Trial Outcomes & Findings for Study Comparing Dual Combination of Product (Budesonide and Formoterol) Given Via Two Different Inhalers. To See Which One Results in the Best Effect on Breathing. (NCT NCT04078126)

Results Overview

Peak change from baseline in FEV1 within 4 hours post-dose was defined as the maximum of the FEV1 assessments within 4 hours post-dosing at each visit minus baseline, provided that there were at least 2 non-missing values during the first 4 hours post dose.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

35 participants

Primary outcome timeframe

baseline and 4 hours post dose after 1 week of treatment

Results posted on

2022-03-18

Participant Flow

This study started recruitment in September 2019 with first subject randomized in January 2020. A total of 35 subjects were randomized at 4 study centers. The study completed in Dec 2020.

Subjects were randomized to an open-label, 2 period crossover study comparing Budesonide Formoterol Fumarate (BFF) Metered Dose Inhalation (MDI) administered with a spacer twice daily (BID) with Symbicort Turbuhaler BID. The subjects underwent an intervening two-week washout period where they used Berodual and Budesonide MDI BID.

Participant milestones

Participant milestones
Measure	BFF MDI/Symbicort Turbuhaler Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation followed by washout period and then Symbicort Turbuhaler	Symbicort Turbuhaler/BFF MDI Subject treated with Symbicort Turbuhaler followed by washout period and then Budesonide Formoterol Fumarate Metered Dose Inhalation
Period 1 STARTED	18	17
Period 1 COMPLETED	18	17
Period 1 NOT COMPLETED	0	0
Washout STARTED	18	17
Washout COMPLETED	18	15
Washout NOT COMPLETED	0	2
Period 2 STARTED	18	15
Period 2 COMPLETED	17	14
Period 2 NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	BFF MDI/Symbicort Turbuhaler Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation followed by washout period and then Symbicort Turbuhaler	Symbicort Turbuhaler/BFF MDI Subject treated with Symbicort Turbuhaler followed by washout period and then Budesonide Formoterol Fumarate Metered Dose Inhalation
Washout Study put on hold due to COVID-19	0	2
Period 2 Study put on hold due to COVID-19	1	1

Baseline Characteristics

Study Comparing Dual Combination of Product (Budesonide and Formoterol) Given Via Two Different Inhalers. To See Which One Results in the Best Effect on Breathing.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall Study n=35 Participants Intent-to-Treat (ITT) Population
Age, Continuous Mean age (SD), years	65.8 Years STANDARD_DEVIATION 5.5 • n=5 Participants
Sex: Female, Male Distribution of Male/Female Participants · Female	19 Participants n=5 Participants
Sex: Female, Male Distribution of Male/Female Participants · Male	16 Participants n=5 Participants
Race (NIH/OMB) Race for all subjects · American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Race for all subjects · Asian	0 Participants n=5 Participants
Race (NIH/OMB) Race for all subjects · Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Race for all subjects · Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) Race for all subjects · White	35 Participants n=5 Participants
Race (NIH/OMB) Race for all subjects · More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Race for all subjects · Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and 4 hours post dose after 1 week of treatment

Population: Modified Intent-to-treat (mITT) Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.

Peak change from baseline in FEV1 within 4 hours post-dose was defined as the maximum of the FEV1 assessments within 4 hours post-dosing at each visit minus baseline, provided that there were at least 2 non-missing values during the first 4 hours post dose.

Outcome measures

Outcome measures
Measure	BFF MDI n=30 Participants Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation	Symbicort Turbuhaler n=30 Participants Subject treated with Symbicort Turbuhaler
Peak Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Within 4 Hours Post-dose Following 1 Week of Treatment	0.256 L Interval 0.19 to 0.322	0.274 L Interval 0.208 to 0.34

SECONDARY outcome

Timeframe: baseline and 4 hours post dose after 1 week of treatment

Population: mITT Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.

FEV1 AUC0-4 was calculated using the trapezoidal rule and was normalized by dividing by the time in hours from dosing to the last measurement included (typically 4 hours).

Outcome measures

Outcome measures
Measure	BFF MDI n=30 Participants Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation	Symbicort Turbuhaler n=30 Participants Subject treated with Symbicort Turbuhaler
Area Under the Curve for Change From Baseline in FEV1 From Area Under the Curve 0 to 4 Hours (AUC0-4 h) Following 1 Week of Treatment	0.194 L Interval 0.133 to 0.254	0.210 L Interval 0.149 to 0.271

SECONDARY outcome

Timeframe: baseline and after 1 week of treatment

Population: mITT Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.

Change from baseline in pre-dose FEV1 following 1 week of treatment was defined as the 45-minute pre-dose value following 1 week of treatment minus baseline.

Outcome measures

Outcome measures
Measure	BFF MDI n=30 Participants Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation	Symbicort Turbuhaler n=30 Participants Subject treated with Symbicort Turbuhaler
Change From Baseline in Pre-dose FEV1 Following 1 Week of Treatment	0.081 L Interval 0.03 to 0.131	0.087 L Interval 0.037 to 0.137

SECONDARY outcome

Timeframe: baseline and 2 hours post dose after 1 week of treatment

Population: mITT Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.

Change from baseline in 2-hour post-dose IC following 1 week of treatment was defined as the 2-hour post-dose assessment of IC following 1 week of treatment minus baseline IC.

Outcome measures

Outcome measures
Measure	BFF MDI n=30 Participants Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation	Symbicort Turbuhaler n=30 Participants Subject treated with Symbicort Turbuhaler
Change From Baseline in 2-hour Post-dose Inspiratory Capacity (IC) Following 1 Week of Treatment	0.379 L Interval 0.242 to 0.517	0.411 L Interval 0.275 to 0.548

SECONDARY outcome

Timeframe: baseline and after 1 week of treatment

Population: mITT Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.

Change from baseline in pre-dose PIF (InCheck device set to no resistance) following 1 week of treatment was defined as the pre-dose PIF (InCheck device set to no resistance) following 1 week of treatment minus baseline PIF. (The InCheck Inspiratory Flow Measurement Device is an inhalation airflow meter that may be set to various resistances similar to marketed inhaler products. For this measurement, the device was set to no resistance.)

Outcome measures

Outcome measures
Measure	BFF MDI n=30 Participants Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation	Symbicort Turbuhaler n=30 Participants Subject treated with Symbicort Turbuhaler
Change From Baseline in Pre-dose Peak Inspiratory Flow (PIF; InCheck Device Set to no Resistance) Following 1 Week of Treatment	1.50 L/min Interval -2.26 to 5.27	5.11 L/min Interval 1.34 to 8.88

SECONDARY outcome

Timeframe: baseline and after 1 week of treatment

Population: mITT Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.

Change from baseline in pre-dose PIF (resistance set equal to Turbuhaler S) following 1 week of treatment was defined as the pre-dose PIF (resistance set equal to Turbuhaler S) following 1 week of treatment minus baseline PIF. (The InCheck Inspiratory Flow Measurement Device is an inhalation airflow meter that may be set to various resistances similar to marketed inhaler products. For this measurement, the device was set to resistance equal to the product Turbuhaler S.)

Outcome measures

Outcome measures
Measure	BFF MDI n=30 Participants Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation	Symbicort Turbuhaler n=30 Participants Subject treated with Symbicort Turbuhaler
Change From Baseline in Pre-dose PIF (Resistance Set Equal to Turbuhaler S) Following 1 Week of Treatment	1.13 L/min Interval -0.78 to 3.03	3.82 L/min Interval 1.91 to 5.72

SECONDARY outcome

Timeframe: baseline and after 1 week of treatment

Population: mITT Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.

Change from baseline in pre-dose PIF (resistance set equal to ELLIPTA) following 1 week of treatment was defined as the pre-dose PIF (resistance set equal to ELLIPTA) following 1 week of treatment minus baseline PIF. (The InCheck Inspiratory Flow Measurement Device is an inhalation airflow meter that may be set to various resistances similar to marketed inhaler products. For this measurement, the device was set to resistance equal to the product ELLIPTA.)

Outcome measures

Outcome measures
Measure	BFF MDI n=30 Participants Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation	Symbicort Turbuhaler n=30 Participants Subject treated with Symbicort Turbuhaler
Change From Baseline in Pre-dose PIF (Resistance Set Equal to ELLIPTA) Following 1 Week of Treatment	1.21 L/min Interval -1.15 to 3.56	2.74 L/min Interval 0.39 to 5.09

SECONDARY outcome

Timeframe: baseline and 2 hours post dose after the first dose of treatment

Population: mITT Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.

Change from baseline in 2-hour post-dose FEV1 following the 1st dose of treatment was defined as the 2-hour post-dose assessment of FEV1 following the 1st dose of treatment (Visit 3 or 5) minus baseline FEV1.

Outcome measures

Outcome measures
Measure	BFF MDI n=30 Participants Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation	Symbicort Turbuhaler n=30 Participants Subject treated with Symbicort Turbuhaler
Change From Baseline in 2-hour Post-dose FEV1 Following the First Dose	0.136 L Interval 0.1 to 0.173	0.093 L Interval 0.057 to 0.13

SECONDARY outcome

Timeframe: baseline and 2 hours post dose after the first dose of treatment

Population: mITT Population included all patients who were randomized to treatment and received at least one dose of study treatment with post-baseline spirometry data from both treatment periods at Visits 4 and 6. Patients with data judged to be impacted by important protocol deviations were excluded. Patients discontinued and restarted due to the study having been put on hold for the COVID-19 pandemic used the instance of enrollment after they restarted.

Change from baseline in 2-hour post-dose IC following the 1st dose of treatment was defined as the 2-hour post-dose assessment of IC following the 1st dose of treatment (Visit 3 or 5) minus baseline IC.

Outcome measures

Outcome measures
Measure	BFF MDI n=28 Participants Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation	Symbicort Turbuhaler n=30 Participants Subject treated with Symbicort Turbuhaler
Change From Baseline in 2-hour Post-dose IC Following the First Dose	0.264 L Interval 0.164 to 0.363	0.258 L Interval 0.161 to 0.356

Adverse Events

BFF MDI

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Symbicort Turbuhaler

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	BFF MDI n=33 participants at risk Subject treated with Budesonide Formoterol Fumarate Metered Dose Inhalation	Symbicort Turbuhaler n=35 participants at risk Subject treated with Symbicort Turbuhaler
Cardiac disorders Angina pectoris	3.0% 1/33 • Number of events 1 • Non-serious adverse events were monitored/assessed from Randomization throughout the Treatment Period and including the washout and follow-up periods, a maximum of 6 weeks. Serious adverse events were recorded from the time of signing of the informed consent, through Run-in, Treatment Period, including washout, and follow-up period, a maximum of 9 weeks. The Safety Population was defined as all subjects who were randomized to treatment and received at least one dose of study treatment. Subjects were analyzed according to the treatment actually received.	0.00% 0/35 • Non-serious adverse events were monitored/assessed from Randomization throughout the Treatment Period and including the washout and follow-up periods, a maximum of 6 weeks. Serious adverse events were recorded from the time of signing of the informed consent, through Run-in, Treatment Period, including washout, and follow-up period, a maximum of 9 weeks. The Safety Population was defined as all subjects who were randomized to treatment and received at least one dose of study treatment. Subjects were analyzed according to the treatment actually received.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/33 • Non-serious adverse events were monitored/assessed from Randomization throughout the Treatment Period and including the washout and follow-up periods, a maximum of 6 weeks. Serious adverse events were recorded from the time of signing of the informed consent, through Run-in, Treatment Period, including washout, and follow-up period, a maximum of 9 weeks. The Safety Population was defined as all subjects who were randomized to treatment and received at least one dose of study treatment. Subjects were analyzed according to the treatment actually received.	2.9% 1/35 • Number of events 1 • Non-serious adverse events were monitored/assessed from Randomization throughout the Treatment Period and including the washout and follow-up periods, a maximum of 6 weeks. Serious adverse events were recorded from the time of signing of the informed consent, through Run-in, Treatment Period, including washout, and follow-up period, a maximum of 9 weeks. The Safety Population was defined as all subjects who were randomized to treatment and received at least one dose of study treatment. Subjects were analyzed according to the treatment actually received.

Additional Information

AstraZeneca AB

Phone: 877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60