RESPIRE 1: Ciprofloxacin Dry Powder for Inhalation in Non-cystic Fibrosis Bronchiectasis (Non-CF BE)

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01764841
• Collaborator: Novartis (Industry)
• Enrollment: 416
• Locations: 151
• Arms: 4
• Actual Duration (Months): 34.2
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate if the time to first pulmonary exacerbation of bronchiectasis or its frequency can be prolonged by inhalation of ciprofloxacin for 28 days every other 28 days or for 14 days every other 14 days over 48 weeks.

Condition or Disease	Intervention/Treatment	Phase
Bronchiectasis	Drug: Ciprofloxacin DPI (BAYQ3939); Drug: Placebo	Phase 3

Detailed Description

Number of participants with Adverse events will be covered in Adverse Events section.

The statistical analysis tests for the efficacy variables will be performed hierarchically. The comparisons ciprofloxacin DPI vs. pooled placebo (according to statistical analysis plan defined for FDA registration) will be performed in parallel for the regimen 28 days on/off and 14 days on/off.

Study Design

• Study Type: Interventional
• Actual Enrollment: 416 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-blind, Placebo-controlled, Multicenter Study Comparing Ciprofloxacin DPI 32.5 mg BID (Twice a Day) Intermittently Administered for 28 Days on / 28 Days Off or 14 Days on / 14 Days Off Versus Placebo to Evaluate the Time to First Pulmonary Exacerbation and Frequency of Exacerbations in Subjects With Non-Cystic Fibrosis Bronchiectasis.
• Actual Study Start Date: May 2, 2013
• Actual Primary Completion Date: Mar 9, 2016
• Actual Study Completion Date: Mar 9, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ciprofloxacin DPI 28 Days on/off (Cipro 28) Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).	Drug: Ciprofloxacin DPI (BAYQ3939); Participants received 32.5 mg ciprofloxacin hydrated (corresponding to 50 mg dry powder) administered BID (every 12 hours) using T-326 powder inhaler device.
Experimental: Ciprofloxacin DPI 14 Days on/off (Cipro 14) Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).	Drug: Ciprofloxacin DPI (BAYQ3939); Participants received 32.5 mg ciprofloxacin hydrated (corresponding to 50 mg dry powder) administered BID (every 12 hours) using T-326 powder inhaler device.
Placebo Comparator: Placebo 28 Days on/off (Placebo 28) Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 cycles).	Drug: Placebo; Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours) using T-326 powder inhaler device.
Placebo Comparator: Placebo 14 Days on/off (Placebo 14) Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 cycles).	Drug: Placebo; Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours) using T-326 powder inhaler device.

Outcome Measures

Primary Outcome Measures

1. Time to First Exacerbation Event Within 48 Weeks [Up to Week 48]

   Time to first exacerbation was defined as the time from randomization until the visit at which the first qualifying exacerbation is recorded by the investigator. Exacerbation events are defined as exacerbations with systemic antibiotic use and presence of fever or malaise / fatigue and worsening of at least three signs/symptoms.

Secondary Outcome Measures

1. Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks [Up to Week 48]

   For this outcome measure, exacerbation events were defined as exacerbations with systemic antibiotic use and presence of fever or malaise / fatigue and worsening of at least three signs/symptoms over 48 weeks.

2. Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks [Up to Week 48]

   For this outcome measure, exacerbation events were defined as exacerbations with systemic antibiotic use and worsening of at least one sign/symptom over 48 weeks.

3. Percentage of Participants With Pathogen Eradication at End of Treatment (Week 44/46) [End of treatment (Week 44/46)]

   Pathogen eradication was defined as a negative culture result for all pre-specified pathogens at end of treatment (week 44 or 46 depending on treatment regimen) that were present in the participant at baseline. There was no imputation for participants who discontinued the study prematurely.

4. Mean Change From Baseline in Patient Reported Outcome Saint George's Respiratory Questionnaire (SGRQ) Symptoms Component Score at End of Treatment (Week 44/46) [Baseline and end of treatment (Week 44/46)]

   The SGRQ was a validated, disease-specific instrument that measures health-related quality of life (HRQoL) in adults with chronic obstructive pulmonary disease (COPD) and asthma and was later validated for use in bronchiectasis. The SGRQ covers 3 dimensions: symptoms, activity and impact on daily life. To determine the outcome, a score ranging from 1 to 100 was calculated for each individual domain and for the total score, and smaller scores indicate better health status. For this outcome measure, the symptoms component score was reported.

5. Percentage of Participants With Occurrence of New Pathogens Present at End of Treatment (Week 44/46) [End of treatment (Week 44/46)]

   New pathogens were any of the pre-specified organisms not cultured before start of study medication. There was no imputation for participants who discontinued the study prematurely.

6. Mean Change From Baseline in Patient Reported Outcome Quality of Life Questionnaire for Bronchiectasis (QoL-B) Respiratory Symptoms Domain Score at End of Treatment (Week 44/46) [Baseline and end of treatment (Week 44/46)]

   The QoL-B was a disease-specific questionnaire developed for non-Cystic fibrosis Bronchiectasis. It covers 8 dimensions: physical functioning, role functioning, emotional functioning, social functioning, vitality, treatment burden, health perceptions, and respiratory symptoms. Each dimension was scored separately on a scale of 0 to 100, and higher scores represent better outcomes. For this outcome measure, the respiratory symptoms domain score was reported.

7. Mean Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at End of Treatment (Week 44/46) [Baseline and end of treatment (Week 44/46)]

   FEV1 was defined as the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration, expressed in liters at body temperature and ambient pressure saturated with water vapor (BTPS).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with a proven and documented diagnosis of non Cystic Fibrosis (CF) idiopathic or post infectious bronchiectasis

• Stable pulmonary status and stable regimen of standard treatment at least for the past 4 weeks

Exclusion Criteria:

• Forced expiratory volume in 1 second (FEV1) <30% or >90% predicted

• Active allergic bronchopulmonary aspergillosis

• Active and actively treated non tuberculosis mycobacterial (NTM) infection or tuberculosis

• Primary diagnosis of Chronic obstructive pulmonary disease (COPD)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Jasper	Alabama	United States	35501
2		Flagstaff	Arizona	United States	86001
3		Phoenix	Arizona	United States	85006-2611
4		Scottsdale	Arizona	United States	85258
5		Fort Smith	Arkansas	United States	72901
6		Los Angeles	California	United States	90048
7		Torrance	California	United States
8		Ventura	California	United States	93003
9		Farmington	Connecticut	United States	06030
10		Waterbury	Connecticut	United States	06708-2513
11		Washington	District of Columbia	United States	20007-2197
12		Celebration	Florida	United States	34747
13		Miami	Florida	United States	33136
14		Orlando	Florida	United States	32803
15		Weston	Florida	United States	33331
16		Winter Park	Florida	United States	32789
17		Lawrenceville	Georgia	United States	30046
18		Marietta	Georgia	United States	30060
19		Chicago	Illinois	United States	60637
20		Michigan City	Indiana	United States	46360
21		Hazard	Kentucky	United States	41701
22		Chesterfield	Missouri	United States	63017
23		Summit	New Jersey	United States	07901
24		New Hyde Park	New York	United States	11042
25		New York	New York	United States	10016
26		Portland	Oregon	United States	97239-3011
27		Philadelphia	Pennsylvania	United States	19104
28		Philadelphia	Pennsylvania	United States	19140
29		Charleston	South Carolina	United States	29425
30		Fort Worth	Texas	United States	76104
31		Houston	Texas	United States	77030
32		Houston	Texas	United States	77043
33		Kingwood	Texas	United States	77339
34		McKinney	Texas	United States	75069
35		Tyler	Texas	United States	75708-3154
36		Abingdon	Virginia	United States	24210
37		Richmond	Virginia	United States	23225
38		Spokane	Washington	United States	99202-1334
39		Tacoma	Washington	United States	98405
40		Buenos Aires	Ciudad Auton. De Buenos Aires	Argentina	C1425DES
41		Godoy Cruz	Mendoza	Argentina	5501
42		Vicente López		Argentina	1638
43		Woolloongabba	Queensland	Australia	4102
44		Adelaide	South Australia	Australia	5000
45		Adelaide	South Australia	Australia	5041
46		Woodville	South Australia	Australia	5011
47		Parkville	Victoria	Australia	3050
48		Prahran	Victoria	Australia	3181
49		Murdoch	Western Australia	Australia	6150
50		Box Hill		Australia	3128
51		Cairns		Australia	4870
52		Frankston		Australia	3199
53		Kogarah		Australia	2217
54		Toorak Gardens		Australia	5065
55		Aarhus C		Denmark	8000
56		Hellerup		Denmark	2900
57		Naestved		Denmark	4700
58		Roskilde		Denmark	4000
59		Clermont Ferrand		France	63000
60		Montpellier		France	34059
61		Nimes		France	30900
62		Toulon		France	83000
63		Heidelberg	Baden-Württemberg	Germany	69126
64		Cottbus	Brandenburg	Germany	03050
65		Frankfurt	Hessen	Germany	60389
66		Neu-Isenburg	Hessen	Germany	63263
67		Hannover	Niedersachsen	Germany	30173
68		Hannover	Niedersachsen	Germany	30625
69		Koblenz	Rheinland-Pfalz	Germany	56068
70		Geesthacht	Schleswig-Holstein	Germany	21502
71		Jena	Thüringen	Germany	07740
72		Berlin		Germany	10717
73		Berlin		Germany	10969
74		Berlin		Germany	12203
75		Hamburg		Germany	22767
76		Afula		Israel	1834111
77		Ashkelon		Israel	7827804
78		Beer Sheva		Israel	8410101
79		Haifa		Israel	3109601
80		Haifa		Israel	3436212
81		Jerusalem		Israel	9112001
82		Petah Tikva		Israel	4941492
83		Ramat Gan		Israel	5262000
84		Rehovot		Israel	7610001
85		Tel Aviv		Israel	6423906
86		Benevento	Campania	Italy	82037
87		Trieste	Friuli-Venezia Giulia	Italy	34149
88		Roma	Lazio	Italy	00168
89		Pavia	Lombardia	Italy	27040
90		Varese	Lombardia	Italy	21049
91		Bari	Puglia	Italy	70020
92		Cagliari	Sardegna	Italy	09126
93		Catania	Sicilia	Italy	95123
94		Pisa	Toscana	Italy	56124
95		Verona	Veneto	Italy	37126
96		Toon	Ehime	Japan	791-0281
97		Nakagun	Ibaraki	Japan	319-1113
98		Koshi	Kumamoto	Japan	861-1196
99		Matsusaka	Mie	Japan	515-8544
100		Tsu	Mie	Japan	514-1101
101		Sakai	Osaka	Japan	591-8555
102		Hamamatsu	Shizuoka	Japan	434-8511
103		Kiyose	Tokyo	Japan	204-8585
104		Mitaka	Tokyo	Japan	181-8611
105		Fukuoka		Japan	811-1394
106		Daugavpils		Latvia	LV-5403
107		Daugavpils		Latvia	LV-5410
108		Jurmala		Latvia	LV-2010
109		Kraslava		Latvia	5601
110		Riga		Latvia	LV-1001
111		Riga		Latvia	LV-1002
112		Riga		Latvia	LV-1011
113		Riga		Latvia	LV-1038
114		Talsu		Latvia	3201
115		Auckland		New Zealand	1051
116		Auckland		New Zealand	1640
117		Christchurch		New Zealand	8011
118		Dunedin		New Zealand
119		Hamilton		New Zealand	3240
120		Tauranga		New Zealand	3110
121		Wellington		New Zealand	6021
122		Bratislava		Slovakia	821 06
123		Presov		Slovakia	080 01
124		Santiago de Compostela	A Coruña	Spain	15706
125		Elda	Alicante	Spain	03600
126		Oviedo	Asturias	Spain	33006
127		Badalona	Barcelona	Spain	08916
128		L'Hospitalet	Barcelona	Spain	08907
129		Sant Boi de Llobregat	Barcelona	Spain	08830
130		Terrassa	Barcelona	Spain	08221
131		Pozuelo de Alarcón	Madrid	Spain	28223
132		Barcelona		Spain	08036
133		Barcelona		Spain	08041
134		Cáceres		Spain	10003
135		Madrid		Spain	28006
136		Madrid		Spain	28034
137		Madrid		Spain	28040
138		Pontevedra		Spain	36071
139		Valencia		Spain	46017
140		Valencia		Spain	46026
141		Cambridge	Cambridgeshire	United Kingdom	CB23 3RE
142		Exeter	Devon	United Kingdom	EX2 5DW
143		Plymouth	Devon	United Kingdom	PL6 8DH
144		Torbay	Devon	United Kingdom	TQ2 7AA
145		Dundee	Dundee City	United Kingdom	DD1 9SY
146		Belfast	North Ireland	United Kingdom	BT12 7AB
147		Shrewsbury	Shropshire	United Kingdom	SY3 8XQ
148		Newcastle Upon Tyne	Tyne And Wear	United Kingdom	NE7 7DN
149		Londonderry		United Kingdom	BT47 6SB
150		London		United Kingdom	SW3 6NP
151		Manchester		United Kingdom	M23 9LT

Sponsors and Collaborators

• Bayer
• Novartis

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT01764841
• Other Study ID Numbers: 15625; 2011-004208-39
• First Posted: Jan 10, 2013
• Last Update Posted: Jan 24, 2018
• Last Verified: Jan 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Bayer: Ciprofloxacin; Dry Powder for Inhalation; Exacerbation; Bronchiectasis
• Additional relevant MeSH terms: Bronchiectasis; Ciprofloxacin

Study Results

Participant Flow

Recruitment Details	Study was conducted at 124 study centers in 14 countries (Argentina, Australia, Denmark, France, Germany, Israel, Italy, Japan, Latvia, New Zealand, Slovakia, Spain, UK and US) between 02 May 2013 (first subject first visit) and 09 March 2016 (last subject last visit).
Pre-assignment Detail	Overall 902 participants were screened, of them 486 were screen failures, and 416 were randomized, out of which 414 participants were assigned to the treatment. One participant from Ciprofloxacin 14 Days on/off group and one participant from Placebo 28 Days on/off group did not receive the study treatment after initial screening.

Arm/Group Title	Ciprofloxacin DPI 28 Days on/Off (Cipro 28)	Ciprofloxacin DPI 14 Days on/Off (Cipro 14)	Placebo 28 Days on/Off (Placebo 28)	Placebo 14 Days on/Off (Placebo 14)
Arm/Group Description	Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).	Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).	Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 cycles).	Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 cycles).
Period Title: Overall Study
STARTED	141	137	70	68
Participants Received Treatment	141	136	69	68
COMPLETED	118	111	56	49
NOT COMPLETED	23	26	14	19

Baseline Characteristics

Arm/Group Title	Ciprofloxacin DPI 28 Days on/Off (Cipro 28)	Ciprofloxacin DPI 14 Days on/Off (Cipro 14)	Placebo 28 Days on/Off (Placebo 28)	Placebo 14 Days on/Off (Placebo 14)	Total
Arm/Group Description	Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).	Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).	Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 cycles).	Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 cycles).	Total of all reporting groups
Overall Participants	141	137	70	68	416
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.2 (12.1)	65.2 (13.5)	64 (13.5)	65.5 (12.9)	64.7 (12.9)
Sex: Female, Male (Count of Participants)
Female	101 71.6%	88 64.2%	52 74.3%	44 64.7%	285 68.5%
Male	40 28.4%	49 35.8%	18 25.7%	24 35.3%	131 31.5%
Saint George's Respiratory Questionnaire (SGRQ) Symptoms Component Score (Score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Score on a scale]	60.72 (19.47)	52.51 (21.48)	55.52 (22.07)	58.72 (20.4)	56.84 (20.95)
Quality of Life Questionnaire for Bronchiectasis (QoL-B) Respiratory Symptoms Domain Score (Score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Score on a scale]	53.01 (18.71)	57.69 (18.72)	55.82 (18.04)	50.67 (19.59)	54.57 (18.87)
Forced Expiratory Volume in One Second (FEV1) (Liter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Liter]	1.521 (0.521)	1.528 (0.625)	1.577 (0.651)	1.468 (0.574)	1.524 (0.587)

Outcome Measures

1. Primary Outcome

Title	Time to First Exacerbation Event Within 48 Weeks
Description	Time to first exacerbation was defined as the time from randomization until the visit at which the first qualifying exacerbation is recorded by the investigator. Exacerbation events are defined as exacerbations with systemic antibiotic use and presence of fever or malaise / fatigue and worsening of at least three signs/symptoms.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included participants who were randomized.

Arm/Group Title	Ciprofloxacin DPI 28 Days on/Off (Cipro 28)	Ciprofloxacin DPI 14 Days on/Off (Cipro 14)	Pooled Placebo
Arm/Group Description	Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).	Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).	Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day or 14-day on-treatment phase followed by a 28-day or 14-day off-treatment phase (48 weeks treatment phase = 6 or 12 cycles).
Measure Participants	141	137	138
Median (97.5% Confidence Interval) [Days]	336	NA	186

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ciprofloxacin DPI 28 Days on/Off (Cipro 28), Pooled Placebo
	Comments	The hazard ratio for time to first exacerbation event within 48 weeks and 97.5% Confidence Interval (CI) was calculated by using Cox proportional hazards model by comparison of Cipro 28/Pooled Placebo reporting groups. P-value was analysed using Wald-type test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0650
	Comments
	Method	Wald-type test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.7331
	Confidence Interval	(2-Sided) 97.5%; 0.5027 to 1.0690
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ciprofloxacin DPI 14 Days on/Off (Cipro 14), Pooled Placebo
	Comments	The hazard ratio for time to first exacerbation event within 48 weeks and 97.5% CI was calculated by using Cox proportional hazards model by comparison of Cipro 14/Pooled Placebo reporting groups. P-value was analysed using Wald-type test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Wald-type test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.5333
	Confidence Interval	(2-Sided) 97.5%; 0.3568 to 0.7971
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants With Exacerbation Events With Worsening of at Least Three Signs/Symptoms Over 48 Weeks
Description	For this outcome measure, exacerbation events were defined as exacerbations with systemic antibiotic use and presence of fever or malaise / fatigue and worsening of at least three signs/symptoms over 48 weeks.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included participants who were randomized.

Arm/Group Title	Ciprofloxacin DPI 28 Days on/Off (Cipro 28)	Ciprofloxacin DPI 14 Days on/Off (Cipro 14)	Pooled Placebo
Arm/Group Description	Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).	Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).	Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day or 14-day on-treatment phase followed by a 28-day or 14-day off-treatment phase (48 weeks treatment phase = 6 or 12 cycles).
Measure Participants	141	137	138
Number of exacerbations: 0	66 46.8%	72 52.6%	44 62.9%
Number of exacerbations: 1	44 31.2%	38 27.7%	58 82.9%
Number of exacerbations: 2	12 8.5%	13 9.5%	19 27.1%
Number of exacerbations: 3	12 8.5%	8 5.8%	7 10%
Number of exacerbations: 4	3 2.1%	3 2.2%	8 11.4%
Number of exacerbations: 5	1 0.7%	2 1.5%	0 0%
Number of exacerbations: 6	0 0%	0 0%	1 1.4%
Number of exacerbations: 7	3 2.1%	1 0.7%	1 1.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ciprofloxacin DPI 28 Days on/Off (Cipro 28), Pooled Placebo
	Comments	A Poisson regression with adjustment for over-/under dispersion was used to analyze the number of exacerbation events over 48 weeks and to test the difference in the frequency of exacerbation between Ciprofloxacin DPI 28 and Pooled placebo group. P-value was analyzed using Wald-type test along with the incidence rate ratio of the comparison.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2944
	Comments
	Method	Poisson regression
	Comments
Method of Estimation	Estimation Parameter	Incidence Rate Ratio
	Estimated Value	0.8615
	Confidence Interval	(2-Sided) 97.5%; 0.6264 to 1.1848
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ciprofloxacin DPI 14 Days on/Off (Cipro 14), Pooled Placebo
	Comments	A Poisson regression with adjustment for over-/under dispersion was used to analyze the number of exacerbation events over 48 weeks and to test the difference in the frequency of exacerbation between Ciprofloxacin DPI 14 and Pooled placebo group. P-value was analyzed using Wald-type test along with the incidence rate ratio of the comparison.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0382
	Comments
	Method	Poisson regression
	Comments
Method of Estimation	Estimation Parameter	Incidence Rate Ratio
	Estimated Value	0.7329
	Confidence Interval	(2-Sided) 97.5%; 0.5237 to 1.0256
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants With Exacerbation Events With Worsening of at Least One Sign/Symptom Over 48 Weeks
Description	For this outcome measure, exacerbation events were defined as exacerbations with systemic antibiotic use and worsening of at least one sign/symptom over 48 weeks.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included participants who were randomized.

Arm/Group Title	Ciprofloxacin DPI 28 Days on/Off (Cipro 28)	Ciprofloxacin DPI 14 Days on/Off (Cipro 14)	Pooled Placebo
Arm/Group Description	Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).	Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).	Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day or 14-day on-treatment phase followed by a 28-day or 14-day off-treatment phase (48 weeks treatment phase = 6 or 12 cycles).
Measure Participants	141	137	138
Number of exacerbations: 0	58 41.1%	68 49.6%	46 65.7%
Number of exacerbations: 1	47 33.3%	42 30.7%	43 61.4%
Number of exacerbations: 2	12 8.5%	15 10.9%	31 44.3%
Number of exacerbations: 3	14 9.9%	5 3.6%	11 15.7%
Number of exacerbations: 4	4 2.8%	2 1.5%	5 7.1%
Number of exacerbations: 5	4 2.8%	3 2.2%	2 2.9%
Number of exacerbations: 6	2 1.4%	2 1.5%	0 0%

4. Secondary Outcome

Title	Percentage of Participants With Pathogen Eradication at End of Treatment (Week 44/46)
Description	Pathogen eradication was defined as a negative culture result for all pre-specified pathogens at end of treatment (week 44 or 46 depending on treatment regimen) that were present in the participant at baseline. There was no imputation for participants who discontinued the study prematurely.
Time Frame	End of treatment (Week 44/46)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included participants who were randomized.

Arm/Group Title	Ciprofloxacin DPI 28 Days on/Off (Cipro 28)	Ciprofloxacin DPI 14 Days on/Off (Cipro 14)	Pooled Placebo
Arm/Group Description	Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).	Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).	Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day or 14-day on-treatment phase followed by a 28-day or 14-day off-treatment phase (48 weeks treatment phase = 6 or 12 cycles).
Measure Participants	141	137	138
No	39.0 27.7%	26.3 19.2%	33.3 47.6%
Yes	24.1 17.1%	28.5 20.8%	16.7 23.9%

5. Secondary Outcome

Title	Mean Change From Baseline in Patient Reported Outcome Saint George's Respiratory Questionnaire (SGRQ) Symptoms Component Score at End of Treatment (Week 44/46)
Description	The SGRQ was a validated, disease-specific instrument that measures health-related quality of life (HRQoL) in adults with chronic obstructive pulmonary disease (COPD) and asthma and was later validated for use in bronchiectasis. The SGRQ covers 3 dimensions: symptoms, activity and impact on daily life. To determine the outcome, a score ranging from 1 to 100 was calculated for each individual domain and for the total score, and smaller scores indicate better health status. For this outcome measure, the symptoms component score was reported.
Time Frame	Baseline and end of treatment (Week 44/46)

Outcome Measure Data

Analysis Population Description

FAS with participants evaluable for this outcome measure.

Arm/Group Title	Ciprofloxacin DPI 28 Days on/Off (Cipro 28)	Ciprofloxacin DPI 14 Days on/Off (Cipro 14)	Placebo 28 Days on/Off (Placebo 28)	Placebo 14 Days on/Off (Placebo 14)
Arm/Group Description	Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).	Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).	Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 cycles).	Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 cycles).
Measure Participants	115	101	46	45
Mean (Standard Deviation) [Score on a scale]	-8.17 (22.92)	-7.20 (20.41)	-4.23 (19.55)	2.78 (16.16)

6. Secondary Outcome

Title	Percentage of Participants With Occurrence of New Pathogens Present at End of Treatment (Week 44/46)
Description	New pathogens were any of the pre-specified organisms not cultured before start of study medication. There was no imputation for participants who discontinued the study prematurely.
Time Frame	End of treatment (Week 44/46)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included participants who were randomized.

Arm/Group Title	Ciprofloxacin DPI 28 Days on/Off (Cipro 28)	Ciprofloxacin DPI 14 Days on/Off (Cipro 14)	Pooled Placebo
Arm/Group Description	Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).	Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).	Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day or 14-day on-treatment phase followed by a 28-day or 14-day off-treatment phase (48 weeks treatment phase = 6 or 12 cycles).
Measure Participants	141	137	138
No	60.3 42.8%	49.6 36.2%	42.8 61.1%
Yes	3.5 2.5%	5.1 3.7%	8.0 11.4%

7. Secondary Outcome

Title	Mean Change From Baseline in Patient Reported Outcome Quality of Life Questionnaire for Bronchiectasis (QoL-B) Respiratory Symptoms Domain Score at End of Treatment (Week 44/46)
Description	The QoL-B was a disease-specific questionnaire developed for non-Cystic fibrosis Bronchiectasis. It covers 8 dimensions: physical functioning, role functioning, emotional functioning, social functioning, vitality, treatment burden, health perceptions, and respiratory symptoms. Each dimension was scored separately on a scale of 0 to 100, and higher scores represent better outcomes. For this outcome measure, the respiratory symptoms domain score was reported.
Time Frame	Baseline and end of treatment (Week 44/46)

Outcome Measure Data

Analysis Population Description

FAS with participants evaluable for this outcome measure.

Arm/Group Title	Ciprofloxacin DPI 28 Days on/Off (Cipro 28)	Ciprofloxacin DPI 14 Days on/Off (Cipro 14)	Placebo 28 Days on/Off (Placebo 28)	Placebo 14 Days on/Off (Placebo 14)
Arm/Group Description	Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).	Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).	Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 cycles).	Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 cycles).
Measure Participants	110	95	46	44
Mean (Standard Deviation) [Score on a scale]	7.70 (18.50)	6.72 (17.90)	8.22 (16.74)	4.45 (17.78)

8. Secondary Outcome

Title	Mean Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at End of Treatment (Week 44/46)
Description	FEV1 was defined as the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration, expressed in liters at body temperature and ambient pressure saturated with water vapor (BTPS).
Time Frame	Baseline and end of treatment (Week 44/46)

Outcome Measure Data

Analysis Population Description

FAS with participants evaluable for this outcome measure.

Arm/Group Title	Ciprofloxacin DPI 28 Days on/Off (Cipro 28)	Ciprofloxacin DPI 14 Days on/Off (Cipro 14)	Placebo 28 Days on/Off (Placebo 28)	Placebo 14 Days on/Off (Placebo 14)
Arm/Group Description	Participants received ciprofloxacin (BAYQ3939) 32.5 milligram (mg) corresponding to 50 mg dry powder for inhalation (DPI) administered twice daily (BID) (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).	Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).	Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 cycles).	Participants received placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 cycles).
Measure Participants	112	98	45	41
Mean (Standard Deviation) [Liter]	-0.012 (0.149)	-0.026 (0.226)	0.024 (0.344)	0.022 (0.352)

Adverse Events

Time Frame	From start of study treatment up to 30 days after the last study drug administration.
Arm/Group Title	Ciprofloxacin DPI 28 Days on/Off (Cipro 28)		Ciprofloxacin DPI 14 Days on/Off (Cipro 14)		Pooled Placebo
Arm/Group Description	Participants received ciprofloxacin (BAYQ3939) 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 28-day on-treatment phase followed by a 28-day off-treatment phase (48 weeks treatment phase = 6 active cycles).		Participants received ciprofloxacin 32.5 mg corresponding to 50 mg DPI administered BID (every 12 hours); a treatment cycle consisted of a 14-day on-treatment phase followed by a 14-day off-treatment phase (48 weeks treatment phase = 12 active cycles).		Participants received matching placebo matched to ciprofloxacin 32.5 mg powder (containing 40 mg dry powder) administered BID (every 12 hours); a treatment cycle consisted of either a 28-day days on-treatment phase followed by 28-day off-treatment phase or 14-day on-treatment phase followed by 14-day off treatment phase (48 weeks treatment phase = 6 cycles and 12 cycles, respectively).
All Cause Mortality
	Ciprofloxacin DPI 28 Days on/Off (Cipro 28)		Ciprofloxacin DPI 14 Days on/Off (Cipro 14)		Pooled Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ciprofloxacin DPI 28 Days on/Off (Cipro 28)		Ciprofloxacin DPI 14 Days on/Off (Cipro 14)		Pooled Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/141 (20.6%)		23/136 (16.9%)		32/137 (23.4%)
Blood and lymphatic system disorders
Anaemia	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Cardiac disorders
Atrial fibrillation	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Atrial flutter	1/141 (0.7%)	1	0/136 (0%)	0	0/137 (0%)	0
Cardiac failure	0/141 (0%)	0	1/136 (0.7%)	1	2/137 (1.5%)	2
Cardiac failure acute	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Cardiac failure congestive	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Cor pulmonale	1/141 (0.7%)	1	0/136 (0%)	0	0/137 (0%)	0
Mitral valve incompetence	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Eye disorders
Angle closure glaucoma	1/141 (0.7%)	1	0/136 (0%)	0	0/137 (0%)	0
Retinal vasculitis	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Gastrointestinal disorders
Ascites	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Gastric ulcer haemorrhage	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
General disorders
Strangulated hernia	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Peripheral swelling	1/141 (0.7%)	1	0/136 (0%)	0	0/137 (0%)	0
General physical health deterioration	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Hepatobiliary disorders
Portal hypertension	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Immune system disorders
Hypogammaglobulinaemia	1/141 (0.7%)	1	0/136 (0%)	0	0/137 (0%)	0
Infections and infestations
Bronchiolitis	1/141 (0.7%)	1	0/136 (0%)	0	0/137 (0%)	0
Cellulitis	1/141 (0.7%)	1	0/136 (0%)	0	1/137 (0.7%)	1
Gastroenteritis clostridial	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Influenza	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Pathogen resistance	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Pneumonia	4/141 (2.8%)	4	4/136 (2.9%)	4	5/137 (3.6%)	5
Urosepsis	1/141 (0.7%)	1	0/136 (0%)	0	0/137 (0%)	0
Infective exacerbation of bronchiectasis	2/141 (1.4%)	3	1/136 (0.7%)	1	1/137 (0.7%)	1
Pyometra	1/141 (0.7%)	1	0/136 (0%)	0	0/137 (0%)	0
Injury, poisoning and procedural complications
Clavicle fracture	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Complications of transplant surgery	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Femoral neck fracture	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Fibula fracture	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Urethral stricture traumatic	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Lumbar vertebral fracture	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Meniscus injury	1/141 (0.7%)	1	0/136 (0%)	0	0/137 (0%)	0
Investigations
Influenza A virus test positive	1/141 (0.7%)	1	0/136 (0%)	0	0/137 (0%)	0
Metabolism and nutrition disorders
Hyponatraemia	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Musculoskeletal and connective tissue disorders
Fracture nonunion	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Lumbar spinal stenosis	1/141 (0.7%)	1	0/136 (0%)	0	0/137 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Breast cancer	1/141 (0.7%)	1	0/136 (0%)	0	0/137 (0%)	0
Malignant melanoma	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Squamous cell carcinoma of skin	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Thyroid cancer recurrent	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Invasive lobular breast carcinoma	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Nervous system disorders
Cerebral atrophy	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Cerebrovascular accident	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Normal pressure hydrocephalus	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Paraesthesia	1/141 (0.7%)	1	0/136 (0%)	0	0/137 (0%)	0
Syncope	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Transient global amnesia	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Renal and urinary disorders
Haematuria	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Renal failure	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Urinary retention	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Urethral stenosis	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	2
Acute kidney injury	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Reproductive system and breast disorders
Prostatic haemorrhage	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchiectasis	16/141 (11.3%)	20	8/136 (5.9%)	9	17/137 (12.4%)	19
Bronchospasm	1/141 (0.7%)	1	0/136 (0%)	0	0/137 (0%)	0
Dyspnoea	1/141 (0.7%)	1	0/136 (0%)	0	0/137 (0%)	0
Epistaxis	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Haemoptysis	2/141 (1.4%)	2	1/136 (0.7%)	1	2/137 (1.5%)	2
Hypoxia	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Pleural effusion	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Pneumonia aspiration	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Pulmonary embolism	1/141 (0.7%)	1	0/136 (0%)	0	0/137 (0%)	0
Pulmonary haemorrhage	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Respiratory failure	0/141 (0%)	0	1/136 (0.7%)	1	1/137 (0.7%)	1
Vascular disorders
Aortic stenosis	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Orthostatic hypotension	0/141 (0%)	0	1/136 (0.7%)	1	0/137 (0%)	0
Deep vein thrombosis	0/141 (0%)	0	0/136 (0%)	0	1/137 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Ciprofloxacin DPI 28 Days on/Off (Cipro 28)		Ciprofloxacin DPI 14 Days on/Off (Cipro 14)		Pooled Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	74/141 (52.5%)		83/136 (61%)		62/137 (45.3%)
Gastrointestinal disorders
Diarrhoea	7/141 (5%)	7	9/136 (6.6%)	11	5/137 (3.6%)	5
Nausea	5/141 (3.5%)	5	10/136 (7.4%)	11	7/137 (5.1%)	7
General disorders
Chest pain	5/141 (3.5%)	5	7/136 (5.1%)	8	7/137 (5.1%)	7
Fatigue	6/141 (4.3%)	6	12/136 (8.8%)	14	3/137 (2.2%)	3
Infections and infestations
Nasopharyngitis	15/141 (10.6%)	20	16/136 (11.8%)	21	10/137 (7.3%)	15
Sinusitis	4/141 (2.8%)	5	10/136 (7.4%)	12	8/137 (5.8%)	10
Upper respiratory tract infection	4/141 (2.8%)	5	9/136 (6.6%)	9	10/137 (7.3%)	13
Investigations
Aspergillus test positive	6/141 (4.3%)	6	7/136 (5.1%)	8	0/137 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	10/141 (7.1%)	13	9/136 (6.6%)	10	6/137 (4.4%)	6
Nervous system disorders
Dizziness	2/141 (1.4%)	2	7/136 (5.1%)	7	1/137 (0.7%)	1
Headache	11/141 (7.8%)	14	14/136 (10.3%)	16	4/137 (2.9%)	6
Respiratory, thoracic and mediastinal disorders
Bronchospasm	6/141 (4.3%)	7	7/136 (5.1%)	13	10/137 (7.3%)	13
Cough	15/141 (10.6%)	18	13/136 (9.6%)	18	9/137 (6.6%)	12
Dyspnoea	15/141 (10.6%)	21	16/136 (11.8%)	26	9/137 (6.6%)	11
Haemoptysis	15/141 (10.6%)	34	16/136 (11.8%)	32	8/137 (5.8%)	10
Sputum increased	8/141 (5.7%)	9	6/136 (4.4%)	8	3/137 (2.2%)	4
Oropharyngeal pain	3/141 (2.1%)	3	7/136 (5.1%)	9	5/137 (3.6%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bayer acknowledges and accepts the interest in the noncommercial scientific publication of Results. In a multicenter study the PIs will not make any publication of the results before the first multi-center publication. Proposed publication/presentation shall be provided to Bayer at least 60 days prior to the intended submission or presentation of the publication in order to allow Bayer to review it. Any difference of opinion shall be discussed.