Trial Outcomes & Findings for Tiotropium Bromide in Cystic Fibrosis (NCT NCT01179347)

Last Updated: 2013-12-24

Results Overview

Mixed Model Repeated Measurement (MMRM) results. Response was defined as change from baseline in percent of predicted at the end of 12-week double-blind treatment period and is therefore expressed in percent of predicted. Means are adjusted for treatment, visit, treatment-by-visit interaction, age group (\<= 11, \>=12), baseline and baseline-by-visit interaction. FEV1 AUC0-4h was normalised for time and was calculated using the trapezoidal rule divided by the observation time (4 h).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

464 participants

Primary outcome timeframe

30 minutes (min) before first dosing of study drug (defined as baseline), at 1 hour (h), 2 h , 3 h, and 4 h post dosing at day 1 and at 30 min before dosing, at 1 hour, 2 h , 3 h, and 4 h post dosing after 12 weeks.

Results posted on

2013-12-24

Participant Flow

First part: double-blind, duration was 12 weeks, 464 patients were randomised to either Tio R5 or placebo in a 2:1 ratio, but 1 randomised patient was not treated. Second part: open-label, all patients received the active treatment for a minimum of 12 weeks to enlarge the safety database.

Participant milestones

Participant milestones
Measure	Placebo Matching Placebo once daily (qd) delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.	Tio R5 qd Tiotropium 5 mcg qd delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.
Double-blind Period (12 Weeks) STARTED	155	308
Double-blind Period (12 Weeks) COMPLETED	147	294
Double-blind Period (12 Weeks) NOT COMPLETED	8	14
Open-label Period (12 Weeks) STARTED	147	294
Open-label Period (12 Weeks) COMPLETED	132	278
Open-label Period (12 Weeks) NOT COMPLETED	15	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Matching Placebo once daily (qd) delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.	Tio R5 qd Tiotropium 5 mcg qd delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.
Double-blind Period (12 Weeks) Adverse Event	2	6
Double-blind Period (12 Weeks) Protocol Violation	2	0
Double-blind Period (12 Weeks) Lost to Follow-up	1	2
Double-blind Period (12 Weeks) Withdrawal by Subject	1	2
Double-blind Period (12 Weeks) Other	2	4
Open-label Period (12 Weeks) Adverse Event	5	9
Open-label Period (12 Weeks) Lack of Efficacy	0	2
Open-label Period (12 Weeks) Lost to Follow-up	1	0
Open-label Period (12 Weeks) Withdrawal by Subject	1	1
Open-label Period (12 Weeks) Protocol Violation	1	0
Open-label Period (12 Weeks) Other	7	4

Baseline Characteristics

Tiotropium Bromide in Cystic Fibrosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=155 Participants Matching Placebo once daily (qd) delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.	Tio R5 qd n=308 Participants Tiotropium 5 mcg qd delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.	Total n=463 Participants Total of all reporting groups
Age, Continuous	20.6 years STANDARD_DEVIATION 13.6 • n=5 Participants	19.3 years STANDARD_DEVIATION 12.0 • n=7 Participants	19.8 years STANDARD_DEVIATION 12.5 • n=5 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	139 Participants n=7 Participants	204 Participants n=5 Participants
Sex: Female, Male Male	90 Participants n=5 Participants	169 Participants n=7 Participants	259 Participants n=5 Participants

PRIMARY outcome

Timeframe: 30 minutes (min) before first dosing of study drug (defined as baseline), at 1 hour (h), 2 h , 3 h, and 4 h post dosing at day 1 and at 30 min before dosing, at 1 hour, 2 h , 3 h, and 4 h post dosing after 12 weeks.

Population: Full Analysis Set (FAS) with imputation reduced to patients with observed wash-out compliance. The FAS was defined as all patients in the treated set who had at least 1 baseline pulmonary function test (PFT) measurement and at least 1 post-baseline on-treatment PFT measurement. No patients \<5 years of age were included in the FAS.

Outcome measures

Outcome measures
Measure	Placebo n=146 Participants Matching Placebo once daily (qd) delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.	Tio R5 qd n=292 Participants Tiotropium 5 mcg qd delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.
Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve 0-4 Hours (AUC0-4h) Response	0.87 Percent of predicted Standard Error 0.80	2.51 Percent of predicted Standard Error 0.57

PRIMARY outcome

Timeframe: Baseline and 12 weeks

MMRM results. Response was defined as change from baseline in percent of predicted at the end of 12-week double-blind treatment period and is therefore expressed in percent of predicted. Trough FEV1 was defined as the pre-dose FEV1 measured just prior to the administration of randomised treatment. Means are adjusted for treatment, visit, treatment-by-visit interaction, age group (\<= 11, \>=12), baseline and baseline-by-visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Matching Placebo once daily (qd) delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.	Tio R5 qd n=287 Participants Tiotropium 5 mcg qd delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.
Trough FEV1 Response	0.72 Percent of predicted Standard Error 0.80	2.12 Percent of predicted Standard Error 0.58

SECONDARY outcome

MMRM results. Response was defined as change from baseline in percent of predicted at the end of 12-week double-blind treatment period and is therefore expressed in percent of predicted. Means are adjusted for treatment, visit, treatment-by-visit interaction, age group (\<= 11, \>=12), baseline and baseline-by-visit interaction. FVC AUC0-4h was normalised for time and was calculated using the trapezoidal rule divided by the observation time (4 h).

Outcome measures

Outcome measures
Measure	Placebo n=137 Participants Matching Placebo once daily (qd) delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.	Tio R5 qd n=282 Participants Tiotropium 5 mcg qd delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.
Forced Vital Capacity (FVC) Area Under the Curve 0-4 Hours (AUC0-4h) Response	0.17 Percent of predicted Standard Error 0.75	1.27 Percent of predicted Standard Error 0.53

SECONDARY outcome

Timeframe: Baseline and 12 weeks

MMRM results. Response was defined as change from baseline in percent of predicted at the end of 12-week double-blind treatment period and is therefore expressed in percent of predicted. Trough FCV was defined as the pre-dose FVC measured just prior to the administration of randomised treatment. Means are adjusted for treatment, visit, treatment-by-visit interaction, age group (\<= 11, \>=12), baseline and baseline-by-visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=135 Participants Matching Placebo once daily (qd) delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.	Tio R5 qd n=277 Participants Tiotropium 5 mcg qd delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.
Trough FVC Response	0.30 Percent of predicted Standard Error 0.77	1.51 Percent of predicted Standard Error 0.55

SECONDARY outcome

Timeframe: Baseline and 12 weeks

MMRM results. Response was defined as change from baseline in percent of predicted at the end of 12-week double-blind treatment period and is therefore expressed in percent of predicted. FEF25-75 is also known as maximum mid-expiratory flow and was measured before bronchodilator (salbutamol) use. Means are adjusted for treatment, visit, treatment-by-visit interaction, age group (\<= 11, \>=12), baseline and baseline-by-visit interaction.

Outcome measures

Outcome measures
Measure	Placebo n=135 Participants Matching Placebo once daily (qd) delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.	Tio R5 qd n=277 Participants Tiotropium 5 mcg qd delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.
Pre-bronchodilator Forced Expiratory Flow Between 25 Percent and 75 Percent of the FVC (FEF25-75) Response	2.15 Percent of predicted Standard Error 1.48	3.02 Percent of predicted Standard Error 1.05

SECONDARY outcome

Timeframe: 12 weeks

Population: FAS reduced to patients having RSSQ information on day 29, 57 or 85.

Selected questions from the Respiratory and Systemic Symptoms Questionnaire (RSSQ), the investigator assessment of physical findings and pulmonary function, and the use of intravenous antibiotics as a concomitant therapy were used to determine if a cystic fibrosis-related pulmonary exacerbation had occurred.

Outcome measures

Outcome measures
Measure	Placebo n=102 Participants Matching Placebo once daily (qd) delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.	Tio R5 qd n=214 Participants Tiotropium 5 mcg qd delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.
Percentage of Participants With at Least 1 Pulmonary Exacerbation During Double-blind Treatment	7.8 Percentage of Participants	8.9 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: FAS reduced to patients having CFQ-R information at baseline and at week 12.

Different format of CFQ-R are used depending of the patients' age. Adolescent and adult format of CFQ-R is used for patients of 14 years and older, for younger children a parent version and a children format is used. In case parent and children questionnaires were filled out, the children questionnaire is taken into account. Scores were calculated for each domain of the CFQ-R which are presented separately. A score of 100 corresponds to the highest quality of life possible, whereas a score of 0 corresponds to the lowest quality of life possible. Increasing score indicates better health.

Outcome measures

Outcome measures
Measure	Placebo n=130 Participants Matching Placebo once daily (qd) delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.	Tio R5 qd n=255 Participants Tiotropium 5 mcg qd delivered by the Respimat inhaler as add-on therapy to usual care in patients with cystic fibrosis.
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Adolescents: Physical (N=83, N=162)	-0.85 Units on a scale Standard Deviation 14.40	-0.15 Units on a scale Standard Deviation 12.95
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Adolescents: Role (N=78, N=157)	0.85 Units on a scale Standard Deviation 12.99	-0.42 Units on a scale Standard Deviation 13.30
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Adolescents: Vitality (N=82, N=161)	-1.22 Units on a scale Standard Deviation 18.06	0.05 Units on a scale Standard Deviation 14.08
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Adolescents: Emotion (N=82, N=161)	-1.54 Units on a scale Standard Deviation 12.05	-0.99 Units on a scale Standard Deviation 12.96
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Adolescents: Social (N=82, N=159)	-1.69 Units on a scale Standard Deviation 10.09	0.70 Units on a scale Standard Deviation 10.19
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Adolescents: Body Image (N=82, N=159)	0.14 Units on a scale Standard Deviation 16.14	3.14 Units on a scale Standard Deviation 15.11
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Adolescents: Eating (N=82, N=161)	-1.49 Units on a scale Standard Deviation 14.89	1.38 Units on a scale Standard Deviation 10.74
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Adolescents: Treatment burden (N=82, N=160)	0.95 Units on a scale Standard Deviation 14.73	0.56 Units on a scale Standard Deviation 14.84
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Adolescents: Health perseptions (N=82, N=159)	-0.81 Units on a scale Standard Deviation 13.83	0.77 Units on a scale Standard Deviation 16.68
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Adolescents: Weight (N=80, N=160)	-2.08 Units on a scale Standard Deviation 29.22	3.75 Units on a scale Standard Deviation 26.96
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Adolescents: Respiratory (N=80, N=159)	0.97 Units on a scale Standard Deviation 13.83	-0.77 Units on a scale Standard Deviation 15.19
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Adolescents: Digestion (N=80, N=159)	-0.83 Units on a scale Standard Deviation 17.03	0.49 Units on a scale Standard Deviation 12.40
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Children: Physical (N=47, N=93)	-2.84 Units on a scale Standard Deviation 15.67	1.43 Units on a scale Standard Deviation 15.19
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Children: Social (N=46, N=93)	2.80 Units on a scale Standard Deviation 15.73	1.59 Units on a scale Standard Deviation 15.70
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Children: Body Image (N=46, N=93)	-1.21 Units on a scale Standard Deviation 18.48	4.66 Units on a scale Standard Deviation 25.71
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Children: Emotion (N=47, N=93)	-1.24 Units on a scale Standard Deviation 12.83	1.12 Units on a scale Standard Deviation 12.18
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Children: Eating (N=47, N=93)	2.84 Units on a scale Standard Deviation 19.03	0.72 Units on a scale Standard Deviation 20.18
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Children: Treatment burden (N=46, N=93)	0.72 Units on a scale Standard Deviation 15.43	-0.48 Units on a scale Standard Deviation 19.10
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Children: Respiratory (N=46, N=93)	-0.91 Units on a scale Standard Deviation 15.34	-1.61 Units on a scale Standard Deviation 16.81
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score Children: Digestion (N=46, N=92)	2.17 Units on a scale Standard Deviation 22.66	-1.09 Units on a scale Standard Deviation 29.84

Adverse Events

Placebo Randomized Group Over the Double-Blind Period

Serious events: 13 serious events

Other events: 27 other events

Deaths: 0 deaths

Tio 5mcg Randomized Group Over the Double-Blind Period

Serious events: 36 serious events

Other events: 63 other events

Deaths: 0 deaths

Placebo Randomized Group Over the Open-Label Period

Serious events: 24 serious events

Other events: 56 other events

Deaths: 0 deaths

Tio 5mcg Randomized Group Over the Study

Serious events: 62 serious events

Other events: 186 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo Randomized Group Over the Double-Blind Period n=155 participants at risk	Tio 5mcg Randomized Group Over the Double-Blind Period n=308 participants at risk	Placebo Randomized Group Over the Open-Label Period n=147 participants at risk	Tio 5mcg Randomized Group Over the Study n=308 participants at risk
Congenital, familial and genetic disorders Cystic fibrosis	0.00% 0/155 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	0.00% 0/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	0.00% 0/147 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	5.2% 16/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.
Gastrointestinal disorders Abdominal pain	0.00% 0/155 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	0.00% 0/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	0.00% 0/147 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	6.2% 19/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.
Gastrointestinal disorders Nausea	0.00% 0/155 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	0.00% 0/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	5.4% 8/147 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	0.00% 0/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.
General disorders Pyrexia	6.5% 10/155 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	4.9% 15/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	8.8% 13/147 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	9.1% 28/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.
Infections and infestations Bronchitis	0.00% 0/155 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	0.00% 0/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	6.8% 10/147 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	7.1% 22/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.
Infections and infestations Nasopharyngitis	0.00% 0/155 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	0.00% 0/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	7.5% 11/147 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	8.1% 25/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.
Infections and infestations Pharyngitis	0.00% 0/155 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	0.00% 0/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	0.00% 0/147 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	5.8% 18/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.
Infections and infestations Upper respiratory tract infection	0.00% 0/155 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	0.00% 0/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	0.00% 0/147 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	7.8% 24/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.
Nervous system disorders Headache	0.00% 0/155 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	0.00% 0/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	5.4% 8/147 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	7.1% 22/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.
Respiratory, thoracic and mediastinal disorders Cough	12.9% 20/155 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	17.9% 55/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	20.4% 30/147 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	26.0% 80/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.00% 0/155 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	0.00% 0/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	0.00% 0/147 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	6.2% 19/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/155 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	0.00% 0/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	6.1% 9/147 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	5.2% 16/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.
Respiratory, thoracic and mediastinal disorders Sputum increased	0.00% 0/155 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	0.00% 0/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	0.00% 0/147 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.	7.5% 23/308 • First administration of trial medication until 30 days after last administration of trial drug, for AE analyses over open-label period and over the study. Over the double-blind period, 30 days of wash-out is only used for premature discontinued patients.

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: [email protected]

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