Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Compare the Pharmacokinetics of Budesonide and Albuterol Delivered by PT027 Compared With PT007 and PT008 Administered Separately.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03772223
Recruitment Status : Recruiting
First Posted : December 11, 2018
Last Update Posted : March 25, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler) Drug: Treatment B (Budesonide metered dose inhaler) Drug: Treatment C (Albuterol Sulfate metered dose inhaler) Phase 1

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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).
Actual Study Start Date : January 21, 2019
Estimated Primary Completion Date : May 10, 2019
Estimated Study Completion Date : May 10, 2019


Arm Intervention/treatment
Experimental: 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.
Drug: Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler)
Randomized participants will receive a single-dose (2 inhalations, 2 x 80/90 µg).

Drug: Treatment B (Budesonide metered dose inhaler)
Randomized participants will receive a single-dose (2 inhalations, 2 x 80 µg).

Drug: Treatment C (Albuterol Sulfate metered dose inhaler)
Randomized participants will receive a single-dose (2 inhalations, 2 x 90 µg).

Experimental: 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.
Drug: Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler)
Randomized participants will receive a single-dose (2 inhalations, 2 x 80/90 µg).

Drug: Treatment B (Budesonide metered dose inhaler)
Randomized participants will receive a single-dose (2 inhalations, 2 x 80 µg).

Drug: Treatment C (Albuterol Sulfate metered dose inhaler)
Randomized participants will receive a single-dose (2 inhalations, 2 x 90 µg).

Experimental: 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.
Drug: Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler)
Randomized participants will receive a single-dose (2 inhalations, 2 x 80/90 µg).

Drug: Treatment B (Budesonide metered dose inhaler)
Randomized participants will receive a single-dose (2 inhalations, 2 x 80 µg).

Drug: Treatment C (Albuterol Sulfate metered dose inhaler)
Randomized participants will receive a single-dose (2 inhalations, 2 x 90 µg).

Experimental: 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.
Drug: Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler)
Randomized participants will receive a single-dose (2 inhalations, 2 x 80/90 µg).

Drug: Treatment B (Budesonide metered dose inhaler)
Randomized participants will receive a single-dose (2 inhalations, 2 x 80 µg).

Drug: Treatment C (Albuterol Sulfate metered dose inhaler)
Randomized participants will receive a single-dose (2 inhalations, 2 x 90 µg).

Experimental: 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.
Drug: Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler)
Randomized participants will receive a single-dose (2 inhalations, 2 x 80/90 µg).

Drug: Treatment B (Budesonide metered dose inhaler)
Randomized participants will receive a single-dose (2 inhalations, 2 x 80 µg).

Drug: Treatment C (Albuterol Sulfate metered dose inhaler)
Randomized participants will receive a single-dose (2 inhalations, 2 x 90 µg).

Experimental: 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.
Drug: Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler)
Randomized participants will receive a single-dose (2 inhalations, 2 x 80/90 µg).

Drug: Treatment B (Budesonide metered dose inhaler)
Randomized participants will receive a single-dose (2 inhalations, 2 x 80 µg).

Drug: Treatment C (Albuterol Sulfate metered dose inhaler)
Randomized participants will receive a single-dose (2 inhalations, 2 x 90 µg).




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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 Outcome Measures :
  1. tlast 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 time of last quantifiable plasma concentration (tlast) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.

  2. tlast 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 tlast after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.

  3. tmax 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 time to reach maximum observed plasma concentration (tmax) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.

  4. tmax 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 tmax after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.

  5. t1/2λz 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 time to apparent elimination half-life (t1/2λz)after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy

  6. t1/2λz 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 t1/2λz after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.

  7. λz 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 terminal elimination rate constant (λz) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.

  8. λz 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 λz after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.

  9. CL/F 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 apparent total body clearance of drug from plasma after extravascular administration (CL/F) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.

  10. CL/F 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 CL/F after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.

  11. Vz/F 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 apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) after single dose administration of albuterol delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.

  12. Vz/F 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 Vz/F after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.

  13. Number of participants with adverse events (AEs)/serious AEs (SAEs) [ Time Frame: From Screening to Post-study Visit (5-7 days) ]
    To assess the safety and tolerability of BDA MDI, BD MDI, and AS MDI.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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 (inclusive) 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 and must not be lactating.
  4. 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.
  5. Must be able to demonstrate proper inhalation technique using the AIM device and placebo MDI at the Screening Visit.
  6. 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:

  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 screening or a positive urine hCG at admission for any of the 3 Treatment Periods.
  3. 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.
  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.
  7. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of Investigational Medicinal Product (IMP).
  8. Any clinically significant abnormalities in clinical chemistry, haematology, 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 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 antibody.
  12. Known or suspected history of drug abuse in the 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 1 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 screening.
  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 and albuterol sulfate.
  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. Known or suspected history of alcohol or excessive intake of alcohol in the last 2 years as judged by the PI.
  21. Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives.
  22. 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.
  23. Vulnerable participant, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03772223


Contacts
Layout table for location contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
Layout table for location information
United Kingdom
Research Site Recruiting
London, United Kingdom, HA1 3UJ
Sponsors and Collaborators
AstraZeneca
Investigators
Layout table for investigator information
Principal Investigator: Pablo Forte Soto Parexel

Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03772223     History of Changes
Other Study ID Numbers: D6930C00003
First Posted: December 11, 2018    Key Record Dates
Last Update Posted: March 25, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:
Pharmacokinectics
Inhaled corticosteroid

Additional relevant MeSH terms:
Layout table for MeSH terms
Anti-Asthmatic Agents
Budesonide
Albuterol
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Respiratory System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action