Trial Outcomes & Findings for Tobramycin Inhalation Powder (TIP) in Cystic Fibrosis Patients Infected With Burkholderia Cepacia Complex (NCT NCT02212587)

Results Overview

The change in sputum density of BCC in colony forming units (CFUs)/ml from day 0 to day 28 of TIP treatment. Sputum density was calculated by doing serial dilutions of sputum on agar plates and counting colony forming units expressed per ml.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

10 participants

Primary outcome timeframe

0 to 28 days

Results posted on

2020-11-04

Participant Flow

Participant milestones

Participant milestones
Measure	TOBI Podhaler TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler
Overall Study STARTED	10
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Tobramycin Inhalation Powder (TIP) in Cystic Fibrosis Patients Infected With Burkholderia Cepacia Complex

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TOBI Podhaler n=10 Participants TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler
Age, Categorical <=18 years	4 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Region of Enrollment Canada	10 participants n=5 Participants
Burkholderia cenocepacia IIIA, n (%)	4 Participants n=5 Participants
Burkholderia cenocepacia IIIB, n (%)	3 Participants n=5 Participants
Burkholderia multivorans, n (%)	3 Participants n=5 Participants
Sputum density log10 CFU/ml, median (range)	7.9 log10 CFU/ml n=5 Participants

PRIMARY outcome

Timeframe: 0 to 28 days

Population: sputum density measurements was calculated for all patients from Day 0 to Day 28

The change in sputum density of BCC in colony forming units (CFUs)/ml from day 0 to day 28 of TIP treatment. Sputum density was calculated by doing serial dilutions of sputum on agar plates and counting colony forming units expressed per ml.

Outcome measures

Outcome measures
Measure	TOBI Podhaler n=10 Participants TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler
The Change in Sputum Density of BCC in Colony Forming Units (CFUs)/ml From Day 0 to Day 28 of TIP Treatment.	-1.4 CFU/ml log10 Interval -3.9 to 0.8

SECONDARY outcome

Timeframe: 0 to 28 days

Population: All patients had lung function measures which were analyzed.

The main lung function measure was relative change in FEV1 from day 0 to Day 28 reported as %.

Outcome measures

Outcome measures
Measure	TOBI Podhaler n=10 Participants TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler
The Change in Pulmonary Function Tests, Including Forced Expiratory Volume in 1 Second (FEV1), Forced Vital Capacity (FVC) and Maximal Mid-expiratory Flow Rate (FEF25-75), Measured at Day 0 and Day 28 of TIP Treatment.	4.6 relative change in FEV1 expressed as % Interval -6.6 to 28.1

OTHER_PRE_SPECIFIED outcome

Timeframe: 0 to 28 days

Population: Sputum inflammatory markers were measured for 8 participants who could produce sputum.

We measured both neutrophil elastase sputum for participants.

Outcome measures

Outcome measures
Measure	TOBI Podhaler n=8 Participants TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler
The Change in the Measurement of Markers of Pulmonary Inflammation (Neutrophil Counts, Neutrophil Elastase and IL-8 Levels in Sputum) Measured at Day 0 and Day 28 of TIP Treatment.	-51.9 NE = ug/ml Interval -188.4 to 47.3

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 28

Population: We did pre and post TIP sputum tobramycin concentrations in 9 participants at Day 28 since one patient stopped taking the drug.

We did trough (0 hour) and peak (1 hour post dose) TIP sputum tobramycin concentrations and reported it for participants.

Outcome measures

Outcome measures
Measure	TOBI Podhaler n=9 Participants TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler
Trough and Peak Sputum Tobramycin Concentration Measured on Day 28 of TIP Treatment. Trough (0 hr)	194 ug/ml Interval 11.0 to 2100.0
Trough and Peak Sputum Tobramycin Concentration Measured on Day 28 of TIP Treatment. Peak (1 hr post dose)	1025 ug/ml Interval 306.0 to 4700.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 0 to 28 days

For all participants, the minimum inhibitory concentration of tobramycin for planktonic and biofilm grown BCC was measured in the lab on the isolate collected before and after TIP treatment.

Outcome measures

Outcome measures
Measure	TOBI Podhaler n=10 Participants TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler
The Change in BCC Planktonic and Biofilm MICs to Tobramycin Measured on Day 0 and on Day 28 of TIP Treatment. Day 0	200 ug/ml (MIC50) Interval 10.0 to 1600.0
The Change in BCC Planktonic and Biofilm MICs to Tobramycin Measured on Day 0 and on Day 28 of TIP Treatment. Day 28	400 ug/ml (MIC50) Interval 10.0 to 1600.0

OTHER_PRE_SPECIFIED outcome

Timeframe: At Dat 0, Day 14, and Day 28

Population: We observed for adverse events in all participants and reported on those that had an adverse event.

The number of participants with adverse events was reported for all participants in the trial.

Outcome measures

Outcome measures
Measure	TOBI Podhaler n=10 Participants TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler
The Number of Participants With Adverse Events Measured at Day 14 and at Day 28 of TIP Treatment.	6 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 0 to 28 days

Population: Sputum inflammatory markers were measured for 8 participants who could produce sputum.

We measured both IL-8 sputum for participants.

Outcome measures

Outcome measures
Measure	TOBI Podhaler n=8 Participants TOBI: New inhalation devices such as the podhaler can administer tobramycin inhalation powder TIP/TOBI and achieve very high sputum drug levels. TOBI will be administered using the Podhaler
The Change in the Measurement of Markers of Pulmonary Inflammation (Neutrophil Counts, Neutrophil Elastase and IL-8 Levels in Sputum) Measured at Day 0 and Day 28 of TIP Treatment.	-127 IL-8 = ng/ml Interval -298.62 to 101.8

Adverse Events

TOBI Podhaler

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Valerie Waters

Hospital of Sick Children

Phone: 416-813-1500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place