A Double-blind, Randomised Study to Assess the Influence of Tiotropium (Spiriva®)

Boehringer Ingelheim

Status and phase

Completed

Phase 1

Conditions

Healthy

Treatments

Drug: tiotropium 18 mcg or 54 mcg qd

Drug: moxifloxacin 200 mg

Drug: placebo matching tiotropium qd

Study type

Interventional

Funder types

Industry

Identifiers

NCT00257452

205.302

Details and patient eligibility

About

To demonstrate that tiotropium (Spiriva®) does not prolong the QT interval of the ECG more than placebo

Full description

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.

Study 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.

Comparison(s):

Placebo, moxifloxacin as active control

Sex

All

Ages

21 to 50 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

All participants in the study should be healthy males or females, ranging from 21 to 50 years of age and their body mass index (BMI) be within 18.5 to 29.9 kg/m2 (BMI calculation: weight in kilograms divided by the square of height in meters). In accordance with GCP and the local legislation all volunteers will have given their written informed consent prior to admission to the study.

Exclusion criteria:

Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance
Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
History of orthostatic hypotension, fainting spells or blackouts
Chronic or relevant acute infections
History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
Intake of drugs with a long half-life (> 24:00 hours) within at least one month or less than ten half-lives of the respective drug before enrolment in the study or during the study
Use of any drugs which might influence the results of the trial up to 7 days prior to enrolment in the study or during the study
Participation in another trial with an investigational drug ( two months prior to administration or during the trial)
Smoker (> 10 cigarettes or > 3 cigars of > 3 pipes/day)
Inability to refrain from smoking on trial days
Alcohol abuse (> 60 g/day)
Drug abuse
Blood donation (> 100 mL within four weeks prior to administration or during the trial)
Any laboratory value outside the reference range if indicative of underlying disease or poor health
Excessive physical activities within the last week before the trial or during the trial
Hypersensitivity to tiotropium, moxifloxacin and/or related drugs of these classes
Heart rate at screening of > 80 bpm or < 45 bpm
Any screening ECG value outside of the reference range of clinical relevance including, but not limited to PR interval > 220 ms, QRS interval > 115 ms, QTcB or QTcF > 450 ms, or QT (uncorrected) > 470 ms

For Female Subjects:

Pregnancy
Positive pregnancy test
No adequate contraception (adequate contraception e.g. sterilisation, IUP, oral contraceptives)
Inability to maintain this adequate contraception during the whole study period Lactation period.