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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.
The study will comprise of:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A | Experimental | Dose A estimated delivered single dose of AZD1402 nebuliser solution administered via a nebuliser. |
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| Treatment B | Experimental | Dose B estimated delivered single dose of AZD1402 inhalation powder administered via an inhaler. |
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| Treatment C | Experimental | Dose C estimated delivered single dose of AZD1402 inhalation powder administered via an inhaler. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients with adverse events | To further assess the safety and tolerability of single inhaled doses of AZD1402 in healthy volunteers. | 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 |
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Inclusion Criteria:
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.
3.1. 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.
3.2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy.
3.3. 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.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Harrow | HA1 3UJ | United Kingdom |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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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. | 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 |
To further assess the safety and tolerability of single inhaled doses of AZD1402 in healthy volunteers. Vital signs including BP and Pulse |
| 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. | 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. | 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. | 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. | 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. | 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. | 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". | Day 1 to Day 3. |
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |