Example 1 - Clinically completed 2005:

• 4-arm parallel design
• 13 days confinement in one period
• oral dose titration over 5 days
• 180 vols.
• 45-65 years
• balanced gender ratio
• exclusion of co-medication
• drop-out rate < 4% (187 enrolled)  

Example 2 -Clinically completed 2005 :

• 5-arm cross over
• 12 days total confinement
• 60 vols.
• 18-45 years
• balanced gender ratio
• exclusion of co-medication
• blinded intra-venous dosing over 7 dosing days
• safety monitoring during the dosing (5-lead ECG, BP, Resp., HR)

Example 3 - Clinically completed 2006:

• 2-arm crossover
• 46 days total confinement
• 80 vols.
• 18-45 years
• balanced gender ratio
• simulation of the supra-therapeutic dosing via blocking of the metabolic pathway of the metabolites

Example 4 - Clinically started 2006:

• 5-arm crossover in one period
• 23 days total confinement
• 84 vols.
• 18-45 years
• balanced gender ratio
• blinded intra-venous dosing via double lumen cathether
• dosing under intensive care conditions in the presence of two anaesthisiologists
• safety monitoring during the dosing and 4 hours subsequently (5-lead ECG, BP, Resp., HR, SPO₂)

There exists an increasing interest to evaluate arrhythmic potentials of compounds according to the Thorough QTc guidance (ICH E14), therefore we expanded the local capacities and trained the staff for this challenge in 2005. We have currently worked with various medical devices and different ECG Core Labs.

_{Guidance for Industry E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs (October 2005) / http://www.fda.gov/cder/guidance/6922fnl.htm}