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

NCT03934333 | Completed Phase 1

• 1 other identifier: D6930C00011
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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).

Conditions

Relative Bioavailability

Keywords

Pharmacokinetics; Inhaled corticosteroid

Outcome Measures

Primary Outcomes (3)

• Area under plasma concentration-time curve from time zero to infinity (AUC) for budesonide

  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

  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

  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 Outcomes (7)

• 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)

• 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)

• 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)

• 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)

Study Arms (2)

A/B (BDA MDI/Pulmicort)

EXPERIMENTAL

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; Drug: Pulmicort Flexhaler 180 mcg

B/A (Pulmicort/ BDA MDI)

EXPERIMENTAL

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; Drug: Pulmicort Flexhaler 180 mcg

Interventions

BDA MDI 160/180 mcg DRUG

Budesonide/albuterol sulfate pressurized inhalation suspension, single dose given as 2 inhalations of 80/90 mcg.

A/B (BDA MDI/Pulmicort); B/A (Pulmicort/ BDA MDI)

Pulmicort Flexhaler 180 mcg DRUG

Pulmicort Flexhaler aerosol, power, single-dose given as 2 inhalations of 90 mcg.

A/B (BDA MDI/Pulmicort); B/A (Pulmicort/ BDA MDI)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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%.

You may not qualify if:

• 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.
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
• Known or suspected history of alcohol or drug abuse, or excessive intake of alcohol, in past 2 years, as judged by the PI.
• 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.
• 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.
• Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 3 months prior to screening.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Baltimore, Maryland, 21225, United States

Location

Study Officials

• Dr. Ronald Goldwater, MD

  MD

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2019
• First Posted: May 1, 2019
• Study Start: May 16, 2019
• Primary Completion: September 10, 2019
• Study Completion: September 10, 2019
• Last Updated: October 1, 2019

Record last verified: 2019-09

Locations

US (1)