Food and Insulin Effect on QT/QTC Interval of ECG

Summary

Moxifloxacin is routinely used as a probe to confirm assay sensitivity in thorough electrocardiogram (ECG) studies. It has been shown that a meal shortens the QT interval, which may affect pharmacokinetics (PK) and/or pharmacodynamics (PD) of the study drug. However, there is no published data clarifying this issue. There is also a paucity of data investigating ethnic differences of the effects of medicines on QTc.

The aims of the study were to compare the effect of different food contents to placebo on the changes in ECG and to demonstrate the effect of insulin, C-peptide and glucose on the ECG. This was done by giving different treatments on separate days, which included intravenous insulin, a high carbohydrate breakfast \[\>70%\], and a calorie reduced low carbohydrate American FDA standard breakfast. Moxifloxacin 400 mg was used as a positive control and was given with and without food to Caucasian and Japanese volunteers to investigate racial differences.

Conditions

• Effects of Different Meals on the QT/QTc Interval
• Insulin and Oral Hypoglycemic [Antidiabetic] Drugs Causing Adverse Effects in Therapeutic Use
• C-Peptide Effects on the QT/QTc Interval
• Moxifloxacin ECG Profile in Fed and Fasted State
• Japanese vs. Caucasian TQT Comparison

Interventions

DRUG

Moxifloxacin 400 mg fasted

Subjects receiving drug (400 mg moxifloxacin),having fasted overnight for 10 hours. This is the standard probe for the assessment of assay sensitivity in Thorough QT (TQT) studies.

OTHER

FDA breakfast

Calorie reduced FDA standard breakfast (58% fat, low carbohydrates)- On the assumption that increases in C-peptide levels are responsible for the QTc shortening observed after a meal, a lesser effect on QTc compared to a carbohydrate rich breakfast should be observed.

OTHER

Continental breakfast

High carbohydrate breakfast (\>70% carbohydrates)- On the assumption that increases in C-peptide levels are responsible for the QTc shortening observed after a meal, a greater effect on QTc compared to a low carbohydrate breakfast (FDA standard breakfast) should be observed.

DRUG

Moxifloxacin 400 mg fed

Currently, there is no published data showing the effects of a single 400 mg oral dose of moxifloxacin on the ECG/QT/QTc after food.

PROCEDURE

Insulin Clamp

A euglycaemic/hyperinsulinaemic clamp, (DeFronzo, 1979) involves acutely raising the plasma insulin levels to a steady state and maintaining a state of euglycaemia with a glucose infusion, thereby effectively stopping endogenous insulin and C-peptide release. This technique will confirm whether hyperinsulinaemia has any effect on the QT/QTc interval.

DRUG

Placebo

Comparison of different meals effect on Moxifloxacin PK profile

Sponsors & Collaborators

• Richmond Pharmacology Limited

  lead INDUSTRY

Principal Investigators

• Ulrike Lorch, MD FRCA FFPM · Richmond Pharmacology Limited

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

20 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2011-07-31

Primary Completion

2011-09-30

Completion

2011-09-30

Countries

• United Kingdom

Study Locations