Trial Outcomes & Findings for Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles (NCT NCT02015663)
NCT ID: NCT02015663
Last Updated: 2017-03-29
Results Overview
The Forced Expiratory Volume in 1 second (FEV1) percent predicted expresses FEV1 as a percentage of the "predicted values" for participants of similar characteristics (height, age, sex, and sometimes race and weight). A positive change from baseline in FEV1 percent predicted indicates improvement in lung function.
TERMINATED
PHASE4
32 participants
Baseline and Day 168
2017-03-29
Participant Flow
The study intended to randomize 200 patients in 18 months; however, after 9 months, only 25 patients were randomized, with a screen fail rate of 50%. Due to premature termination, summaries and analyses planned in the protocol were eliminated in the statistical analysis plan prior to database lock. No inferential analysis will be provided.
Participant milestones
| Measure |
Tobramycin Inhalation Powder Once Daily
Tobramycin Inhalation Powder (112 mg) once daily during 168 days
|
Tobramycin Inhalation Powder Twice Daily
Tobramycin Inhalation Powder (112 mg) twice daily on days 1-28, days 57-84 and days 113-140
|
|---|---|---|
|
Overall Study
STARTED
|
16
|
16
|
|
Overall Study
COMPLETED
|
1
|
4
|
|
Overall Study
NOT COMPLETED
|
15
|
12
|
Reasons for withdrawal
| Measure |
Tobramycin Inhalation Powder Once Daily
Tobramycin Inhalation Powder (112 mg) once daily during 168 days
|
Tobramycin Inhalation Powder Twice Daily
Tobramycin Inhalation Powder (112 mg) twice daily on days 1-28, days 57-84 and days 113-140
|
|---|---|---|
|
Overall Study
unsatisfactory therapeutic effect
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Adverse Event
|
3
|
0
|
|
Overall Study
Administrative problems
|
10
|
11
|
Baseline Characteristics
Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles
Baseline characteristics by cohort
| Measure |
Tobramycin Inhalation Powder Once Daily
n=16 Participants
Tobramycin Inhalation Powder (112 mg) once daily during 168 days
|
Tobramycin Inhalation Powder Twice Daily
n=16 Participants
Tobramycin Inhalation Powder (112 mg) twice daily on days 1-28, days 57-84 and days 113-140
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
34.9 year
STANDARD_DEVIATION 14.31 • n=5 Participants
|
26.5 year
STANDARD_DEVIATION 11.09 • n=7 Participants
|
30.7 year
STANDARD_DEVIATION 13.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Day 168Population: The study intended to randomize 200 patients within 18 months; however, after 9 months, only 32 patients were successfully randomized, with a screen fail rate of 50%. Study was terminated with only safety data analyzed. No data collected met the pre-specified powering of 200 patients needed for analysis (only 32 patients randomized)
The Forced Expiratory Volume in 1 second (FEV1) percent predicted expresses FEV1 as a percentage of the "predicted values" for participants of similar characteristics (height, age, sex, and sometimes race and weight). A positive change from baseline in FEV1 percent predicted indicates improvement in lung function.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Day 168Population: The study intended to randomize 200 patients within 18 months; however, after 9 months, only 32 patients were successfully randomized, with a screen fail rate of 50%. Study was terminated with only safety data analyzed. No data collected met the pre-specified powering of 200 patients needed for analysis (only 32 patients randomized)
The Forced Expiratory Volume in 1 second (FEV1) percent predicted expresses FEV1 as a percentage of the "predicted values" for participants of similar characteristics (height, age, sex, and sometimes race and weight). A positive change from baseline in FEV1 percent predicted indicates improvement in lung function.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Day 168Population: The study intended to randomize 200 patients within 18 months; however, after 9 months, only 32 patients were successfully randomized, with a screen fail rate of 50%. Study was terminated with only safety data analyzed. No data collected met the pre-specified powering of 200 patients needed for analysis (only 32 patients randomized)
Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC will be assessed via spirometry. A positive change from baseline in FVC indicates improvement in lung function.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and day 168Population: The study intended to randomize 200 patients within 18 months; however, after 9 months, only 32 patients were successfully randomized, with a screen fail rate of 50%. Study was terminated with only safety data analyzed. No data collected met the pre-specified powering of 200 patients needed for analysis (only 32 patients randomized)
The Forced Expiratory Flow (FEF) 25%-75% measurement describes the amount of air expelled from the lungs during the middle half (25% - 75%) of the forced vital capacity test and is measured using spirometry. A positive change from baseline in FEF indicates improvement in lung function. The predicted percent will be assessed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and day 168Population: The study intended to randomize 200 patients within 18 months; however, after 9 months, only 32 patients were successfully randomized, with a screen fail rate of 50%. Study was terminated with only safety data analyzed. No data collected met the pre-specified powering of 200 patients needed for analysis (only 32 patients randomized)
Change from baseline in Pseudomonas aeruginosa sputum density will be measured by log10 colony forming units per gram of sputum.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1 to day 168Population: The study intended to randomize 200 patients within 18 months; however, after 9 months, only 32 patients were successfully randomized, with a screen fail rate of 50%. Study was terminated with only safety data analyzed. No data collected met the pre-specified powering of 200 patients needed for analysis (only 32 patients randomized)
Time to the first hospitalization due to respiratory-related events (number of days) per patient.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1 to day 168Population: The study intended to randomize 200 patients within 18 months; however, after 9 months, only 32 patients were successfully randomized, with a screen fail rate of 50%. Study was terminated with only safety data analyzed. No data collected met the pre-specified powering of 200 patients needed for analysis (only 32 patients randomized)
Percentage of patients with hospitalization due to respiratory-related events
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1 to day 168Population: The study intended to randomize 200 patients within 18 months; however, after 9 months, only 32 patients were successfully randomized, with a screen fail rate of 50%. Study was terminated with only safety data analyzed. No data collected met the pre-specified powering of 200 patients needed for analysis (only 32 patients randomized)
The number of days in length of hospital stay per patient due to respiratory-related events will be measured.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1 to day 168Population: The study intended to randomize 200 patients within 18 months; however, after 9 months, only 32 patients were successfully randomized, with a screen fail rate of 50%. Study was terminated with only safety data analyzed. No data collected met the pre-specified powering of 200 patients needed for analysis (only 32 patients randomized)
Time to first usage of anti-pseudomonal antibiotic per patient will be assessed by number of days
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1 to day 168Population: The study intended to randomize 200 patients within 18 months; however, after 9 months, only 32 patients were successfully randomized, with a screen fail rate of 50%. Study was terminated with only safety data analyzed. No data collected met the pre-specified powering of 200 patients needed for analysis (only 32 patients randomized)
Percentage of patients who use anti-pseudomonal antibiotic will be assessed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1 to day 168Population: The study intended to randomize 200 patients within 18 months; however, after 9 months, only 32 patients were successfully randomized, with a screen fail rate of 50%. Study was terminated with only safety data analyzed. No data collected met the pre-specified powering of 200 patients needed for analysis (only 32 patients randomized)
Number of days of use of anti-pseudomonal antibiotic per patient will be assessed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and day 168Population: The study intended to randomize 200 patients within 18 months; however, after 9 months, only 32 patients were successfully randomized, with a screen fail rate of 50%. Study was terminated with only safety data analyzed. No data collected met the pre-specified powering of 200 patients needed for analysis (only 32 patients randomized)
Change from baseline in tobramycin minimal inhibitory concentration for Pseudomonas aeruginosa will be measured by laboratory testing.
Outcome measures
Outcome data not reported
Adverse Events
Tobramycin Inhalation Powder Once Daily
Tobramycin Inhalation Powder Twice Daily
Total Events
Serious adverse events
| Measure |
Tobramycin Inhalation Powder Once Daily
n=16 participants at risk
Tobramycin Inhalation Powder (112 mg) once daily during 168 days
|
Tobramycin Inhalation Powder Twice Daily
n=15 participants at risk
Tobramycin Inhalation Powder (112 mg) twice daily on days 1-28, days 57-84 and days 113-140
|
Total Events
n=31 participants at risk
|
|---|---|---|---|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
12.5%
2/16
|
6.7%
1/15
|
9.7%
3/31
|
|
Reproductive system and breast disorders
Endometriosis
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
Other adverse events
| Measure |
Tobramycin Inhalation Powder Once Daily
n=16 participants at risk
Tobramycin Inhalation Powder (112 mg) once daily during 168 days
|
Tobramycin Inhalation Powder Twice Daily
n=15 participants at risk
Tobramycin Inhalation Powder (112 mg) twice daily on days 1-28, days 57-84 and days 113-140
|
Total Events
n=31 participants at risk
|
|---|---|---|---|
|
Cardiac disorders
Palpitations
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
|
Ear and labyrinth disorders
Hypoacusis
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Ear and labyrinth disorders
Tinnitus
|
12.5%
2/16
|
6.7%
1/15
|
9.7%
3/31
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
|
Gastrointestinal disorders
Abdominal pain
|
12.5%
2/16
|
6.7%
1/15
|
9.7%
3/31
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/16
|
13.3%
2/15
|
6.5%
2/31
|
|
Gastrointestinal disorders
Constipation
|
6.2%
1/16
|
6.7%
1/15
|
6.5%
2/31
|
|
Gastrointestinal disorders
Diarrhoea
|
12.5%
2/16
|
6.7%
1/15
|
9.7%
3/31
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
|
Gastrointestinal disorders
Nausea
|
18.8%
3/16
|
0.00%
0/15
|
9.7%
3/31
|
|
Gastrointestinal disorders
Post-tussive vomiting
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
1/16
|
6.7%
1/15
|
6.5%
2/31
|
|
General disorders
Asthenia
|
6.2%
1/16
|
13.3%
2/15
|
9.7%
3/31
|
|
General disorders
Chest discomfort
|
12.5%
2/16
|
0.00%
0/15
|
6.5%
2/31
|
|
General disorders
Chills
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
|
General disorders
Fatigue
|
6.2%
1/16
|
6.7%
1/15
|
6.5%
2/31
|
|
General disorders
Pain
|
0.00%
0/16
|
13.3%
2/15
|
6.5%
2/31
|
|
General disorders
Pyrexia
|
6.2%
1/16
|
6.7%
1/15
|
6.5%
2/31
|
|
Immune system disorders
Drug hypersensitivity
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
0.00%
0/16
|
26.7%
4/15
|
12.9%
4/31
|
|
Infections and infestations
Otitis media
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Infections and infestations
Urinary tract infection
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Injury, poisoning and procedural complications
Anaemia postoperative
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Injury, poisoning and procedural complications
Gastrointestinal disorder postoperative
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Injury, poisoning and procedural complications
Procedural pain
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Injury, poisoning and procedural complications
Vaccination complication
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Investigations
Hepatic enzyme increased
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Investigations
Liver function test abnormal
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
|
Investigations
Oxygen saturation decreased
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
|
Investigations
Pulmonary function test decreased
|
18.8%
3/16
|
6.7%
1/15
|
12.9%
4/31
|
|
Investigations
Weight decreased
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign ovarian tumour
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Nervous system disorders
Aphonia
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Nervous system disorders
Dizziness
|
0.00%
0/16
|
13.3%
2/15
|
6.5%
2/31
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
|
Nervous system disorders
Neuralgia
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/16
|
13.3%
2/15
|
6.5%
2/31
|
|
Psychiatric disorders
Depression
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
|
Reproductive system and breast disorders
Cervical dysplasia
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Reproductive system and breast disorders
Fallopian tube cyst
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Reproductive system and breast disorders
Haemorrhagic ovarian cyst
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Reproductive system and breast disorders
Ovarian cyst
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
62.5%
10/16
|
60.0%
9/15
|
61.3%
19/31
|
|
Respiratory, thoracic and mediastinal disorders
Dry throat
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
12.5%
2/16
|
20.0%
3/15
|
16.1%
5/31
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
12.5%
2/16
|
6.7%
1/15
|
9.7%
3/31
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
18.8%
3/16
|
6.7%
1/15
|
12.9%
4/31
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal oedema
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
|
Respiratory, thoracic and mediastinal disorders
Prolonged expiration
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Respiratory, thoracic and mediastinal disorders
Rhonchi
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
6.2%
1/16
|
6.7%
1/15
|
6.5%
2/31
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
6.2%
1/16
|
13.3%
2/15
|
9.7%
3/31
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
6.2%
1/16
|
0.00%
0/15
|
3.2%
1/31
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/16
|
6.7%
1/15
|
3.2%
1/31
|
Additional Information
Clinical Disclosure Office
Novartis Pharmaceuticals
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