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

Healthy Subjects Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02055703
• Other study ID #: E2609-A001-003
• Status: Completed
• Phase: Phase 1
• First received: January 23, 2014
• Last updated: November 2, 2015
• Start date: January 2014
• Est. completion date: May 2014

Study information

• Verified date: November 2015
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 195
• Est. completion date: May 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• E2609

• itraconazole

• rifampin

• digoxin

• donepezil

Locations

Country	Name	City	State
United States	WCT Early Development	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Primary	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)	No
Primary	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)	No
Secondary	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	Yes
Secondary	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	No