Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Dose-finding Study to Assess the Efficacy, Safety and Tolerability of Tobramycin Inhalation Powder in Patients With Non-Cystic Fibrosis Bronchiectasis and Pulmonary P. Aeruginosa Infection (iBEST-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02712983
Recruitment Status : Completed
First Posted : March 18, 2016
Results First Posted : August 14, 2020
Last Update Posted : August 25, 2020
Sponsor:
Collaborators:
Queen's University Belfast, UK
University Hospital Antwerp, BE
University of Milan, IT
Fundacion Clinic per a la Recerca Biomedica
Erasmus Medical Center
Papworth Hospital Cambridge, UK
Royal Brompton Hospital Trust, UK
University of Dundee
University of Edinburgh
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Non-cystic Fibrosis Bronchiectasis
Interventions Drug: TIP
Drug: TIP and placebo
Drug: Placebo
Enrollment 107
Recruitment Details A total of 107 subjects were enrolled in the trial from 6 countries (Belgium [2 sites], France [4 sites], Germany [5 sites], Italy [6 sites], Spain [8 sites] and United Kingdom [9 sites]).
Pre-assignment Details This study planned to recruit approximately 180 subjects to one of the 3 cohorts in a ratio of 1:1:1. The subjects within each cohort were randomized to blinded TIP or placebo with the following randomization scheme: TIP:TIP/Placebo cyclical:Placebo, in a 2:2:1 ratio.
Arm/Group Title Cohort A (3 Capsules o.d.): TIP Cohort A (3 Capsules o.d.): TIP/PBO Cohort A (3 Capsules o.d.): PBO Cohort B (5 Capsules o.d.): TIP Cohort B (5 Capsules o.d.): TIP/PBO Cohort B (5 Capsules o.d.): PBO Cohort C (4 Capsules b.i.d.): TIP Cohort C (4 Capsules b.i.d.): TIP/PBO Cohort C (4 Capsules b.i.d.): PBO
Hide Arm/Group Description Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical Cohort A (3 capsules o.d.): Inhaled placebo (PBO) Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical Cohort B (5 capsules o.d.): inhaled placebo (PBO) Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical Cohort C (4 capsules b.i.d.): inhaled placebo (PBO)
Period Title: Treatment Phase
Started [1] 14 13 7 15 14 7 15 15 7
Pharmacokinetic Analysis Set 14 13 0 15 14 0 15 14 0
Completed 9 12 6 7 10 7 6 6 5
Not Completed 5 1 1 8 4 0 9 9 2
Reason Not Completed
Adverse Event             3             1             1             4             3             0             6             6             1
Protocol Deviation             0             0             0             2             0             0             1             0             0
Technical Problems             0             0             0             0             0             0             1             0             0
Physician Decision             0             0             0             0             0             0             0             1             1
Subject Decision             2             0             0             2             1             0             1             2             0
[1]
All randomized patients (Full Analysis Set and Safety Set)
Period Title: Post-Treatment Efficacy Follow-Up Phase
Started [1] 0 [2] 1 [2] 0 [2] 1 [2] 2 [2] 1 [2] 2 [2] 3 [2] 0 [2]
Completed 0 0 0 0 0 0 0 0 0
Not Completed 0 1 0 1 2 1 2 3 0
Reason Not Completed
Adverse Event             0             1             0             0             0             0             1             1             0
Lost to Follow-up             0             0             0             1             0             0             0             0             0
Subject Decision             0             0             0             0             2             1             1             2             0
[1]
All patients who discontinued treatment and entered Post-Treatment Efficacy Follow-Up Phase
[2]
All patients who entered Post-Treatment Efficacy Fup Phase
Arm/Group Title Cohort A (3 Capsules o.d.): TIP Cohort A (3 Capsules o.d.): TIP/PBO Cohort A (3 Capsules o.d.): PBO Cohort B (5 Capsules o.d.): TIP Cohort B (5 Capsules o.d.): TIP/PBO Cohort B (5 Capsules o.d.): PBO Cohort C (4 Capsules b.i.d.): TIP Cohort C (4 Capsules b.i.d.): TIP/PBO Cohort C (4 Capsules b.i.d.): PBO Total
Hide Arm/Group Description Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical Cohort A (3 capsules o.d.): Inhaled placebo (PBO) Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical Cohort B (5 capsules o.d.): inhaled placebo (PBO) Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical Cohort C (4 capsules b.i.d.): inhaled placebo (PBO) Total of all reporting groups
Overall Number of Baseline Participants 14 13 7 15 14 7 15 15 7 107
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants 13 participants 7 participants 15 participants 14 participants 7 participants 15 participants 15 participants 7 participants 107 participants
63.4  (12.66) 57.5  (11.83) 61.3  (7.45) 64.3  (17.86) 62.4  (16.71) 69.1  (13.21) 66.1  (12.23) 60.8  (12.94) 71.3  (10.39) 63.4  (13.64)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 13 participants 7 participants 15 participants 14 participants 7 participants 15 participants 15 participants 7 participants 107 participants
Female
9
  64.3%
10
  76.9%
3
  42.9%
10
  66.7%
7
  50.0%
6
  85.7%
9
  60.0%
8
  53.3%
4
  57.1%
66
  61.7%
Male
5
  35.7%
3
  23.1%
4
  57.1%
5
  33.3%
7
  50.0%
1
  14.3%
6
  40.0%
7
  46.7%
3
  42.9%
41
  38.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 14 participants 13 participants 7 participants 15 participants 14 participants 7 participants 15 participants 15 participants 7 participants 107 participants
Caucasian 12 11 7 13 11 5 15 15 7 96
Asian 1 0 0 0 0 1 0 0 0 2
Pacific Islander 0 0 0 1 0 0 0 0 0 1
Other 1 2 0 1 3 1 0 0 0 8
1.Primary Outcome
Title Change From Baseline to Day 29 in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs)
Hide Description Microbiological data was collected to understand the direct impact of the drug on the pathogens. Sputum samples were cultured for the presence of three Pseudomonas aeruginosa (P. aeruginosa) biotypes measured were mucoid, dry and small colony variant. Change was determined using the formula = (Post-baseline value - baseline value). If no P. aeruginosa was isolated for a visit, log10 colony forming units (CFU) was imputed with log10 (19) for all biotypes. Only values for all morphotypes presented.
Time Frame Baseline (Visit 101/Day 1), Visit 102 (Day 8), Visit 103 (Day 29)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. Only the participants who had microbiological data at specified time points were included.
Arm/Group Title Cohort A (3 Capsules o.d.): TIP Cohort A (3 Capsules o.d.): TIP/PBO Cohort B (5 Capsules o.d.): TIP Cohort B (5 Capsules o.d.): TIP/PBO Cohort C (4 Capsules b.i.d.): TIP Cohort C (4 Capsules b.i.d.): TIP/PBO Pooled TIP Pooled TIP/PBO Pooled PBO
Hide Arm/Group Description:
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP)
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Pooled Tobramycin inhalation powder (TIP): For efficacy analysis, subjects assigned to TIP groups were pooled across the 3 cohorts.
Pooled Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical: For efficacy analysis, subjects assigned to TIP/PBO groups were pooled across the 3 cohorts.
Pooled inhaled placebo (PBO): For efficacy analysis, subjects assigned to Placebo groups were pooled across the 3 cohorts, as the number of placebo capsules was not expected to impact the efficacy assessments.
Overall Number of Participants Analyzed 14 13 15 14 15 15 44 42 21
Mean (Standard Deviation)
Unit of Measure: log10 CFUs
Baseline Number Analyzed 14 participants 13 participants 14 participants 13 participants 15 participants 15 participants 43 participants 41 participants 21 participants
6.80  (1.202) 7.67  (1.507) 6.10  (2.419) 6.98  (1.804) 6.79  (0.908) 5.73  (1.885) 6.57  (1.625) 6.74  (1.892) 7.09  (2.012)
Change from BL at Day 8 Number Analyzed 10 participants 11 participants 9 participants 12 participants 13 participants 10 participants 32 participants 33 participants 21 participants
-2.82  (1.440) -3.23  (2.204) -2.04  (2.274) -3.98  (1.865) -4.54  (1.283) -3.47  (1.583) -3.30  (1.937) -3.58  (1.878) -0.72  (1.765)
Change from BL at Day 29 Number Analyzed 14 participants 10 participants 9 participants 10 participants 13 participants 12 participants 36 participants 32 participants 21 participants
-2.61  (2.600) -2.80  (2.823) -1.56  (2.885) -3.57  (2.218) -4.36  (1.101) -2.58  (2.871) -2.98  (2.474) -2.96  (2.618) 0.05  (1.518)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP, Pooled PBO
Comments Day 8 Cohort A: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-3.62 to -1.22
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.60
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Day 8 Cohort A: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.1
Confidence Interval (2-Sided) 95%
-3.30 to -0.98
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.58
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP, Pooled PBO
Comments Day 8 Cohort B: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-3.20 to -0.68
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.63
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Day 8 Cohort B: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -3.3
Confidence Interval (2-Sided) 95%
-4.38 to -2.15
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.56
Estimation Comments [Not Specified]
Other Statistical Analysis LS Mean Diff (SE) vs pooled placebo
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP, Pooled PBO
Comments Day 8 Cohort C: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -4.0
Confidence Interval (2-Sided) 95%
-5.06 to -2.88
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.55
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP/PBO, Pooled PBO
Comments Day 8 Cohort C: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -3.4
Confidence Interval (2-Sided) 95%
-4.57 to -2.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.61
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Pooled TIP, Pooled PBO
Comments Day 8: Pooled TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-3.66 to -1.89
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.44
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Pooled TIP/PBO, Pooled PBO
Comments Day 8: Pooled TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.9
Confidence Interval (2-Sided) 95%
-3.79 to -2.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.43
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP, Pooled PBO
Comments Day 29 Cohort A: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-4.28 to -1.31
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.75
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Day 29 Cohort A: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-4.03 to -0.67
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.84
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP, Pooled PBO
Comments Day 29 Cohort B: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.3
Confidence Interval (2-Sided) 95%
-4.04 to -0.52
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.88
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Day 29 Cohort B: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -3.5
Confidence Interval (2-Sided) 95%
-5.16 to -1.85
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.83
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP, Pooled PBO
Comments Day 29 Cohort C: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -4.6
Confidence Interval (2-Sided) 95%
-6.13 to -3.09
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.76
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP/PBO, Pooled PBO
Comments Day 29 Cohort C: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -3.1
Confidence Interval (2-Sided) 95%
-4.68 to -1.52
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.79
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Pooled TIP, Pooled PBO
Comments Day 29: Pooled TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -3.2
Confidence Interval (2-Sided) 95%
-4.43 to -2.02
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.61
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Pooled TIP/PBO, Pooled PBO
Comments Day 29: Pooled TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -3.0
Confidence Interval (2-Sided) 95%
-4.19 to -1.78
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.61
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to Each Post-baseline Visit in Pseudomonas Aeruginosa (P. Aeruginosa) Density in Sputum (log10 CFUs)
Hide Description Microbiological data was collected to understand the direct impact of the drug on the pathogens. Sputum samples were cultured for the presence of three Pseudomonas aeruginosa (P. aeruginosa) biotypes measured were mucoid, dry and small colony variant. Change was determined using the formula = (Post-baseline value - baseline value). If no P. aeruginosa was isolated for a visit, log10 colony forming units (CFU) was imputed with log10 (19) for all biotypes. Only values for all morphotypes are presented.
Time Frame Baseline (Visit 101/Day 1), Visit 104 (Day 57), Visit 105 (Day 85), Visit 106 (Day 113), End of Treatment (EOT), Visit 201 (Day 141), Visit 202 (Day 169)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. Only the participants who had microbiological data at specified time points were included.
Arm/Group Title Cohort A (3 Capsules o.d.): TIP Cohort A (3 Capsules o.d.): TIP/PBO Cohort B (5 Capsules o.d.): TIP Cohort B (5 Capsules o.d.): TIP/PBO Cohort C (4 Capsules b.i.d.): TIP Cohort C (4 Capsules b.i.d.): TIP/PBO Pooled TIP Pooled TIP/PBO Pooled PBO
Hide Arm/Group Description:
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP)
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Pooled Tobramycin inhalation powder (TIP): For efficacy analysis, subjects assigned to TIP groups were pooled across the 3 cohorts.
Pooled Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical: For efficacy analysis, subjects assigned to TIP/PBO groups were pooled across the 3 cohorts.
Pooled inhaled placebo (PBO): For efficacy analysis, subjects assigned to Placebo groups were pooled across the 3 cohorts, as the number of placebo capsules was not expected to impact the efficacy assessments.
Overall Number of Participants Analyzed 14 13 15 14 15 15 44 42 21
Mean (Standard Deviation)
Unit of Measure: log10 CFUs
Baseline (BL) Number Analyzed 14 participants 13 participants 14 participants 13 participants 15 participants 15 participants 43 participants 41 participants 21 participants
6.80  (1.202) 7.67  (1.507) 6.10  (2.419) 6.98  (1.804) 6.79  (0.908) 5.73  (1.885) 6.57  (1.625) 6.74  (1.892) 7.09  (2.012)
Change from BL at Day 57 Number Analyzed 11 participants 11 participants 8 participants 11 participants 13 participants 10 participants 32 participants 32 participants 17 participants
-1.72  (3.066) -0.72  (2.677) -0.90  (1.894) -1.62  (2.804) -3.53  (2.220) -0.49  (2.305) -2.25  (2.646) -0.96  (2.576) 0.20  (1.408)
Change from BL at Day 85 Number Analyzed 11 participants 9 participants 6 participants 10 participants 9 participants 8 participants 26 participants 27 participants 17 participants
-2.47  (2.446) -2.94  (2.492) -2.81  (3.653) -3.88  (2.470) -3.08  (1.624) -2.00  (2.951) -2.76  (2.446) -3.01  (2.641) -0.36  (2.238)
Change from BL at Day 113 Number Analyzed 8 participants 10 participants 4 participants 9 participants 7 participants 6 participants 19 participants 25 participants 16 participants
-2.94  (1.977) -1.03  (2.002) -1.82  (2.331) -1.99  (3.020) -3.17  (2.378) -1.54  (3.534) -2.79  (2.141) -1.50  (2.707) -0.20  (1.513)
Change from BL at EOT Number Analyzed 12 participants 11 participants 11 participants 12 participants 12 participants 13 participants 35 participants 36 participants 21 participants
-2.49  (1.896) -1.08  (1.907) -0.84  (1.766) -1.86  (2.607) -2.60  (2.531) -1.29  (3.300) -2.01  (2.192) -1.42  (2.650) -0.34  (1.445)
Change from BL at Day 141 Number Analyzed 11 participants 11 participants 6 participants 11 participants 9 participants 7 participants 26 participants 29 participants 17 participants
-0.90  (2.113) -0.82  (2.117) 0.10  (1.551) -2.17  (2.863) -0.92  (2.385) -0.87  (3.640) -0.68  (2.067) -1.34  (2.793) -0.06  (2.191)
Change from BL at Day 169 Number Analyzed 10 participants 10 participants 7 participants 8 participants 6 participants 7 participants 23 participants 25 participants 18 participants
-0.62  (2.324) -1.19  (1.885) 0.46  (1.651) -1.27  (2.684) 0.62  (1.038) 1.33  (4.219) 0.03  (1.882) -0.51  (3.036) 0.62  (2.694)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP, Pooled PBO
Comments Day 57 Cohort A: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.1
Confidence Interval (2-Sided) 95%
-3.82 to -0.36
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.87
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Day 57 Cohort A: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-2.21 to 1.29
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.88
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP, Pooled PBO
Comments Day 57 Cohort B: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-3.87 to 0.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.99
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Day 57 Cohort B: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -1.6
Confidence Interval (2-Sided) 95%
-3.34 to 0.16
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.88
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP, Pooled PBO
Comments Day 57 Cohort C: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -3.9
Confidence Interval (2-Sided) 95%
-5.50 to -2.22
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.82
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP/PBO, Pooled PBO
Comments Day 57 Cohort C: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-3.26 to 0.41
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.92
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Pooled TIP, Pooled PBO
Comments Day 57: Pooled TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.6
Confidence Interval (2-Sided) 95%
-3.98 to -1.25
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.68
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Pooled TIP/PBO, Pooled PBO
Comments Day 57: Pooled TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-2.50 to 0.19
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.67
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP, Pooled PBO
Comments Day 85 Cohort A: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-4.00 to -0.38
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Day 85 Cohort A: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-3.81 to 0.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.99
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP, Pooled PBO
Comments Day 85 Cohort B: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.7
Confidence Interval (2-Sided) 95%
-4.96 to -0.53
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.11
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Day 85 Cohort B: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -3.6
Confidence Interval (2-Sided) 95%
-5.44 to -1.73
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.93
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP, Pooled PBO
Comments Day 85 Cohort C: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -3.0
Confidence Interval (2-Sided) 95%
-4.90 to -1.07
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.96
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP/PBO, Pooled PBO
Comments Day 85 Cohort C: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.6
Confidence Interval (2-Sided) 95%
-4.66 to -0.53
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Pooled TIP, Pooled PBO
Comments Day 85: Pooled TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.6
Confidence Interval (2-Sided) 95%
-4.11 to -1.17
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.74
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Pooled TIP/PBO, Pooled PBO
Comments Day 85: Pooled TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.7
Confidence Interval (2-Sided) 95%
-4.12 to -1.23
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.72
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP, Pooled PBO
Comments Day 113 Cohort A: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-4.55 to -1.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.87
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Day 113 Cohort A: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-1.61 to 1.71
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.83
Estimation Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP, Pooled PBO
Comments Day 113 Cohort B: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.6
Confidence Interval (2-Sided) 95%
-4.93 to -0.29
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Day 113 Cohort B: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -1.9
Confidence Interval (2-Sided) 95%
-3.62 to -0.25
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.84
Estimation Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP, Pooled PBO
Comments Day 113 Cohort C: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -3.1
Confidence Interval (2-Sided) 95%
-4.94 to -1.30
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.91
Estimation Comments [Not Specified]
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP/PBO, Pooled PBO
Comments Day 113 Cohort C: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-4.37 to -0.43
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.98
Estimation Comments [Not Specified]
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Pooled TIP, Pooled PBO
Comments Day 113: Pooled TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-4.24 to -1.45
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.70
Estimation Comments [Not Specified]
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Pooled TIP/PBO, Pooled PBO
Comments Day 113: Pooled TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-2.73 to -0.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.65
Estimation Comments [Not Specified]
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP, Pooled PBO
Comments EoT Cohort A: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-3.64 to -0.73
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.73
Estimation Comments [Not Specified]
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP/PBO, Pooled PBO
Comments EoT Cohort A: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-1.61 to 1.43
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.76
Estimation Comments [Not Specified]
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP, Pooled PBO
Comments EoT Cohort B: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-2.81 to 0.25
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.77
Estimation Comments [Not Specified]
Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP/PBO, Pooled PBO
Comments EoT Cohort B: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-3.14 to -0.22
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.73
Estimation Comments [Not Specified]
Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP, Pooled PBO
Comments EoT Cohort C: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-3.89 to -0.98
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.73
Estimation Comments [Not Specified]
Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP/PBO, Pooled PBO
Comments EoT Cohort C: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-3.12 to -0.22
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.73
Estimation Comments [Not Specified]
Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Pooled TIP, Pooled PBO
Comments EoT: Pooled TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.0
Confidence Interval (2-Sided) 95%
-3.08 to -0.85
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.56
Estimation Comments [Not Specified]
Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Pooled TIP/PBO, Pooled PBO
Comments EoT: Pooled TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-2.25 to -0.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.56
Estimation Comments [Not Specified]
Hide Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP, Pooled PBO
Comments Day 141 Cohort A: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-2.63 to 0.99
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.91
Estimation Comments [Not Specified]
Hide Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Day 141 Cohort A: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-1.83 to 1.98
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.95
Estimation Comments [Not Specified]
Hide Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP, Pooled PBO
Comments Day 141 Cohort B: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-2.03 to 2.41
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.11
Estimation Comments [Not Specified]
Hide Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Day 141 Cohort B: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-3.68 to -0.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.92
Estimation Comments [Not Specified]
Hide Statistical Analysis 37
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP, Pooled PBO
Comments Day 141 Cohort C (4 capsules b.i.d.): TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-2.78 to 1.07
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.96
Estimation Comments [Not Specified]
Hide Statistical Analysis 38
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP/PBO, Pooled PBO
Comments Day 141 Cohort C: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-3.36 to 0.89
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.06
Estimation Comments [Not Specified]
Hide Statistical Analysis 39
Statistical Analysis Overview Comparison Group Selection Pooled TIP, Pooled PBO
Comments Day 141: Pooled TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-1.97 to 0.98
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.74
Estimation Comments [Not Specified]
Hide Statistical Analysis 40
Statistical Analysis Overview Comparison Group Selection Pooled TIP/PBO, Pooled PBO
Comments Day 141: Pooled TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-2.45 to 0.45
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.73
Estimation Comments [Not Specified]
Hide Statistical Analysis 41
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP, Pooled PBO
Comments Day 169 Cohort A: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-3.24 to 0.61
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.96
Estimation Comments [Not Specified]
Hide Statistical Analysis 42
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Day 169 Cohort A: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-3.05 to 0.91
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.99
Estimation Comments [Not Specified]
Hide Statistical Analysis 43
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP, Pooled PBO
Comments Day 169 Cohort B: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-2.73 to 1.62
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 44
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Day 169 Cohort B: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -2.1
Confidence Interval (2-Sided) 95%
-4.22 to -0.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 45
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP, Pooled PBO
Comments Day 169 Cohort C: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-2.48 to 2.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 46
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP/PBO, Pooled PBO
Comments Day 169 Cohort C: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-2.33 to 2.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 47
Statistical Analysis Overview Comparison Group Selection Pooled TIP, Pooled PBO
Comments Day 169: Pooled TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-2.24 to 0.86
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.77
Estimation Comments [Not Specified]
Hide Statistical Analysis 48
Statistical Analysis Overview Comparison Group Selection Pooled TIP/PBO, Pooled PBO
Comments Day 169: Pooled TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-2.61 to 0.40
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.75
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time to First Onset of Pulmonary Exacerbation by Exacerbation Category
Hide Description The time to first onset of pulmonary exacerbation compared to placebo was analyzed. Participants with pulmonary exacerbation were categorized as: a) Overall, b) Category 1 (Oral): treated with oral antibiotics only and c) Category 2 (Parenteral): treated with parenteral Antibiotics and/or requiring hospitalization. Participants were censored at the time of completion of study or early discontinuation if they did not have a pulmonary exacerbation during the study period.
Time Frame Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Cohort A (3 Capsules o.d.): TIP Cohort A (3 Capsules o.d.): TIP/PBO Cohort B (5 Capsules o.d.): TIP Cohort B (5 Capsules o.d.): TIP/PBO Cohort C (4 Capsules b.i.d.): TIP Cohort C (4 Capsules b.i.d.): TIP/PBO Pooled TIP Pooled TIP/PBO Pooled PBO
Hide Arm/Group Description:
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP)
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Pooled Tobramycin inhalation powder (TIP): For efficacy analysis, subjects assigned to TIP groups were pooled across the 3 cohorts.
Pooled Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical: For efficacy analysis, subjects assigned to TIP/PBO groups were pooled across the 3 cohorts.
Pooled inhaled placebo (PBO): For efficacy analysis, subjects assigned to Placebo groups were pooled across the 3 cohorts, as the number of placebo capsules was not expected to impact the efficacy assessments.
Overall Number of Participants Analyzed 14 13 15 14 15 15 44 42 21
Median (Full Range)
Unit of Measure: Days
Overall Number Analyzed 6 participants 4 participants 5 participants 5 participants 4 participants 6 participants 15 participants 15 participants 10 participants
NA [1] 
(39.00 to NA)
NA [1] 
(48.00 to NA)
NA [1] 
(15.00 to NA)
NA [1] 
(85.00 to NA)
NA [1] 
(127.00 to NA)
NA [1] 
(24.00 to NA)
NA [1] 
(127.00 to NA)
NA [1] 
(85.00 to NA)
173.00 [1] 
(77.00 to NA)
Oral Number Analyzed 2 participants 4 participants 3 participants 4 participants 1 participants 3 participants 6 participants 11 participants 8 participants
NA [1] 
(NA to NA)
NA [1] 
(48.00 to NA)
NA [1] 
(22.00 to NA)
NA [1] 
(85.00 to NA)
NA [1] 
(NA to NA)
NA [1] 
(84.00 to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
173.00 [1] 
(106.00 to NA)
Parenteral Number Analyzed 4 participants 0 participants 2 participants 2 participants 1 participants 4 participants 7 participants 6 participants 1 participants
NA [1] 
(110.00 to NA)
NA [1] 
(60.00 to NA)
NA [1] 
(154.00 to NA)
NA [1] 
(NA to NA)
NA [1] 
(33.00 to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
NA: Not estimable due to insufficient number of participants with events
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP, Pooled PBO
Comments Overall Cohort A: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.14 to 3.18
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Overall Cohort A: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
0.18 to 1.85
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP, Pooled PBO
Comments Overall Cohort B: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.26
Confidence Interval (2-Sided) 95%
0.42 to 3.77
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Overall Cohort B: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.20 to 1.83
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP, Pooled PBO
Comments Overall Cohort C: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.21 to 2.17
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP/PBO, Pooled PBO
Comments Overall Cohort C: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.27
Confidence Interval (2-Sided) 95%
0.44 to 3.62
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Pooled TIP, Pooled PBO
Comments Overall Pooled TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.44 to 2.23
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Pooled TIP/PBO, Pooled PBO
Comments Overall Pooled TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.34 to 1.71
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP, Pooled PBO
Comments Oral Cohort A: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
0.08 to 1.83
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Oral Cohort A: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.25 to 2.89
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP, Pooled PBO
Comments Oral Cohort B: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.25 to 3.93
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Oral Cohort B: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.19 to 2.36
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP, Pooled PBO
Comments Oral Cohort C: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
0.02 to 1.57
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP/PBO, Pooled PBO
Comments Oral Cohort C: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.16 to 2.41
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Pooled TIP, Pooled PBO
Comments Oral Pooled TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.13 to 1.31
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Pooled TIP/PBO, Pooled PBO
Comments Oral Pooled TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.28 to 1.80
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP, Pooled PBO
Comments Parenteral Cohort A: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 10.71
Confidence Interval (2-Sided) 95%
1.10 to 104.19
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP, Pooled PBO
Comments Parenteral Cohort B: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 4.62
Confidence Interval (2-Sided) 95%
0.41 to 52.29
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Parenteral Cohort B: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 3.23
Confidence Interval (2-Sided) 95%
0.28 to 37.06
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP, Pooled PBO
Comments Parenteral Cohort C: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.61
Confidence Interval (2-Sided) 95%
0.10 to 25.94
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP/PBO, Pooled PBO
Comments Parenteral Cohort C: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 11.30
Confidence Interval (2-Sided) 95%
1.09 to 117.34
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Pooled TIP, Pooled PBO
Comments Parenteral Pooled TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 4.30
Confidence Interval (2-Sided) 95%
0.50 to 37.32
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
4.Secondary Outcome
Title Duration of Pulmonary Exacerbation by Exacerbation Category
Hide Description The duration of pulmonary exacerbation compared to placebo was analyzed. Participants with pulmonary exacerbation were categorized as: a) Overall, b) Category 1 (Oral): treated with oral antibiotics only and c) Category 2 (Parenteral): treated with parenteral Antibiotics and/or requiring hospitalization.
Time Frame Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Cohort A (3 Capsules o.d.): TIP Cohort A (3 Capsules o.d.): TIP/PBO Cohort B (5 Capsules o.d.): TIP Cohort B (5 Capsules o.d.): TIP/PBO Cohort C (4 Capsules b.i.d.): TIP Cohort C (4 Capsules b.i.d.): TIP/PBO Pooled TIP Pooled TIP/PBO Pooled PBO
Hide Arm/Group Description:
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP)
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Pooled Tobramycin inhalation powder (TIP): For efficacy analysis, subjects assigned to TIP groups were pooled across the 3 cohorts.
Pooled Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical: For efficacy analysis, subjects assigned to TIP/PBO groups were pooled across the 3 cohorts.
Pooled inhaled placebo (PBO): For efficacy analysis, subjects assigned to Placebo groups were pooled across the 3 cohorts, as the number of placebo capsules was not expected to impact the efficacy assessments.
Overall Number of Participants Analyzed 14 13 15 14 15 15 44 42 21
Mean (Standard Deviation)
Unit of Measure: Days
Overall Number Analyzed 10 participants 8 participants 6 participants 7 participants 4 participants 8 participants 20 participants 23 participants 13 participants
15.7  (6.22) 18.0  (8.26) 20.2  (6.37) 10.3  (5.12) 25.5  (27.09) 14.8  (6.73) 19.0  (12.64) 15.2  (7.39) 14.5  (5.61)
Oral Number Analyzed 2 participants 7 participants 4 participants 5 participants 1 participants 3 participants 7 participants 15 participants 11 participants
19.5  (12.02) 15.4  (4.24) 19.3  (3.20) 8.3  (4.16) 14.0 [1]   (NA) 16.3  (5.51) 18.6  (5.77) 14.0  (5.24) 15.6  (5.75)
Parenteral Number Analyzed 5 participants 0 participants 2 participants 2 participants 1 participants 4 participants 8 participants 6 participants 1 participants
15.0  (5.52) 22.0  (12.73) 16.0 [1]   (NA) 66.0 [1]   (NA) 16.8  (4.86) 23.1  (18.73) 16.6  (4.22) 10.0 [1]   (NA)
[1]
NA: Not estimable due to insufficient number of participants with events
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP, Pooled PBO
Comments Overall Cohort A: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value 9.8
Confidence Interval (2-Sided) 95%
-27.15 to 46.81
Parameter Dispersion
Type: Standard Error of the Mean
Value: 18.15
Estimation Comments ANCOVA model includes treatment as a fixed-effect factor and number of pulmonary exacerbations in the 12 months prior to screening as a covariate.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Overall Cohort A: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value 19.8
Confidence Interval (2-Sided) 95%
-22.63 to 62.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 20.81
Estimation Comments ANCOVA model includes treatment as a fixed-effect factor and number of pulmonary exacerbations in the 12 months prior to screening as a covariate.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP, Pooled PBO
Comments Overall Cohort B: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value 8.0
Confidence Interval (2-Sided) 95%
-31.32 to 47.26
Parameter Dispersion
Type: Standard Error of the Mean
Value: 19.29
Estimation Comments ANCOVA model includes treatment as a fixed-effect factor and number of pulmonary exacerbations in the 12 months prior to screening as a covariate.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Overall Cohort B: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value 12.7
Confidence Interval (2-Sided) 95%
-26.49 to 51.89
Parameter Dispersion
Type: Standard Error of the Mean
Value: 19.24
Estimation Comments ANCOVA model includes treatment as a fixed-effect factor and number of pulmonary exacerbations in the 12 months prior to screening as a covariate.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP, Pooled PBO
Comments Overall Cohort C: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value 46.5
Confidence Interval (2-Sided) 95%
3.37 to 89.61
Parameter Dispersion
Type: Standard Error of the Mean
Value: 21.17
Estimation Comments ANCOVA model includes treatment as a fixed-effect factor and number of pulmonary exacerbations in the 12 months prior to screening as a covariate.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP/PBO, Pooled PBO
Comments Overall Cohort C: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value 3.2
Confidence Interval (2-Sided) 95%
-34.21 to 40.64
Parameter Dispersion
Type: Standard Error of the Mean
Value: 18.37
Estimation Comments ANCOVA model includes treatment as a fixed-effect factor and number of pulmonary exacerbations in the 12 months prior to screening as a covariate.
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Pooled TIP, Pooled PBO
Comments Overall Pooled TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value 21.4
Confidence Interval (2-Sided) 95%
-8.03 to 50.89
Parameter Dispersion
Type: Standard Error of the Mean
Value: 14.46
Estimation Comments ANCOVA model includes treatment as a fixed-effect factor and number of pulmonary exacerbations in the 12 months prior to screening as a covariate.
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Pooled TIP/PBO, Pooled PBO
Comments Overall Pooled TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Diff (SE) vs pooled placebo
Estimated Value 11.9
Confidence Interval (2-Sided) 95%
-17.52 to 41.29
Parameter Dispersion
Type: Standard Error of the Mean
Value: 14.44
Estimation Comments ANCOVA model includes treatment as a fixed-effect factor and number of pulmonary exacerbations in the 12 months prior to screening as a covariate.
5.Secondary Outcome
Title Exposure Adjusted Rate of Pulmonary Exacerbations (PE) Over the Entire Study Period
Hide Description The exposure adjusted rate of pulmonary exacerbation compared to placebo was analyzed. Participants with pulmonary exacerbation were categorized as: a) Overall, b) Category 1 (Oral): treated with oral antibiotics only and c) Category 2 (Parenteral): treated with parenteral Antibiotics and/or requiring hospitalization. The Exposure adjusted rate = (Number of pulmonary exacerbations reported during the study period) / (sum of study duration in days for all participants/ 365.25). Only descriptive analysis performed.
Time Frame Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Cohort A (3 Capsules o.d.): TIP Cohort A (3 Capsules o.d.): TIP/PBO Cohort B (5 Capsules o.d.): TIP Cohort B (5 Capsules o.d.): TIP/PBO Cohort C (4 Capsules b.i.d.): TIP Cohort C (4 Capsules b.i.d.): TIP/PBO Pooled TIP Pooled TIP/PBO Pooled PBO
Hide Arm/Group Description:
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP)
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Pooled Tobramycin inhalation powder (TIP): For efficacy analysis, subjects assigned to TIP groups were pooled across the 3 cohorts.
Pooled Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical: For efficacy analysis, subjects assigned to TIP/PBO groups were pooled across the 3 cohorts.
Pooled inhaled placebo (PBO): For efficacy analysis, subjects assigned to Placebo groups were pooled across the 3 cohorts, as the number of placebo capsules was not expected to impact the efficacy assessments.
Overall Number of Participants Analyzed 14 13 15 14 15 15 44 42 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: pulmonary exacerbation per study years
Overall Number Analyzed 6 participants 4 participants 5 participants 5 participants 4 participants 6 participants 15 participants 15 participants 10 participants
1.71
(0.92 to 3.17)
1.39
(0.70 to 2.78)
1.29
(0.58 to 2.87)
1.20
(0.57 to 2.51)
0.66
(0.25 to 1.76)
1.46
(0.73 to 2.93)
1.21
(0.78 to 1.87)
1.35
(0.90 to 2.03)
1.41
(0.82 to 2.42)
Oral Number Analyzed 2 participants 4 participants 3 participants 4 participants 1 participants 3 participants 6 participants 11 participants 8 participants
0.34
(0.09 to 1.37)
1.22
(0.58 to 2.56)
0.86
(0.32 to 2.29)
0.85
(0.36 to 2.05)
0.16
(0.02 to 1.17)
0.55
(0.18 to 1.70)
0.42
(0.20 to 0.89)
0.88
(0.53 to 1.46)
1.19
(0.66 to 2.15)
Parenteral Number Analyzed 4 participants 0 participants 2 participants 2 participants 1 participants 4 participants 7 participants 6 participants 1 participants
0.85
(0.36 to 2.05)
0.43
(0.11 to 1.72)
0.34
(0.09 to 1.37)
0.16
(0.02 to 1.17)
0.73
(0.27 to 1.95)
0.48
(0.24 to 0.96)
0.35
(0.16 to 0.78)
0.11
(0.02 to 0.77)
6.Secondary Outcome
Title Percentage of Participants With at Least One Pulmonary Exacerbation by Exacerbation Category
Hide Description

Pulmonary exacerbations are defined as events requiring antibiotic therapy AND for which at least 3 of the following 6 symptoms, signs, or findings were present outside of normal variation: 1. Increased sputum volume, or change in viscosity/consistency or purulence for more than 24 hours; 2. Increased shortness of breath at rest or on exercise for more than 24 hours; 3. Increased cough for more than 24 hours; 4. Fever of ≥38° Celsius within the last 24 hours; 5. Increased malaise/fatigue/lethargy for more than 24 hours; 6. A reduction in forced expiratory volume in the first second of expiration (FEV1) or forced vital capacity (FVC) of least 10% from screening.

Participants were categorized as: a) Overall, b) Category 1: treated with oral antibiotics only and c) Category 2: treated with parenteral Antibiotics and/or requiring hospitalization.

Only descriptive analysis performed.

Time Frame Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Cohort A (3 Capsules o.d.): TIP Cohort A (3 Capsules o.d.): TIP/PBO Cohort B (5 Capsules o.d.): TIP Cohort B (5 Capsules o.d.): TIP/PBO Cohort C (4 Capsules b.i.d.): TIP Cohort C (4 Capsules b.i.d.): TIP/PBO Pooled TIP Pooled TIP/PBO Pooled PBO
Hide Arm/Group Description:
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP)
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Pooled Tobramycin inhalation powder (TIP): For efficacy analysis, subjects assigned to TIP groups were pooled across the 3 cohorts.
Pooled Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical: For efficacy analysis, subjects assigned to TIP/PBO groups were pooled across the 3 cohorts.
Pooled inhaled placebo (PBO): For efficacy analysis, subjects assigned to Placebo groups were pooled across the 3 cohorts, as the number of placebo capsules was not expected to impact the efficacy assessments.
Overall Number of Participants Analyzed 14 13 15 14 15 15 44 42 21
Measure Type: Count of Participants
Unit of Measure: Participants
Overall No of participants with no events
8
  57.1%
9
  69.2%
10
  66.7%
9
  64.3%
11
  73.3%
9
  60.0%
29
  65.9%
27
  64.3%
11
  52.4%
No. of participants with 1 event
3
  21.4%
1
   7.7%
4
  26.7%
3
  21.4%
4
  26.7%
4
  26.7%
11
  25.0%
8
  19.0%
7
  33.3%
No. of participants with 2 events
2
  14.3%
2
  15.4%
1
   6.7%
2
  14.3%
0
   0.0%
2
  13.3%
3
   6.8%
6
  14.3%
3
  14.3%
No. of participants with 3 events
1
   7.1%
1
   7.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.3%
1
   2.4%
0
   0.0%
Oral No of participants with no events
12
  85.7%
9
  69.2%
12
  80.0%
10
  71.4%
14
  93.3%
12
  80.0%
38
  86.4%
31
  73.8%
13
  61.9%
No. of participants with 1 event
2
  14.3%
2
  15.4%
2
  13.3%
3
  21.4%
1
   6.7%
3
  20.0%
5
  11.4%
8
  19.0%
5
  23.8%
No. of participants with 2 events
0
   0.0%
1
   7.7%
1
   6.7%
1
   7.1%
0
   0.0%
0
   0.0%
1
   2.3%
2
   4.8%
3
  14.3%
No. of participants with 3 events
0
   0.0%
1
   7.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.4%
0
   0.0%
Parenteral No of participants with no events
10
  71.4%
13
 100.0%
13
  86.7%
12
  85.7%
14
  93.3%
11
  73.3%
37
  84.1%
36
  85.7%
20
  95.2%
No. of participants with 1 event
3
  21.4%
0
   0.0%
2
  13.3%
2
  14.3%
1
   6.7%
4
  26.7%
6
  13.6%
6
  14.3%
1
   4.8%
No. of participants with 2 events
1
   7.1%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.3%
0
   0.0%
0
   0.0%
No. of participants with 3 events
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
7.Secondary Outcome
Title Percentage of Participants Who Permanently Discontinued Study Drug Due to Pulmonary Exacerbation
Hide Description The percentage of participants who permanently discontinued study drug due to pulmonary exacerbation compared to placebo was analyzed.
Time Frame Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Cohort A (3 Capsules o.d.): TIP Cohort A (3 Capsules o.d.): TIP/PBO Cohort B (5 Capsules o.d.): TIP Cohort B (5 Capsules o.d.): TIP/PBO Cohort C (4 Capsules b.i.d.): TIP Cohort C (4 Capsules b.i.d.): TIP/PBO Pooled TIP Pooled TIP/PBO Pooled PBO
Hide Arm/Group Description:
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP)
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Pooled Tobramycin inhalation powder (TIP): For efficacy analysis, subjects assigned to TIP groups were pooled across the 3 cohorts.
Pooled Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical: For efficacy analysis, subjects assigned to TIP/PBO groups were pooled across the 3 cohorts.
Pooled inhaled placebo (PBO): For efficacy analysis, subjects assigned to Placebo groups were pooled across the 3 cohorts, as the number of placebo capsules was not expected to impact the efficacy assessments.
Overall Number of Participants Analyzed 14 13 15 14 15 15 44 42 21
Measure Type: Count of Participants
Unit of Measure: Participants
2
  14.3%
0
   0.0%
1
   6.7%
0
   0.0%
0
   0.0%
2
  13.3%
41
  93.2%
40
  95.2%
0
   0.0%
8.Secondary Outcome
Title Time to Permanent Study Drug Discontinuation Due to Pulmonary Exacerbation
Hide Description The time to permanent study drug discontinuation due to Pulmonary exacerbation. Participants were censored at the time of last contact if they did not permanently discontinue study drug due to pulmonary exacerbation requiring during the study period. Only descriptive analysis performed.
Time Frame Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Cohort A (3 Capsules o.d.): TIP Cohort A (3 Capsules o.d.): TIP/PBO Cohort B (5 Capsules o.d.): TIP Cohort B (5 Capsules o.d.): TIP/PBO Cohort C (4 Capsules b.i.d.): TIP Cohort C (4 Capsules b.i.d.): TIP/PBO Pooled TIP Pooled TIP/PBO Pooled PBO
Hide Arm/Group Description:
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP)
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Pooled Tobramycin inhalation powder (TIP): For efficacy analysis, subjects assigned to TIP groups were pooled across the 3 cohorts.
Pooled Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical: For efficacy analysis, subjects assigned to TIP/PBO groups were pooled across the 3 cohorts.
Pooled inhaled placebo (PBO): For efficacy analysis, subjects assigned to Placebo groups were pooled across the 3 cohorts, as the number of placebo capsules was not expected to impact the efficacy assessments.
Overall Number of Participants Analyzed 14 13 15 14 15 15 44 42 21
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(94.00 to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(84.00 to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
NA: Not estimable due to insufficient number of participants with events
9.Secondary Outcome
Title Time to First Use (Overall, Oral, and Parenteral) of Anti-pseudomonal Antibiotics Usage
Hide Description The time to first use of anti-pseudomonal antibiotics administered compared to placebo was analyzed. Participants were censored at the time of last contact if they did not have anti-pseudomonal antibiotics over the entire study period.
Time Frame From Baseline (Visit 101/Day 1) up to approximately Day 173
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set. Only the participants who required antipseudomonal antibiotics were included.
Arm/Group Title Cohort A (3 Capsules o.d.): TIP Cohort A (3 Capsules o.d.): TIP/PBO Cohort B (5 Capsules o.d.): TIP Cohort B (5 Capsules o.d.): TIP/PBO Cohort C (4 Capsules b.i.d.): TIP Cohort C (4 Capsules b.i.d.): TIP/PBO Pooled TIP Pooled TIP/PBO Pooled PBO
Hide Arm/Group Description:
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort A (3 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP)
Cohort B (5 capsules o.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP)
Cohort C (4 capsules b.i.d.): Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical
Pooled Tobramycin inhalation powder (TIP): For efficacy analysis, subjects assigned to TIP groups were pooled across the 3 cohorts.
Pooled Tobramycin inhalation powder (TIP) and inhaled placebo (PBO) cyclical: For efficacy analysis, subjects assigned to TIP/PBO groups were pooled across the 3 cohorts.
Pooled inhaled placebo (PBO): For efficacy analysis, subjects assigned to Placebo groups were pooled across the 3 cohorts, as the number of placebo capsules was not expected to impact the efficacy assessments.
Overall Number of Participants Analyzed 14 13 15 14 15 15 44 42 21
Median (Full Range)
Unit of Measure: Days
Overall Number Analyzed 8 participants 4 participants 6 participants 7 participants 3 participants 7 participants 17 participants 18 participants 12 participants
122.00 [1] 
(29.00 to NA)
NA [1] 
(50.00 to NA)
116.00 [1] 
(17.00 to NA)
161.00 [1] 
(58.00 to NA)
NA [1] 
(127.00 to NA)
NA [1] 
(11.00 to NA)
NA [1] 
(110.00 to NA)
NA [1] 
(84.00 to NA)
141.00 [1] 
(57.00 to NA)
Oral Number Analyzed 5 participants 4 participants 5 participants 6 participants 2 participants 6 participants 12 participants 16 participants 10 participants
NA [1] 
(43.00 to NA)
NA [1] 
(50.00 to NA)
NA [1] 
(17.00 to NA)
NA [1] 
(85.00 to NA)
NA [1] 
(NA to NA)
NA [1] 
(11.00 to NA)
NA [1] 
(NA to NA)
NA [1] 
(85.00 to NA)
173.00 [1] 
(106.00 to NA)
Parenteral Number Analyzed 5 participants 0 participants 2 participants 4 participants 1 participants 4 participants 8 participants 8 participants 3 participants
NA [1] 
(105.0 to NA)
NA [1] 
(63.00 to NA)
NA [1] 
(95.00 to NA)
NA [1] 
(NA to NA)
NA [1] 
(37.00 to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
NA: Not estimable due to insufficient number of participants with events
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP, Pooled PBO
Comments Overall Cohort A: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.26
Confidence Interval (2-Sided) 95%
0.51 to 3.13
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Overall Cohort A: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.15 to 1.46
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP, Pooled PBO
Comments Overall Cohort B: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.18
Confidence Interval (2-Sided) 95%
0.44 to 3.21
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Overall Cohort B: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.32 to 2.18
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP, Pooled PBO
Comments Overall Cohort C: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
0.10 to 1.27
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP/PBO, Pooled PBO
Comments Overall Cohort C: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.43 to 2.99
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Pooled TIP, Pooled PBO
Comments Overall Pooled TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.37 to 1.76
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Pooled TIP/PBO, Pooled PBO
Comments Overall Pooled TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.36 to 1.61
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP, Pooled PBO
Comments Oral Cohort A: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.30 to 2.55
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Oral Cohort A: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.20 to 2.03
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP, Pooled PBO
Comments Oral Cohort B: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
0.40 to 3.60
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Oral Cohort B: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.31 to 2.55
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP, Pooled PBO
Comments Oral Cohort C: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.28
Confidence Interval (2-Sided) 95%
0.06 to 1.27
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP/PBO, Pooled PBO
Comments Oral Cohort C: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.30
Confidence Interval (2-Sided) 95%
0.45 to 3.73
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Pooled TIP, Pooled PBO
Comments Oral Pooled TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.27 to 1.60
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Pooled TIP/PBO, Pooled PBO
Comments Oral Pooled TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.40 to 2.02
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Cohort A (3 Capsules o.d.): TIP, Pooled PBO
Comments Parenteral Cohort A: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 3.72
Confidence Interval (2-Sided) 95%
0.84 to 16.52
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP, Pooled PBO
Comments Parenteral Cohort B: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.34
Confidence Interval (2-Sided) 95%
0.22 to 8.16
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Cohort B (5 Capsules o.d.): TIP/PBO, Pooled PBO
Comments Parenteral Cohort B: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.15
Confidence Interval (2-Sided) 95%
0.46 to 10.05
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP, Pooled PBO
Comments Parenteral Cohort C: TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
0.05 to 4.87
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Cohort C (4 Capsules b.i.d.): TIP/PBO, Pooled PBO
Comments Parenteral Cohort C: TIP/PBO, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.56
Confidence Interval (2-Sided) 95%
0.53 to 12.49
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Pooled TIP, Pooled PBO
Comments Paremteral Pooled TIP, Pooled PBO
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.36
Confidence Interval (2-Sided) 95%
0.33 to 5.68
Estimation Comments Based on Cox proportional hazards model with treatment as fixed effect and number of pulmonary exacerbations in the 12 months prior to screening as a covariate, stratified by baseline macrolide use.
10.Secondary Outcome
Title Percentage of Participants Requiring Anti-pseudomonal Antibiotics
Hide Description The percentage of participants requiring anti-pseudomonal antibiotics compared to placebo was analyzed. Only descriptive analysis performed.
Time Frame Baseline (Visit 101/Day 1) to Visit 202 (Day 169)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Cohort A (3 Capsules o.d.): TIP Cohort A (3 Capsules o.d.): TIP/PBO Cohort B (5 Capsules o.d.): TIP Cohort B (5 Capsules o.d.): TIP/PBO Cohort C (4 Capsules b.i.d.): TIP Cohort C (4 Capsules b.i.d.): TIP/PBO Pooled TIP Pooled TIP/PBO Pooled PBO