Tiotropium and Salmeterol PK Study in COPD Patients

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00673478
First received: May 6, 2008
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

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).


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: Tiotropium+Salmeterol
Drug: Salmeterol
Drug: Tiotropium
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Area under the concentration-time curve (AUC0-∞ ) of tiotropium in plasma [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Maximum measured concentration of tiotropium in plasma (Cmax) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Amount of tiotropium that was eliminated in urine (Ae0-8) from time point 0 to 8 hours post-inhalation [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • AUC0-∞ of salmeterol in plasma [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Cmax salmeterol in plasma [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Time from dosing to the maximum concentration of tiotropium and salmeterol in plasma (tmax) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Terminal rate constant in plasma (λz) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Terminal half-life (t½) of tiotropium and salmeterol in plasma) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Mean residence time (MRTih) of tiotropium and salmeterol in the body after inhalational administration [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Apparent clearance (CL/F) of tiotropium and salmeterol in plasma after extravascular administration) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Apparent volume of distribution (Vz/F) during the terminal phase (λz) following an extravascular dose) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Fraction of tiotropium eliminated in urine from time point t1 to time point t2 (fet1-t2) (fe0-2, fe2-4, fe4-8, fe0-8) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • All adverse events [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
  • Blood pressure (seated) recorded in conjunction with 12-lead ECG recordings pre-dose and following the morning dose of randomized treatment [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
  • Number of patients with abnormalities in routine blood chemistry, haematology and urinalysis [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Trough forced expiratory volume in one second (FEV1) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Trough forced vital capacity (FVC) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • FEV1 area under the curve 0 to 8 hours (FEV1 AUC0-8h) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • FVC area under the curve 0 to 8 hours (FVC AUC0-8h) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Individual FEV1and FVC measurements at each time point at the end of each 4-week treatment period. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: May 2008
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00673478

Locations
Belgium
1184.24.32001 Boehringer Ingelheim Investigational Site
Genk, Belgium
1184.24.32002 Boehringer Ingelheim Investigational Site
Hasselt, Belgium
Netherlands
1184.24.31001 Boehringer Ingelheim Investigational Site
Heerlen, Netherlands
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00673478     History of Changes
Other Study ID Numbers: 1184.24, EudraCT 2007-000207-15
Study First Received: May 6, 2008
Last Updated: April 30, 2014
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
Netherlands: Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Disease Attributes
Lung Diseases, Obstructive
Pathologic Processes
Respiratory Tract Diseases
Albuterol
Salmeterol
Tiotropium
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cholinergic Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Parasympatholytics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Respiratory System Agents
Therapeutic Uses
Tocolytic Agents

ClinicalTrials.gov processed this record on October 22, 2014