Pharmacokinetic and Pharmacodynamic Study in Healthy Subjects Comparing the Interactions Between E5501 and Verapamil and Cyclosporine.

An Open-label, Single-sequence, Four-treatment Period Study to Evaluate Pharmacokinetic and Pharmacodynamic Interactions Between E5501 and Verapamil, and E5501 and Cyclosporine, Known P-glycoprotein Inhibitors in Healthy Subjects

36 healthy adult men and women will be enrolled with the goal of having 24 subjects complete the entire study. The study will consist of a pre-treatment phase and a treatment phase. The pre-treatment phase will include screening and baseline period 1. The treatment phase consists of 4 treatment period: Treatment Period 1 - administration of the first E5501 oral dose; Treatment Period 2 - administration of verapamil and the second E5501 oral dose; Treatment Period 3 - administration of the third E5501 dose; Treatment Period 4 - concomitant administration of cyclosporine and the fourth E5501 dose. A baseline period will precede each treatment period. The screening period will be up to 13 days in duration. After fulfilling screening requirements, subjects will check into the clinic on Day -1 for baseline assessments. They will be domiciled in the clinical testing facility for 6 days for Treatment Periods 1, 3, and 4 and will return intermittently for study procedures for 8 outpatient visits. They will be domiciled in the clinical testing facility for at least 14 days for Treatment Period 2 and will return intermittently for study procedures for 7 outpatient visits.

Study Overview

• Status: Completed
• Conditions: Idiopathic Thrombocytopenic Purpura (ITP)
• Intervention / Treatment: Drug: E5501

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion:

• Healthy adult men and women (age 18 to 55 years)
• Body mass index greater than or equal to 18kg/m2 and less than or equal to 32kg/m2 at the time of Screening and at each Baseline
• Platelet count between 120x109/L and 300x109/L at Baseline
• Women of childbearing potential must agree to use a highly effective method of contraception, other than estrogen-based hormonal contraceptives, during the treatment phase of the study

Exclusion:

• Evidence of clinically significant cardiovascular, hepatic, gastrointestinal, renal, respiratory, endocrine, hematologic, neurologic, or psychiatric disease or abnormalities or a known history of any gastrointestinal surgery that could impact the PK of the study
• Agents associated with thrombotic events (including oral contraceptives) must be discontinued within 30 days of first study drug administration
• Evidence of organ dysfunction or any clinically significant event or illness in the subject's medical history, e.g., history of splenectomy
• History of arterial or venous thrombosis, including partial or complete thromboses (e.g., stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis, or pulmonary embolism). Known family history of hereditary thrombophilic disorders (e.g., Factor V Leiden, antithrombin III deficiency, etc.)
• Hemoglobin less than the lower limit of normal levels (women, 7.1 mmol/L; men, 8.1 mmol/L) In addition, other standard criteria for healthy volunteers will be used.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: E5501 plus minus verapamil; plus minus cyclosporine	Drug: E5501; 20 mg oral dose of E5501; 240 mg once daily oral dose of sustained release verapamil; 400 mg oral dose of cyclosporine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma concentrations of E5501	Periodically over the course of Days 1-11

Secondary Outcome Measures

Outcome Measure	Time Frame
Platelet counts	Periodically over the course of Days 1-34

Collaborators and Investigators

• Sponsor: Eisai Inc.
• Investigators: Study Director: Gina Pastino, Eisai Inc.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: September 19, 2011
• First Submitted That Met QC Criteria: September 19, 2011
• First Posted (Estimate): September 20, 2011

Study Record Updates

• Last Update Posted (Estimate): May 21, 2012
• Last Update Submitted That Met QC Criteria: May 18, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Thrombocytopenia; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic
• Other Study ID Numbers: E5501-A001-008