Clinical trial NCT02055703: A 3-Part, Open-Label, Drug-Drug Interaction Study of Concomitant Administration of E2609 With Itraconazole, Rifampin, Digoxin, or Donepezil
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Healthy Subjects
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2014-02-05
Enrollment: 195
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Up to 48 days (Part A)
measure: To evaluate the PK of single oral doses of digoxin in subjects dosed alone or in combination with E2609
timeFrame: Up to 48 days (Part B)
measure: 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
timeFrame: Up to 86 day (Part C)
Secondary outcomes:
measure: Safety and tolerability of single oral doses of E2609 in subjects in the presence and absence of rifampin, itraconazole, digoxin, or donepezil
timeFrame: Up to 182 days
measure: To evaluate the effects of DNA sequence variants potentially involved in absorption, distribution and metabolism of E2609.
timeFrame: Up to 182 days
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: WCT Early Development
state: Texas
Study officials:
References: