Study to Assess Effect of Device and Formulation on Pharmacokinetics (PK) of AZD1402

NCT03921268 | Completed Phase 1

• 1 other identifier: D2912C00001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate and compare the pharmacokinetics profiles of AZD1402 after oral inhalation as an inhalation powder and a nebuliser solution. To further assess the safety and tolerability of single doses of AZD1402 in healthy volunteers. To evaluate the taste characteristics of the test formulations.

Conditions

Asthma

Outcome Measures

Primary Outcomes (12)

• Area under serum concentration-time curve from zero to infinity [AUC]

  To evaluate and compare the pharmacokinetics (PK) profiles of AZD1402 after oral inhalation as an inhalation powder administered using the Plastiape Monodose inhaler and a nebuliser solution administered using the InnoSpire Go nebuliser.

  Pharmacokinetic Blood Sampling : Day 1: Pre-dose and 5, 20, 40minutes, and 1, 2, 3, 4, 6, 8, 12, 15 and 18 hours post-dose Day 2: 24 and 36 hours postdose. Day 3: 48 hours post-dose

• Area under the serum concentration-time curve from zero to infinity divided by dose [AUC/D]

  To evaluate and compare the PK profiles of AZD1402 after oral inhalation as an inhalation powder administered using the Plastiape Monodose inhaler and a nebuliser solution administered using the InnoSpire Go nebuliser.

  Pharmacokinetic Blood Sampling : Day 1: Pre-dose and 5, 20, 40minutes, and 1, 2, 3, 4, 6, 8, 12, 15 and 18 hours post-dose Day 2: 24 and 36 hours postdose. Day 3: 48 hours post-dose

• Area under the serum concentration-curve from time zero to time of last quantifiable concentration [AUClast]

  To evaluate and compare the PK profiles of AZD1402 after oral inhalation as an inhalation powder administered using the Plastiape Monodose inhaler and a nebuliser solution administered using the InnoSpire Go nebuliser.

  Pharmacokinetic Blood Sampling : Day 1: Pre-dose and 5, 20, 40minutes, and 1, 2, 3, 4, 6, 8, 12, 15 and 18 hours post-dose Day 2: 24 and 36 hours postdose. Day 3: 48 hours post-dose

• Area under the serum concentration-time curve from time zero to time of last quantifiable concentration divided by dose [AUClast/D]

  To evaluate and compare the PK profiles of AZD1402 after oral inhalation as an inhalation powder administered using the Plastiape Monodose inhaler and a nebuliser solution administered using the InnoSpire Go nebuliser.

  Pharmacokinetic Blood Sampling : Day 1: Pre-dose and 5, 20, 40minutes, and 1, 2, 3, 4, 6, 8, 12, 15 and 18 hours post-dose Day 2: 24 and 36 hours postdose. Day 3: 48 hours post-dose

• Maximum observed serum concentration [Cmax]

  To evaluate and compare the PK profiles of AZD1402 after oral inhalation as an inhalation powder administered using the Plastiape Monodose inhaler and a nebuliser solution administered using the InnoSpire Go nebuliser.

  Pharmacokinetic Blood Sampling : Day 1: Pre-dose and 5, 20, 40minutes, and 1, 2, 3, 4, 6, 8, 12, 15 and 18 hours post-dose Day 2: 24 and 36 hours postdose. Day 3: 48 hours post-dose

• Observed maximum serum concentration divided by the dose administered [Cmax/D]

  To evaluate and compare the PK profiles of AZD1402 after oral inhalation as an inhalation powder administered using the Plastiape Monodose inhaler and a nebuliser solution administered using the InnoSpire Go nebuliser.

  Pharmacokinetic Blood Sampling : Day 1: Pre-dose and 5, 20, 40minutes, and 1, 2, 3, 4, 6, 8, 12, 15 and 18 hours post-dose Day 2: 24 and 36 hours postdose. Day 3: 48 hours post-dose

• Time to reach maximum observed serum concentration [tmax]

  To evaluate and compare the PK profiles of AZD1402 after oral inhalation as an inhalation powder administered using the Plastiape Monodose inhaler and a nebuliser solution administered using the InnoSpire Go nebuliser.

  Pharmacokinetic Blood Sampling : Day 1: Pre-dose and 5, 20, 40minutes, and 1, 2, 3, 4, 6, 8, 12, 15 and 18 hours post-dose Day 2: 24 and 36 hours postdose. Day 3: 48 hours post-dose

• Terminal elimination rate constant [λz]

  To evaluate and compare the PK profiles of AZD1402 after oral inhalation as an inhalation powder administered using the Plastiape Monodose inhaler and a nebuliser solution administered using the InnoSpire Go nebuliser.

  Pharmacokinetic Blood Sampling : Day 1: Pre-dose and 5, 20, 40minutes, and 1, 2, 3, 4, 6, 8, 12, 15 and 18 hours post-dose Day 2: 24 and 36 hours postdose. Day 3: 48 hours post-dose

• Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve [t½z]

  To evaluate and compare the PK profiles of AZD1402 after oral inhalation as an inhalation powder administered using the Plastiape Monodose inhaler and a nebuliser solution administered using the InnoSpire Go nebuliser.

  Pharmacokinetic Blood Sampling : Day 1: Pre-dose and 5, 20, 40minutes, and 1, 2, 3, 4, 6, 8, 12, 15 and 18 hours post-dose Day 2: 24 and 36 hours postdose. Day 3: 48 hours post-dose

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

  To evaluate and compare the PK profiles of AZD1402 after oral inhalation as an inhalation powder administered using the Plastiape Monodose inhaler and a nebuliser solution administered using the InnoSpire Go nebuliser.

  Pharmacokinetic Blood Sampling : Day 1: Pre-dose and 5, 20, 40minutes, and 1, 2, 3, 4, 6, 8, 12, 15 and 18 hours post-dose Day 2: 24 and 36 hours postdose. Day 3: 48 hours post-dose

• Apparent total body clearance of drug from serum after extravascular administration [CL/F]

  To evaluate and compare the PK profiles of AZD1402 after oral inhalation as an inhalation powder administered using the Plastiape Monodose inhaler and a nebuliser solution administered using the InnoSpire Go nebuliser.

  Pharmacokinetic Blood Sampling : Day 1: Pre-dose and 5, 20, 40minutes, and 1, 2, 3, 4, 6, 8, 12, 15 and 18 hours post-dose Day 2: 24 and 36 hours postdose. Day 3: 48 hours post-dose

• Apparent volume of distribution during the terminal phase after extravascular administration [Vz/F]

  To evaluate and compare the PK profiles of AZD1402 after oral inhalation as an inhalation powder administered using the Plastiape Monodose inhaler and a nebuliser solution administered using the InnoSpire Go nebuliser.

  Pharmacokinetic Blood Sampling : Day 1: Pre-dose and 5, 20, 40minutes, and 1, 2, 3, 4, 6, 8, 12, 15 and 18 hours post-dose Day 2: 24 and 36 hours postdose. Day 3: 48 hours post-dose

Secondary Outcomes (9)

• Number of patients with adverse events

  Spontaneous plus Day 1: Pre-dose and 3 and 12 hours post-dose, Day 2: 24 hours post-dose, Day 3: 48 hours post-dose

• Number of patients with abnormal findings in vital signs

  Day 1: Pre-dose and 10 minutes post-dose

• Number of patients with abnormal electrocardiograms

  Day 1: pre-dose and 5 hours post-dose

• Number of patients with abnormal physical examination

  Day 3: 48 hours post-dose (brief)

• Number of patients with abnormal findings in spirometry

  Day 1: pre-dose and 0.5 and 1 hour post-dose

Study Arms (3)

Treatment A

EXPERIMENTAL

Dose A estimated delivered single dose of AZD1402 nebuliser solution administered via a nebuliser.

Drug: AZD1402

Treatment B

EXPERIMENTAL

Dose B estimated delivered single dose of AZD1402 inhalation powder administered via an inhaler.

Drug: AZD1402

Treatment C

EXPERIMENTAL

Dose C estimated delivered single dose of AZD1402 inhalation powder administered via an inhaler.

Drug: AZD1402

Interventions

AZD1402 DRUG

AZD1402 (PRS-060) is presented as a solution and dry powder for oral inhalation and belongs to a new class of therapeutics, Anticalin® proteins, which are modified lipocalins. AZD1402 is an inhaled IL-4Rα antagonist, which is being developed as controller therapy for asthma.

Also known as: PRS-060

Treatment A; Treatment B; Treatment C

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 female subjects 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 at Day -1 of Treatment Period 1, must not be lactating and must be of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria.
• Postmenopausal defined as amenorrhea for 2 years or more following cessation of all exogenous hormonal treatments and folliclestimulating hormone (FSH) levels in the postmenopausal range at the Screening Visit.
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy.
• Bilateral Tubal ligation at least 5 years prior to the Screening Visit with no subsequent pregnancies.
• Have a body mass index (BMI) between 18 and 35 kg/m2 inclusive and weigh at least 50 kg.
• Must be able to demonstrate proper inhalation technique using the Aerosol Inhalation Monitor (AIM) device at the Screening Visit.
• Subjects must be able to perform reliable spirometry testing according to American Thoracic Society (ATS)/ European Respiratory Society (ERS) criteria at the Screening Visit.
• Provision of signed, written and dated informed consent for optional genetic research. If a subject decline to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this protocol.

You may not qualify if:

• Subjects who have a significant history of recurrent or ongoing 'dry eye syndrome' of any cause that may be chronic or acute, that may affect the interpretation of safety data associated with the potential for anti-drug antibodies targeted to AZD1402 (structurally related to Tlc).
• History or clinical manifestations of any clinically significant medical disorder that, in the opinion of the Investigator, may put the subject at risk because of participation in the study, influence the results of the study or affect the subject'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.
• Any clinically significant illness, infection, medical/ surgical procedure, or trauma within 4 weeks of Day 1 of Treatment Period 1, or planned inpatient surgery or hospitalization during the study period.
• Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, at the Screening Visit and/or on Day - 1 of Treatment Period 1, as judged by the PI.
• Any clinically significant abnormal findings in vital signs at the Screening Visit and/or on Day -1 of Treatment Period 1, as judged by the PI.
• Any clinically significant abnormalities on 12-lead ECG at the Screening Visit., as judged by the PI.
• History of, or known significant infection including helminth, hepatitis A, B, or C, HIV, TB (i.e., positive result for interferon (INF) gamma release assay (IGRA), QuantiFERON TB-Gold), that may put the subject at risk during participation in the study.
• Subjects with history of latent or active TB.
• Subjects with any history of malignancy or neoplastic disease.
• Subjects with a disease history suggesting abnormal immune function.
• History of anaphylaxis following any biologic therapy and known history of allergy or reaction to any component of the investigational product formulation.
• Subjects who are not able to perform correct spirometry tests at the Screening Visit.
• Subjects with a forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) \< 80% of the predicted (calculated) values and FEV1/FVC ratio \< 0.7 in pulmonary function test (spirometry) at the Screening Visit.
• Males who are sexually active with a female partner of childbearing potential and who have not had a vasectomy and who do not agree to comply with highly effective methods of contraception from Day 1 of Treatment Period 1 until 90 days after the last dose of IMP.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Harrow, HA1 3UJ, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

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

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: March 15, 2019
• First Posted: April 19, 2019
• Study Start: March 25, 2019
• Primary Completion: June 13, 2019
• Study Completion: June 13, 2019
• Last Updated: June 21, 2019

Record last verified: 2019-06

Locations

GB (1)