Healthy Volunteers
Conditions
Keywords
Healthy volunteers, pharmacokinetic, inhalation
Brief summary
Relative bioavailability study to compare inhalation of Terbutaline Sulphate 1,5mg via current version of Turbuhaler with inhalation via a new version
Detailed description
An Open-label, Single-dose, 2-period Cross over Study in Healthy Male and Female Volunteers to Assess Relative Bioavailability of Terbutaline Sulphate 1.5 mg after Inhalation via the M3 Turbuhaler (New Version) Compared with the M2 Turbuhaler (Current Version)
Interventions
DRUGterbutaline sulphate delivered dose
0.4 mg terbutaline sulphate (delivered dose) per inhalation
DRUGterbutaline sulphate metered dose
0.5 mg terbutaline sulphate (metered dose) per inhalation
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Female and male volunteers aged between 18 and 65 years, both inclusive 2. Healthy as judged by the Principal Investigator after medical history, physical examination, 12-lead ECG, laboratory tests (including HIV, HBsAg and hepatitis C antibody tests) and assessments of pulse rate and blood pressure 3. Ability to use a Turbuhaler according to the provided instructions, as judged by the Principal Investigator or the study nurse 4. Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weighing at least 50 kg and no more than 100 kg -
Exclusion criteria
1. History or presence of respiratory, gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs (except for cholecystectomy) 2. Current smokers or those who have smoked or used nicotine products within the previous 3 months should be excluded 3. Plasma donation within 1 month of screening or any blood donation or blood loss of more than 500 mL during the 3 months prior to screening 4. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Principal Investigator or history of hypersensitivity to terbutaline (or drugs of a similar chemical structure or class) or inhaled lactose 5. Positive screen for drugs of abuse and/or alcohol and/or cotinine at screening (Visit 1) or on admission to the study centre (Day -1) prior to administration of the investigational medical product (IMP) on Day 1 -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Zero to the Time of Last Measurable Concentration [AUC(0-t)] | 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 |
| Maximum Observed Plasma Concentration (Cmax) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | 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 |
| Area Under the Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) | 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 |
| Area Under the Plasma Concentration-time Curve From Zero to 36 Hours Postdose [AUC(0-36)] | 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 |
| Terminal Half-life (t1/2) | 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 |
Countries
United Kingdom
Participant flow
Recruitment details
This was a single centre study conducted in the UK.
Pre-assignment details
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
Participants by arm
| Arm | Count |
|---|---|
| Randomized Subjects All randomized subjects | 34 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Randomized Subjects |
|---|---|
| Age, Continuous | 42 years STANDARD_DEVIATION 11 |
| Gender Female | 18 Participants |
| Gender Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 34 | 11 / 33 |
| serious Total, serious adverse events | 0 / 34 | 0 / 33 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Zero to the Time of Last Measurable Concentration [AUC(0-t)]
These will be taken at each treatment period
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Bricanyl Turbuhaler M3 | Area Under the Plasma Concentration-time Curve From Zero to the Time of Last Measurable Concentration [AUC(0-t)] | 89.04 nmol*h/L |
| Bricanyl Turbuhaler M2 | Area Under the Plasma Concentration-time Curve From Zero to the Time of Last Measurable Concentration [AUC(0-t)] | 100.9 nmol*h/L |
Comparison: No increase in the exposure of plasma terbutaline after administration of Bricanyl Turbuhaler M3 will be concluded if the upper bound of the 90% CIs for the ratios of AUC and Cmax are both below 1.2590% CI: [81.03, 96.02]
Primary
Maximum Observed Plasma Concentration (Cmax)
These will be taken at each treatment period
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Bricanyl Turbuhaler M3 | Maximum Observed Plasma Concentration (Cmax) | 12.00 nmol/L |
| Bricanyl Turbuhaler M2 | Maximum Observed Plasma Concentration (Cmax) | 13.12 nmol/L |
Comparison: No increase in the exposure of plasma terbutaline after administration of Bricanyl Turbuhaler M3 will be concluded if the upper bound of the 90% CIs for the ratios of AUC and Cmax are both below 1.2590% CI: [84.82, 98.58]
Secondary
Area Under the Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC)
These will be taken at each treatment period
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Bricanyl Turbuhaler M3 | Area Under the Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) | 96.63 nmol*h/L |
| Bricanyl Turbuhaler M2 | Area Under the Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) | 109.7 nmol*h/L |
Secondary
Area Under the Plasma Concentration-time Curve From Zero to 36 Hours Postdose [AUC(0-36)]
These will be taken at each treatment period
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Bricanyl Turbuhaler M3 | 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 |
| Bricanyl Turbuhaler M2 | Area Under the Plasma Concentration-time Curve From Zero to 36 Hours Postdose [AUC(0-36)] | 101 nmol*h/L | Geometric Coefficient of Variation 27.8 |
Secondary
Terminal Half-life (t1/2)
These will be taken at each treatment period
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Bricanyl Turbuhaler M3 | Terminal Half-life (t1/2) | 11.7 hour | Geometric Coefficient of Variation 8.9 |
| Bricanyl Turbuhaler M2 | Terminal Half-life (t1/2) | 11.8 hour | Geometric Coefficient of Variation 10.9 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
These will be taken at each treatment period
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bricanyl Turbuhaler M3 | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 1.33 hour |
| Bricanyl Turbuhaler M2 | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 1.33 hour |
p-value: 0.805290% CI: [-0.17, 0.17]Wilcoxon signed rank test