A Study to Evaluate the Effect of Repeat Oral Doses of YM443 on Cardiac Repolarization in Healthy Adults

A Phase 1, Randomized, Double-Blind, Placebo- and Active- Controlled, Crossover Study to Evaluate the Effect of Repeat Oral Doses of YM443 on Cardiac Repolarization in Healthy Male and Female Adult Subjects

This study evaluates whether YM443 causes any changes in the electrocardiogram of healthy adults.

Study Overview

• Status: Completed
• Conditions: Functional Dyspepsia
• Intervention / Treatment: Drug: Placebo; Drug: Moxifloxacin; Drug: YM443

Detailed Description

Each subject participates in all four treatment periods separated by washout periods.

In order to maintain the blind between arms, all subjects will receive the same number of tablets per day in each period of either active drug or placebo.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Tacoma, Washington, United States, 98418

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy Male or non pregnant, non lactating female
• Weighing at least 45 kg
• Body Mass Index (BMI) between 18 and 32 kg/m2

Exclusion Criteria:

• The subject has evidence of any cardiac conduction abnormalities
• The subject has a previous history of any medical or psychiatric condition that would preclude participation in the study
• The subject has participated in another clinical trial in the last 30 days
• The subject anticipates an inability to abstain from alcohol, or caffeine use, or from grapefruit and grapefruit juice from 48 hours prior to the administration of the first dose of YM443 on Day 1 of Period 1 and throughout the duration of the study
• The subject has used tobacco-containing products and nicotine or nicotine-containing products within six months prior to Screening
• The subject consumes more than 5 units of alcoholic beverages (one unit is 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits) per week or has a history of substance abuse, drug addiction, or alcoholism within 2 years prior to Screening
• The subject has donated any whole blood or cellular blood component or has undergone significant loss of blood or has received transfusion of any blood or blood products within 56 days of Day -1 of Period 1 or has donated plasma within 7 days of Day -1 of Period 1

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: A. Placebo	Drug: Placebo; Oral
Experimental: B. Ym443 Lower Dose	Drug: YM443; Oral; Other Names: Z-338; acotiamide hydrochloride
Experimental: C. YM443 Higher Dose	Drug: YM443; Oral; Other Names: Z-338; acotiamide hydrochloride
Active Comparator: D. Moxiflocxacin	Drug: Moxifloxacin; Oral; Other Names: Avelox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean change in the QTcF (Fridericia's correction) between each active treatment and placebo	Following four days of dosing

Secondary Outcome Measures

Outcome Measure	Time Frame
The mean change of the QTcI (Individual correction) and QTcB (Bazett's correction) between each active treatment and placebo.	Following four days of dosing
The pharmacokinetics of YM443 in these subjects	Day 5
The safety and tolerability of YM443	Following four days of dosing

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Publications and helpful links

Helpful Links

• Link to Results on JAPIC

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: February 23, 2009
• First Submitted That Met QC Criteria: February 24, 2009
• First Posted (Estimate): February 25, 2009

Study Record Updates

• Last Update Posted (Estimate): March 24, 2014
• Last Update Submitted That Met QC Criteria: March 21, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Healthy Subjects; QT interval; Cardiac Conduction; Cardiac Repolarization; YM443 (Z-338, acotiamide hydrochloride); Evaluation of QT Interval
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Dyspepsia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Cholinergic Agents; Enzyme Inhibitors; Antineoplastic Agents; Gastrointestinal Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cholinesterase Inhibitors; Moxifloxacin; Z 338
• Other Study ID Numbers: 443-CL-048