Study is Being Conducted in Healthy VolunteersPhase 1NCT02934607
A Study to Assess How Much Drug Reaches the Blood When Given From Symbicort pMDI With Spacer Compared to That of Symbicort pMDI Without Spacer in Healthy Volunteers
A Phase 1 study testing Symbicort pMDI with spacer device and Symbicort pMDI without spacer device in people with Study is Being Conducted in Healthy Volunteers, run by AstraZeneca at 1 site in United Kingdom.
Trial summary
This study will be conducted to establish the relative bioavailability of budesonide and formoterol delivered via Symbicort pressurized metered-dose inhaler (pMDI) with and without a spacer device. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Study is Being Conducted in Healthy Volunteers
- What is being tested?
- Symbicort pMDI with spacer device and Symbicort pMDI without spacer device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 4 Nov 2016to 27 Mar 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male and/or female subjects aged 18 years (inclusive) and older, with suitable veins for cannulation or repeated venipuncture.
- Females must have a negative pregnancy test at screening and on first admission to the unit, must not be lactating.
- Body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
- Forced expiratory volume in 1 second (FEV1) ≥ 80% of predicted value and FEV1/Forced vital capacity (FVC) ratio ≥ 70%.
- Non-smokers.
Who cannot join
- History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study.
- History of diagnosed COPD or asthma. (Note: Subjects with a history of childhood asthma only will not be excluded from the study).
- History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
- Any clinically significant abnormalities in clinical chemistry, 12-lead electrocardiogram (ECG) at screening, haematology, or urinalysis results at screening or vital signs at screening and first admission to the study unit.
- Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) antibody.
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- Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
- Participation in another clinical study with a non-biologic investigational product or new formulation of a marketed non-biologic drug within 3 months prior to the screening visit.
- Participation in another clinical trial with any marketed or investigational biologic within 4 months or 5 half-lives whichever is longer, prior to the screening visit.
- Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening.
- History of severe or ongoing allergy/hypersensitivity (e.g., food allergy) or history of hypersensitivity to drugs with a similar chemical structure or class to Symbicort.
- Positive screen for drugs of abuse, alcohol or cotinine at screening and on first admission to the study unit.
- Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
- Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half-life. (Note: Hormonal contraception and hormonal replacement therapy are allowed for females, as applicable).
- Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives.
- Judgment by the investigator that the subject should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements.
- Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised, Open-Label, Single-Dose, Single-Centre, Crossover Study in Healthy Subjects to Assess the Relative Bioavailability of Symbicort pMDI 160/4.5µg Administered With a Spacer (With and Without Charcoal) and Symbicort pMDI 160/4.5µg Administered Without a Spacer (With and Without Charcoal)
This study will be conducted to establish the relative bioavailability of budesonide and formoterol delivered via Symbicort pressurized metered-dose inhaler (pMDI) with and without a spacer device.
Administration under each condition will occur with the concomitant administration of activated charcoal to estimate exposure through the lung and without activated charcoal to estimate total systemic exposure.
Read the detailed description
Study Design:
This study will be a randomised, open-label, single-dose, crossover study in healthy subjects (males and females), performed at a single study centre.
The study will comprise:
- A screening period of maximum 28 days;
- Four treatment periods during which subjects will be resident from the afternoon before dosing with Symbicort until at least 24 hours after dosing; discharged on the morning of Day 2; and
- A final visit within 5 to 7 days after the last administration of Symbicort. There will be a minimum washout period of 3 days between each dose administration of Symbicort. Subjects will receive single doses of Symbicort on 4 occasions under fasted conditions. During screening, spirometry testing will be performed by a technologist or a qualified designee to ensure subjects perform adequate manoeuvres to achieve optimal lung function. Device and inhalation training will be conducted on admission to each treatment period, and prior to dosing on Day 1 of each treatment period.
Duration:
Approximately 7 weeks
Statistical Analysis:
- For total systemic exposure: Treatment B versus Treatment A
- For lung exposure: Treatment D versus Treatment C Treatment ratio will be assessed on the ratio of log-transformed Cmax, AUC0-t and AUC of budesonide and formoterol using a 2-sided 90% confidence interval (CI) approach based on a repeated measures analysis of variance (ANOVA) model including period and treatment as fixed effects, and subject as a random effect. The estimated treatment differences and the 90% CIs on the log scale will be back-transformed to obtain the Gmean ratios for each pair of treatments. The least squares means (and 95% CIs), Gmean ratios and 90% CIs will be tabulated for each comparison and analyte (budesonide and formoterol).
Sample Size:
The sample size is 56 to ensure adequate number of subjects are randomised and at least 44 evaluable subjects complete the study.
Assuming an intra-subject coefficient of variation (CV) of 33% (based on the variability of AUC0-12 for budesonide and AUC0-12 and Cmax for formoterol observed in a similarly designed crossover study in healthy adults), 44 evaluable subjects will give at least 80% power to show that the 90% CI for the treatment effects lies entirely within the range 0.8 to 1.25, i.e., would rule out a 20% change (on a log scale) in exposure to budesonide and formoterol.
- Being tested
- Symbicort pMDI with spacer device, Symbicort pMDI without spacer device
- Keywords
- Asthma, Chronic obstructive pulmonary disease, Spacer device, Symbicort, Pressurized metered-dose inhaler, Relative bioavailability, Crossover, AstraZeneca, Safety, Activated charcoal, AeroChamber Plus Flow-Vu spacer device
- Medical subject headings
- Asthma, Pulmonary Disease, Chronic Obstructive, Anthrax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Symbicort pMDI with spacer deviceDrug
Relative bioavailability of budesonide and formoterol delivered via Symbicort pressurized metered-dose inhaler (pMDI) with a spacer device (test)
Symbicort pMDI without spacer deviceDrug
Relative bioavailability of budesonide and formoterol delivered via Symbicort pMDI without a spacer device (reference)
| Study group | Role | What they receive |
|---|---|---|
| Treatment A | Active comparator | 2 x 160/4.5 µg Symbicort pMDI administered with no spacer device; no activated charcoal (systemic exposure). Receives: Drug: Symbicort pMDI without spacer device |
| Treatment B | Experimental | 2 x 160/4.5 µg Symbicort pMDI administered through AeroChamber Plus Flow-Vu spacer device; no activated charcoal (systemic exposure). Receives: Drug: Symbicort pMDI with spacer device |
| Treatment C | Active comparator | 160/4.5 µg Symbicort pMDI administered with no spacer device; with activated charcoal (lung exposure). Receives: Drug: Symbicort pMDI without spacer device |
| Treatment D | Experimental | 160/4.5 µg Symbicort pMDI administered through AeroChamber Plus Flow-Vu spacer device; with activated charcoal (lung exposure). Receives: Drug: Symbicort pMDI with spacer device |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum observed plasma concentration (Cmax) of Symbicort pMDI administered with spacer device without charcoal
To assess Cmax of Symbicort pMDI administered through a spacer device without charcoal under fasted condition (total systemic exposure).
The analysis was done on pharmacokinetic analysis set.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t) of Symbicort pMDI administered with spacer device without charcoal
To assess AUC0-t of Symbicort pMDI administered through a spacer device without charcoal under fasted condition (total systemic exposure).
The analysis was done on pharmacokinetic analysis set.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Cmax of Symbicort pMDI administered with spacer device with charcoal
To assess Cmax of Symbicort pMDI administered through a spacer device with charcoal under fasted condition (lung exposure).
The analysis was done on pharmacokinetic analysis set.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
AUC0-t of Symbicort pMDI administered with spacer device with charcoal
To assess AUC0-t of Symbicort pMDI administered through a spacer device with charcoal under fasted condition (lung exposure).
The analysis was done on pharmacokinetic analysis set.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Cmax of Symbicort pMDI administered without spacer device without charcoal
To assess Cmax of Symbicort pMDI administered without a spacer device without charcoal under fasted condition (total systemic exposure).
The analysis was done on pharmacokinetic analysis set.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
AUC0-t of Symbicort pMDI administered without spacer device without charcoal
To assess AUC0-t of Symbicort pMDI administered without a spacer device without charcoal under fasted condition (total systemic exposure).
The analysis was done on pharmacokinetic analysis set.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Cmax of Symbicort pMDI administered without spacer device with charcoal
To assess Cmax of Symbicort pMDI administered without a spacer device with charcoal under fasted condition (lung exposure).
The analysis was done on pharmacokinetic analysis set.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
AUC0-t of Symbicort pMDI administered without spacer device with charcoal
To assess AUC0-t of Symbicort pMDI administered without a spacer device with charcoal under fasted condition (lung exposure).
The analysis was done on pharmacokinetic analysis set.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Secondary outcomes (16)
AUC after single doses of budesonide and formoterol delivered via Symbicort pMDI with spacer device
To characterise the AUC after single doses of budesonide and formoterol delivered via Symbicort pMDI when administered with spacer device and with and without charcoal under fasted condition to healthy subjects.
The analysis was done on pharmacokinetic analysis set population.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Tmax after single doses of budesonide and formoterol delivered via Symbicort pMDI with spacer device
To characterise the tmax after single doses of budesonide and formoterol delivered via Symbicort pMDI when administered with spacer device and with and without charcoal under fasted condition to healthy subjects.
The analysis was done on pharmacokinetic analysis set population.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½,λz) after single doses of budesonide and formoterol delivered via Symbicort pMDI with spacer device
To characterise the t½,λz after single doses of budesonide and formoterol delivered via Symbicort pMDI when administered with spacer device and with and without charcoal under fasted condition to healthy subjects.
The analysis was done on pharmacokinetic analysis set population.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Apparent volume of distribution during the terminal phase (extravascular administration) (Vz/F) after single doses of budesonide and formoterol delivered via Symbicort pMDI with spacer device
To characterise the Vz/F after single doses of budesonide and formoterol delivered via Symbicort pMDI when administered with spacer device and with and without charcoal under fasted condition to healthy subjects.
The analysis was done on pharmacokinetic analysis set population.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) after single doses of budesonide and formoterol delivered via Symbicort pMDI with spacer device
To characterise the CL/F after single doses of budesonide and formoterol delivered via Symbicort pMDI when administered with spacer device and with and without charcoal under fasted condition to healthy subjects.
The analysis was done on pharmacokinetic analysis set population.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Time of last quantifiable plasma concentration (tlast) after single doses of budesonide and formoterol delivered via Symbicort pMDI with spacer device
To characterise the tlast after single doses of budesonide and formoterol delivered via Symbicort pMDI when administered with spacer device and with and without charcoal under fasted condition to healthy subjects.
The analysis was done on pharmacokinetic analysis set population.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Terminal elimination rate constant (λz) after single doses of budesonide and formoterol delivered via Symbicort pMDI with space device
To characterise the λz after single doses of budesonide and formoterol delivered via Symbicort pMDI when administered with spacer device and with and without charcoal under fasted condition to healthy subjects.
The analysis was done on pharmacokinetic analysis set population.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Percentage of subjects who experienced treatment-related adverse events (AEs) after administration of single doses of budesonide and formoterol delivered via Symbicort pMDI with spacer device
To assess the safety in terms of percentage of subjects who experienced treatment-related AEs after administration of single doses of budesonide and formoterol delivered via Symbicort pMDI with spacer device and with and without charcoal to healthy subjects.
The analysis was done on the safety analysis set population which included all subjects who received at least 1 dose of Symbicort pMDI and for whom any safety post-dose data were available.
Measured: From signing the informed consent form until 5-7 days post final dose (approximately 7 weeks)
AUC after single doses of budesonide and formoterol delivered via Symbicort pMDI without spacer device
To characterise the AUC after single doses of budesonide and formoterol delivered via Symbicort pMDI when administered without spacer device and with and without charcoal under fasted condition to healthy subjects.
The analysis was done on pharmacokinetic analysis set population.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
tmax after single doses of budesonide and formoterol delivered via Symbicort pMDI without spacer device
To characterise the tmax after single doses of budesonide and formoterol delivered via Symbicort pMDI when administered without spacer device and with and without charcoal under fasted condition to healthy subjects.
The analysis was done on pharmacokinetic analysis set population.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
t½,λz after single doses of budesonide and formoterol delivered via Symbicort pMDI without spacer device
To characterise the t½,λz after single doses of budesonide and formoterol delivered via Symbicort pMDI when administered without spacer device and with and without charcoal under fasted condition to healthy subjects.
The analysis was done on pharmacokinetic analysis set population.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Vz/F after single doses of budesonide and formoterol delivered via Symbicort pMDI without spacer device
To characterise the Vz/F after single doses of budesonide and formoterol delivered via Symbicort pMDI when administered without spacer and with and without charcoal under fasted condition to healthy subjects.
The analysis was done on pharmacokinetic analysis set population.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
CL/F after single doses of budesonide and formoterol delivered via Symbicort pMDI without spacer device
To characterise the CL/F after single doses of budesonide and formoterol delivered via Symbicort pMDI when administered without spacer device and with and without charcoal under fasted condition to healthy subjects.
The analysis was done on pharmacokinetic analysis set population.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
tlast after single doses of budesonide and formoterol delivered via Symbicort pMDI without spacer device
To characterise the tlast after single doses of budesonide and formoterol delivered via Symbicort pMDI when administered without spacer device and with and without charcoal under fasted condition to healthy subjects.
The analysis was done on pharmacokinetic analysis set population.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
λz after single doses of budesonide and formoterol delivered via Symbicort pMDI without spacer device
To characterise the λz after single doses of budesonide and formoterol delivered via Symbicort pMDI when administered without spacer device and with and without charcoal under fasted condition to healthy subjects.
The analysis was done on pharmacokinetic analysis set population.
Measured: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Percentage of subjects who experienced treatment-related AEs after administration of single dose of budesonide and formoterol delivered via Symbicort pMDI without a spacer device
To assess the safety in terms of percentage of subjects who experienced treatment-related AEs after administration of single doses of budesonide and formoterol delivered via Symbicort pMDI without the spacer device and with and without charcoal to healthy subjects. The analysis was done on the safety analysis set population which included all subjects who received at least 1 dose of Symbicort pMDI and for whom any safety post-dose data were available.
Measured: From signing the informed consent form until 5-7 days post final dose (approximately 7 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2016 (estimated)
- Study start4 Nov 2016
- Primary completion27 Mar 2017
- Study completion27 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Study is Being Conducted in Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- Dr Rainard Fuhr, Dr. med, Principal investigator, PAREXEL Early Phase Clinical Unit London, United Kingdom
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02934607
- Sponsor's protocol ID
- D589WC00001
- Other IDs
- 2016-001866-27, 2016
- Status last verified
- Aug 2018
- First submitted
- 14 Sep 2016
- Last updated
- 20 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Gillen M, Forte P, Svensson JO, Lamarca R, Burke J, Rask K, Larsdotter Nilsson U, Eckerwall G. Effect of a spacer on total systemic and lung bioavailability in healthy volunteers and in vitro performance of the Symbicort(R) (budesonide/formoterol) pressurized metered dose inhaler. Pulm Pharmacol Ther. 2018 Oct;52:7-17. doi: 10.1016/j.pupt.2018.08.001. Epub 2018 Aug 2.
PubMed 30077809
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Open-Label, Single-Dose, Single-Centre, Crossover Study in Healthy Subjects to Assess the Relative Bioavailability of Symbicort pMDI 160/4.5µg Administered With a Spacer (With and Without Charcoal) and Symbicort pMDI 160/4.5µg Administered Without a Spacer (With and Without Charcoal)
- ClinicalTrials.gov ID
- NCT02934607
- Acronym / sponsor ID
- D589WC00001
- Keywords
- Asthma, Chronic obstructive pulmonary disease, Spacer device, Symbicort, Pressurized metered-dose inhaler, Relative bioavailability, Crossover, AstraZeneca
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 4 Nov 2016 (actual)
- Primary completion
- 27 Mar 2017 (actual)
- Study completion
- 27 Mar 2017 (actual)
- First posted
- 17 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will be conducted to establish the relative bioavailability of budesonide and formoterol delivered via Symbicort pressurized metered-dose inhaler (pMDI) with and without a spacer device.
Administration under each condition will occur with the concomitant administration of activated charcoal to estimate exposure through the lung and without activated charcoal to estimate total systemic exposure.
Detailed description
Study Design:
This study will be a randomised, open-label, single-dose, crossover study in healthy subjects (males and females), performed at a single study centre.
The study will comprise:
- A screening period of maximum 28 days;
- Four treatment periods during which subjects will be resident from the afternoon before dosing with Symbicort until at least 24 hours after dosing; discharged on the morning of Day 2; and
- A final visit within 5 to 7 days after the last administration of Symbicort. There will be a minimum washout period of 3 days between each dose administration of Symbicort. Subjects will receive single doses of Symbicort on 4 occasions under fasted conditions. During screening, spirometry testing will be performed by a technologist or a qualified designee to ensure subjects perform adequate manoeuvres to achieve optimal lung function. Device and inhalation training will be conducted on admission to each treatment period, and prior to dosing on Day 1 of each treatment period.
Duration:
Approximately 7 weeks
Statistical Analysis:
- For total systemic exposure: Treatment B versus Treatment A
- For lung exposure: Treatment D versus Treatment C Treatment ratio will be assessed on the ratio of log-transformed Cmax, AUC0-t and AUC of budesonide and formoterol using a 2-sided 90% confidence interval (CI) approach based on a repeated measures analysis of variance (ANOVA) model including period and treatment as fixed effects, and subject as a random effect. The estimated treatment differences and the 90% CIs on the log scale will be back-transformed to obtain the Gmean ratios for each pair of treatments. The least squares means (and 95% CIs), Gmean ratios and 90% CIs will be tabulated for each comparison and analyte (budesonide and formoterol).
Sample Size:
The sample size is 56 to ensure adequate number of subjects are randomised and at least 44 evaluable subjects complete the study.
Assuming an intra-subject coefficient of variation (CV) of 33% (based on the variability of AUC0-12 for budesonide and AUC0-12 and Cmax for formoterol observed in a similarly designed crossover study in healthy adults), 44 evaluable subjects will give at least 80% power to show that the 90% CI for the treatment effects lies entirely within the range 0.8 to 1.25, i.e., would rule out a 20% change (on a log scale) in exposure to budesonide and formoterol.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Treatment A | Active comparator | Drug: Symbicort pMDI without spacer device2 x 160/4.5 µg Symbicort pMDI administered with no spacer device; no activated charcoal (systemic exposure). |
| Treatment B | Experimental | Drug: Symbicort pMDI with spacer device2 x 160/4.5 µg Symbicort pMDI administered through AeroChamber Plus Flow-Vu spacer device; no activated charcoal (systemic exposure). |
| Treatment C | Active comparator | Drug: Symbicort pMDI without spacer device160/4.5 µg Symbicort pMDI administered with no spacer device; with activated charcoal (lung exposure). |
| Treatment D | Experimental | Drug: Symbicort pMDI with spacer device160/4.5 µg Symbicort pMDI administered through AeroChamber Plus Flow-Vu spacer device; with activated charcoal (lung exposure). |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male and/or female subjects aged 18 years (inclusive) and older, with suitable veins for cannulation or repeated venipuncture.
- Females must have a negative pregnancy test at screening and on first admission to the unit, must not be lactating.
- Body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
- Forced expiratory volume in 1 second (FEV1) ≥ 80% of predicted value and FEV1/Forced vital capacity (FVC) ratio ≥ 70%.
Key exclusion criteria (17 listed)
- History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study.
- History of diagnosed COPD or asthma. (Note: Subjects with a history of childhood asthma only will not be excluded from the study).
- History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
- Any clinically significant abnormalities in clinical chemistry, 12-lead electrocardiogram (ECG) at screening, haematology, or urinalysis results at screening or vital signs at screening and first admission to the study unit.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Symbicort pMDI with spacer deviceRelative bioavailability of budesonide and formoterol delivered via Symbicort pressurized metered-dose inhaler (pMDI) with a spacer device (test) | Drug | Treatment B, Treatment D |
| Symbicort pMDI without spacer deviceRelative bioavailability of budesonide and formoterol delivered via Symbicort pMDI without a spacer device (reference) | Drug | Treatment A, Treatment C |
Primary outcome
Maximum observed plasma concentration (Cmax) of Symbicort pMDI administered with spacer device without charcoal
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
To assess Cmax of Symbicort pMDI administered through a spacer device without charcoal under fasted condition (total systemic exposure). The analysis was done on pharmacokinetic analysis set.
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t) of Symbicort pMDI administered with spacer device without charcoal
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
To assess AUC0-t of Symbicort pMDI administered through a spacer device without charcoal under fasted condition (total systemic exposure). The analysis was done on pharmacokinetic analysis set.
Cmax of Symbicort pMDI administered with spacer device with charcoal
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
To assess Cmax of Symbicort pMDI administered through a spacer device with charcoal under fasted condition (lung exposure). The analysis was done on pharmacokinetic analysis set.
AUC0-t of Symbicort pMDI administered with spacer device with charcoal
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
To assess AUC0-t of Symbicort pMDI administered through a spacer device with charcoal under fasted condition (lung exposure). The analysis was done on pharmacokinetic analysis set.
Cmax of Symbicort pMDI administered without spacer device without charcoal
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
To assess Cmax of Symbicort pMDI administered without a spacer device without charcoal under fasted condition (total systemic exposure). The analysis was done on pharmacokinetic analysis set.
AUC0-t of Symbicort pMDI administered without spacer device without charcoal
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
To assess AUC0-t of Symbicort pMDI administered without a spacer device without charcoal under fasted condition (total systemic exposure). The analysis was done on pharmacokinetic analysis set.
Cmax of Symbicort pMDI administered without spacer device with charcoal
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
To assess Cmax of Symbicort pMDI administered without a spacer device with charcoal under fasted condition (lung exposure). The analysis was done on pharmacokinetic analysis set.
AUC0-t of Symbicort pMDI administered without spacer device with charcoal
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
To assess AUC0-t of Symbicort pMDI administered without a spacer device with charcoal under fasted condition (lung exposure). The analysis was done on pharmacokinetic analysis set.
16 secondary outcomes
AUC after single doses of budesonide and formoterol delivered via Symbicort pMDI with spacer device
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Tmax after single doses of budesonide and formoterol delivered via Symbicort pMDI with spacer device
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½,λz) after single doses of budesonide and formoterol delivered via Symbicort pMDI with spacer device
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Apparent volume of distribution during the terminal phase (extravascular administration) (Vz/F) after single doses of budesonide and formoterol delivered via Symbicort pMDI with spacer device
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) after single doses of budesonide and formoterol delivered via Symbicort pMDI with spacer device
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Time of last quantifiable plasma concentration (tlast) after single doses of budesonide and formoterol delivered via Symbicort pMDI with spacer device
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Terminal elimination rate constant (λz) after single doses of budesonide and formoterol delivered via Symbicort pMDI with space device
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Percentage of subjects who experienced treatment-related adverse events (AEs) after administration of single doses of budesonide and formoterol delivered via Symbicort pMDI with spacer device
Time frame: From signing the informed consent form until 5-7 days post final dose (approximately 7 weeks)
AUC after single doses of budesonide and formoterol delivered via Symbicort pMDI without spacer device
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
tmax after single doses of budesonide and formoterol delivered via Symbicort pMDI without spacer device
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
t½,λz after single doses of budesonide and formoterol delivered via Symbicort pMDI without spacer device
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Vz/F after single doses of budesonide and formoterol delivered via Symbicort pMDI without spacer device
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
CL/F after single doses of budesonide and formoterol delivered via Symbicort pMDI without spacer device
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
tlast after single doses of budesonide and formoterol delivered via Symbicort pMDI without spacer device
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
λz after single doses of budesonide and formoterol delivered via Symbicort pMDI without spacer device
Time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing
Percentage of subjects who experienced treatment-related AEs after administration of single dose of budesonide and formoterol delivered via Symbicort pMDI without a spacer device
Time frame: From signing the informed consent form until 5-7 days post final dose (approximately 7 weeks)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2018.
- Background: PubMed 30077809Gillen M, Forte P, Svensson JO, Lamarca R, Burke J, Rask K, Larsdotter Nilsson U, Eckerwall G. Effect of a spacer on total systemic and lung bioavailability in healthy volunteers and in vitro performance of the Symbicort(R) (budesonide/formoterol) pressurized metered dose inhaler. Pulm Pharmacol Ther. 2018 Oct;52:7-17. doi: 10.1016/j.pupt.2018.08.001. Epub 2018 Aug 2.
- Redacted protocolLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr Rainard Fuhr, Dr. med principal investigator
PAREXEL Early Phase Clinical Unit London, United Kingdom
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Symbicort pMDI with spacer device and Symbicort pMDI without spacer device in people with Study is Being Conducted in Healthy Volunteers, run by AstraZeneca at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum observed plasma concentration (Cmax) of Symbicort pMDI administered with spacer device without charcoal (time frame: Pre-dose and at 5, 20, and 40 minutes and at 1, 2, 4, 8, 10, 12, 18 and 24 hours after Symbicort dosing). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02934607, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2018.