Tiotropium and Salmeterol PK Study in COPD Patients

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

A Randomised, Open-label, 4-way Crossover Study to Characterize the Pharmacokinetics, Safety and Efficacy of FDC Tiotropium/Salmeterol, Tiotropium, Salmeterol and a Free Combination of Tiotropium Plus Salmeterol Following 4-week Treatment Periods in Patients With COPD.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00673478
• Other study ID #: 1184.24
• Secondary ID: EudraCT 2007-000
• Status: Completed
• Phase: Phase 3
• First received: May 6, 2008
• Last updated: April 30, 2014
• Start date: May 2008

Study information

• Verified date: April 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicines and Health Products, FAMHPNetherlands: Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to characterize the pharmacokinetics (i.e. systemic exposure to tiotropium and salmeterol) of tiotropium qd + salmeterol qd or bid versus tiotropium qd and salmeterol bid following 4-week treatment periods in patients with chronic obstructive pulmonary disease (COPD).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

COPD patients of >= 40 years old with moderate to severe COPD who are current or ex-smokers with a smoking history of at least 10 pack-years

Exclusion Criteria:

1. Recent history of myocardial infarction, life-threatening cardiac arrhythmia or hospitalisation for cardiac failure

2. History of asthma

3. Malignancy requiring treatment within past 5 years

4. Life-threatening pulmonary obstruction, cystic fibrosis or clinically evident bronchiectasis

5. Known active tuberculosis

6. Pregnant or nusing women

7. Known hypersensitivity to components of the study medication

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Disease
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Tiotropium+Salmeterol

• Salmeterol

• Tiotropium

Locations

Country	Name	City	State
Belgium	1184.24.32001 Boehringer Ingelheim Investigational Site	Genk
Belgium	1184.24.32002 Boehringer Ingelheim Investigational Site	Hasselt
Netherlands	1184.24.31001 Boehringer Ingelheim Investigational Site	Heerlen

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Belgium,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the concentration-time curve (AUC0-8 ) of tiotropium in plasma		16 weeks	No
Primary	Maximum measured concentration of tiotropium in plasma (Cmax)		16 weeks	No
Primary	Amount of tiotropium that was eliminated in urine (Ae0-8) from time point 0 to 8 hours post-inhalation		16 weeks	No
Primary	AUC0-8 of salmeterol in plasma		16 weeks	No
Primary	Cmax salmeterol in plasma		16 weeks	No
Secondary	Area under the concentration time curve (AUCt1-t2) of tiotropium and salmeterol in plasma over the time interval t1 to t2 for time intervals 0 to 4, 0 to 6, and 0 to 8 hours after inhalation (AUC0-4, AUC0-6, and AUC0-8)		16 weeks	No
Secondary	Time from dosing to the maximum concentration of tiotropium and salmeterol in plasma (tmax)		16 weeks	No
Secondary	Terminal rate constant in plasma (?z)		16 weeks	No
Secondary	Terminal half-life (t½) of tiotropium and salmeterol in plasma)		16 weeks	No
Secondary	Mean residence time (MRTih) of tiotropium and salmeterol in the body after inhalational administration		16 weeks	No
Secondary	Apparent clearance (CL/F) of tiotropium and salmeterol in plasma after extravascular administration)		16 weeks	No
Secondary	Apparent volume of distribution (Vz/F) during the terminal phase (?z) following an extravascular dose)		16 weeks	No
Secondary	Amount of tiotropium that is eliminated in urine from the time point t1 to time point t2 (Aet1-t2) (Ae0-2, Ae2-4, Ae4-8, Ae0-8)		16 weeks	No
Secondary	Fraction of tiotropium eliminated in urine from time point t1 to time point t2 (fet1-t2) (fe0-2, fe2-4, fe4-8, fe0-8)		16 weeks	No
Secondary	Renal clearance of tiotropium from the time point t1 until the time point t2 (CLR,t1-t2) (CLR,0-2, CLR, 2-4, CLR,4-8, CLR,0-8)		16 weeks	No
Secondary	All adverse events		20 weeks	No
Secondary	Blood pressure (seated) recorded in conjunction with 12-lead ECG recordings pre-dose and following the morning dose of randomized treatment		20 weeks	No
Secondary	Number of patients with abnormalities in routine blood chemistry, haematology and urinalysis		16 weeks	No
Secondary	Trough forced expiratory volume in one second (FEV1)		16 weeks	No
Secondary	Trough forced vital capacity (FVC)		16 weeks	No
Secondary	FEV1 area under the curve 0 to 8 hours (FEV1 AUC0-8h)		16 weeks	No
Secondary	FVC area under the curve 0 to 8 hours (FVC AUC0-8h)		16 weeks	No
Secondary	Individual FEV1and FVC measurements at each time point at the end of each 4-week treatment period.		16 weeks	No