A Double-Blind, Randomised Study to Assess the Influence of Tiotropium (Spiriva®)
To demonstrate that tiotropium (Spiriva®) does not prolong the QT interval of the ECG more than placebo
Drug: tiotropium 18 mcg or 54 mcg qd
Drug: placebo matching tiotropium qd
Drug: moxifloxacin 200 mg
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Primary Purpose: Treatment
|Official Title:||A Double-Blind, Randomised, Placebo Controlled, Three-Way Cross-Over Study With an Open Label Positive Control (Moxifloxacin) to Assess the Influence of Inhaled Tiotropium Once Daily Over Twelve Days on the QTC Interval of the ECG in Healthy Male and Female Volunteers|
- The primary parameter is the QT interval of the ECG. Frequency correction will primarily be performed using the Fridericia correction (QTcF). If the data suggest that QTcF is poor for the study population, an alternative correction will be used.
- Secondary endpoints are a) the mean change from baseline of the corresponding QTcF value of all ECGs taken from 5 minutes to 2 hours after dosing at day 1 and b) several other derived endpoints
|Study Start Date:||October 2004|
|Estimated Study Completion Date:||July 2005|
The objective of this study is to demonstrate that tiotropium does not prolong the QT interval more than placebo. This will be achieved by testing non-inferiority hypothesis.
There is one primary variable to be tested for non-inferiority: tiotropium high dose compared to placebo:
H0: µ(TIO,12) - µ(PBO,12) >= 10 ms vs. H1: µ(TIO,12) - µ(PBO,12) < 10 ms where µ(TIO,12), µ(PBO,12) represent the mean change from baseline QTcF between 5 minutes and 2 hours after 12 days of treatment (taking the mean of the time-matched differences between baseline and post-baseline values in each treatment period) with tiotropium 54 µg, or placebo, respectively.
If the data suggest that the Fridericia correction is poor for the study population, an alternative correction will be explored (QTcN). The other correction formula would be used as a replacement for the Fridericia correction and would be defined before unblinding of the data.
Placebo, moxifloxacin as active control
|Ingelheim/Rhein, Germany, 55216|
|Study Chair:||Boehringer Ingelheim Study Coordinator||B.I. Pharma GmbH & Co. KG|