Pharmacokinetics of the Fixed Dose Combination of Tiotropium Plus BI 54903 Versus the Combination of the Monoproducts of Tiotropium and BI 54903 in Healthy Volunteers

An Open Label, Randomised, Two-way Crossover Phase I Study to Assess Safety, Tolerability and Pharmacokinetics of the Fixed Dose Combination of Tiotropium Plus BI 54903 Via Respimat® B Versus the Combination of the Monoproducts of Tiotropium Via Respimat® A and BI 54903 Via Respimat® B in Healthy Volunteers

The primary objective is to compare the systemic exposure to tiotropium and CD 1857 after treatment with the fixed dose combination (fixed dose combination (FDC), Treatment A) of tiotropium plus BI 54903 (ethanolic solution for inhalation (EIS), Respimat (RMT) B) with the systemic exposure following inhalation of the free combination (Treatment B) of tiotropium (aqueous solution for inhalation (AIS), RMT A) plus BI 54903 (EIS, RMT B), when administered once-daily over 21 days via Respimat(R) (RMT).

The secondary objectives are:

to compare the systemic exposure to tiotropium and CD 1857 after single dose administration of FDC and of the free combination of tiotropium/BI 54903 to compare the systemic exposure to BI 54903 after a single dose and at steady state after multiple doses of the FDC and of the free combination of tiotropium/BI 54903 to compare the safety and tolerability of tiotropium and BI 54903 when administered as FDC and as free dose combination, respectively

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Tiotropium; Drug: BI 54903

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Ingelheim, Germany
    • 1298.2.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Healthy males and females according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests.
2. Age 21 to 50 years.

Exclusion criteria:

1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
2. Any evidence of a clinically relevant concomitant disease
3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
4. History or evidence of relevant psychiatric disorders or neurological disorders
5. History or evidence of relevant autonomic dysfunction (orthostatic hypotension, fainting spells or blackouts)
6. Chronic or relevant acute infections
7. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
8. Intake of any prescription drugs or over-the-counter (over the counter (OTC)) medication (vitamins, herbal supplements, dietary supplements) with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
9. Participation in another trial with an investigational drug within two months prior to administration or during the trial
10. Smoker (more than 10 cigarettes daily)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A: Tiotropium medium dose; Oral inhalation daily for 21 days	Drug: Tiotropium; Medium dose of oral inhalation
Experimental: Treatment A: BI 54903 high dose; Oral inhalation daily for 21 days	Drug: BI 54903; Medium dose of oral inhalation
Experimental: Treatment B: Tiotropium medium dose; Oral inhalation daily for 21 days	Drug: Tiotropium; Medium dose of oral inhalation
Experimental: Treatment C: BI 54903 high dose; Oral inhalation daily for 21 days	Drug: BI 54903; Medium dose of oral inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration time curve of CD 1857 in plasma over a uniform dosing interval τ (AUCτ,ss)	on several time points until day 22
Maximum concentration of CD 1857 in plasma at steady state (Cmax,ss)	on several time points until day 22
AUCτ,ss for Tiotropium	on several time points until day 22
Cmax,ss for Tiotropium	on several time points until day 22

Secondary Outcome Measures

Outcome Measure	Time Frame
AUCτ,ss for BI 54903	on several time points until day 22
Cmax,ss for BI 54903	on several time points until day 22
Ae0-24 (Amount of analyte that is eliminated in urine) for tiotropium	on Day 1 and 21
Change in physical examination	9 weeks
Change in vital signs	9 weeks
Change in 12-lead electrocardiogram	9 weeks
Change in clinical laboratory tests	9 weeks
Occurrence of Adverse Events	9 weeks
Assessment of tolerability by the investigator	9 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): June 1, 2011
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: March 1, 2011
• First Submitted That Met QC Criteria: March 3, 2011
• First Posted (Estimate): March 4, 2011

Study Record Updates

• Last Update Posted (Estimate): November 1, 2013
• Last Update Submitted That Met QC Criteria: October 31, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide
• Other Study ID Numbers: 1298.2; 2010-023780-18 (EudraCT Number: EudraCT)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No