A Study to Compare the Pharmacokinetics of Budesonide Delivered by PT027 Compared With Pulmicort Flexhaler (ELBRUS)

September 28, 2019 updated by: AstraZeneca

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)

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
11

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21225
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Provision of signed and dated, written informed consent prior to any study specific procedures.
  2. Healthy male and female participants aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
  3. Females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit, must not be lactating.
  4. 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.
  5. 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.
  6. 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:

  1. Pregnant or nursing female participants or participants who are trying to conceive
  2. 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.
  3. 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.
  4. History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
  5. Participants who have cancer that has not been in complete remission for at least 5 years.
  6. Any history of asthma or Chronic obstructive pulmonary disease (COPD).
  7. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
  8. Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results at the Screening Visit, as judged by the PI.
  9. Any clinically significant abnormal findings in vital signs at the Screening Visit, as judged by the PI.
  10. Any clinically significant abnormalities on 12-lead electrocardiogram (ECG) at the Screening Visit, as judged by the PI.
  11. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
  12. Known or suspected history of alcohol or drug abuse, or excessive intake of alcohol, in past 2 years, as judged by the PI.
  13. Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study. The period of exclusion begins 3 months after the final dose or one month after the last visit whichever is the longest.
  14. Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to the Screening Visit.
  15. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the PI or history of hypersensitivity to drugs with a similar chemical structure or class to budesonide, albuterol sulfate and any component of the MDI and DPI.
  16. Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 3 months prior to screening.
  17. Positive screen for drugs of abuse, cotinine or alcohol at the Screening Visit or on each admission to the Clinical Unit.
  18. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
  19. 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.
  20. Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives.
  21. Judgment by the PI that the participant 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.
  22. Vulnerable participants, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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).
Drug: BDA MDI 160/180 mcg
Budesonide/albuterol sulfate pressurized inhalation suspension, single dose given as 2 inhalations of 80/90 mcg.
Drug: Pulmicort Flexhaler 180 mcg
Pulmicort Flexhaler aerosol, power, single-dose given as 2 inhalations of 90 mcg.
Experimental: 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).
Drug: BDA MDI 160/180 mcg
Budesonide/albuterol sulfate pressurized inhalation suspension, single dose given as 2 inhalations of 80/90 mcg.
Drug: Pulmicort Flexhaler 180 mcg
Pulmicort Flexhaler aerosol, power, single-dose given as 2 inhalations of 90 mcg.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
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)
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
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)
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
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)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to reach maximum observed plasma concentration (tmax)
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 determine tmax for budesonide delivered by BDA MDI and Pulmicort Flexhaler
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 of last quantifiable plasma concentration (tlast)
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 determine tlast for budesonide delivered by BDA MDI and Pulmicort Flexhaler
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)
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 determine t½λz for budesonide delivered by BDA MDI and Pulmicort Flexhaler
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)
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 determine λz for budesonide delivered by BDA MDI and Pulmicort Flexhaler
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)
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 determine CL/F for budesonide delivered by BDA MDI and Pulmicort Flexhaler
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)
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 determine Vz/F for budesonide delivered by BDA MDI and Pulmicort Flexhaler
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
Time Frame: From screening (Day -27 to Day -2) to post study visit ( 5-7 days)
To assess the safety and tolerability of BDA MDI and Pulmicort Flexhaler
From screening (Day -27 to Day -2) to post study visit ( 5-7 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AstraZeneca

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Dr. Ronald Goldwater, MD, MD

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 16, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 10, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 10, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 29, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 29, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 1, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 1, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 28, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • D6930C00011

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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