Efficacy and Safety Comparison of Tiotropium Daily + Salmeterol Daily or Twice Daily Versus Tiotropium Daily in Patients With COPD

NCT00662792 | Completed Phase 3 Results

• 1 other identifier: 1184.13
• Study Type: interventional
• Target: 147
• Locations: 1 country
• Sites: 12

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.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (4)

• Response in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0 - 12 Hours (AUC0-12)

  FEV1 AUC was defined as the area under the FEV1 curve normalized for time. It was calculated from time 0 to 12 h (FEV1 AUC0-12), using the trapezoidal rule divided by the corresponding duration (12 h) to give the results in liter (L). FEV1 AUC0-12h response is defined as the change from baseline: FEV1 AUC0-12h response = FEV1 AUC0-12h - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.

  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.

• Response in Forced Expiratory Volume in Second (FEV1) Area Under the Curve From 12 - 24 Hours (AUC12 -24)

  The FEV1 AUC was defined as the area under the FEV1 curve (AUC) normalised for time. It was calculated from time 12 to 24 h (FEV1 AUC12-24), using the trapezoidal rule divided by the corresponding duration (i.e. 12 h) to give the results in L. AUC12-24h response is defined as the change from baseline: FEV1 AUC12-24h response = FEV1 AUC12-24h - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit (Visit 2) just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.

  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.

• Response in Peak Forced Expiratory Volume in 1 Second (FEV1)

  Peak FEV1 was defined as the highest FEV1 reading observed within 3 hours after inhalation of the last morning dose of each randomized treatment. Peak FEV1 response is defined as change from baseline: Peak FEV1 response = Peak FEV1 - FEV1 (Baseline). The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.

  At baseline and within 3 hours post-morning dose after 6 weeks of treatment.

• Response in Trough Forced Expiratory Volume in 1 Second (FEV1)

  Trough FEV1 is determined at the end of each treatment period and is defined as the pre-dose FEV1 measured just prior to the last administration of the morning dose of randomized treatment. Trough FEV1 response is defined as the change from baseline: Trough FEV1 response = Trough FEV1 - FEV1 (Baseline) The FEV1 baseline value is defined as the pre-dose FEV1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.

  At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment.

Secondary Outcomes (24)

• Response in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0-24 Hours (AUC0-24)

  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.

• Response in Forced Vital Capacity (FVC) Area Under the Curve From 0 to 12 Hours (AUC0-12)

  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.

• Response in Forced Vital Capacity (FVC) Area Under the Curve From 12 to 24 Hours (AUC12-24)

  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.

• Response in Forced Vital Capacity (FVC) Area Under the Curve From 0 - 24 Hours (AUC0-24)

  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.

• Response in Peak Forced Vital Capacity (FVC)

  At baseline and within 3 hours post-morning dose after 6 weeks of treatment.

Study Arms (4)

T+S_PE/ Tio18GEL / Salm50DPI / T18GEL+S_DPI

EXPERIMENTAL

7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\_PE)/ 18 µg Tiotropium (Tio18GEL) / 50 µg Salmeterol MDPI (Salm50DPI) / 18 µg Tiotropium (T18GEL) plus 50 µg Salmeterol MDPI (S\_DPI) BID

Drug: Tiotropium (Tio18GEL); Drug: Salmeterol MDPI (Salm50DPI); Drug: Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI); Drug: Tiotropium/Salmeterol (T+S_PE)

Tio18GEL/ T18GEL+S_DPI/ T+S_PE/ Salm50DPI

EXPERIMENTAL

18 µg Tiotropium (Tio18GEL) / 18 µg Tiotropium (T18GEL) + 50 µg Salmeterol MDPI (S\_DPI) BID / 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\_PE) / 50 µg Salmeterol MDPI (Salm50DPI)

Drug: Tiotropium (Tio18GEL); Drug: Salmeterol MDPI (Salm50DPI); Drug: Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI); Drug: Tiotropium/Salmeterol (T+S_PE)

Salm50DPI/ T+S_PE/ T18GEL+S_DPI/ Tio18GEL

EXPERIMENTAL

50 µg Salmeterol MDPI (Salm50DPI) / 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\_PE) / 18 µg Tiotropium (T18GEL) + 50 µg Salmeterol MDPI (S\_DPI) BID / 18 µg Tiotropium (Tio18GEL)

Drug: Tiotropium (Tio18GEL); Drug: Salmeterol MDPI (Salm50DPI); Drug: Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI); Drug: Tiotropium/Salmeterol (T+S_PE)

T18GEL+S_DPI/ Salm50DPI/ Tio18GEL/ T+S_PE

EXPERIMENTAL

18 µg Tiotropium (T18GEL) + 50 µg Salmeterol MDPI (S\_DPI) BID / 50 µg Salmeterol MDPI (Salm50DPI) / 18 µg Tiotropium (Tio18GEL) / 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\_PE)

Drug: Tiotropium (Tio18GEL); Drug: Salmeterol MDPI (Salm50DPI); Drug: Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI); Drug: Tiotropium/Salmeterol (T+S_PE)

Interventions

Tiotropium (Tio18GEL) DRUG

18 µg Tiotropium (Tio18GEL) inhalation powder

Salm50DPI/ T+S_PE/ T18GEL+S_DPI/ Tio18GEL; T+S_PE/ Tio18GEL / Salm50DPI / T18GEL+S_DPI; T18GEL+S_DPI/ Salm50DPI/ Tio18GEL/ T+S_PE; Tio18GEL/ T18GEL+S_DPI/ T+S_PE/ Salm50DPI

Salmeterol MDPI (Salm50DPI) DRUG

50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID)

Salm50DPI/ T+S_PE/ T18GEL+S_DPI/ Tio18GEL; T+S_PE/ Tio18GEL / Salm50DPI / T18GEL+S_DPI; T18GEL+S_DPI/ Salm50DPI/ Tio18GEL/ T+S_PE; Tio18GEL/ T18GEL+S_DPI/ T+S_PE/ Salm50DPI

Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI) DRUG

18 µg Tiotropium (T18GEL) inhalation powder plus 50 µg Salmeterol MDPI (S\_DPI) twice daily (BID)

Salm50DPI/ T+S_PE/ T18GEL+S_DPI/ Tio18GEL; T+S_PE/ Tio18GEL / Salm50DPI / T18GEL+S_DPI; T18GEL+S_DPI/ Salm50DPI/ Tio18GEL/ T+S_PE; Tio18GEL/ T18GEL+S_DPI/ T+S_PE/ Salm50DPI

Tiotropium/Salmeterol (T+S_PE) DRUG

Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S\_PE) inhalation powder

Salm50DPI/ T+S_PE/ T18GEL+S_DPI/ Tio18GEL; T+S_PE/ Tio18GEL / Salm50DPI / T18GEL+S_DPI; T18GEL+S_DPI/ Salm50DPI/ Tio18GEL/ T+S_PE; Tio18GEL/ T18GEL+S_DPI/ T+S_PE/ Salm50DPI

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.
• Male or female patients 40 years of age or older.
• Patients must be current or ex-smokers with a smoking history of 10 pack-years.
• Patients must be able to perform technically acceptable pulmonary function tests
• Patients must be able to inhale medication in a competent manner.
• Patients must be able to perform all necessary recordings in the diary.

You may not qualify if:

• Significant diseases other than COPD
• Patients with a recent history of myocardial infarction.
• Patients with any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the past year.
• Hospitalisation for cardiac failure during the past year.
• Malignancy within the last five years excluded basal cell carcinoma.
• Patients with a history of asthma or who have a total blood eosinophil count 600/mm3.
• Patients with a history of life threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis.
• Known active tuberculosis.
• Patients with a history of alcohol or drug abuse.
• Thoracotomy with pulmonary resection.
• Rehabilitation program within the last six weeks
• Patients who regularly use daytime oxygen therapy
• Patients who have taken an investigational drug within 30 days
• Use of not allowed medications
• Known hypersensitivity to used drugs or other components of the study medication.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (12)

1184.13.1302 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1184.13.1309 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1184.13.1308 Boehringer Ingelheim Investigational Site

Cottbus, Germany

Location

1184.13.1311 Boehringer Ingelheim Investigational Site

Großhansdorf, Germany

Location

1184.13.1312 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1184.13.1305 Boehringer Ingelheim Investigational Site

Mainz, Germany

Location

1184.13.1301 Boehringer Ingelheim Investigational Site

Mannheim, Germany

Location

1184.13.1306 Boehringer Ingelheim Investigational Site

Rodgau-Dudenhofen, Germany

Location

1184.13.1310 Boehringer Ingelheim Investigational Site

Rüdersdorf, Germany

Location

1184.13.1307 Boehringer Ingelheim Investigational Site

Schwerin, Germany

Location

1184.13.1304 Boehringer Ingelheim Investigational Site

Wiesbaden, Germany

Location

1184.13.1303 Boehringer Ingelheim Investigational Site

Wiesloch, Germany

Location

Related Links

• Related Info

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Tiotropium Bromide; Salmeterol Xinafoate

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; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Amines; Phenethylamines; Ethylamines

Results Point of Contact

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

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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2008
• First Posted: April 21, 2008
• Study Start: April 15, 2008
• Primary Completion: July 22, 2009
• Study Completion: July 22, 2009
• Last Updated: June 28, 2022
• Results First Posted: June 28, 2022

Record last verified: 2022-06

Locations

DE (12)