A 3-Part, Open-Label, Drug-Drug Interaction Study of Concomitant Administration of E2609 With Itraconazole, Rifampin, Digoxin, or Donepezil

This study will be a single-center, open-label, drug-drug interaction study in healthy male and female subjects. The study will consist of 3 parts: A, B, and C. In Part A, the effect of itraconazole or rifampin on the pharmacokinetics (PK) of E2609 and metabolites will be assessed. Approximately 32 subjects will be assigned to 1 of 2 treatment groups (itraconazole or rifampin) in equal numbers, with approximately 16 subjects per group. In Part B, the effects of steady-state dosing of E2609 on the PK of digoxin will be assessed in approximately 18 subjects. In Part C, the effects of donepezil administered in combination with, or 2 hours after, E2609 dosing on the PK of E2609 and metabolites, will be assessed in approximately 24 subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: donepezil; Drug: digoxin; Drug: itraconazole; Drug: E2609; Drug: rifampin

• Study Type: Interventional
• Enrollment (Actual): 195
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78217
      • WCT Early Development

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 Criteria

1. Healthy male or female subjects aged 18-55 years inclusive at the time of informed consent
2. Provide written informed consent
3. Willing and able to comply with all aspects of the protocol

Exclusion Criteria

1. Any history of seizures or epilepsy (not including a history of simple febrile seizures in childhood) or disturbance of consciousness likely to be due to seizures
2. A prolonged QT/QTc interval (QTc greater than 450 ms) as demonstrated by the mean of triplicate electrocardiograms (ECGs), recorded at least 1 min apart, at Screening or Baseline Periods
3. Evidence of clinically significant disease (eg, psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system) that in the opinion of the investigator(s) could affect the subject's safety or interfere with the study assessments or subjects who have a congenital abnormality in metabolism within 4 weeks before dosing.
4. Any laboratory abnormalities considered clinically significant by the investigator, which may require further investigations or treatment
5. Clinically significant illness which required medical treatment within 8 weeks or a clinically significant infection within 4 weeks of dosing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: E2609; Experimental drug for Parts A, B, and C	Drug: donepezil; Drug: digoxin; Drug: itraconazole; Drug: rifampin
Active Comparator: itraconazole; Comparator drug for Part A1	Drug: E2609
Active Comparator: rifampin; Comparator drug for Part A2	Drug: E2609
Active Comparator: digoxin; Comparator drug for Part B	Drug: E2609
Active Comparator: donepezil; Comparator drug for Part C	Drug: E2609

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the pharmacokinetics (PK) of single oral doses of E2609 and metabolites in subjects dosed alone or in combination with either rifampin or itraconazole	Primary PK Parameters being measured: AUC(0-t), AUC(0-inf), Cmax, tmax.	Up to 48 days (Part A)
To evaluate the PK of single oral doses of digoxin in subjects dosed alone or in combination with E2609	Primary PK Parameters being measured: AUC(0-t), AUC(0-inf), Cmax, tmax.	Up to 48 days (Part B)
To evaluate the PK of single oral doses of E2609 and metabolites in subjects dosed alone, in combination with donepezil, or 2 hours before donepezil dosing	Primary PK Parameters being measured: AUC(0-t), AUC(0-inf), Cmax, tmax.	Up to 86 day (Part C)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of single oral doses of E2609 in subjects in the presence and absence of rifampin, itraconazole, digoxin, or donepezil	Safety assessments include monitoring and recording all adverse events (AEs), regular measurement of vital signs, and the performance of physical examinations.	Up to 182 days
To evaluate the effects of DNA sequence variants potentially involved in absorption, distribution and metabolism of E2609.	DNA samples will be collected, stored, and may be used to examine the role of genetic variability in other genes potentially involved in absorption, distribution, metabolism, and excretion.	Up to 182 days

Collaborators and Investigators

• Sponsor: Eisai Inc.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: January 23, 2014
• First Submitted That Met QC Criteria: February 4, 2014
• First Posted (Estimate): February 5, 2014

Study Record Updates

• Last Update Posted (Estimate): November 3, 2015
• Last Update Submitted That Met QC Criteria: November 2, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Healthy Subjects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Anti-Infective Agents; Cholinergic Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Cardiotonic Agents; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Nootropic Agents; 14-alpha Demethylase Inhibitors; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Cholinesterase Inhibitors; Digoxin; Rifampin; Itraconazole; Donepezil
• Other Study ID Numbers: E2609-A001-003