A Double-Blind, Randomised Study to Assess the Influence of Tiotropium (Spiriva®) - Full Text View

Sponsored by:	Boehringer Ingelheim Pharmaceuticals
Information provided by:	Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00257452

Purpose

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

Condition	Intervention	Phase
Healthy	Drug: tiotropium 18 mcg or 54 mcg qd Drug: placebo matching tiotropium qd Drug: moxifloxacin 200 mg	Phase I

Drug Information available for: Tiotropium bromide Moxifloxacin Tiotropium Moxifloxacin hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Safety Study
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

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:

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 Outcome Measures:

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

Estimated Enrollment:	56
Study Start Date:	October 2004
Estimated Study Completion Date:	July 2005

Detailed 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

Eligibility

Ages Eligible for Study:	21 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00257452

Locations

Germany
Humanpharmakologisches Zentrum
Ingelheim/Rhein, Germany, 55216

Sponsors and Collaborators

Boehringer Ingelheim Pharmaceuticals

Investigators

Study Chair:

Boehringer Ingelheim Study Coordinator

B.I. Pharma GmbH & Co. KG

More Information

No publications provided

Study ID Numbers:	205.302
Study First Received:	November 21, 2005
Last Updated:	February 16, 2007
ClinicalTrials.gov Identifier:	NCT00257452 History of Changes
Health Authority:	Germany: Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), Kurt-Georg-Kiesinger-Allee 3, D-53175 Bonn

Study placed in the following topic categories:

Neurotransmitter Agents
Cholinergic Antagonists
Moxifloxacin
Anti-Asthmatic Agents
Peripheral Nervous System Agents

Healthy
Cholinergic Agents
Tiotropium
Bronchodilator Agents

Additional relevant MeSH terms:

Anti-Infective Agents
Respiratory System Agents
Parasympatholytics
Neurotransmitter Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Asthmatic Agents

Cholinergic Agents
Pharmacologic Actions
Moxifloxacin
Autonomic Agents
Therapeutic Uses
Peripheral Nervous System Agents
Tiotropium
Bronchodilator Agents

ClinicalTrials.gov processed this record on May 07, 2009