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

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00257452
First received: November 21, 2005
Last updated: October 31, 2013
Last verified: October 2013
  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 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Mean change from baseline of the corresponding QTcF values of all ECGs taken from 5 minutes to 2 hours after dosing [ Time Frame: Day 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mean change from baseline of the corresponding QTcF values of all ECGs taken from 5 minutes to 2 hours after dosing [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Mean change from baseline of the corresponding QTcF values of all ECGs taken from 5 minutes to 24 hours after dosing [ Time Frame: Day 1 and 12 ] [ Designated as safety issue: No ]
  • Difference (tiotropium minus placebo) between the maximal time-matched change from baseline of the QTcF values of all ECGs taken from 0:05 - 23:50 after dosing [ Time Frame: Day 1 and 12 ] [ Designated as safety issue: No ]

Estimated Enrollment: 56
Study Start Date: October 2004
Estimated Study Completion Date: July 2005
Primary Completion Date: July 2005 (Final data collection date for primary outcome measure)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Germany
Humanpharmakologisches Zentrum
Ingelheim/Rhein, Germany, 55216
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Study Coordinator B.I. Pharma GmbH & Co. KG
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00257452     History of Changes
Other Study ID Numbers: 205.302
Study First Received: November 21, 2005
Last Updated: October 31, 2013
Health Authority: Germany: Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), Kurt-Georg-Kiesinger-Allee 3, D-53175 Bonn

Additional relevant MeSH terms:
Tiotropium
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on September 18, 2014