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

NCT02055703 | Completed Phase 1

• 1 other identifier: E2609-A001-003
• Study Type: interventional
• Target: 195
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Subjects

Keywords

Healthy Subjects

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Safety and tolerability of single oral doses of E2609 in subjects in the presence and absence of rifampin, itraconazole, digoxin, or donepezil

  Up to 182 days

• To evaluate the effects of DNA sequence variants potentially involved in absorption, distribution and metabolism of E2609.

  Up to 182 days

Study Arms (5)

E2609

EXPERIMENTAL

Experimental drug for Parts A, B, and C

Drug: itraconazole; Drug: rifampin; Drug: digoxin; Drug: donepezil

itraconazole

ACTIVE COMPARATOR

Comparator drug for Part A1

Drug: E2609

rifampin

ACTIVE COMPARATOR

Comparator drug for Part A2

Drug: E2609

digoxin

ACTIVE COMPARATOR

Comparator drug for Part B

Drug: E2609

donepezil

ACTIVE COMPARATOR

Comparator drug for Part C

Drug: E2609

Interventions

E2609 DRUG

digoxin; donepezil; itraconazole; rifampin

itraconazole DRUG

E2609

rifampin DRUG

E2609

digoxin DRUG

E2609

donepezil DRUG

E2609

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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
• 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
• 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.
• Any laboratory abnormalities considered clinically significant by the investigator, which may require further investigations or treatment
• Clinically significant illness which required medical treatment within 8 weeks or a clinically significant infection within 4 weeks of dosing

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (1)

WCT Early Development

San Antonio, Texas, 78217, United States

Location

MeSH Terms

Interventions

Itraconazole; Rifampin; Digoxin; Donepezil

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Glycosides; Carbohydrates; Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2014
• First Posted: February 5, 2014
• Study Start: January 1, 2014
• Primary Completion: April 1, 2014
• Study Completion: May 1, 2014
• Last Updated: November 3, 2015

Record last verified: 2015-11

Locations

US (1)