Trial Outcomes & Findings for Efficacy and Safety of 2 Doses of Tiotropium Via Respimat in Adult Patients With Mild Persistent Asthma (NCT NCT01316380)

NCT ID: NCT01316380

Last Updated: 2015-04-15

Results Overview

Peak FEV1 0-3h response was defined as the difference between the maximum FEV1 measured within the first 3 hours post dosing after a treatment period of 12 weeks and the FEV1 baseline measurement (10 minutes before the first dose of trial medication). Mixed Model Repeated Measure (MMRM) results. Means are adjusted for treatment, pooled centre, visit, baseline, treatment\*visit and baseline\*visit.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 465 participants
• Primary outcome timeframe: Baseline and 12 weeks
• Results posted on: 2015-04-15

Participant Flow

Participant milestones

Measure	Placebo Patients treated with matching placebo	Tio R2.5 Patients treated with tiotropium inhalation solution 2.5 microgram qd	Tio R5 Patients treated with tiotropium inhalation solution 5 microgram qd
Overall Study STARTED	156	154	155
Overall Study COMPLETED	154	149	152
Overall Study NOT COMPLETED	2	5	3

Reasons for withdrawal

Measure	Placebo Patients treated with matching placebo	Tio R2.5 Patients treated with tiotropium inhalation solution 2.5 microgram qd	Tio R5 Patients treated with tiotropium inhalation solution 5 microgram qd
Overall Study Adverse Event	0	2	1
Overall Study Protocol Violation	0	0	1
Overall Study Withdrawal by Subject	1	2	0
Overall Study Other	0	1	1
Overall Study Not treated	1	0	0

Baseline Characteristics

Efficacy and Safety of 2 Doses of Tiotropium Via Respimat in Adult Patients With Mild Persistent Asthma

Baseline characteristics by cohort

Measure	Placebo n=155 Participants Patients treated with matching placebo	Tio R2.5 n=154 Participants Patients treated with tiotropium inhalation solution 2.5 microgram qd	Tio R5 n=155 Participants Patients treated with tiotropium inhalation solution 5 microgram qd	Total n=464 Participants Total of all reporting groups
Age, Continuous	42.8 Years STANDARD_DEVIATION 12.1 • n=5 Participants	43.8 Years STANDARD_DEVIATION 14.0 • n=7 Participants	41.9 Years STANDARD_DEVIATION 13.0 • n=5 Participants	42.9 Years STANDARD_DEVIATION 13 • n=4 Participants
Sex: Female, Male Female	103 Participants n=5 Participants	82 Participants n=7 Participants	96 Participants n=5 Participants	281 Participants n=4 Participants
Sex: Female, Male Male	52 Participants n=5 Participants	72 Participants n=7 Participants	59 Participants n=5 Participants	183 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and 12 weeks

Population: All patients from Full Analysis Set (FAS) FAS is defined as all patients in the treated set who received at least one dose of randomized trial medication.

Peak FEV1 0-3h response was defined as the difference between the maximum FEV1 measured within the first 3 hours post dosing after a treatment period of 12 weeks and the FEV1 baseline measurement (10 minutes before the first dose of trial medication). Mixed Model Repeated Measure (MMRM) results. Means are adjusted for treatment, pooled centre, visit, baseline, treatment*visit and baseline*visit.

Outcome measures

Measure	Placebo n=154 Participants Patients treated with matching placebo	Tio R2.5 n=151 Participants Patients treated with tiotropium inhalation solution 2.5 microgram qd	Tio R5 n=152 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Peak Forced Expiratory Volume in 1 Second (FEV1) Response Within 3 Hours Post Dosing (0-3h) After a Treatment Period of 12 Weeks.	0.134 Liter Standard Error 0.026	0.293 Liter Standard Error 0.026	0.262 Liter Standard Error 0.026

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: All patients from FAS.

The trough FEV1 is defined as the pre-dose FEV1 measured 10 minutes before the last administration of randomised treatment. Trough FEV1 response was defined as the difference between the trough FEV1 measured after a treatment period of 12 weeks and the trough FEV1 baseline measurement. MMRM results. Means are adjusted for treatment, pooled centre, visit, baseline, treatment*visit and baseline*visit.

Outcome measures

Measure	Placebo n=154 Participants Patients treated with matching placebo	Tio R2.5 n=151 Participants Patients treated with tiotropium inhalation solution 2.5 microgram qd	Tio R5 n=152 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Trough FEV1 Response Determined After a Treatment Period of 12 Weeks.	0.015 Liter Standard Error 0.026	0.125 Liter Standard Error 0.026	0.137 Liter Standard Error 0.027

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: All patients from FAS.

Peak FVC 0-3h response was defined as the difference between the maximum FVC measured within the first 3 hours post dosing after a treatment period of 12 weeks and the FVC baseline measurement (10 minutes before the first dose of trial medication). Mixed Model Repeated Measure (MMRM) results. Means are adjusted for treatment, pooled centre, visit, baseline, treatment*visit and baseline*visit.

Outcome measures

Measure	Placebo n=154 Participants Patients treated with matching placebo	Tio R2.5 n=151 Participants Patients treated with tiotropium inhalation solution 2.5 microgram qd	Tio R5 n=152 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Peak (Within 3 Hours Post-dosing) Forced Vital Capacity (FVC) Response at the End of the 12-week Treatment Period.	0.126 Liter Standard Error 0.030	0.231 Liter Standard Error 0.030	0.183 Liter Standard Error 0.03

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: All patients from FAS.

The AUC0-3h was calculated as area under the curve from zero to 3 hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. The trough value was assigned to zero time. Response was defined as change from baseline in FEV1 AUC0-3h after a treatment period of 12 weeks. MMRM results. Means are adjusted for treatment, pooled centre, visit, baseline, treatment*visit baseline*visit.

Outcome measures

Measure	Placebo n=154 Participants Patients treated with matching placebo	Tio R2.5 n=151 Participants Patients treated with tiotropium inhalation solution 2.5 microgram qd	Tio R5 n=152 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
FEV1 Area Under the Curve (AUC0-3h) Response at the End of the 12-week Treatment Period.	0.048 Liter Standard Error 0.024	0.198 Liter Standard Error 0.024	0.174 Liter Standard Error 0.025

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: All patients from FAS.

The AUC0-3h was calculated as area under the curve from zero to 3 hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. The trough value was assigned to zero time. Response was defined as change from baseline in FVC AUC0-3h after a treatment period of 12 weeks. MMRM results. Means are adjusted for treatment, pooled centre, visit, baseline, treatment*visit baseline*visit.

Outcome measures

Measure	Placebo n=154 Participants Patients treated with matching placebo	Tio R2.5 n=151 Participants Patients treated with tiotropium inhalation solution 2.5 microgram qd	Tio R5 n=152 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
FVC (AUC0-3h) Response at the End of the 12-week Treatment Period.	-0.000 Liter Standard Error 0.028	0.101 Liter Standard Error 0.028	0.061 Liter Standard Error 0.028

SECONDARY outcome

Timeframe: 12 weeks

Population: All patients from FAS.

For the ACQ, the total score was calculated as the mean of the responses to 6 self administered questions and one question which was completed by clinical staff based upon pre-bronchodilator FEV1. The score ranges from 0 (no impairment) to 6 (maximum impairment). Response was categorised as: responder (change from baseline <= -0.5), no change (-0.5 <change from baseline < 0.5) and worsening (change from baseline >= 0.5).

Outcome measures

Measure	Placebo n=154 Participants Patients treated with matching placebo	Tio R2.5 n=149 Participants Patients treated with tiotropium inhalation solution 2.5 microgram qd	Tio R5 n=152 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Asthma Control Questionnaire (ACQ) Responder After 12 Weeks of Treatment Responder	91 Number of patients	91 Number of patients	90 Number of patients
Asthma Control Questionnaire (ACQ) Responder After 12 Weeks of Treatment No change	61 Number of patients	48 Number of patients	57 Number of patients
Asthma Control Questionnaire (ACQ) Responder After 12 Weeks of Treatment Worsening	2 Number of patients	10 Number of patients	5 Number of patients

SECONDARY outcome

Timeframe: 12 weeks

Population: All patients from FAS.

Severe asthma exacerbations are defined as all asthma exacerbations that required treatment with systemic (including oral) corticosteroids for at least 3 days.

Outcome measures

Measure	Placebo n=155 Participants Patients treated with matching placebo	Tio R2.5 n=154 Participants Patients treated with tiotropium inhalation solution 2.5 microgram qd	Tio R5 n=155 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Time to First Severe Asthma Exacerbation During the 12-week Treatment.	NA Days Since only 4 of the 155 patients in the placebo group, 6 of the 154 patients in the Tio R2.5 group and 1 of the 155 patients in the Tio R5 group had severe exacerbations, the median times were not calculable (nc).	NA Days Since only 4 of the 155 patients in the placebo group, 6 of the 154 patients in the Tio R2.5 group and 1 of the 155 patients in the Tio R5 group had severe exacerbations, the median times were not calculable (nc).	NA Days Since only 4 of the 155 patients in the placebo group, 6 of the 154 patients in the Tio R2.5 group and 1 of the 155 patients in the Tio R5 group had severe exacerbations, the median times were not calculable (nc).

SECONDARY outcome

Timeframe: 12 weeks

Population: All patients from FAS.

An asthma exacerbation was defined as an episode of progressive increase in 1 or more asthma symptom that were outside the patient's usual range of day-to-day asthma symptoms and lasted for at least 2 consecutive days or as a decrease in a patient's best morning PEF of 30% or more from a patient's mean morning PEF for at least 2 consecutive days that may or may not have been accompanied by symptoms.

Outcome measures

Measure	Placebo n=155 Participants Patients treated with matching placebo	Tio R2.5 n=154 Participants Patients treated with tiotropium inhalation solution 2.5 microgram qd	Tio R5 n=155 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Time to First Asthma Exacerbation During the 12-week Treatment.	NA Days Interval 87.0 to Since 22 of the 155 in the placebo group, 21 of the 154 patients in the Tio R2.5 group and 13 of the 155 patients in the Tio R5 group reported at least one asthma exacerbation, the median times were not calculable (nc).	NA Days Since 22 of the 155 in the placebo group, 21 of the 154 patients in the Tio R2.5 group and 13 of the 155 patients in the Tio R5 group reported at least one asthma exacerbation, the median times were not calculable (nc).	NA Days Since 22 of the 155 in the placebo group, 21 of the 154 patients in the Tio R2.5 group and 13 of the 155 patients in the Tio R5 group reported at least one asthma exacerbation, the median times were not calculable (nc).

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: All patients from FAS.

Use of PRN (pro re nata, or as necessary) salbutamol/albuterol rescue medication (puffs during 24 h period), determined as a weekly mean response from baseline for each week during the treatment period as well as for the last 7 days before treatment stop/Visit 5.

The mean was adjusted for treatment, centre, week, baseline, treatment*week and baseline*week.

Outcome measures

Measure	Placebo n=153 Participants Patients treated with matching placebo	Tio R2.5 n=150 Participants Patients treated with tiotropium inhalation solution 2.5 microgram qd	Tio R5 n=152 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Use of Rescue Medication During 24h Period	-0.815 puffs of rescue medication Standard Error 0.093	-0.594 puffs of rescue medication Standard Error 0.093	-0.848 puffs of rescue medication Standard Error 0.093

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: All patients from FAS.

Use of PRN (pro re nata, or as necessary) salbutamol/albuterol rescue medication (puffs during daytime), determined as a weekly mean response from baseline for each week during the treatment period as well as for the last 7 days before treatment stop/Visit 5.

The mean was adjusted for treatment, centre, week, baseline, treatment*week and baseline*week.

Outcome measures

Measure	Placebo n=153 Participants Patients treated with matching placebo	Tio R2.5 n=149 Participants Patients treated with tiotropium inhalation solution 2.5 microgram qd	Tio R5 n=152 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Use of Rescue Medication During Daytime	-0.428 puffs of rescue medication Standard Error 0.055	-0.331 puffs of rescue medication Standard Error 0.055	-0.436 puffs of rescue medication Standard Error 0.055

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: All patients from FAS.

Use of PRN (pro re nata, or as necessary) salbutamol/albuterol rescue medication (puffs during nighttime), determined as a weekly mean response from baseline for each week during the treatment period as well as for the last 7 days before treatment stop/Visit 5.

The mean was adjusted for treatment, centre, week, baseline, treatment*week and baseline*week.

Outcome measures

Measure	Placebo n=152 Participants Patients treated with matching placebo	Tio R2.5 n=150 Participants Patients treated with tiotropium inhalation solution 2.5 microgram qd	Tio R5 n=152 Participants Patients treated with tiotropium inhalation solution 5 microgram qd
Use of Rescue Medication During Nighttime	-0.376 puffs of rescue medication Standard Error 0.049	-0.245 puffs of rescue medication Standard Error 0.049	-0.386 puffs of rescue medication Standard Error 0.049

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

Tio R2.5

Serious events: 0 serious events

Other events: 30 other events

Deaths: 0 deaths

Tio R5

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=155 participants at risk Enter description here, if needed	Tio R2.5 n=154 participants at risk Enter description here, if needed	Tio R5 n=155 participants at risk Enter description here, if needed
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer in situ	0.00% 0/155 • 12 weeks	0.00% 0/154 • 12 weeks	0.65% 1/155 • 12 weeks
Respiratory, thoracic and mediastinal disorders Asthma	0.65% 1/155 • 12 weeks	0.00% 0/154 • 12 weeks	0.00% 0/155 • 12 weeks

Other adverse events

Measure	Placebo n=155 participants at risk Enter description here, if needed	Tio R2.5 n=154 participants at risk Enter description here, if needed	Tio R5 n=155 participants at risk Enter description here, if needed
Respiratory, thoracic and mediastinal disorders Asthma	12.3% 19/155 • 12 weeks	15.6% 24/154 • 12 weeks	11.0% 17/155 • 12 weeks
Investigations Peak expiratory flow rate decreased	3.9% 6/155 • 12 weeks	5.8% 9/154 • 12 weeks	3.9% 6/155 • 12 weeks

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

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