Evaluation of AZD8154 Concentrations in Blood

NCT04480879 | Terminated Phase 1

• 1 other identifier: D8900C00005
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study is intended to evaluate the systemic pharmacokinetic (PK) characteristics and the safety of AZD8154 following administration of the Monodose DPI formulation compared with the administration of the nebuliser suspension.

Conditions

Asthma

Keywords

Phase 1, Phosphoinositide 3-kinase inhibitor, open-label crossover study

Outcome Measures

Primary Outcomes (6)

• Area under the plasma concentration time curve from zero to infinity (AUCinf)

  To evaluate the PK characteristics of AZD8154 following inhaled single dose administration of a Monodose DPI formulation when compared with inhaled single dose administration of a nebuliser suspension.

  Study Day 1 to 4 (Pre dose, 10 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 and 72 hours post dose)

• Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast)

  To evaluate the PK characteristics of AZD8154 following inhaled single dose administration of a Monodose DPI formulation when compared with inhaled single dose administration of a nebuliser suspension.

  Study Day 1 to 4 (Pre dose, 10 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 and 72 hours post dose)

• Maximum observed plasma (peak) drug concentration (Cmax)

  To evaluate the PK characteristics of AZD8154 following inhaled single dose administration of a Monodose DPI formulation when compared with inhaled single dose administration of a nebuliser suspension.

  Study Day 1 to 4 (Pre dose, 10 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 and 72 hours post dose)

• Dose normalised AUCinf

  To evaluate the PK characteristics of AZD8154 following inhaled single dose administration of a Monodose DPI formulation when compared with inhaled single dose administration of a nebuliser suspension.

  Study Day 1 to 4 (Pre dose, 10 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 and 72 hours post dose)

• Dose normalised AUClast

  To evaluate the PK characteristics of AZD8154 following inhaled single dose administration of a Monodose DPI formulation when compared with inhaled single dose administration of a nebuliser suspension.

  Study Day 1 to 4 (Pre dose, 10 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 and 72 hours post dose)

• Dose normalised Cmax

  To evaluate the PK characteristics of AZD8154 following inhaled single dose administration of a Monodose DPI formulation when compared with inhaled single dose administration of a nebuliser suspension.

  Study Day 1 to 4 (Pre dose, 10 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48 and 72 hours post dose)

Secondary Outcomes (44)

• Time to reach peak or maximum observed concentration or response following drug administration (tmax)

  Study Day 1 to 4 (Pre dose, 10 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 12, 18, 24, 36, 48 and 72 hours post dose)

• Half life associated with terminal slope of a semi logarithmic concentration time curve (t½λz)

  Study Day 1 to 4 (Pre dose, 10 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 12, 18, 24, 36, 48 and 72 hours post dose)

• Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT)

  Study Day 1 to 4 (Pre dose, 10 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 12, 18, 24, 36, 48 and 72 hours post dose)

• Terminal elimination rate constant (λz)

  Study Day 1 to 4 (Pre dose, 10 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 12, 18, 24, 36, 48 and 72 hours post dose)

• Apparent total body clearance of drug from plasma after extravascular administration (CL/F)

  Study Day 1 to 4 (Pre dose, 10 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 12, 18, 24, 36, 48 and 72 hours post dose)

Study Arms (3)

AZD8154 nebuliser suspension

EXPERIMENTAL

The study subjects will receive 1 mg delivered dose of AZD8154 nebuliser suspension

Drug: AZD8154 nebuliser

AZD8154 Monodose

EXPERIMENTAL

The study subjects will receive 1 mg capsule delivered dose of AZD8154 Monodose DPI formulation

Drug: AZD8154 Monodose DPI presented in capsules

AZD8154 Placebo Monodose DPI

PLACEBO COMPARATOR

The study subjects will receive AZD8154 placebo Monodose DPI formulation dosed to correspond to 1 mg delivered dose AZD8154 Monodose DPI formulation

Drug: AZD8154 Placebo Monodose DPI presented in capsules

Interventions

AZD8154 nebuliser DRUG

Nebuliser suspension

AZD8154 nebuliser suspension

AZD8154 Monodose DPI presented in capsules DRUG

AZD8154 Monodose DPI formulation delivered dose

AZD8154 Monodose

AZD8154 Placebo Monodose DPI presented in capsules DRUG

The dose correspond to AZD8154 Monodose DPI formulation

AZD8154 Placebo Monodose DPI

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/or healthy female subjects of non childbearing potential aged 18 to 55 years (inclusive at the Screening Visit) with suitable veins for cannulation or repeated venipuncture.
• Females must have a negative pregnancy test at Screening Visit and on admission to the Clinical Unit, must not be lactating and must be of non childbearing potential, confirmed at Screening by fulfilling 1 of the following criteria (i) Females are considered postmenopausal if they have had amenorrhea for at least 12 months without an alternative medical cause. The following age specific requirements apply: Women under 50 years old are considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments and with luteinising hormone and follicle stimulating hormone levels are in the postmenopausal range.
• Women over 50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments.
• (ii) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
• Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 60 kg and no more than 100 kg inclusive.
• Subject has a forced expiratory volume in 1 second ≥ 80% of the predicted value regarding age, height, gender and ethnicity at the Screening Visit.

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the Principal Investigator, 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.
• Subject is immune compromised.
• History of diabetes, impaired fasting glucose, metabolic syndrome, hypertriglyceridemia or familial lipid disorders.
• Current or previous history of malignancy of any kind except cutaneous basal or squamous cell carcinoma successful treated with therapy.
• History of any respiratory disorders such as asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis (IPF), or infantile bronchiolitis.
• Subject with latent or active tuberculosis, as confirmed by a positive QuantiFERON® TB Gold test or as judged by the Investigator at the Screening Visit.
• History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs, or bowel disorders not otherwise specified.
• Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of the IMP.
• Any clinically important abnormalities in clinical chemistry, haematology or urinalysis results, defined as the following:
• (i) Alanine aminotransferase and/or aspartate aminotransferase \> 1.5 x the upper limit of the normal (ULN) laboratory range.
• (ii) Bilirubin \> 1.5 times the ULN laboratory range. (iii) Absolute neutrophil count \< lower limit of normal (LLN). (iv) Absolute lymphocyte count \< LLN.
• Any positive result at the Screening Visit for serum hepatitis B surface antigen OR hepatitis B core antibodies, hepatitis C virus antibody (anti HCV) and human immunodeficiency virus.
• Abnormal vital signs, after 5 minutes supine rest, defined as any of the following:
• (i) Systolic blood pressure (BP) \< 90 mmHg or \> 140 mmHg. (ii) Diastolic BP \< 50 mmHg or \> 90 mmHg. (iii) Pulse \< 50 or \> 90 beats per minute (bpm).
• Any clinically important abnormalities in rhythm, conduction or morphology of the 12 lead safety ECG as judged by the Investigator.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Berlin, 14050, Germany

Location

MeSH Terms

Conditions

Asthma

Interventions

Capsules

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Design

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

Study Record Dates

• First Submitted: July 17, 2020
• First Posted: July 21, 2020
• Study Start: July 17, 2020
• Primary Completion: September 2, 2020
• Study Completion: September 2, 2020
• Last Updated: August 24, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

DE (1)