Tiotropium Respimat Pharmacokinetic Study in COPD

NCT01222533 | Completed Phase 2 Results

• 2 other identifiers: 205.4582009-016251-21
• Study Type: interventional
• Target: 154
• Locations: 5 countries
• Sites: 11

Brief Summary

The purpose of this study is compare the effect of different doses of tiotropium delivered by the HandiHaler and Respimat device on lung function. Additionally, the study will investigate the pharmacokinetic profile of these different doses. Studying the pharmacokinetic profile shows what happens to the medication in the body over a period of hours and provides information on potential effects of the medication.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (2)

• Maximum Plasma Concentration at Steady-state (Cmax,ss)

  Cmax,ss is the maximum measured concentration of tiotropium in plasma at steady-state.

  Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 minutes (min) before study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 hour (h), 2 h, 4 h and 6 h post dosing.

• Area Under the Curve 0 to 6 Hours at Steady-state (AUC0-6h,ss)

  AUC0-6h,ss is the area under the concentration time curve of tiotropium in plasma over the time interval 0 to 6 hours post-dose at steady-state. AUC0-6h,ss was calculated using the linear up/log down algorithm.

  Based on blood sampling for PK assessments done at 4 weeks at the following time points: 5 minutes (min) before study drug (baseline) and at 2 min , 5 min, 7 min, 9 min, 12 min, 15 min, 20 min, 30 min, 40 min, 1 hour (h), 2 h, 4 h and 6 h post dosing.

Secondary Outcomes (14)

• Trough Forced Expiratory Volume in One Second (FEV1) at the End of Each Treatment Period

  4 weeks

• FEV1 Area Under the Curve 0 to 6 Hours (AUC0-6h) at the End of Each Treatment Period

  4 weeks

• FEV1 Area Under the Curve 0 to 3 Hours (AUC0-3h) at the End of Each Treatment Period

  4 weeks

• Trough Forced Vital Capacity (FVC) at the End of Each Treatment Period

  4 weeks

• FVC AUC0-6h at the End of Each Treatment Period

  4 weeks

Other Outcomes (10)

• Maximum Heart Rate (HR)

  6.5 hours (including pre dose)

• Mean Heart Rate (HR)

  6.5 hours (including pre dose)

• SVPB Total

  6.5 hours (including pre dose)

Study Arms (5)

Tiotropium low

EXPERIMENTAL

Tiotropium inhalation solution low dose

Drug: Tiotropium low

Tiotropium medium

EXPERIMENTAL

Tiotropium inhalation solution medium dose

Drug: Tiotropium medium

Tiotropium high

EXPERIMENTAL

Tiotropium inhalation solution high dose

Drug: Tiotropium high

Tiotropium 18mcg

ACTIVE COMPARATOR

Tiotropium inhalation powder 18mcg

Drug: Tiotropium 18mcg

Tiotropium placebo

PLACEBO COMPARATOR

Placebo inhalation solution

Drug: Tiotropium placebo

Interventions

Tiotropium medium DRUG

Tiotropium inhalation solution medium dose

Tiotropium medium

Tiotropium low DRUG

Tiotropium inhalation solution low dose

Tiotropium low

Tiotropium high DRUG

Tiotropium inhalation solution high dose

Tiotropium high

Tiotropium 18mcg DRUG

Tiotropium inhalation powder 18mcg

Tiotropium 18mcg

Tiotropium placebo DRUG

Placebo inhalation solution

Tiotropium placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patient must sign an informed consent consistent with IInternational Conference on Harmonisation- Good Clinical Practice (ICH-GCP) guidelines and local legislation prior to any study-related procedures, including medication washout and restrictions.
• Relatively stable, moderate to very severe Chronic Obstructive Pulmonary Disease (COPD)
• Current or ex-smokers (smoking history of at least 10 pack years)
• Able to perform lung function tests
• Able to use study inhalers

You may not qualify if:

• Significant diseases other than COPD
• Recent myocardial infarction, unstable or life-threatening cardiac arrhythmia, hospitalisation for cardiac failure.
• Malignancy requiring resection, radiation therapy or chemotherapy within the last 5 years
• History of asthma, life-threatening pulmonary obstruction, cystic fibrosis or clinically evident bronchiectasis 5 Active tuberculosis
• \. History of alcohol or drug abuse 7. Pulmonary resection 8. Recent completion of a pulmonary rehabilitation program or current participation which will not be continued 9. Daytime oxygen therapy for more than 1 hour per day. 10. Use of other investigational drugs, restrictions on the use of some respiratory medications during the study period.
• \. Current participation in another clinical trial 12. Pregnant or nursing women 13. Women of childbearing potential not using a highly effective method of contraception (e.g: implants, injectable, oral contraceptives)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (11)

205.458.32003 Boehringer Ingelheim Investigational Site

Genk, Belgium

Location

205.458.32001 Boehringer Ingelheim Investigational Site

Ghent, Belgium

Location

205.458.32002 Boehringer Ingelheim Investigational Site

Hasselt, Belgium

Location

205.458.45001 Boehringer Ingelheim Investigational Site

Copenhagen K, Denmark

Location

205.458.45003 Boehringer Ingelheim Investigational Site

København NV, Denmark

Location

205.458.45002 Boehringer Ingelheim Investigational Site

Odense C, Denmark

Location

205.458.35801 Boehringer Ingelheim Investigational Site

Helsinki, Finland

Location

205.458.35802 Boehringer Ingelheim Investigational Site

Tampere, Finland

Location

205.458.49001 Boehringer Ingelheim Investigational Site

Hanover, Germany

Location

205.458.31001 Atrium Medisch Centrum Parkstad

Heerlen, Netherlands

Location

205.458.31002 Ommelander ziekenhuis groep, locatie Lucas

Winschoten, Netherlands

Location

Related Publications (2)

• Hohlfeld JM, Furtwaengler A, Konen-Bergmann M, Wallenstein G, Walter B, Bateman ED. Cardiac safety of tiotropium in patients with COPD: a combined analysis of Holter-ECG data from four randomised clinical trials. Int J Clin Pract. 2015 Jan;69(1):72-80. doi: 10.1111/ijcp.12596. Epub 2014 Dec 11.

  PMID: 25496316 DERIVED

• Hohlfeld JM, Sharma A, van Noord JA, Cornelissen PJ, Derom E, Towse L, Peterkin V, Disse B. Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease. J Clin Pharmacol. 2014 Apr;54(4):405-14. doi: 10.1002/jcph.215. Epub 2013 Nov 27.

  PMID: 24165906 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Tiotropium Bromide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2010
• First Posted: October 18, 2010
• Study Start: October 1, 2010
• Primary Completion: November 1, 2011
• Last Updated: May 16, 2014
• Results First Posted: December 10, 2012

Record last verified: 2013-08

Locations

NL (2); DE (1); FI (2); BE (3); DK (3)