human chorionic gonadotropin test result at Screening and Baseline. Females of child-bearing potential must agree to use a medically acceptable method of contraception commencing at least one menstrual cycle prior to starting study drug, throughout the entire study period and for 90 days after study drug discontinuation. The only subjects who will be exempt from this requirement are postmenopausal women or subjects who have been surgically sterilized or who are otherwise proven sterile.
- Male subjects who are partners of women of childbearing potential and are not abstinent or have not undergone a successful vasectomy must use, or their partners must use, a highly effective method of contraception commencing at least one menstrual cycle prior to starting study drug, throughout the entire study period and for 90 days after study drug discontinuation.
- Are willing and able to comply with all aspects of the protocol.
Exclusion:
- A family history, past medical history or clinical signs or symptoms of a bleeding diathesis
- History of any medical condition which will result in an increased risk of bleeding including but not limited to active or recurrent gastric ulcers, recent head trauma or surgery, severe hypertension, bacterial endocarditis etc
- Subjects with a history of spontaneous gum bleeding or clinical signs or symptoms on physical exam
- Clinically significant ocular disease or untreated visual or ocular symptoms
- Clinically significant abnormal electrocardiograms ECGs prior to dosing (Screening or Baselines) including a QT interval corrected for heart rate using Fredericia's formula (QTcF) and/or Bazett's formula (QTcB) greater than 450 ms
- Any history or past medical condition that will result in QTc prolongation or tachyarrhythmia such as Torsades de Points (includes hypokalemia, known family history of long QT syndrome, or any other known risk factors for Torsades de Points)
- A platelet count less than 150,000 or greater than 390,000 per mL at Screening or Baseline Period 1
- Abnormal (less than 80%) arachidonic acid induced platelet aggregation at Baseline Period 1
- History of unexplained syncope, hepato-bliary disease, sinus bradycardia, heart blocks, sick-sinus syndrome, cardiogenic shock, heart failure, seizures, or chronic obstructive lung disease
- Subjects with hypotension (less than 90 mm Hg systolic) and bradycardia (HR less than 40 beats per minute) or symptomatic bradycardia (HR less than 50 beats per minute)
- Received blood, donated blood, or experienced significant blood loss within 60 days prior to check-in
- Hypersensitivity to diltiazem or related compounds or ingredients in the formulation
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Study Arm 1
|
E5555 single 100 mg oral dose in Treatment Period 1 Day 1 and in Treatment Period 2 Day 8. Diltiazem 360 mg orally each day for 14 days (Days 1-14) in Treatment Period 2.
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Experimental: Study Arm 2
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E5555 single 300 mg oral dose in Treatment Period 1 and in Treatment Period 2 Day 8. Diltiazem 360 mg orally each day for 14 days (Days 1-14) in Treatment Period 2.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Evaluate the effects of diltiazem on the pharmacokinetics (PK ie. Cmax, Tmax, AUC and half-life) of E5555 and its known metabolites.
Time Frame: 18 days
|
18 days
|
Evaluate the effects of diltiazem on the thrombin- and thrombin receptor activating peptide (TRAP) -induced platelet aggregation of E5555 and its known metabolites
Time Frame: 18 days
|
18 days
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To evaluate the effects of co-adminstration of diltiazem and E5555 on the PK(ie. Cmax, Tmax, AUC and half-life) of diltiazem and its metabolites
Time Frame: 18 days
|
18 days
|
To evaluate effects of co-adminstration of diltiazem and E5555 on QTcF compared to E5555 alone
Time Frame: 18 days
|
18 days
|
To assess safety and tolerability of a single dose of E5555 when given alone or in combination with diltiazem by recording the number of all adverse events following drug administration
Time Frame: 18 days
|
18 days
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Chukwuemeka Okereke, Eisai Limited
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2010
Primary Completion (Actual)
December 1, 2010
Study Registration Dates
First Submitted
November 16, 2010
First Submitted That Met QC Criteria
December 14, 2010
First Posted (Estimate)
December 16, 2010
Study Record Updates
Last Update Posted (Estimate)
July 11, 2014
Last Update Submitted That Met QC Criteria
July 10, 2014
Last Verified
July 1, 2014
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- E5555-A001-022
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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