Trial Outcomes & Findings for 4 Week 2 Way Crossover Double Blind Treatment Phase With Combivent CFC Versus Albuterol Followed by a 4 Week Open Label Combivent Respimat When All Drugs Are Used for Symptom Relief as Needed in Pts With Moderate to Severe Asthma (NCT NCT00818454)
NCT ID: NCT00818454
Last Updated: 2014-02-14
Results Overview
Change from baseline after 4 weeks in Forced Expiratory Volume Area Under (FEV1 AUC) the Curve from 0 to 6 hours.
COMPLETED
PHASE2
226 participants
Test day baseline and test day FEV1 AUC 0-6, after 4 weeks
2014-02-14
Participant Flow
* Crossover Part of the Study (Treatment Period 1) * Crossover Part of the Study (Washout Period of 1 Week) * Crossover Part of the Study (Treatment Period 2) * Parallel Part of the Study Following Second Randomization (Treatment Period 3)
Participant milestones
| Measure |
Albuterol HFA First, Then Combivent CFC
Albuterol Hydrofluoroalkene, Combivent Chlorofluorocarbon
|
Combivent CFC First, Then Albuterol HFA
Combivent Chlorofluorocarbon, Albuterol Hydrofluoroalkene
|
Placebo Respimat
Placebo Respimat (matching Combivent Respimat)
|
Combivent Respimat
Combivent Respimat (contains the effective dose of albuterol)
|
|---|---|---|---|---|
|
Treatment Period 1
STARTED
|
115
|
111
|
0
|
0
|
|
Treatment Period 1
COMPLETED
|
112
|
110
|
0
|
0
|
|
Treatment Period 1
NOT COMPLETED
|
3
|
1
|
0
|
0
|
|
Washout Period of 1 Week
STARTED
|
112
|
110
|
0
|
0
|
|
Washout Period of 1 Week
COMPLETED
|
108
|
107
|
0
|
0
|
|
Washout Period of 1 Week
NOT COMPLETED
|
4
|
3
|
0
|
0
|
|
Treatment Period 2
STARTED
|
108
|
107
|
0
|
0
|
|
Treatment Period 2
COMPLETED
|
106
|
106
|
0
|
0
|
|
Treatment Period 2
NOT COMPLETED
|
2
|
1
|
0
|
0
|
|
Treatment Period 3
STARTED
|
0
|
0
|
26
|
139
|
|
Treatment Period 3
COMPLETED
|
0
|
0
|
26
|
138
|
|
Treatment Period 3
NOT COMPLETED
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Albuterol HFA First, Then Combivent CFC
Albuterol Hydrofluoroalkene, Combivent Chlorofluorocarbon
|
Combivent CFC First, Then Albuterol HFA
Combivent Chlorofluorocarbon, Albuterol Hydrofluoroalkene
|
Placebo Respimat
Placebo Respimat (matching Combivent Respimat)
|
Combivent Respimat
Combivent Respimat (contains the effective dose of albuterol)
|
|---|---|---|---|---|
|
Treatment Period 1
Adverse Event
|
0
|
1
|
0
|
0
|
|
Treatment Period 1
Other
|
3
|
0
|
0
|
0
|
|
Washout Period of 1 Week
Adverse Event
|
1
|
1
|
0
|
0
|
|
Washout Period of 1 Week
Protocol Violation
|
2
|
0
|
0
|
0
|
|
Washout Period of 1 Week
Other
|
1
|
2
|
0
|
0
|
|
Treatment Period 2
Other
|
2
|
1
|
0
|
0
|
|
Treatment Period 3
Adverse Event
|
0
|
0
|
0
|
1
|
Baseline Characteristics
4 Week 2 Way Crossover Double Blind Treatment Phase With Combivent CFC Versus Albuterol Followed by a 4 Week Open Label Combivent Respimat When All Drugs Are Used for Symptom Relief as Needed in Pts With Moderate to Severe Asthma
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=226 Participants
Participants randomized to crossover part at randomization 1
|
|---|---|
|
Age, Continuous
|
47.1 Years
STANDARD_DEVIATION 13.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
130 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
96 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
215 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Amer. Ind./Alaska Nat
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black/African Amer.
|
44 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hawaiian/Pacif. Isle
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
174 Participants
n=5 Participants
|
|
Body mass index
|
31.1 Kilograms per square meter
STANDARD_DEVIATION 6.7 • n=5 Participants
|
|
Smoking history
Never smoked
|
163 Participants
n=5 Participants
|
|
Smoking history
Ex-smoker
|
63 Participants
n=5 Participants
|
|
Smoking history
Currently smokes
|
0 Participants
n=5 Participants
|
|
Alcohol history
Non drinker
|
76 Participants
n=5 Participants
|
|
Alcohol history
Drinks - no interference
|
150 Participants
n=5 Participants
|
|
Alcohol history
Drinks - possible interference
|
0 Participants
n=5 Participants
|
|
Height
|
169.9 Centimeters
STANDARD_DEVIATION 11.0 • n=5 Participants
|
|
Weight
|
89.9 Kilograms
STANDARD_DEVIATION 21.0 • n=5 Participants
|
PRIMARY outcome
Timeframe: Test day baseline and test day FEV1 AUC 0-6, after 4 weeksPopulation: Full analysis set 1 (FAS1) consisted of all patients who were dispensed study medication, were documented to have taken at least one dose of investigational treatment, and had non-missing Visit 3 baseline values and non-missing responses for both peak FEV1 and FEV1 AUC0-6 at Visit 3.
Change from baseline after 4 weeks in Forced Expiratory Volume Area Under (FEV1 AUC) the Curve from 0 to 6 hours.
Outcome measures
| Measure |
Albuterol HFA
n=191 Participants
Albuterol Hydrofluoroalkene
|
Combivent CFC
n=193 Participants
Combivent Chlorofluorocarbon
|
|---|---|---|
|
FEV1 AUC0-6 Response (Crossover Part of the Study)
|
0.167 liters
Standard Error 0.026
|
0.252 liters
Standard Error 0.026
|
PRIMARY outcome
Timeframe: Test day baseline and test day peak FEV1, after 4 weeksPopulation: Full analysis set 1 (FAS1) consisted of all patients who were dispensed study medication, were documented to have taken at least one dose of investigational treatment, and had non-missing Visit 3 baseline values and non-missing responses for both peak FEV1 and FEV1 AUC0-6 at Visit 3.
Change from baseline after 4 weeks in peak Forced Expiratory Volume response
Outcome measures
| Measure |
Albuterol HFA
n=191 Participants
Albuterol Hydrofluoroalkene
|
Combivent CFC
n=193 Participants
Combivent Chlorofluorocarbon
|
|---|---|---|
|
Peak FEV1 Response (Crossover Part of the Study)
|
0.357 liters
Standard Error 0.031
|
0.434 liters
Standard Error 0.031
|
SECONDARY outcome
Timeframe: Baseline, 4 weeksPopulation: Full analysis set 1 (FAS1) consisted of all patients who were dispensed study medication, were documented to have taken at least one dose of investigational treatment, and had non-missing Visit 3 baseline values and non-missing responses for both peak FEV1 and FEV1 AUC0-6 at Visit 3.
Change from baseline after 4 weeks in Mini-AQLQ score. Worst score - 1 (most severe), best score - 7 (less severe)
Outcome measures
| Measure |
Albuterol HFA
n=191 Participants
Albuterol Hydrofluoroalkene
|
Combivent CFC
n=193 Participants
Combivent Chlorofluorocarbon
|
|---|---|---|
|
Mini Asthma Quality of Life Questionnaire (Crossover Part of the Study)
|
0.150 Scores on scale
Standard Error 0.05
|
0.220 Scores on scale
Standard Error 0.05
|
SECONDARY outcome
Timeframe: Baseline, 4 weeksPopulation: Full analysis set 1 (FAS1) consisted of all patients who were dispensed study medication, were documented to have taken at least one dose of investigational treatment, and had non-missing Visit 3 baseline values and non-missing responses for both peak FEV1 and FEV1 AUC0-6 at Visit 3.
Change from baseline after 4 weeks in ACQ score. Worst score - 6(most severe), best score - 0 (no symptoms)
Outcome measures
| Measure |
Albuterol HFA
n=191 Participants
Albuterol Hydrofluoroalkene
|
Combivent CFC
n=193 Participants
Combivent Chlorofluorocarbon
|
|---|---|---|
|
Asthma Control Questionnaire (Crossover Part of the Study)
|
-0.25 Scores on scale
Standard Error 0.04
|
-0.25 Scores on scale
Standard Error 0.04
|
SECONDARY outcome
Timeframe: Baseline, 4 weeksPopulation: Full analysis set 1 (FAS1) consisted of all patients who were dispensed study medication, were documented to have taken at least one dose of investigational treatment, and had non-missing Visit 3 baseline values and non-missing responses for both peak FEV1 and FEV1 AUC0-6 at Visit 3.
Change from baseline in weekly mean of puffs of blinded study medication (albuterol HFA or combivent CFC) used during day
Outcome measures
| Measure |
Albuterol HFA
n=176 Participants
Albuterol Hydrofluoroalkene
|
Combivent CFC
n=178 Participants
Combivent Chlorofluorocarbon
|
|---|---|---|
|
Puffs Study Medication Used During Day (Crossover Part of the Study)
|
-0.49 Puffs
Standard Error 0.07
|
-0.53 Puffs
Standard Error 0.07
|
SECONDARY outcome
Timeframe: Baseline, 4 weeksPopulation: Full analysis set 1 (FAS1) consisted of all patients who were dispensed study medication, were documented to have taken at least one dose of investigational treatment, and had non-missing Visit 3 baseline values and non-missing responses for both peak FEV1 and FEV1 AUC0-6 at Visit 3.
Change from baseline in weekly mean of puffs of blinded study medication (albuterol HFA or combivent CFC) used during night
Outcome measures
| Measure |
Albuterol HFA
n=178 Participants
Albuterol Hydrofluoroalkene
|
Combivent CFC
n=180 Participants
Combivent Chlorofluorocarbon
|
|---|---|---|
|
Puffs Study Medication Used During Night (Crossover Part of the Study)
|
-0.10 Puffs
Standard Error 0.05
|
-0.12 Puffs
Standard Error 0.05
|
SECONDARY outcome
Timeframe: Baseline, 4 weeksPopulation: Full analysis set 1 (FAS1) consisted of all patients who were dispensed study medication, were documented to have taken at least one dose of investigational treatment, and had non-missing Visit 3 baseline values and non-missing responses for both peak FEV1 and FEV1 AUC0-6 at Visit 3.
Change from baseline in weekly mean of puffs of open-label albuterol used during day
Outcome measures
| Measure |
Albuterol HFA
n=176 Participants
Albuterol Hydrofluoroalkene
|
Combivent CFC
n=178 Participants
Combivent Chlorofluorocarbon
|
|---|---|---|
|
Puffs Open-label Albuterol Used During Day (Crossover Part of the Study)
|
-2.24 Puffs
Standard Error 0.05
|
-2.28 Puffs
Standard Error 0.05
|
SECONDARY outcome
Timeframe: Baseline, 4 weeksPopulation: Full analysis set 1 (FAS1) consisted of all patients who were dispensed study medication, were documented to have taken at least one dose of investigational treatment, and had non-missing Visit 3 baseline values and non-missing responses for both peak FEV1 and FEV1 AUC0-6 at Visit 3.
Change from baseline in weekly mean of puffs of open-label albuterol used during night
Outcome measures
| Measure |
Albuterol HFA
n=178 Participants
Albuterol Hydrofluoroalkene
|
Combivent CFC
n=180 Participants
Combivent Chlorofluorocarbon
|
|---|---|---|
|
Puffs Open-label Albuterol Used During Night (Crossover Part of the Study)
|
-0.92 Puffs
Standard Error 0.02
|
-0.93 Puffs
Standard Error 0.02
|
SECONDARY outcome
Timeframe: Test day baseline and test day FEV1 AUC 0-6, after 4 weeksPopulation: These analyses were done on FAS2. FAS2 is all patients who were dispensed study medication, were documented to have taken at least one dose of investigational treatment, and had a non-missing Visit 7 baseline value and non-missing responses for both peak FEV1 and FEV1 AUC0-6 at Visit 7.
Change from baseline after 4 weeks in Forced Expiratory Volume Area Under the Curve from 0 to 6 hours
Outcome measures
| Measure |
Albuterol HFA
n=26 Participants
Albuterol Hydrofluoroalkene
|
Combivent CFC
n=139 Participants
Combivent Chlorofluorocarbon
|
|---|---|---|
|
FEV1 AUC0-6 Response (Parallel Part of the Study)
|
0.041 liters
Standard Error 0.046
|
0.236 liters
Standard Error 0.020
|
SECONDARY outcome
Timeframe: Test day baseline and test day peak FEV1, after 4 weeksPopulation: These analyses were done on FAS2. FAS2 is all patients who were dispensed study medication, were documented to have taken at least one dose of investigational treatment, and had a non-missing Visit 7 baseline value and non-missing responses for both peak FEV1 and FEV1 AUC0-6 at Visit 7.
Change from baseline after 4 weeks in peak Forced Expiratory Volume response
Outcome measures
| Measure |
Albuterol HFA
n=26 Participants
Albuterol Hydrofluoroalkene
|
Combivent CFC
n=139 Participants
Combivent Chlorofluorocarbon
|
|---|---|---|
|
Peak FEV1 Response
|
0.199 liters
Standard Error 0.053
|
0.412 liters
Standard Error 0.023
|
Adverse Events
Albuterol HFA First, Then Combivent CFC
Combivent CFC First, Then Albuterol HFA
Placebo Respimat
Combivent Respimat
Serious adverse events
| Measure |
Albuterol HFA First, Then Combivent CFC
n=222 participants at risk
Albuterol Hydrofluoroalkene, Combivent Chlorofluorocarbon
|
Combivent CFC First, Then Albuterol HFA
n=219 participants at risk
Combivent Chlorofluorocarbon, Albuterol Hydrofluoroalkene
|
Placebo Respimat
n=26 participants at risk
Placebo Respimat (matching Combivent Respimat)
|
Combivent Respimat
n=139 participants at risk
Combivent Respimat (contains the effective dose of albuterol)
|
|---|---|---|---|---|
|
Infections and infestations
Cellulitis
|
0.45%
1/222 • 29 days (Treatment phase 1) + 29 days (Treatment phase 2) + 29 days (Treatment phase 3)
|
0.00%
0/219 • 29 days (Treatment phase 1) + 29 days (Treatment phase 2) + 29 days (Treatment phase 3)
|
0.00%
0/26 • 29 days (Treatment phase 1) + 29 days (Treatment phase 2) + 29 days (Treatment phase 3)
|
0.00%
0/139 • 29 days (Treatment phase 1) + 29 days (Treatment phase 2) + 29 days (Treatment phase 3)
|
|
Infections and infestations
Staphylococcal infection
|
0.45%
1/222 • 29 days (Treatment phase 1) + 29 days (Treatment phase 2) + 29 days (Treatment phase 3)
|
0.00%
0/219 • 29 days (Treatment phase 1) + 29 days (Treatment phase 2) + 29 days (Treatment phase 3)
|
0.00%
0/26 • 29 days (Treatment phase 1) + 29 days (Treatment phase 2) + 29 days (Treatment phase 3)
|
0.00%
0/139 • 29 days (Treatment phase 1) + 29 days (Treatment phase 2) + 29 days (Treatment phase 3)
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/222 • 29 days (Treatment phase 1) + 29 days (Treatment phase 2) + 29 days (Treatment phase 3)
|
0.46%
1/219 • 29 days (Treatment phase 1) + 29 days (Treatment phase 2) + 29 days (Treatment phase 3)
|
0.00%
0/26 • 29 days (Treatment phase 1) + 29 days (Treatment phase 2) + 29 days (Treatment phase 3)
|
0.00%
0/139 • 29 days (Treatment phase 1) + 29 days (Treatment phase 2) + 29 days (Treatment phase 3)
|
Other adverse events
| Measure |
Albuterol HFA First, Then Combivent CFC
n=222 participants at risk
Albuterol Hydrofluoroalkene, Combivent Chlorofluorocarbon
|
Combivent CFC First, Then Albuterol HFA
n=219 participants at risk
Combivent Chlorofluorocarbon, Albuterol Hydrofluoroalkene
|
Placebo Respimat
n=26 participants at risk
Placebo Respimat (matching Combivent Respimat)
|
Combivent Respimat
n=139 participants at risk
Combivent Respimat (contains the effective dose of albuterol)
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.45%
1/222 • 29 days (Treatment phase 1) + 29 days (Treatment phase 2) + 29 days (Treatment phase 3)
|
5.0%
11/219 • 29 days (Treatment phase 1) + 29 days (Treatment phase 2) + 29 days (Treatment phase 3)
|
0.00%
0/26 • 29 days (Treatment phase 1) + 29 days (Treatment phase 2) + 29 days (Treatment phase 3)
|
0.00%
0/139 • 29 days (Treatment phase 1) + 29 days (Treatment phase 2) + 29 days (Treatment phase 3)
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
- Publication restrictions are in place
Restriction type: OTHER