Phase 3
Completed N=1,460
Respimat® Combivent Trial in Chronic Obstructive Pulmonary Disease (COPD)
Pulmonary Disease, Chronic Obstructive
Source: ClinicalTrials.gov NCT00400153 ↗
Enrolled (actual)
1,460
Serious AEs
—
Results posted
Jun 2009
Primary outcomePrimary: FEV1 AUC0-6 at Day 85 — 0.145; 0.149; 0.119 liters — p=0.7135
Summary
The primary objective of this study is to compare the effect of ipratropium bromide/salbutamol inhalation spray combination administered by the Respimat® inhaler (20 mcg/100 mcg), ipratropium bromide inhalation spray administered by the Respimat® inhaler (20 mcg), and COMBIVENT® MDI administered q.i.d on FEV1 at intervals over a treatment period of 12 weeks in patients with COPD. Specifically, non-inferiority of Combivent Respimat® to COMBIVENT® MDI in FEV1 AUC from 0 to 6 hours , superiority of Combivent Respimat® to Atrovent Respimat® monotherapy in FEV1 AUC from 0 to 4 hours, and non-inferiority of Combivent Respimat® to Atrovent Respimat® monotherapy in FEV1 AUC from 4 to 6 hours will be analyzed. In addition, steady state pharmacokinetics over one dosing interval following 4 weeks of therapy will be characterized in a subgroup of patients.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY FEV1 AUC0-6 at Day 85 |
0.145; 0.149; 0.119 | 0.7135 |
| PRIMARY FEV1 AUC0-4 at Day 85 |
0.189; 0.190; 0.142 | < 0.0001 sig |
| PRIMARY FEV1 AUC4-6 at Day 85 |
0.056; 0.066; 0.073 | 0.1389 |
| SECONDARY FEV1 AUC0-6 at Day 1 |
0.173; 0.189; 0.124 | 0.124 |
| SECONDARY FEV1 AUC0-6 at Day 29 |
0.154; 0.161; 0.127 | 0.4888 |
| SECONDARY FEV1 AUC0-6 at Day 57 |
0.146; 0.16; 0.118 | 0.1433 |
| SECONDARY FEV1 AUC0-4 at Day 1 |
0.211; 0.227; 0.149 | < 0.0001 sig |
| SECONDARY FEV1 AUC0-4 at Day 29 |
0.197; 0.198; 0.153 | < 0.0001 sig |
| SECONDARY FEV1 AUC0-4 at Day 57 |
0.188; 0.200; 0.141 | < 0.0001 sig |
| SECONDARY FEV1 AUC4-6 at Day 1 |
0.1; 0.115; 0.074 | 0.0258 sig |
| SECONDARY FEV1 AUC4-6 at Day 29 |
0.068; 0.087; 0.078 | 0.3749 |
| SECONDARY FEV1 AUC4-6 at Day 57 |
0.063; 0.084; 0.073 | 0.3355 |
| SECONDARY Peak FEV1 Response at Day 1 |
0.302; 0.323; 0.237 | < 0.0001 sig |
| SECONDARY Peak FEV1 Response at Day 29 |
0.302; 0.296; 0.237 | < 0.0001 sig |
| SECONDARY Peak FEV1 Response at Day 57 |
0.284; 0.296; 0.223 | < 0.0001 sig |
| SECONDARY Peak FEV1 Response at Day 85 |
0.293; 0.290; 0.225 | < 0.0001 sig |
| SECONDARY Time to Onset of Therapeutic FEV1 Response at Day 1 |
13; 12; 28 | — |
| SECONDARY Time to Onset of Therapeutic FEV1 Response at Day 29 |
12; 13; 27 | — |
| SECONDARY Time to Onset of Therapeutic FEV1 Response at Day 57 |
13; 12; 29 | — |
| SECONDARY Time to Onset of Therapeutic FEV1 Response at Day 85 |
12; 13; 27 | — |
| SECONDARY Duration of Therapeutic FEV1 Response at Day 1 |
189; 219; 104 | — |
| SECONDARY Duration of Therapeutic FEV1 Response at Day 29 |
170; 178; 122 | — |
| SECONDARY Duration of Therapeutic FEV1 Response at Day 57 |
165; 194; 84 | — |
| SECONDARY Duration of Therapeutic FEV1 Response at Day 85 |
168; 172; 70 | — |
| SECONDARY Time to Peak FEV1 Response at Day 1 |
60; 60; 120 | — |
| SECONDARY Time to Peak FEV1 Response at Day 29 |
60; 60; 120 | — |
| SECONDARY Time to Peak FEV1 Response at Day 57 |
60; 60; 60 | — |
| SECONDARY Time to Peak FEV1 Response at Day 85 |
60; 60; 60 | — |
| SECONDARY FVC AUC0-6 at Day 1 |
0.337; 0.354; 0.25 | 0.417 |
| SECONDARY FVC AUC0-6 at Day 29 |
0.3; 0.319; 0.246 | 0.3505 |
| SECONDARY FVC AUC0-6 at Day 57 |
0.284; 0.303; 0.22 | 0.3499 |
| SECONDARY FVC AUC0-6 at Day 85 |
0.279; 0.283; 0.219 | 0.8288 |
| SECONDARY FVC AUC0-4 at Day 1 |
0.408; 0.422; 0.297 | < 0.0001 sig |
| SECONDARY FVC AUC0-4 at Day 29 |
0.381; 0.388; 0.291 | < 0.0001 sig |
| SECONDARY FVC AUC0-4 at Day 57 |
0.361; 0.380; 0.264 | < 0.0001 sig |
| SECONDARY FVC AUC0-4 at Day 85 |
0.359; 0.359; 0.265 | < 0.0001 sig |
| SECONDARY FVC AUC4-6 at Day 1 |
0.2; 0.221; 0.156 | 0.0688 |
| SECONDARY FVC AUC4-6 at Day 29 |
0.137; 0.180; 0.156 | 0.3895 |
| SECONDARY FVC AUC4-6 at Day 57 |
0.128; 0.147; 0.13 | 0.959 |
| SECONDARY FVC AUC4-6 at Day 85 |
0.117; 0.130; 0.124 | 0.7652 |
| SECONDARY Peak FVC Response at Day 1 |
0.6; 0.612; 0.479 | < 0.0001 sig |
| SECONDARY Peak FVC Response at Day 29 |
0.594; 0.591; 0.465 | < 0.0001 sig |
| SECONDARY Peak FVC Response at Day 57 |
0.562; 0.577; 0.445 | < 0.0001 sig |
| SECONDARY Peak FVC Response at Day 85 |
0.575; 0.562; 0.449 | < 0.0001 sig |
| SECONDARY Rescue Medication Use on Pulmonary Test Day 1 |
8; 9; 7 | — |
| SECONDARY Rescue Medication Use on Pulmonary Test Day 29 |
10; 7; 7 | — |
| SECONDARY Rescue Medication Use on Pulmonary Test Day 57 |
7; 7; 6 | — |
| SECONDARY Rescue Medication Use on Pulmonary Test Day 85 |
5; 7; 10 | — |
| SECONDARY Night-time Rescue Medication Use |
0.977; 0.977; 0.997 | 0.9943 |
| SECONDARY Daytime Rescue Medication Use |
2.3; 2.191; 2.456 | 0.3659 |
| SECONDARY Night-time Symptom Score |
0.922; 0.914; 0.857 | 0.809 |
| SECONDARY Daytime Symptom Score |
1.015; 1.002; 0.999 | 0.6674 |
| SECONDARY Trough Peak Expiratory Flow Rate (PEFR) |
191.95; 190.290; 189.51 | 0.4238 |
| SECONDARY Physician's Global Evaluation Score on Pulmonary Function Testing Day 29 |
4.936; 4.859; 4.99 | 0.173 |
| SECONDARY Physician's Global Evaluation Score on Pulmonary Function Testing Day 57 |
4.971; 4.965; 5.04 | 0.924 |
| SECONDARY Physician's Global Evaluation Score on Pulmonary Function Testing Day 85 |
5.115; 5.018; 5.097 | 0.139 |
| SECONDARY Percentage of Patients With Chronic Obstructive Pulmonary Disease (COPD) Exacerbation During the On-treatment Period |
14.81; 13.03; 10.35 | — |
| SECONDARY COPD Exacerbation Rate During the On-treatment Period |
0.76; 0.69; 0.53 | — |
| SECONDARY COPD Exacerbation During the On-treatment Period |
3.27; 2.93; 2.13 | — |
| SECONDARY Frequency Distribution of Satisfaction Rating With Inhaler Attributes |
16; 13; 27; 20; 37; 17 | — |
| SECONDARY Mean Rating Scores of Satisfaction With Inhaler - Overall Feeling of Inhaling Medicine |
5.411; 5.810 | < 0.0001 sig |
| SECONDARY Mean Rating Scores of Satisfaction With Inhaler - Feeling That the Inhaled Dose Goes to the Lung |
5.326; 5.808 | <0.0001 sig |
| SECONDARY Mean Rating Scores of Satisfaction With Inhaler - Telling the Amount of Medication Left |
4.573; 6.184 | <0.0001 sig |
| SECONDARY Mean Rating Scores of Satisfaction With Inhaler - The Inhaler Works Reliably |
5.682; 6.190 | <0.0001 sig |
| SECONDARY Mean Rating Scores of Satisfaction With Inhaler - Ease of Inhaling a Dose From the Inhaler |
5.729; 6.150 | < 0.0001 sig |
| SECONDARY Mean Rating Scores of Satisfaction With Inhaler - Instructions for Use |
6.048; 6.275 | < 0.0001 sig |
| SECONDARY Mean Rating Scores of Satisfaction With Inhaler - The Inhaler is Durable |
6.014; 6.279 | < 0.0001 sig |
| SECONDARY Mean Rating Scores of Satisfaction With Inhaler - Using the Inhaler |
5.749; 6.127 | < 0.0001 sig |
| SECONDARY Mean Rating Scores of Satisfaction With Inhaler - Speed of Medicine Coming Out of the Inhaler |
5.715; 6.117 | < 0.0001 sig |
| SECONDARY Mean Rating Scores of Satisfaction With Inhaler - Overall Satisfaction With Inhaler |
5.639; 6.103 | < 0.0001 sig |
| SECONDARY Device Preference (Respimat or MDI) |
584; 146; 105 | — |
| SECONDARY Rating of Action of Turning Clear Base of Respimat |
587; 204; 40; 4; 0 | — |
| SECONDARY Noncompartmental Pharmacokinetic Parameters of Ipratropium at Steady State |
128; 123; 115 | — |
| SECONDARY Noncompartmental Parameters of Albuterol at Steady State |
4.09; 5.52 | — |
| SECONDARY Cumulative Amounts of Ipratropium [μg] Excreted in Urine for 0-2 Hours |
0.747; 0.692; 0.723 | — |
| SECONDARY Cumulative Amounts of Albuterol [μg] Excreted in Urine for 0-2 Hours |
14.7; 20.3 | — |
| SECONDARY Cumulative Amounts of Ipratropium [μg] Excreted in Urine for 0-6 Hours |
1.66; 1.41; 1.51 | — |
| SECONDARY Cumulative Amounts of Albuterol [μg] Excreted in Urine for 0-6 Hours |
33.7; 39.4 | — |
Eligibility Criteria
Inclusion Criteria
Outpatients of either sex, 40 years or older, with a diagnosis of COPD (FEV1 65% predicted normal and FEV1/FVC 70%).
Exclusion Criteria
Patients with significant diseases other than COPD that may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study, with a history of asthma or allergic rhinitis, who regularly use daytime oxygen therapy for more than 1 hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy or using oral corticosteroid me dication at unstable doses (i.e., less than 6 weeks on a stable dose) or at a dose in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day will be excluded.
Data sourced from ClinicalTrials.gov (NCT00400153). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.