A Phase 1, Randomized, Open-label, Single-dose, 3-way Cross-over Study to Compare the Pharmacokinetics of Budesonide and Albuterol Delivered by PT027 Compared With PT007 and PT008 Administered Separately (LOGAN).
Overview
- Phase
- Phase 1
- Intervention
- Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler)
- Conditions
- Healthy Volunteers
- Sponsor
- AstraZeneca
- Enrollment
- 91
- Locations
- 1
- Primary Endpoint
- AUC for albuterol
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This is a Phase 1 study to compare the pharmacokinetics of budesonide and albuterol delivered by PT027 compared with PT007 and PT008 administered separately.
Detailed Description
This study will be a randomized, 3-way cross-over study in healthy male and female participants, performed at a single study centre. A total of 90 healthy male or female participants will be randomized in this study to ensure that at least 81 participants are evaluable. The study will comprise: A screening period of maximum 27 days; Three treatment periods during which participants will be resident from the morning before dosing with Budesonide/Albuterol Sulfate metered dose inhaler (BDA MDI), Budesonide metered dose inhaler (BD MDI), and Albuterol Sulfate metered dose inhaler (AS MDI \[Day -1\]) 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 BDA MDI, BD MDI, or AS MDI. There will be a minimum washout period of 7 days between each dose administration.
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 (inclusive) 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 and must not be lactating.
- •Have a body mass index 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 AIM device and placebo MDI at the Screening Visit.
- •Forced expiratory volume in 1 second in litres (FEV1) ≥ 80% of predicted value and forced vital capacity in litres (FEV1)/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 screening or a positive urine hCG at admission for any of the 3 Treatment Periods.
- •History of any clinically significant disease or disorder which, in the opinion of the Principal Investigator (PI), may either put the subject at risk because of participation in the study, or influence the results or the participant'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.
- •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, haematology, 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 at the Screening Visit, as judged by the PI.
Arms & Interventions
Treatment sequence 1 (ABC)
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler \[BDA MDI\] - PT027) , Treatment B (Budesonide metered dose inhaler \[BD MDI\] - PT008), and Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
Intervention: Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler)
Treatment sequence 1 (ABC)
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler \[BDA MDI\] - PT027) , Treatment B (Budesonide metered dose inhaler \[BD MDI\] - PT008), and Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
Intervention: Treatment B (Budesonide metered dose inhaler)
Treatment sequence 1 (ABC)
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler \[BDA MDI\] - PT027) , Treatment B (Budesonide metered dose inhaler \[BD MDI\] - PT008), and Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
Intervention: Treatment C (Albuterol Sulfate metered dose inhaler)
Treatment sequence 2 (BCA)
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment B (Budesonide metered dose inhaler \[BD MDI\] - PT008), Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007), and Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler \[BDA MDI\] - PT027). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
Intervention: Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler)
Treatment sequence 2 (BCA)
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment B (Budesonide metered dose inhaler \[BD MDI\] - PT008), Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007), and Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler \[BDA MDI\] - PT027). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
Intervention: Treatment B (Budesonide metered dose inhaler)
Treatment sequence 2 (BCA)
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment B (Budesonide metered dose inhaler \[BD MDI\] - PT008), Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007), and Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler \[BDA MDI\] - PT027). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
Intervention: Treatment C (Albuterol Sulfate metered dose inhaler)
Treatment sequence 3 (CBA)
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007), Treatment B (Budesonide metered dose inhaler \[BD MDI\] - PT008), and Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler \[BDA MDI\] - PT027). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
Intervention: Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler)
Treatment sequence 3 (CBA)
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007), Treatment B (Budesonide metered dose inhaler \[BD MDI\] - PT008), and Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler \[BDA MDI\] - PT027). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
Intervention: Treatment B (Budesonide metered dose inhaler)
Treatment sequence 3 (CBA)
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007), Treatment B (Budesonide metered dose inhaler \[BD MDI\] - PT008), and Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler \[BDA MDI\] - PT027). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
Intervention: Treatment C (Albuterol Sulfate metered dose inhaler)
Treatment sequence 4 (ACB)
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler \[BDA MDI\] - PT027), Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007), and Treatment B (Budesonide metered dose inhaler \[BD MDI\] - PT008). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
Intervention: Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler)
Treatment sequence 4 (ACB)
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler \[BDA MDI\] - PT027), Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007), and Treatment B (Budesonide metered dose inhaler \[BD MDI\] - PT008). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
Intervention: Treatment B (Budesonide metered dose inhaler)
Treatment sequence 4 (ACB)
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler \[BDA MDI\] - PT027), Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007), and Treatment B (Budesonide metered dose inhaler \[BD MDI\] - PT008). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
Intervention: Treatment C (Albuterol Sulfate metered dose inhaler)
Treatment sequence 5 (BAC)
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment B (Budesonide metered dose inhaler \[BD MDI\] - PT008), Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler \[BDA MDI\] - PT027), and Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
Intervention: Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler)
Treatment sequence 5 (BAC)
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment B (Budesonide metered dose inhaler \[BD MDI\] - PT008), Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler \[BDA MDI\] - PT027), and Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
Intervention: Treatment B (Budesonide metered dose inhaler)
Treatment sequence 5 (BAC)
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment B (Budesonide metered dose inhaler \[BD MDI\] - PT008), Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler \[BDA MDI\] - PT027), and Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
Intervention: Treatment C (Albuterol Sulfate metered dose inhaler)
Treatment sequence 6 (CAB)
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007), Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler \[BDA MDI\] - PT027), and Treatment B (Budesonide metered dose inhaler \[BD MDI\] - PT008). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
Intervention: Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler)
Treatment sequence 6 (CAB)
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007), Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler \[BDA MDI\] - PT027), and Treatment B (Budesonide metered dose inhaler \[BD MDI\] - PT008). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
Intervention: Treatment B (Budesonide metered dose inhaler)
Treatment sequence 6 (CAB)
Participants will be randomized to each of the 6 different treatment sequences. Each treatment sequence consist of Treatment C (Albuterol Sulfate metered dose inhaler \[AS MDI\] - PT007), Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler \[BDA MDI\] - PT027), and Treatment B (Budesonide metered dose inhaler \[BD MDI\] - PT008). Each randomized participant will receive a single-dose (2 inhalations) on Day 1 of this Treatment Period.
Intervention: Treatment C (Albuterol Sulfate metered dose inhaler)
Outcomes
Primary Outcomes
AUC for albuterol
Time Frame: At 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 Day 2 (24 hours post dose)
To determine the area under the plasma concentration-time curve from time zero to infinity (AUC) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
AUC for budesonide
Time Frame: At 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 Day 2 (24 hours post dose)
To determine the AUC after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
AUC(0-t) for albuterol
Time Frame: At 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 Day 2 (24 hours post dose)
To determine the area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUC(\[0-t\]) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
AUC(0-t) for budesonide
Time Frame: At 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 Day 2 (24 hours post dose)
To determine the AUC(0-t) after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
Cmax for albuterol
Time Frame: At 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 Day 2 (24 hours post dose)
To determine observed maximum plasma concentration (Cmax) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
Cmax for budesonide
Time Frame: At 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 Day 2 (24 hours post dose)
To determine Cmax after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.
Secondary Outcomes
- tlast for albuterol(At 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 Day 2 (24 hours post dose))
- tlast for budesonide(At 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 Day 2 (24 hours post dose))
- tmax for albuterol(At 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 Day 2 (24 hours post dose))
- tmax for budesonide(At 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 Day 2 (24 hours post dose))
- t1/2λz for albuterol(At 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 Day 2 (24 hours post dose))
- t1/2λz for budesonide(At 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 Day 2 (24 hours post dose))
- λz for albuterol(At 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 Day 2 (24 hours post dose))
- λz for budesonide(At 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 Day 2 (24 hours post dose))
- CL/F for albuterol(At 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 Day 2 (24 hours post dose))
- CL/F for budesonide(At 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 Day 2 (24 hours post dose))
- Vz/F for albuterol(At 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 Day 2 (24 hours post dose))
- Vz/F for budesonide(At 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 Day 2 (24 hours post dose))
- Number of participants with adverse events (AEs)/serious AEs (SAEs)(From Screening to Post-study Visit (5-7 days))