Trial Outcomes & Findings for Relative Bioavailability Study to Compare Inhalation of Terbutaline Sulphate 1,5mg Via Turbuhaler M3 With Turbuhaler M2 (NCT NCT02178059)

Results Overview

These will be taken at each treatment period

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

34 participants

Primary outcome timeframe

Samples will be taken at predose, and at 5, 10, 20, 40, 80, 100 minutes and at 2, 4, 6, 9, 12, 18, 24, 30, and 36 hours postdose

Results posted on

2017-03-01

Participant Flow

This was a single centre study conducted in the UK.

Healthy subjects were assessed for eligibility at a screening visit (Visit 1) within 28 days of administration of the first dose of terbutaline via Bricanyl Turbuhaler M2 or Bricanyl Turbuhaler M3 (Visit 2). Subjects were randomly assigned to 1 of 2 treatment sequences: M3 then M2 or M2 then M3

Participant milestones

Participant milestones
Measure	M3 First, Then M2 Sequence 1: M3 first then M2	M2 First, Then M3 Sequence 2: M2 first, then M3
First Intervention STARTED	17	17
First Intervention COMPLETED	17	17
First Intervention NOT COMPLETED	0	0
Washout STARTED	17	17
Washout COMPLETED	16	17
Washout NOT COMPLETED	1	0
Second Intervention STARTED	16	17
Second Intervention COMPLETED	16	17
Second Intervention NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	M3 First, Then M2 Sequence 1: M3 first then M2	M2 First, Then M3 Sequence 2: M2 first, then M3
Washout Physician Decision	1	0

Baseline Characteristics

Relative Bioavailability Study to Compare Inhalation of Terbutaline Sulphate 1,5mg Via Turbuhaler M3 With Turbuhaler M2

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Randomized Subjects n=34 Participants All randomized subjects
Age, Continuous	42 years STANDARD_DEVIATION 11 • n=5 Participants
Gender Female	18 Participants n=5 Participants
Gender Male	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: Samples will be taken at predose, and at 5, 10, 20, 40, 80, 100 minutes and at 2, 4, 6, 9, 12, 18, 24, 30, and 36 hours postdose

Population: The PK analysis set included all healthy subjects who received at least 1 dose of the IMP and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the IMP.

These will be taken at each treatment period

Outcome measures

Outcome measures
Measure	Bricanyl Turbuhaler M3 n=34 Participants Bricanyl Turbuhaler M3: 0.4 mg terbutaline sulphate (delivered dose) per inhalation	Bricanyl Turbuhaler M2 n=33 Participants Bricanyl Turbuhaler M2: 0.5 mg terbutaline sulphate (metered dose) per inhalation
Area Under the Plasma Concentration-time Curve From Zero to the Time of Last Measurable Concentration [AUC(0-t)]	89.04 nmol*h/L Interval 80.84 to 98.07	100.9 nmol*h/L Interval 91.54 to 111.3

PRIMARY outcome

Timeframe: Samples will be taken at predose, and at 5, 10, 20, 40, 80, 100 minutes and at 2, 4, 6, 9, 12, 18, 24, 30, and 36 hours postdose

Population: The PK analysis set included all healthy subjects who received at least 1 dose of the IMP and had at least 1 postdose PK measurement without important protocol deviations/violations or events thought to significantly affect the PK of the IMP.

These will be taken at each treatment period

Outcome measures

Outcome measures
Measure	Bricanyl Turbuhaler M3 n=34 Participants Bricanyl Turbuhaler M3: 0.4 mg terbutaline sulphate (delivered dose) per inhalation	Bricanyl Turbuhaler M2 n=33 Participants Bricanyl Turbuhaler M2: 0.5 mg terbutaline sulphate (metered dose) per inhalation
Maximum Observed Plasma Concentration (Cmax)	12.00 nmol/L Interval 10.73 to 13.4	13.12 nmol/L Interval 11.73 to 14.67

SECONDARY outcome

Timeframe: Samples will be taken at predose, and at 5, 10, 20, 40, 80, 100 minutes and at 2, 4, 6, 9, 12, 18, 24, 30, and 36 hours postdose

These will be taken at each treatment period

Outcome measures

Outcome measures
Measure	Bricanyl Turbuhaler M3 n=34 Participants Bricanyl Turbuhaler M3: 0.4 mg terbutaline sulphate (delivered dose) per inhalation	Bricanyl Turbuhaler M2 n=33 Participants Bricanyl Turbuhaler M2: 0.5 mg terbutaline sulphate (metered dose) per inhalation
Time to Reach Maximum Observed Plasma Concentration (Tmax)	1.33 hour Interval 1.33 to 1.67	1.33 hour Interval 1.33 to 1.67

SECONDARY outcome

Timeframe: Samples will be taken at predose, and at 5, 10, 20, 40, 80, 100 minutes and at 2, 4, 6, 9, 12, 18, 24, 30, and 36 hours postdose

These will be taken at each treatment period

Outcome measures

Outcome measures
Measure	Bricanyl Turbuhaler M3 n=34 Participants Bricanyl Turbuhaler M3: 0.4 mg terbutaline sulphate (delivered dose) per inhalation	Bricanyl Turbuhaler M2 n=33 Participants Bricanyl Turbuhaler M2: 0.5 mg terbutaline sulphate (metered dose) per inhalation
Area Under the Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC)	96.63 nmol*h/L Interval 87.68 to 106.5	109.7 nmol*h/L Interval 99.43 to 121.0

SECONDARY outcome

Timeframe: Samples will be taken at predose, and at 5, 10, 20, 40, 80, 100 minutes and at 2, 4, 6, 9, 12, 18, 24, 30, and 36 hours postdose

These will be taken at each treatment period

Outcome measures

Outcome measures
Measure	Bricanyl Turbuhaler M3 n=34 Participants Bricanyl Turbuhaler M3: 0.4 mg terbutaline sulphate (delivered dose) per inhalation	Bricanyl Turbuhaler M2 n=33 Participants Bricanyl Turbuhaler M2: 0.5 mg terbutaline sulphate (metered dose) per inhalation
Area Under the Plasma Concentration-time Curve From Zero to 36 Hours Postdose [AUC(0-36)]	89.0 nmol*h/L Geometric Coefficient of Variation 29.5	101 nmol*h/L Geometric Coefficient of Variation 27.8

SECONDARY outcome

Timeframe: Samples will be taken at predose, and at 5, 10, 20, 40, 80, 100 minutes and at 2, 4, 6, 9, 12, 18, 24, 30, and 36 hours postdose

These will be taken at each treatment period

Outcome measures

Outcome measures
Measure	Bricanyl Turbuhaler M3 n=34 Participants Bricanyl Turbuhaler M3: 0.4 mg terbutaline sulphate (delivered dose) per inhalation	Bricanyl Turbuhaler M2 n=33 Participants Bricanyl Turbuhaler M2: 0.5 mg terbutaline sulphate (metered dose) per inhalation
Terminal Half-life (t1/2)	11.7 hour Geometric Coefficient of Variation 8.9	11.8 hour Geometric Coefficient of Variation 10.9

Adverse Events

Bricanyl Turbuhaler M3

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Bricanyl Turbuhaler M2

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Bricanyl Turbuhaler M3 n=34 participants at risk Bricanyl Turbuhaler M3: 0.4 mg terbutaline sulphate (delivered dose) per inhalation	Bricanyl Turbuhaler M2 n=33 participants at risk Bricanyl Turbuhaler M2: 0.5 mg terbutaline sulphate (metered dose) per inhalation
Musculoskeletal and connective tissue disorders Back Pain	5.9% 2/34 • Number of events 2	0.00% 0/33
Nervous system disorders Headache	26.5% 9/34 • Number of events 10	21.2% 7/33 • Number of events 8
Nervous system disorders Dizziness	5.9% 2/34 • Number of events 2	12.1% 4/33 • Number of events 4

Additional Information

Göran Eckerwall, Medical Science Director

AstraZeneca R&D

Phone: 1-800-236-9933

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If a publication (e.g., in a scientific journal) based on the results of this study is envisaged, approval from AstraZeneca will be obtained and a draft manuscript will be submitted to AstraZeneca for scrutiny and comment. The choice of conduit will be mutually agreed on by the Principal Investigator and AstraZeneca.
Publication restrictions are in place

Restriction type: OTHER