Clinical trial NCT00662792: Efficacy and Safety Comparison of Tiotropium Daily + Salmeterol Daily or Twice Daily Versus Tiotropium Daily in Patients With COPD
Official title: A Randomised, Double-blind Clinical Efficacy and Safety Comparison of Tiotropium/Salmeterol 7.5/25 Inhalation Powder in the Morning Via Tiotropium/Salmeterol HandiHaler, Tiotropium 18 Mcg Inhalation Powder in the Morning Via Spiriva HandiHaler, Salmeterol 50 Mcg MDPI in the Morning and Evening and the Free Combination Tiotropium 18 Mcg Inhalation Powder in the Morning Via Spiriva HandiHaler Plus Salmeterol 50 Mcg MDPI in the Morning and Evening Following Chronic Administration (6-week Treatment Periods) in Patients With COPD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-04-21
Enrollment: 147
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary objective of this trial is to establish superiority of the once-daily Tiotropium plus Salmeterol Inhalation Powder in daytime lung function response and non-inferiority in night-time lung function response over the comparator treatments inhaled in their established dose regimens when administered for 6-week periods to patients with chronic obstructive pulmonary disease (COPD). The main secondary objective is to evaluate the safety of the Tiotropium plus Salmeterol Inhalation Powder versus the comparator treatments.


Eligibility criteria: Inclusion Criteria:

1. All patients must sign an informed consent consistent with ICH-GCP guidelines and local legislations prior to any study-related procedures, which includes medication washout and restrictions.
2. All patients must have a diagnosis of COPD and must meet the following criteria:

   relatively stable\* airway obstruction with a post-bronchodilator FEV1 \< 80% of predicted normal and post-bronchodilator FEV1 \< 70% of post-bronchodilator FVC at Visit 1 (according to GOLD criteria).

   \* The randomisation of patients with any respiratory infection or COPD exacerbation in the 6 weeks prior to the Screening Visit (Visit 1) or during the baseline period should be postponed. Patients may be randomised 6 weeks following recovery from the infection or exacerbation. Predicted normal values will be calculated according to ECSC.
3. Male or female patients 40 years of age or older.
4. Patients must be current or ex-smokers with a smoking history of 10 pack-years.
5. Patients must be able to perform technically acceptable pulmonary function tests
6. Patients must be able to inhale medication in a competent manner.
7. Patients must be able to perform all necessary recordings in the diary.

Exclusion Criteria:

1. Significant diseases other than COPD
2. Patients with clinically significant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a significant disease as defined in exclusion criterion No. 1.
3. Patients with a recent history of myocardial infarction.
4. Patients with any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the past year.
5. Hospitalisation for cardiac failure during the past year.
6. Malignancy within the last five years excluded basal cell carcinoma.
7. Patients with a history of asthma or who have a total blood eosinophil count 600/mm3.
8. Patients with a history of life threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis.
9. Known active tuberculosis.
10. Patients with a history of alcohol or drug abuse.
11. Thoracotomy with pulmonary resection.
12. Rehabilitation program within the last six weeks
13. Patients who regularly use daytime oxygen therapy
14. Patients who have taken an investigational drug within 30 days
15. Use of not allowed medications
16. Known hypersensitivity to used drugs or other components of the study medication.
17. Pregnant or nursing women
18. Women of childbearing potential not using a highly effective method of birth control. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner. Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years.
19. Patients who are currently participating in another study.

Primary outcomes:
measure: Response in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0 - 12 Hours (AUC0-12)
timeFrame: At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose after 6 weeks of treatment.
measure: Response in Forced Expiratory Volume in Second (FEV1) Area Under the Curve From 12 - 24 Hours (AUC12 -24)
timeFrame: At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment.
measure: Response in Peak Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: At baseline and within 3 hours post-morning dose after 6 weeks of treatment.
measure: Response in Trough Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment.
Secondary outcomes:
measure: Response in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0-24 Hours (AUC0-24)
timeFrame: At baseline and 10 minutes (min) prior and 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment.
measure: Response in Forced Vital Capacity (FVC) Area Under the Curve From 0 to 12 Hours (AUC0-12)
timeFrame: At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose after 6 weeks of treatment.
measure: Response in Forced Vital Capacity (FVC) Area Under the Curve From 12 to 24 Hours (AUC12-24)
timeFrame: At baseline and 10 minutes (min) prior to inhalation and 30 min, 60 min, 2, 10, 11 and 12 hours after inhalation of the evening dose after 6 weeks of treatment.
measure: Response in Forced Vital Capacity (FVC) Area Under the Curve From 0 - 24 Hours (AUC0-24)
timeFrame: At baseline and 10 minutes (min) prior and 60 min, 2, 3, 4, 6, 8, 10 and 12 hour after inhalation the morning dose and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment.
measure: Response in Peak Forced Vital Capacity (FVC)
timeFrame: At baseline and within 3 hours post-morning dose after 6 weeks of treatment.
measure: Response in Trough Forced Vital Capacity (FVC)
timeFrame: At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment.
measure: Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve Form 0 to 12 Hours (AUC0-12)
timeFrame: At baseline and 10 minutes (min) prior and 30 min, 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose after 6 weeks of treatment.
measure: Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve From 12 to 24 Hours (AUC12-24)
timeFrame: At baseline and 10 minutes (min) prior and 30 min, 60 min, 2, 10, 11 and 12 hours after inhalation of the evening dose after 6 weeks of treatment.
measure: Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve From 0 to 24 Hours (AUC0-24)
timeFrame: At baseline and 10 minutes (min) prior and 60 min, 2, 3, 4, 6, 8, 10 and 12 hours after inhalation of the morning dose and 30 min, 60 min, 2, 10, 11, and 12 hours after inhalation of the evening dose after 6 weeks of treatment.
measure: Response in Peak PEF (Peak Expiratory Flow Rate)
timeFrame: At baseline and within 3 hours post-morning dose after 6 weeks of treatment.
measure: Response in Trough Peak Expiratory Flow Rate (PEF)
timeFrame: At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment.
measure: Response in Individual Forced Expiratory Volume in 1 Second (FEV1) Over a 24 Hour Observation Period
timeFrame: At baseline, pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 12.5, 13, 14, 22, 23, and 24 hours post morning dose after 6 weeks of treatment.
measure: Response in Individual Forced Vital Capacity (FVC) Over a 24 Hour Observation Period
timeFrame: At baseline, pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 12.5, 13, 14, 22, 23 and 24 hours post morning dose after 6 weeks of treatment.
measure: Response in Individual Peak Expiratory Flow (PEF) Over a 24 Hour Observation Period
timeFrame: At baseline, pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 12.5, 13, 14, 22, 23, and 24 hours post morning dose after 6 weeks of treatment.
measure: Response in Morning and Evening Peak Expiratory Flow Rate (PEF), Recorded by Patients at Home
timeFrame: At baseline and last 3 weeks of 6-week treatment period.
measure: Response in Morning and Evening Forced Expiratory Volume in 1 Second (FEV1) Recorded by Participants at Home
timeFrame: At baseline and last 3 weeks of 6-week treatment period.
measure: Response in Mean Number of Days With Rescue Medication Use
timeFrame: At baseline and last 3 weeks of 6-week treatment period.
measure: Response in Mean Number of Puffs of Rescue Medication
timeFrame: At baseline and last 3 weeks of 6-week treatment period.
measure: Response in Mean Number of Days With Night-time Awakenings
timeFrame: At baseline and last 3 weeks of 6-week treatment period.
measure: Response in Mean Number of Days With Night-time Awakenings Due to Shortness of Breath (SOB)
timeFrame: At baseline and last 3 weeks of 6-week treatment period.
measure: Response in Means Number of Awakenings Due to Shortness of Breath (SOB)
timeFrame: At baseline and last 3 weeks of 6-week treatment period.
measure: Response in Average Shortness of Breath (SOB) Score at Night
timeFrame: At baseline and last 3 weeks of 6-week treatment period.
measure: Number of Participants With Drug Related Adverse Events
timeFrame: From first drug administration until last drug administration (average duration of 42 days) + 30 days, up to 91 days for T+S_PE, up to 98 days for Tio18GEL, up 89 days for Salm50DPI and up to 113 days for T18GEL+S_DPI.
measure: Number of Patients With Marked Changes in Vital Signs
timeFrame: At baseline and 6 hours following the morning dose of study medication after 6 weeks of treatment.
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: 1184.13.1302 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1184.13.1309 Boehringer Ingelheim Investigational Site
city: Cottbus
country: Germany
facility: 1184.13.1308 Boehringer Ingelheim Investigational Site
city: Großhansdorf
country: Germany
facility: 1184.13.1311 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1184.13.1312 Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: 1184.13.1305 Boehringer Ingelheim Investigational Site
city: Mannheim
country: Germany
facility: 1184.13.1301 Boehringer Ingelheim Investigational Site
city: Rodgau-Dudenhofen
country: Germany
facility: 1184.13.1306 Boehringer Ingelheim Investigational Site
city: Rüdersdorf
country: Germany
facility: 1184.13.1310 Boehringer Ingelheim Investigational Site
city: Schwerin
country: Germany
facility: 1184.13.1307 Boehringer Ingelheim Investigational Site
city: Wiesbaden
country: Germany
facility: 1184.13.1304 Boehringer Ingelheim Investigational Site
city: Wiesloch
country: Germany
facility: 1184.13.1303 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: