Pulmonary Disease, Chronic ObstructivePhase 3NCT00662792

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

A Phase 3 study testing Tiotropium (Tio18GEL), Salmeterol MDPI (Salm50DPI) and Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI) in people with Pulmonary Disease, Chronic Obstructive, run by Boehringer Ingelheim at 12 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 40 years and older
Conditions the study is for: Pulmonary Disease, Chronic Obstructive
What is being tested?: Tiotropium (Tio18GEL), Salmeterol MDPI (Salm50DPI) and Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI)
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 147 participants
Where: 12 sitesGermany
Study dates: 15 Apr 2008to 22 Jul 2009
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

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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.

Who cannot join

Significant diseases other than COPD
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.
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.

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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.
Pregnant or nursing women
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.
Patients who are currently participating in another study.

Trial locations and contacts

12 sites in 1 country.

City, postcode or hospital

12 sites in 1 country

Germany12 sites

1184.13.1302 Boehringer Ingelheim Investigational Site
Berlin
1184.13.1309 Boehringer Ingelheim Investigational Site
Berlin
1184.13.1308 Boehringer Ingelheim Investigational Site
Cottbus
1184.13.1311 Boehringer Ingelheim Investigational Site
Großhansdorf
1184.13.1312 Boehringer Ingelheim Investigational Site
Hamburg
1184.13.1305 Boehringer Ingelheim Investigational Site
Mainz
1184.13.1301 Boehringer Ingelheim Investigational Site
Mannheim
1184.13.1306 Boehringer Ingelheim Investigational Site
Rodgau-Dudenhofen
1184.13.1310 Boehringer Ingelheim Investigational Site
Rüdersdorf
1184.13.1307 Boehringer Ingelheim Investigational Site
Schwerin
1184.13.1304 Boehringer Ingelheim Investigational Site
Wiesbaden
1184.13.1303 Boehringer Ingelheim Investigational Site
Wiesloch

Other trials in Germany

About this study

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

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
Being tested: Tiotropium (Tio18GEL), Salmeterol MDPI (Salm50DPI), Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI), Tiotropium/Salmeterol (T+S_PE)
Medical subject headings: Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Tiotropium (Tio18GEL)Drug
18 µg Tiotropium (Tio18GEL) inhalation powder
Salmeterol MDPI (Salm50DPI)Drug
50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID)
Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI)Drug
18 µg Tiotropium (T18GEL) inhalation powder plus 50 µg Salmeterol MDPI (S_DPI) twice daily (BID)
Tiotropium/Salmeterol (T+S_PE)Drug
Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S_PE) inhalation powder

Study groups in NCT00662792
Study group	Role	What they receive
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 Receives: 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) Receives: 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) Receives: 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) Receives: Drug: Tiotropium (Tio18GEL); Drug: Salmeterol MDPI (Salm50DPI); Drug: Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI); Drug: Tiotropium/Salmeterol (T+S_PE)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
FEV1 AUC was defined as the area under the FEV1 curve normalized for time. It was calculated from time 0 to 24 h (FEV1 AUC0-24), using the trapezoidal rule divided by the corresponding duration (24 h) to give the results in liter (L). FEV1 AUC0-24h response is defined as the change from baseline:
FEV1 AUC0-24h response = FEV1 AUC0-24h - 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.
Measured: 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)
FVC AUC was defined as the area under the FVC curve normalized for time. It was calculated from time 0 to 12 h (FVC AUC0-12), using the trapezoidal rule divided by the corresponding duration (12 h) to give the results in liter (L). FVC AUC0-12h response is defined as the change from baseline:
FVC AUC0-12h response = FVC AUC0-12h - FVC (Baseline). The baseline value for FVC based parameters is defined as the pre-dose FVC measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.
Measured: 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)
The FVC AUC was defined as the area under the FVC curve (AUC) normalised for time. It was calculated from time 12 to 24 h (FVC 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:
FVC AUC12-24h response = FVC AUC12-24h - FVC (Baseline). The FVC baseline value is defined as the pre-dose FVC measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.
Measured: 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)
The FVC AUC was defined as the area under the FVC curve (AUC) normalised for time. It was calculated from time 0 to 24 h (FVC AUC0-24), using the trapezoidal rule divided by the corresponding duration (i.e. 24 h) to give the results in L. AUC response was defined as the change from the baseline FVC; baseline was defined as the FVC measured on randomisation visit. Mean is adjusted mean.
Measured: 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)
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.
Measured: At baseline and within 3 hours post-morning dose after 6 weeks of treatment.
Response in Trough Forced Vital Capacity (FVC)
Trough FVC1 is determined at the end of each 6-week treatment period and is defined as the pre-dose FVC1 measured just prior to the last administration of the morning dose of randomized treatment.
Trough FVC1 response is defined as the change from baseline:
Trough FVC1 response = Trough FVC1 - FVC1 (Baseline) The FVC1 baseline value is defined as the pre-dose FVC1 measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.
Measured: At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment.
Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve Form 0 to 12 Hours (AUC0-12)
PEF(L/min) AUC0-12(h) response is defined as the change from baseline. AUC0-12(h) was calculated as the area under the curve from 0 to 12 hours using the trapezoidal rule, divided by the full duration (12 hours) to report in liter/minutes.
PEF AUC0-12h response = PEF AUC0-12h - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.
Measured: 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.
Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve From 12 to 24 Hours (AUC12-24)
PEF(L/min) AUC12-24(h) response is defined as the change from baseline. AUC12-24(h) was calculated as the area under the curve from 12 to 24 hours using the trapezoidal rule, divided by the full duration (12 hours) to report in liter/minutes.
PEF AUC12-24h response = PEF AUC12-24h - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.
Measured: 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.
Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve From 0 to 24 Hours (AUC0-24)
PEF(L/min) AUC0-24(h) response is defined as the change from baseline. AUC0-24(h) was calculated as the area under the curve from 0 to 24 hours using the trapezoidal rule, divided by the full duration (24 hours) to report in liter/minutes.
PEF AUC0-24h response = PEF AUC0-24h - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.
Measured: 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 Peak PEF (Peak Expiratory Flow Rate)
Peak PEF was defined as the highest PEF reading observed within 3 hours after inhalation of the last morning dose of randomized treatment.
Peak PEF response is defined as change from baseline:
Peak PEF response = Peak PEF - PEF (Baseline). The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.
Measured: At baseline and within 3 hours post-morning dose after 6 weeks of treatment.
Response in Trough Peak Expiratory Flow Rate (PEF)
Trough PEF is determined at the end of each treatment period and is defined as the pre-dose PEF measured just prior to the last administration of the morning dose of randomized treatment. Trough PEF response is defined as the change from baseline:
Trough PEF response = Trough PEF - PEF (Baseline) The PEF baseline value is defined as the pre-dose PEF measurement in the morning at the randomization visit just prior to administration of the first dose of randomized treatment. Mean is adjusted mean.
Measured: At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment.
Response in Individual Forced Expiratory Volume in 1 Second (FEV1) Over a 24 Hour Observation Period
Response in individual forced expiratory volume in 1 second (FEV1) over a 24 hour observation period. Response is defined as change from baseline.
Means are adjusted for treatment, centre, treatment period and patient within centre.
Measured: 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.
Response in Individual Forced Vital Capacity (FVC) Over a 24 Hour Observation Period
Response in forced vital capacity (FVC) over a 24 hour observation period. Response is defined as change from baseline.
Measured: 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.
Response in Individual Peak Expiratory Flow (PEF) Over a 24 Hour Observation Period
Response in individual peak expiratory flow (PEF) over a 24 hour observation period. Response is defined as change from baseline.
Means are adjusted for treatment, centre, treatment period and patient within centre.
Measured: 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.
Response in Morning and Evening Peak Expiratory Flow Rate (PEF), Recorded by Patients at Home
The mean PEF is defined as the mean of the values obtained during the weeks after the first three weeks of treatment. Morning and evening mean PEF were calculated and analyzed separately. PEF was measured twice daily (in the morning prior to inhalation of study medication and in the evening prior to inhalation of study medication).
Morning and evening mean PEF response are defined as the change from morning and evening baseline, respectively.
Morning and evening mean PEF baseline are defined as the mean of the morning and evening values, respectively obtained from the last week preceding the randomization visit.
Mean is adjusted for treatment, center, treatment period and patient within center.
Measured: At baseline and last 3 weeks of 6-week treatment period.
Response in Morning and Evening Forced Expiratory Volume in 1 Second (FEV1) Recorded by Participants at Home
Per treatment period, the morning mean FEV1 (mean of the pre-dose morning FEV1 measurements) and evening mean FEV1 (mean of the pre-dose evening FEV1 measurement) were calculated. Per treatment period the data obtained after the first 3 weeks were used for calculating these means.
Morning and evening mean FEV1 responses are defined as the change from morning and evening baseline, respectively. The baseline values, morning and evening mean FEV1(Baseline), are defined as the mean of the morning and evening values, respectively obtained from the last week preceding the randomization visit .
Mean is adjusted for treatment, centre, treatment period and patient within centre.
Measured: At baseline and last 3 weeks of 6-week treatment period.
Response in Mean Number of Days With Rescue Medication Use
Response (change from baseline) in mean number of days with rescue medication use in day-time, night-time and 24-hours. Per treatment period, the response in mean number of days using rescue medication was calculated for day-time (from inhalation of morning dose until 12 hours thereafter), night-time (from inhalation of evening dose until 12 hours thereafter) and 24h-total (from inhalation of morning dose until 24 hours thereafter) separately.
Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating means. Mean is adjusted mean.
Measured: At baseline and last 3 weeks of 6-week treatment period.
Response in Mean Number of Puffs of Rescue Medication
Response in mean number of puffs of rescue medication. Per treatment period, the response in mean number of puffs rescue medication used was calculated, for day-time (from inhalation of morning dose until 12 hours thereafter), night-time (from inhalation of evening dose until 12 hours thereafter) and 24h-total (from inhalation of morning dose until 24 hours thereafter) separately. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating means. Night-time, day-time and 24h-total mean number of puffs rescue medication used responses are defined as the change from night-time, day-time and 24h-total baseline, respectively.
The baseline values, night-time, day-time and 24h-total mean mean number of puffs rescue medication used (Baseline), are defined as the mean of the night-time, day-time and 24h-total values, respectively obtained from the last week preceding the randomisation visit.
Measured: At baseline and last 3 weeks of 6-week treatment period.
Response in Mean Number of Days With Night-time Awakenings
Response in mean number of days with night-time awakenings. Per treatment period, the mean number days with awakening during the night was calculated. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating this mean. Mean number of days with night-time awakenings response is defined as the change from baseline. The baseline value, mean number of days with night-time awakenings (Baseline), is defined as the mean of the number of days with night-time awakenings obtained from the last week preceding the randomization visit.
Measured: At baseline and last 3 weeks of 6-week treatment period.
Response in Mean Number of Days With Night-time Awakenings Due to Shortness of Breath (SOB)
Per treatment period, the mean number days with awakening (only chronic obstructive pulmonary disease (COPD) related awakenings) during the night was calculated. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating the mean.
Mean number of days with COPD related awakenings response is defined as the change from baseline.
The baseline value, mean number of days with COPD related awakenings (Baseline), is defined as the mean of the number of days with COPD related awakenings obtained from the last week preceding the randomization visit.
Measured: At baseline and last 3 weeks of 6-week treatment period.
Response in Means Number of Awakenings Due to Shortness of Breath (SOB)
Per treatment period, the mean number of awakening (only chronic obstructive pulmonary disease (COPD) related awakenings) during the night was calculated. Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating this mean. Mean number of COPD related awakenings response is defined as the change from baseline. The baseline value, mean number of COPD related awakenings (Baseline), is defined as the mean of the number of days with COPD related awakenings obtained from the last week preceding the randomization visit.
Measured: At baseline and last 3 weeks of 6-week treatment period.
Response in Average Shortness of Breath (SOB) Score at Night
Response in average shortness of breath (SOB) score at night. The SOB measured the shortness of breath, ranging from 1 to 5, where 1 = not at all, 2 = a little bit, 3 = somewhat, 4 = quite a bit and 5 = very much. A higher score indicates a worse outcome.
Per 6-week treatment period the data obtained after the first 3 weeks was used for calculating the mean.
Measured: At baseline and last 3 weeks of 6-week treatment period.
Number of Participants With Drug Related Adverse Events
Number of participants with drug related adverse events.
Measured: 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.
Number of Patients With Marked Changes in Vital Signs
Marked changes from baseline in vital signs were defined as followed:
Systolic blood pressure
- Increase of ≥25 millimetre of mercury (mmHg) above baseline
- Decrease below 100 mmHg if not at that level at baseline and a decrease of >10 mmHg below baseline
Diastolic blood pressure
- Increase above 90 mmHg and an increase of >10 mmHg above baseline
- Decrease below 60 mmHg if not at that level at baseline and a decrease of >10 mmHg below baseline
Pulse
- Increase above 100 bpm if not at that level at baseline and an increase of >10 bpm above baseline
- Decrease below 60 bpm if not at that level at baseline and a decrease of >10 bpm below baseline
Baseline is defined as the pre-dose measurement at randomisation visit.
Measured: At baseline and 6 hours following the morning dose of study medication after 6 weeks of treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Apr 200822 Jul 2009

First posted21 Apr 2008 (estimated)
Study start15 Apr 2008
Primary completion22 Jul 2009
Study completion22 Jul 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 147 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00662792
Sponsor's protocol ID: 1184.13
Status last verified: Jun 2022
First submitted: 17 Apr 2008
Last updated: 28 Jun 2022
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of Belumosudil Compared With Best Available Therapy in Participants Aged 12 Years or Older With Chronic Graft-versus-host Disease
Chronic Graft Versus Host Disease

All Pulmonary Disease, Chronic Obstructive trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00662792
Acronym / sponsor ID: 1184.13
Conditions: Pulmonary Disease, Chronic Obstructive
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 147 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 15 Apr 2008 (actual)
Primary completion: 22 Jul 2009 (actual)
Study completion: 22 Jul 2009 (actual)
First posted: 21 Apr 2008 (estimated)
Results: Posted 28 Jun 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
T+S_PE/ Tio18GEL / Salm50DPI / T18GEL+S_DPI	Experimental	Drug: Tiotropium (Tio18GEL), Drug: Salmeterol MDPI (Salm50DPI), Drug: Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI), Drug: Tiotropium/Salmeterol (T+S_PE)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
Tio18GEL/ T18GEL+S_DPI/ T+S_PE/ Salm50DPI	Experimental	Drug: Tiotropium (Tio18GEL), Drug: Salmeterol MDPI (Salm50DPI), Drug: Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI), Drug: Tiotropium/Salmeterol (T+S_PE)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)
Salm50DPI/ T+S_PE/ T18GEL+S_DPI/ Tio18GEL	Experimental	Drug: Tiotropium (Tio18GEL), Drug: Salmeterol MDPI (Salm50DPI), Drug: Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI), Drug: Tiotropium/Salmeterol (T+S_PE)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)
T18GEL+S_DPI/ Salm50DPI/ Tio18GEL/ T+S_PE	Experimental	Drug: Tiotropium (Tio18GEL), Drug: Salmeterol MDPI (Salm50DPI), Drug: Tiotropium (T18GEL) + Salmeterol MDPI (S_DPI), Drug: Tiotropium/Salmeterol (T+S_PE)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)

Who may qualify

Ages: 40 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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).
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.

Key exclusion criteria (19 listed)

Significant diseases other than COPD
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.
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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Tiotropium (Tio18GEL)18 µg Tiotropium (Tio18GEL) inhalation powder	Drug	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)50 µg Salmeterol MDPI (Salm50DPI) twice daily (BID)	Drug	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)18 µg Tiotropium (T18GEL) inhalation powder plus 50 µg Salmeterol MDPI (S_DPI) twice daily (BID)	Drug	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)Fixed-dose combination of 7.5 µg/ 25 µg Tiotropium/Salmeterol (T+S_PE) inhalation powder	Drug	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

Primary outcome

Response in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0 - 12 Hours (AUC0-12)
Time frame: 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.
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.
Response in Forced Expiratory Volume in Second (FEV1) Area Under the Curve From 12 - 24 Hours (AUC12 -24)
Time frame: 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.
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.
Response in Peak Forced Expiratory Volume in 1 Second (FEV1)
Time frame: At baseline and within 3 hours post-morning dose after 6 weeks of treatment.
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.
Response in Trough Forced Expiratory Volume in 1 Second (FEV1)
Time frame: At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment.
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.

24 secondary outcomes

Response in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0-24 Hours (AUC0-24)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: At baseline and within 3 hours post-morning dose after 6 weeks of treatment.
Response in Trough Forced Vital Capacity (FVC)
Time frame: At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment.
Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve Form 0 to 12 Hours (AUC0-12)
Time frame: 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.
Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve From 12 to 24 Hours (AUC12-24)
Time frame: 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.
Response in Peak Expiratory Flow Rate (PEF) Area Under the Curve From 0 to 24 Hours (AUC0-24)
Time frame: 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 Peak PEF (Peak Expiratory Flow Rate)
Time frame: At baseline and within 3 hours post-morning dose after 6 weeks of treatment.
Response in Trough Peak Expiratory Flow Rate (PEF)
Time frame: At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment.
Response in Individual Forced Expiratory Volume in 1 Second (FEV1) Over a 24 Hour Observation Period
Time frame: 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.
Response in Individual Forced Vital Capacity (FVC) Over a 24 Hour Observation Period
Time frame: 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.
Response in Individual Peak Expiratory Flow (PEF) Over a 24 Hour Observation Period
Time frame: 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.
Response in Morning and Evening Peak Expiratory Flow Rate (PEF), Recorded by Patients at Home
Time frame: At baseline and last 3 weeks of 6-week treatment period.
Response in Morning and Evening Forced Expiratory Volume in 1 Second (FEV1) Recorded by Participants at Home
Time frame: At baseline and last 3 weeks of 6-week treatment period.
Response in Mean Number of Days With Rescue Medication Use
Time frame: At baseline and last 3 weeks of 6-week treatment period.
Response in Mean Number of Puffs of Rescue Medication
Time frame: At baseline and last 3 weeks of 6-week treatment period.
Response in Mean Number of Days With Night-time Awakenings
Time frame: At baseline and last 3 weeks of 6-week treatment period.
Response in Mean Number of Days With Night-time Awakenings Due to Shortness of Breath (SOB)
Time frame: At baseline and last 3 weeks of 6-week treatment period.
Response in Means Number of Awakenings Due to Shortness of Breath (SOB)
Time frame: At baseline and last 3 weeks of 6-week treatment period.
Response in Average Shortness of Breath (SOB) Score at Night
Time frame: At baseline and last 3 weeks of 6-week treatment period.
Number of Participants With Drug Related Adverse Events
Time frame: 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.
Number of Patients With Marked Changes in Vital Signs
Time frame: At baseline and 6 hours following the morning dose of study medication after 6 weeks of treatment.

Results and safety

Results posted to the registry on 28 Jun 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
T+S_PE/ Tio18GEL / Salm50DPI / T18GEL+S_DPI	34	32
Tio18GEL/ T18GEL+S_DPI/ T+S_PE/ Salm50DPI	38	31
Salm50DPI/ T+S_PE/ T18GEL+S_DPI/ Tio18GEL	36	32
T18GEL+S_DPI/ Salm50DPI/ Tio18GEL/ T+S_PE	39	39

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

Time frame: 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.. Mean (Standard Error). Unit: Liter (L)

Measure	7.5 µg /25 µg Tio /Salmeterol (T+S_PE) n = 127	18 µg Tiotropium (Tio18GEL) n = 128	50 µg Salmeterol MDPI (Salm50DPI) n = 125	18 µg Tiotropium Free Combination (T18GEL+S_DPI) n = 127
Value	0.187 (0.026)	0.117 (0.026)	0.057 (0.026)	0.211 (0.026)

7.5 µg /25 µg Tio /Salmeterol (T+S_PE) vs 50 µg Salmeterol MDPI (Salm50DPI): Difference of adjusted means: 0.130 (95% CI 0.102 to 0.158), p <0.0001, ANOVA
7.5 µg /25 µg Tio /Salmeterol (T+S_PE) vs 18 µg Tiotropium (Tio18GEL): Difference of adjusted means: 0.070 (95% CI 0.042 to 0.097), p <.0001, ANOVA
7.5 µg /25 µg Tio /Salmeterol (T+S_PE) vs 18 µg Tiotropium Free Combination (T18GEL+S_DPI): Difference of adjusted means: -0.024 (95% CI -0.052 to 0.004), p = 0.0914, ANOVA

Population analysed: Full Analysis Set (FAS): All patients where baseline data and any on-treatment efficacy data are available. This definition was applied separately for each endpoint, so that the number of patients analysed may vary across endpoints.

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

Time frame: 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.. Mean (Standard Error). Unit: Liter (L)

Measure	7.5 µg /25 µg Tio /Salmeterol (T+S_PE) n = 127	18 µg Tiotropium (Tio18GEL) n = 128	50 µg Salmeterol MDPI (Salm50DPI) n = 125	18 µg Tiotropium Free Combination (T18GEL+S_DPI) n = 127
Value	0.068 (0.025)	0.003 (0.025)	0.003 (0.025)	0.124 (0.025)

7.5 µg /25 µg Tio /Salmeterol (T+S_PE) vs 50 µg Salmeterol MDPI (Salm50DPI): Difference of adjusted means: 0.064 (95% CI 0.036 to 0.093), p <.0001, ANOVA
7.5 µg /25 µg Tio /Salmeterol (T+S_PE) vs 18 µg Tiotropium (Tio18GEL): Difference of adjusted means: 0.064 (95% CI 0.036 to 0.093), p <.0001, ANOVA
7.5 µg /25 µg Tio /Salmeterol (T+S_PE) vs 18 µg Tiotropium Free Combination (T18GEL+S_DPI): Difference of adjusted means: -0.057 (95% CI -0.086 to -0.028), p = 0.0001, ANOVA

Primary outcome: Response in Peak Forced Expiratory Volume in 1 Second (FEV1)

Time frame: At baseline and within 3 hours post-morning dose after 6 weeks of treatment.. Mean (Standard Error). Unit: Liter

Measure	7.5 µg /25 µg Tio /Salmeterol (T+S_PE) n = 127	18µg Tiotropium (Tio18GEL) n = 128	50 µg Salmeterol MDPI (Salm50DPI) n = 125	18 µg Tiotropium Free Combination (T18GEL+S_DPI) n = 127
Value	0.296 (0.026)	0.229 (0.026)	0.161 (0.026)	0.320 (0.026)

7.5 µg /25 µg Tio /Salmeterol (T+S_PE) vs 50 µg Salmeterol MDPI (Salm50DPI): Difference of adjusted means: 0.134 (95% CI 0.102 to 0.166), p <.0001, ANOVA
7.5 µg /25 µg Tio /Salmeterol (T+S_PE) vs 18µg Tiotropium (Tio18GEL): Difference of adjusted means: 0.066 (95% CI 0.034 to 0.098), p <.0001, ANOVA
7.5 µg /25 µg Tio /Salmeterol (T+S_PE) vs 18 µg Tiotropium Free Combination (T18GEL+S_DPI): Difference of adjusted means: -0.026 (95% CI -0.058 to 0.006), p = 0.1093, ANOVA

Primary outcome: Response in Trough Forced Expiratory Volume in 1 Second (FEV1)

Time frame: At baseline and 5 minutes prior to the last administration of the morning dose after 6 weeks of treatment.. Mean (Standard Error). Unit: Liter

Measure	7.5 µg /25 µg Tio /Salmeterol (T+S_PE) n = 127	18µg Tiotropium (Tio18GEL) n = 128	50 µg Salmeterol MDPI (Salm50DPI) n = 125	18 µg Tiotropium Free Combination (T18GEL+S_DPI) n = 127
Value	0.062 (0.024)	0.032 (0.024)	0.003 (0.024)	0.097 (0.024)

7.5 µg /25 µg Tio /Salmeterol (T+S_PE) vs 50 µg Salmeterol MDPI (Salm50DPI): Differences of adjusted means: 0.058 (95% CI 0.024 to 0.092), p = 0.0008, ANOVA
7.5 µg /25 µg Tio /Salmeterol (T+S_PE) vs 18µg Tiotropium (Tio18GEL): Difference of adjusted means: 0.029 (95% CI -0.004 to 0.063), p = 0.0857, ANOVA
7.5 µg /25 µg Tio /Salmeterol (T+S_PE) vs 18 µg Tiotropium Free Combination (T18GEL+S_DPI): Difference of adjusted means: -0.037 (95% CI -0.071 to -0.003), p = 0.0317, ANOVA

24 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
7.5 µg /25 µg Tio /Salmeterol (T+S_PE)	1 of 132 (0.8%)	14 of 132 (10.6%)	0 of 132
18 µg Tiotropium (Tio18GEL)	7 of 135 (5.2%)	15 of 135 (11.1%)	1 of 135
50 µg Salmeterol MDPI (Salm50DPI)	4 of 137 (2.9%)	14 of 137 (10.2%)	0 of 137
18 µg Tiotropium Free Combination (T18GEL+S_DPI)	2 of 132 (1.5%)	11 of 132 (8.3%)	0 of 132
Total Treated	13 of 146 (8.9%)	47 of 146 (32.2%)	1 of 146

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Boehringer Ingelheim study chair

Boehringer Ingelheim

12 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0 - 12 Hours (AUC0-12) (time frame: 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.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00662792.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2022.