A Phase 1, Randomized, Open-label, Single-dose, 2-way Cross-over Study to Compare the Pharmacokinetics of Budesonide Delivered by PT027 Compared With Pulmicort Flexhaler (ELBRUS)
Overview
- Phase
- Phase 1
- Intervention
- BDA MDI 160/180 mcg
- Conditions
- Relative Bioavailability
- Sponsor
- AstraZeneca
- Enrollment
- 11
- Locations
- 1
- Primary Endpoint
- Maximum observed plasma concentration (Cmax) for budesonide
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This study is to compare the systemic exposure of budesonide delivered by the combination inhaler (budesonide/albuterol sulfate pressurized inhalation suspension [BDA metered dose inhaler {BDA MDI}]) with Pulmicort Flexhaler dry-powder inhaler (DPI).
Detailed Description
This study will be an open-label, randomized, 2-way cross-over study in healthy adult male or female participants, performed at a single study center.Participants will receive single doses of BDA MDI or Pulmicort Flexhaler on 2 occasions, under fasted conditions. There will be a minimum washout period of 3 days between each dose administration. A total of 66 participants will be randomized in this study to ensure that at least 62 participants are evaluable. The study will comprise of screening period of maximum 27 days; Two treatment periods during which participants will be resident from the day prior to administration of budesonide/albuterol sulfate pressurized inhalation suspension metered dose inhaler (BDA MDI) or Pulmicort Flexhaler (Day -1) until at least 24 hours after dosing. Participants will be discharged on the morning of Day 2; and a final follow-up visit within 5 to 7 days after the last administration of BDA MDI or Pulmicort Flexhaler.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provision of signed and dated, written informed consent prior to any study specific procedures.
- •Healthy male and female participants aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
- •Females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit, must not be lactating.
- •Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
- •Must be able to demonstrate proper inhalation technique using the Vitalograph Aerosol Inhalation Monitor (AIM) device 3 repeated times as well as be able to use the BDA MDI and Pulmicort Flexhaler devices according to instructions.
- •Forced expiratory volume in 1 second in liters (FEV1) ≥80% of predicted value and FEV1/forced vital capacity in liters (FVC) ratio ≥70%.
Exclusion Criteria
- •Pregnant or nursing female participants or participants who are trying to conceive
- •For female participants, a positive serum human chorionic gonadotropin (hCG) test at the Screening Visit or a positive urine hCG at admission for any of the 2 Treatment Periods.
- •History of any clinically significant disease or disorder which, in the opinion of the PI, 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 or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- •Participants who have cancer that has not been in complete remission for at least 5 years.
- •Any history of asthma or Chronic obstructive pulmonary disease (COPD).
- •Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
- •Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results at the Screening Visit, as judged by the PI.
- •Any clinically significant abnormal findings in vital signs at the Screening Visit, as judged by the PI.
- •Any clinically significant abnormalities on 12-lead electrocardiogram (ECG) at the Screening Visit, as judged by the PI.
Arms & Interventions
A/B (BDA MDI/Pulmicort)
For each participant, the BDA MDI/Pulmicort Flexhaler DPI will be administered as a single dose (2 inhalations) on Day 1 of the respective treatment period per the assigned treatment sequence. The IMP will be administered in the morning, at approximately the same time of day throughout the study (±30 minutes).
Intervention: BDA MDI 160/180 mcg
A/B (BDA MDI/Pulmicort)
For each participant, the BDA MDI/Pulmicort Flexhaler DPI will be administered as a single dose (2 inhalations) on Day 1 of the respective treatment period per the assigned treatment sequence. The IMP will be administered in the morning, at approximately the same time of day throughout the study (±30 minutes).
Intervention: Pulmicort Flexhaler 180 mcg
B/A (Pulmicort/ BDA MDI)
For each participant, the Pulmicort Flexhaler DPI / BDA MDI will be administered as a single dose (2 inhalations) on Day 1 of the respective treatment period per the assigned treatment sequence. The IMP should be administered in the morning, at approximately the same time of day throughout the study (±30 minutes).
Intervention: BDA MDI 160/180 mcg
B/A (Pulmicort/ BDA MDI)
For each participant, the Pulmicort Flexhaler DPI / BDA MDI will be administered as a single dose (2 inhalations) on Day 1 of the respective treatment period per the assigned treatment sequence. The IMP should be administered in the morning, at approximately the same time of day throughout the study (±30 minutes).
Intervention: Pulmicort Flexhaler 180 mcg
Outcomes
Primary Outcomes
Maximum observed plasma concentration (Cmax) for budesonide
Time Frame: On Day 1 (Pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose) and on Day 2 (24 hours post-dose)
To compare the systemic exposure of budesonide after single-dose administration of BDA MDI versus Pulmicort Flexhaler
Area under the plasma concentration-curve from time zero to time of last quantifiable concentration [AUC(0-t)] for budesonide
Time Frame: On Day 1 (Pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose) and on Day 2 (24 hours post-dose)
To compare the systemic exposure of budesonide after single-dose administration of BDA MDI versus Pulmicort Flexhaler
Area under plasma concentration-time curve from time zero to infinity (AUC) for budesonide
Time Frame: On Day 1 (Pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose) and on Day 2 (24 hours post-dose)
To compare the systemic exposure of budesonide after single-dose administration of BDA MDI versus Pulmicort Flexhaler
Secondary Outcomes
- Time of last quantifiable plasma concentration (tlast)(On Day 1 (Pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose) and on Day 2 (24 hours post-dose))
- Terminal elimination rate constant (λz)(On Day 1 (Pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose) and on Day 2 (24 hours post-dose))
- Apparent total body clearance of drug from plasma after extravascular administration (CL/F)(On Day 1 (Pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose) and on Day 2 (24 hours post-dose))
- Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)(On Day 1 (Pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose) and on Day 2 (24 hours post-dose))
- Time to reach maximum observed plasma concentration (tmax)(On Day 1 (Pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose) and on Day 2 (24 hours post-dose))
- Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz)(On Day 1 (Pre-dose and 5, 15, 20, 30 and 45 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post dose) and on Day 2 (24 hours post-dose))
- Number of participants with adverse events and serious adverse events(From screening (Day -27 to Day -2) to post study visit ( 5-7 days))