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.
This study will be a randomized, open-label, 3-period, 3-treatment, single dose, single-center, crossover study. Eighteen healthy male and female subjects will be randomized in this study to ensure that at least 12 subjects are evaluable. A subject will be considered to be evaluable if the subject completes all 3 Treatment Periods with no important protocol deviations. Subjects will be randomized to 1 of 6 treatment sequences and will receive each of the 3 single dose treatments of AZD1402 listed below. * Treatment A: Dose A estimated delivered dose of AZD1402 nebuliser solution administered via a nebuliser. * Treatment B: Dose B estimated delivered dose of AZD1402 inhalation powder administered via an inhaler. * Treatment C: Dose C estimated delivered dose of AZD1402 inhalation powder administered via an inhaler. The study will comprise of: * A Screening Period of up to 28 days before the first administration of AZD1402. * Three Treatment Periods during which subjects will be resident at the Clinical Unit from the day before dosing with AZD1402 (Day -1) until at least 48 hours after dosing and discharged on Day 3. * A Follow-up Visit 10 to 12 days after the last administration of AZD1402 in Treatment Period 3. Each Treatment Period will be separated by a minimum washout period of 5 days between doses. All subjects will sign an Informed Consent Form before they participate in any specific study related procedures. Subjects will attend a Screening Visit within 28 days before receiving their first dose of AZD1402. If they are eligible, they will return for Treatment Period 1 when they will have baseline assessments and receive 1 of 3 treatments in a randomized order. For each Treatment Period, the subjects will receive a single dose of Investigational Medicinal Product (IMP) in the morning of Day 1 and have further assessments for 48 hours after dosing.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
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.
Research Site
Harrow, United Kingdom
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
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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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Number of patients with adverse events
To further assess the safety and tolerability of single inhaled doses of AZD1402 in healthy volunteers.
Time frame: 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
To further assess the safety and tolerability of single inhaled doses of AZD1402 in healthy volunteers. Vital signs including BP and Pulse
Time frame: Day 1: Pre-dose and 10 minutes post-dose
Number of patients with abnormal electrocardiograms
To further assess the safety and tolerability of single inhaled doses of AZD1402 in healthy volunteers.
Time frame: Day 1: pre-dose and 5 hours post-dose
Number of patients with abnormal physical examination
To further assess the safety and tolerability of single inhaled doses of AZD1402 in healthy volunteers.
Time frame: Day 3: 48 hours post-dose (brief)
Number of patients with abnormal findings in spirometry
To further assess the safety and tolerability of single inhaled doses of AZD1402 in healthy volunteers.
Time frame: Day 1: pre-dose and 0.5 and 1 hour post-dose
Number of patients with abnormal findings in hematology
To further assess the safety and tolerability of single inhaled doses of AZD1402 in healthy volunteers.
Time frame: Day 3: 48 hours post-dose
Number of patients with abnormal findings in clinical chemistry
To further assess the safety and tolerability of single inhaled doses of AZD1402 in healthy volunteers.
Time frame: Day 3: 48 hours post-dose
Number of patients with abnormal findings in urinalysis
To further assess the safety and tolerability of single inhaled doses of AZD1402 in healthy volunteers.
Time frame: Day 3: 48 hours post-dose
Standardized taste questionnaires
To evaluate the taste characteristics of the test formulations. This will be done immediately after dosing (within 5 minutes). The taste score will be based on 6 attributes: Sweet, Salty, Sour, Bitter, Metallic and Hot/Spicy. Each attribute is with a scale of 0 to 10, where 0= "extremely low/not at all" and 10= "extremely high". If the test formulation is having a smell, another 0 to 10 scale will be there for smell with 0= "extremely bad" and 10= "extremely nice". There will be one score scale with 0="I dislike it extremely much" and 10="I like it extremely much" and another scale of taking test formulation again with 0="Never - under no circumstances" and 10= "Yes, definitely".
Time frame: Day 1 to Day 3.