NCT02308748

Ability of Late Sodium or Calcium Current Block to Balance the ECG Effects of Potassium Current Block

Five Period Crossover Study of the Ability of Late Sodium or Calcium Current Block (Mexiletine, Lidocaine, or Diltiazem) to Balance the Electrocardiographic Effects of hERG Potassium Current Block (Dofetilide or Moxifloxacin)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 22 (actual)
• Sponsor: Food and Drug Administration (FDA) · Federal
• Sex: All
• Age: 18 Years – 35 Years
• Healthy volunteers: Accepted

Summary

The primary objective of this research study is to test the hypothesis that late sodium current blocking drugs (mexiletine or lidocaine) can attenuate the effect of hERG potassium channel blocking drugs (dofetilide) on ventricular repolarization (QTc) by shortening early repolarization (J-Tpeakc). The secondary object is to assess the ability of calcium channel block (diltiazem) to reduce the QTc prolongation associated with hERG block (moxifloxacin).

Detailed description

This is a randomized, double-blind, 5-period crossover study in healthy male and female subjects, 18 to 35 years of age, to compare the electrophysiological response of hERG potassium channel blocking drugs with and without the addition of late sodium or calcium channel blocking drugs. The 5 treatment periods are 1) dofetilide alone, 2) mexiletine with and without dofetilide, 3) lidocaine with and without dofetilide, 4) moxifloxacin with and without diltiazem and 5) placebo. During each treatment period, 12 blood samples for pharmacokinetic measurements are obtained with matched 12-lead ECG recordings.

Conditions

• Drug-induced QT Prolongation
• Pharmacokinetics
• Pharmacodynamics

Interventions

Type	Name	Description
DRUG	Dofetilide	* 8 am: Placebo * 12 pm (noon): 250 µg * 5:30 pm: 250 µg
DRUG	Mexiletine	* 8 am: weight x 4 mg/kg * 12 pm (noon): Same as at 8 am * 5:30 pm: Same as at 8 am
DRUG	Lidocaine	* 9 am : 30 µg/min per kg (loading) for 60 minutes and 10 µg/min per kg (maintenance) for 30 minutes * 2 pm: 55 µg/min per kg (loading) for 60 minutes and 20 µg/min per kg (maintenance) for 30 minutes * 7:30 pm: 52 µg/min per kg (loading) for 60 minutes and 20 µg/min per kg (maintenance) for 30 minutes
DRUG	Moxifloxacin	* 9 am: 5.63 mg/h per kg (loading) for 1 hour and 0.26 mg/h per kg (maintenance for 30 minutes) * 2 pm: 6.14 mg/h per kg (loading) for 1 hour and 0.49 mg/h per kg (maintenance for 30 minutes) * 7:30 pm: 2.23 mg/h per kg (loading) for 1 hour and 0.49 mg/h per kg (maintenance for 30 minutes)
DRUG	Diltiazem	• 7:30 pm: 330 µg/h per kg (loading) for 60 minutes and 61 µg/h per kg (maintenance) for 30 minutes
DRUG	Placebo	Placebo (#2 Gelcap or IV saline)

Timeline

• Start date: 2014-05-01
• Primary completion: 2014-06-01
• Completion: 2014-06-01
• First posted: 2014-12-04
• Last updated: 2016-06-08
• Results posted: 2016-06-08