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

NCT03772223 | Completed Phase 1

• 1 other identifier: D6930C00003
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

Pharmacokinectics; Inhaled corticosteroid

Outcome Measures

Primary Outcomes (6)

• AUC for albuterol

  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.

  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)

• AUC for budesonide

  To determine the AUC after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.

  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)

• AUC(0-t) for albuterol

  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.

  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)

• AUC(0-t) for budesonide

  To determine the AUC(0-t) after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.

  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)

• Cmax for albuterol

  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.

  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)

• Cmax for budesonide

  To determine Cmax after single dose administration of budesonide delivered via BDA MDI with BD MDI monotherapy and AS MDI monotherapy.

  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)

Secondary Outcomes (13)

• 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)

Study Arms (6)

Treatment sequence 1 (ABC)

EXPERIMENTAL

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); Drug: Treatment B (Budesonide metered dose inhaler); Drug: Treatment C (Albuterol Sulfate metered dose inhaler)

Treatment sequence 2 (BCA)

EXPERIMENTAL

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); Drug: Treatment B (Budesonide metered dose inhaler); Drug: Treatment C (Albuterol Sulfate metered dose inhaler)

Treatment sequence 3 (CBA)

EXPERIMENTAL

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); Drug: Treatment B (Budesonide metered dose inhaler); Drug: Treatment C (Albuterol Sulfate metered dose inhaler)

Treatment sequence 4 (ACB)

EXPERIMENTAL

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); Drug: Treatment B (Budesonide metered dose inhaler); Drug: Treatment C (Albuterol Sulfate metered dose inhaler)

Treatment sequence 5 (BAC)

EXPERIMENTAL

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); Drug: Treatment B (Budesonide metered dose inhaler); Drug: Treatment C (Albuterol Sulfate metered dose inhaler)

Treatment sequence 6 (CAB)

EXPERIMENTAL

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); Drug: Treatment B (Budesonide metered dose inhaler); Drug: Treatment C (Albuterol Sulfate metered dose inhaler)

Interventions

Treatment A (Budesonide/Albuterol Sulfate metered dose inhaler) DRUG

Randomized participants will receive a single-dose (2 inhalations, 2 x 80/90 µg).

Treatment sequence 1 (ABC); Treatment sequence 2 (BCA); Treatment sequence 3 (CBA); Treatment sequence 4 (ACB); Treatment sequence 5 (BAC); Treatment sequence 6 (CAB)

Treatment B (Budesonide metered dose inhaler) DRUG

Randomized participants will receive a single-dose (2 inhalations, 2 x 80 µg).

Treatment sequence 1 (ABC); Treatment sequence 2 (BCA); Treatment sequence 3 (CBA); Treatment sequence 4 (ACB); Treatment sequence 5 (BAC); Treatment sequence 6 (CAB)

Treatment C (Albuterol Sulfate metered dose inhaler) DRUG

Randomized participants will receive a single-dose (2 inhalations, 2 x 90 µg).

Treatment sequence 1 (ABC); Treatment sequence 2 (BCA); Treatment sequence 3 (CBA); Treatment sequence 4 (ACB); Treatment sequence 5 (BAC); Treatment sequence 6 (CAB)

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 (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%.

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 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.
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus antibody.
• Known or suspected history of drug abuse in the 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 screening.
• 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.
• 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

London, HA1 3UJ, United Kingdom

Location

MeSH Terms

Interventions

Budesonide

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Pablo Forte Soto

  Parexel

  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: December 10, 2018
• First Posted: December 11, 2018
• Study Start: January 21, 2019
• Primary Completion: May 10, 2019
• Study Completion: May 10, 2019
• Last Updated: May 21, 2019

Record last verified: 2019-05

Locations

GB (1)