Trial Outcomes & Findings for Evaluation of Lung Clearance Index in Cystic Fibrosis (CF) Patients, Infected With P.Aeruginosa (NCT NCT02248922)
NCT ID: NCT02248922
Last Updated: 2018-10-09
Results Overview
The Lung Clearance Index (LCI), measured by Multiple Breath Washout of a tracer gas reflects the obstruction of airways in the lung. Wash-out was completed by definition at the time point when the inhaled gas concentration declined to 2.5% of its concentration at baseline. Washout took longer in patients with more severe disease as gas was trapped in narrowed airways (leading to a higher LCI). A LCI of 7.5 and below is normal.
TERMINATED
PHASE4
17 participants
Baseline, week 4
2018-10-09
Participant Flow
At least 35 patients were planned to be recruited in the study. However, in total, 17 patients entered into the study and completed. Reason for termination was challenge with enrollment and recruitment. A significant decrease in the eligible patient population was main driver.
Participant milestones
| Measure |
Tobramycin Inhalation Solution(TIS)
300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) twice a day (BID) 28days on / 28 days off
|
Tobramycin Inhalation Powder (TIP)
TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)twice a day (BID) 28days on / 28 days off
|
|---|---|---|
|
Overall Study
STARTED
|
5
|
12
|
|
Overall Study
COMPLETED
|
5
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Evaluation of Lung Clearance Index in Cystic Fibrosis (CF) Patients, Infected With P.Aeruginosa
Baseline characteristics by cohort
| Measure |
Tobramycin Inhalation Solution(TIS)
n=5 Participants
300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) twice a day (BID) 28days on / 28 days off
|
Tobramycin Inhalation Powder (TIP)
n=12 Participants
TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)twice a day (BID) 28days on / 28 days off
|
Total
n=17 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
20.2 years
STANDARD_DEVIATION 8.26 • n=5 Participants
|
28.9 years
STANDARD_DEVIATION 9.79 • n=7 Participants
|
26.4 years
STANDARD_DEVIATION 9.99 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, week 4Population: Safety Set consisted of All 17 patients (in both arms: TIS and TIP) that entered the study (provided informed consent) and had been exposed to at least one dose of study drug. The efficacy analysis was based on safety set of Tobramycin ALL and not for each separate dosage form arm.
The Lung Clearance Index (LCI), measured by Multiple Breath Washout of a tracer gas reflects the obstruction of airways in the lung. Wash-out was completed by definition at the time point when the inhaled gas concentration declined to 2.5% of its concentration at baseline. Washout took longer in patients with more severe disease as gas was trapped in narrowed airways (leading to a higher LCI). A LCI of 7.5 and below is normal.
Outcome measures
| Measure |
Tobramycin ALL
n=17 Participants
300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) or TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)twice a day (BID) 28days on / 28 days off
|
|---|---|
|
Change From Baseline in Lung Clearance Index (LCI) After 4 Weeks Following Onset of Study
Baseline
|
17.985 units on a scale
Standard Error 1.1494
|
|
Change From Baseline in Lung Clearance Index (LCI) After 4 Weeks Following Onset of Study
Week 4
|
17.101 units on a scale
Standard Error 0.8409
|
SECONDARY outcome
Timeframe: Baseline, week 4Population: Safety Set consisted of All 17 patients (in both arms: TIS and TIP) that entered the study (provided informed consent) and had been exposed to at least one dose of study drug. The efficacy analysis was based on safety set of Tobramycin ALL and not for each separate dosage form arm.
Change of FEV1 (Forced expiry volume in the first second) measured by Spirometry
Outcome measures
| Measure |
Tobramycin ALL
n=17 Participants
300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) or TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)twice a day (BID) 28days on / 28 days off
|
|---|---|
|
Change From Baseline of Forced Expiratory Volume at 1 Second (FEV1) After 4 Weeks Following Onset of Study
Baseline
|
76.964 % predicted
Standard Error 4.5121
|
|
Change From Baseline of Forced Expiratory Volume at 1 Second (FEV1) After 4 Weeks Following Onset of Study
Week 4
|
77.481 % predicted
Standard Error 4.9877
|
SECONDARY outcome
Timeframe: Baseline, week 4Population: Safety Set consisted of All 17 patients (in both arms: TIS and TIP) that entered the study and had been exposed to at least one dose of study drug. The efficacy analysis was based on safety set of Tobramycin ALL and not for each separate dosage form arm. n is the number of patients of safety set with a non-missing value at the specific time point.
Microbacterial density of Pseudomonas aeruginosa in Sputum-Samples in CFU (Colony Forming Units) per gram sputum.
Outcome measures
| Measure |
Tobramycin ALL
n=17 Participants
300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) or TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)twice a day (BID) 28days on / 28 days off
|
|---|---|
|
Change From Baseline of Colony-forming Units (CFU) After 4 Weeks Following Onset of Study
Baseline
|
56594.3 CFU per gram sputum
Standard Error 28018.89
|
|
Change From Baseline of Colony-forming Units (CFU) After 4 Weeks Following Onset of Study
Week 4
|
26113.0 CFU per gram sputum
Standard Error 27280.98
|
SECONDARY outcome
Timeframe: Baseline, week 1Population: Safety Set consisted of All 17 patients (in both arms: TIS and TIP) that entered the study (provided informed consent) and had been exposed to at least one dose of study drug. The efficacy analysis was based on safety set of Tobramycin ALL and not for each separate dosage form arm.
The Lung Clearance Index (LCI), measured by Multiple Breath Washout of a tracer gas reflects the obstruction of airways in the lung. Wash-out was completed by definition at the time point when the inhaled gas concentration declined to 2.5% of its concentration at baseline. Washout took longer in patients with more severe disease as gas was trapped in narrowed airways (leading to a higher LCI). A LCI of 7.5 and below is normal.
Outcome measures
| Measure |
Tobramycin ALL
n=17 Participants
300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) or TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)twice a day (BID) 28days on / 28 days off
|
|---|---|
|
Change From Baseline in Lung Clearance Index (LCI) After 1 Week
Baseline
|
17.985 units on a scale
Standard Error 1.1494
|
|
Change From Baseline in Lung Clearance Index (LCI) After 1 Week
Week 1
|
17.506 units on a scale
Standard Error 1.0002
|
SECONDARY outcome
Timeframe: week 4, week 8Population: Safety Set consisted of All 17 patients (in both arms: TIS and TIP) that entered the study (provided informed consent) and had been exposed to at least one dose of study drug. The efficacy analysis was based on safety set of Tobramycin ALL and not for each separate dosage form arm.
The Lung Clearance Index (LCI), measured by Multiple Breath Washout of a tracer gas reflects the obstruction of airways in the lung. Wash-out was completed by definition at the time point when the inhaled gas concentration declined to 2.5% of its concentration at baseline. Washout took longer in patients with more severe disease as gas was trapped in narrowed airways (leading to a higher LCI). A LCI of 7.5 and below is normal.
Outcome measures
| Measure |
Tobramycin ALL
n=17 Participants
300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) or TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)twice a day (BID) 28days on / 28 days off
|
|---|---|
|
Change of Lung Clearance Index (LCI) Between Week 4 (End of Study Drug Inhalation in the Current Treatment Cycle) and Week 8 (Prior to Start of Study Drug Inhalation in the Following Treatment Cycle)
Week 4
|
17.101 Units on a scale
Standard Error 0.8409
|
|
Change of Lung Clearance Index (LCI) Between Week 4 (End of Study Drug Inhalation in the Current Treatment Cycle) and Week 8 (Prior to Start of Study Drug Inhalation in the Following Treatment Cycle)
Week 8
|
16.489 Units on a scale
Standard Error 1.1473
|
SECONDARY outcome
Timeframe: week 4, week 8Population: Safety Set consisted of All 17 patients (in both arms: TIS and TIP) that entered the study (provided informed consent) and had been exposed to at least one dose of study drug. The efficacy analysis was based on safety set of Tobramycin ALL and not for each separate dosage form arm.
Change of FEV1 (Forced expiry volume in the first second) measured by Spirometry
Outcome measures
| Measure |
Tobramycin ALL
n=17 Participants
300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) or TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)twice a day (BID) 28days on / 28 days off
|
|---|---|
|
Change of Forced Expiratory Volume at 1 Second(FEV1) Between Week 4 (End of Study Drug Inhalation in the Current Treatment Cycle) and Week 8 (Prior to Start of Study Drug Inhalation in the Following Treatment Cycle)
Week 4
|
77.481 % predicted
Standard Error 4.9877
|
|
Change of Forced Expiratory Volume at 1 Second(FEV1) Between Week 4 (End of Study Drug Inhalation in the Current Treatment Cycle) and Week 8 (Prior to Start of Study Drug Inhalation in the Following Treatment Cycle)
Week 8
|
78.705 % predicted
Standard Error 5.4782
|
SECONDARY outcome
Timeframe: week 4, week 8Population: Safety Set consisted of All 17 patients (in both arms: TIS and TIP) that entered the study and had been exposed to at least one dose of study drug. The efficacy analysis was based on safety set of Tobramycin ALL and not for each separate dosage form arm. n is the number of patients of safety set with a non-missing value at the specific time point.
Microbacterial density of Pseudomonas aeruginosa in Sputum-Samples in CFU (Colony Forming Units) per gram sputum.
Outcome measures
| Measure |
Tobramycin ALL
n=17 Participants
300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) or TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)twice a day (BID) 28days on / 28 days off
|
|---|---|
|
Change of Colony-forming Units (CFU) Between Week 4 (End of Study Drug Inhalation in the Current Treatment Cycle) and Week 8 (Prior to Start of Study Drug Inhalation in the Following Treatment Cycle)
Week 4
|
26113.0 CFU per gram sputum
Standard Error 27280.98
|
|
Change of Colony-forming Units (CFU) Between Week 4 (End of Study Drug Inhalation in the Current Treatment Cycle) and Week 8 (Prior to Start of Study Drug Inhalation in the Following Treatment Cycle)
Week 8
|
56285.0 CFU per gram sputum
Standard Error 28022.28
|
Adverse Events
Tobramycin Inhalation Solution(TIS)
Tobramycin Inhalation Powder (TIP)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Tobramycin Inhalation Solution(TIS)
n=5 participants at risk
300mg nebulized Tobramycin (Tobramycin inhalation solution(TIS)) twice a day (BID) 28days on / 28 days off
|
Tobramycin Inhalation Powder (TIP)
n=12 participants at risk
TOBI Podhaler (Tobramycin inhalation powder(TIP), equivalent dry powder)twice a day (BID) 28days on / 28 days off
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/5 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment through study completion, an average of 11 weeks.
AE additional description
|
8.3%
1/12 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment through study completion, an average of 11 weeks.
AE additional description
|
|
Injury, poisoning and procedural complications
Sunburn
|
20.0%
1/5 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment through study completion, an average of 11 weeks.
AE additional description
|
0.00%
0/12 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment through study completion, an average of 11 weeks.
AE additional description
|
|
Investigations
Forced expiratory volume decreased
|
0.00%
0/5 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment through study completion, an average of 11 weeks.
AE additional description
|
8.3%
1/12 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment through study completion, an average of 11 weeks.
AE additional description
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/5 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment through study completion, an average of 11 weeks.
AE additional description
|
8.3%
1/12 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment through study completion, an average of 11 weeks.
AE additional description
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
20.0%
1/5 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment through study completion, an average of 11 weeks.
AE additional description
|
0.00%
0/12 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment through study completion, an average of 11 weeks.
AE additional description
|
|
Respiratory, thoracic and mediastinal disorders
Obstructive airways disorder
|
0.00%
0/5 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment through study completion, an average of 11 weeks.
AE additional description
|
8.3%
1/12 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment through study completion, an average of 11 weeks.
AE additional description
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single- site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER