AsthmaPhase 1NCT04480879
Evaluation of AZD8154 Concentrations in Blood
A Phase 1 study testing AZD8154 nebuliser and AZD8154 Monodose DPI presented in capsules in people with Asthma, run by AstraZeneca at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma
- What is being tested?
- AZD8154 nebuliser and AZD8154 Monodose DPI presented in capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteGermany
- Study dates
- 17 Jul 2020to 2 Sep 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
- 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.
Who cannot join
- 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.
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- 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:
- Alanine aminotransferase and/or aspartate aminotransferase > 1.5 x the upper limit of the normal (ULN) laboratory range.
- 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:
- 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.
- Prolonged QT interval corrected for heart rate using Fridericia's formula (QTcF) > 450 ms or shortened QTcF < 340 ms or family history of long QT syndrome.
- PR (PQ) interval shortening < 120 ms (PR > 110 ms but < 120 ms is acceptable if there is no evidence of ventricular pre excitation).
- PR (PQ) interval prolongation (> 220 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third degree atrioventricular (AV) block, or AV dissociation.
- Persistent or intermittent complete bundle branch block (BBB), incomplete bundle branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS > 110 ms. Subjects with QRS > 110 ms but < 115 ms are acceptable if there is no evidence of e.g., ventricular hypertrophy or pre excitation.
- Previous use of a mechanistic target of rapamycin (mTOR) antagonist (e.g., rapamycin, everolimus) or PI3K inhibitor (selective or non selective PI3K inhibitors).
- Known or suspected history of drug abuse as judged by the Investigator.
- Current smokers or those who have smoked or used nicotine products (including e cigarettes) within the previous 3 months.
- History of alcohol abuse or excessive intake of alcohol as judged by the Investigator.
- Positive screen for drugs of abuse or cotinine (nicotine) at the Screening Visit or admission to the Clinical Unit or positive screen for alcohol on admission to the Clinical Unit before the first administration of the IMP.
- History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD8154.
- Receipt of live attenuated vaccines 2 months before first administration of the IMP and 3 months after the last IMP administration.
- Excessive intake of caffeine-containing drinks or food (e.g., coffee, tea, chocolate) as judged by the Investigator.
- Use of drugs with cytochrome P450 (CYP) 3A enzyme inducing or inhibition properties within 3 weeks before first administration of IMP.
- Use of any prescribed or nonprescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks before the first administration of the IMP or longer if the medication has a long half life.
- Plasma donation within 1 month of the Screening Visit or any blood donation/blood loss > 500 mL during the 2 months before the Screening Visit.
- Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration the IMP in this study. The period of exclusion begins 3 months after the final dose or 1 month after the last visit whichever is the longest.
- Involvement of any Astra Zeneca or study site employee or their close relatives.
- Judgement by the Investigator that the subject should not participate in the study if they have any ongoing or recent (i.e., during the Screening Period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements.
- Subjects who cannot communicate reliably with the Investigator and/or is not able to read speak and understand the German language.
- Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship or committed to an institution by governmental or juridical order.
- Subject has a positive test result for SARS-CoV-2 RT-PCR before randomisation.
- Subject has clinical signs and symptoms consistent with COVID-19, e.g., fever, dry cough, dyspnoea, sore throat, fatigue, or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on first admission.
- History of severe COVID-19 (hospitalisation, extracorporeal membrane oxygenation, mechanically ventilated).
- Subjects who are regularly exposed to COVID-19 as part of their daily life (e.g., health care professionals working in COVID-19 wards or at emergency departments).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised, 3 Period, Single Dose, Open-label Crossover Study to Evaluate the Systemic Exposure of AZD8154 While Administered Via Inhalation Using a Nebuliser Formulation and a Monodose Dry Powder Inhaler (DPI) Formulation in Healthy Subjects
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.
Read the detailed description
This study will be a randomised, open-label, 3-period, single-dose, single-centre, crossover study in healthy males and healthy females of non-childbearing potential.
The study will comprise:
- A Screening Period of maximum 28 days;
- Three treatment periods during which subjects will be resident at the Clinical Unit from the morning of the day before dosing with AZD8154 or placebo (Day 1) until 72 hours following dosing for collection of PK samples; discharged on the morning of Day 4 of each treatment period;
- A Follow up Visit within 6 ± 1 days after last dose administration of investigational medicinal products (IMPs) (i.e., AZD8154 or placebo).
A total of 15 healthy subjects will be randomised in this study to ensure that at least 12 subjects are evaluable.
Each subject will be involved in the study for approximately 9 weeks.
- Conditions
- Asthma
- Being tested
- AZD8154 nebuliser, AZD8154 Monodose DPI presented in capsules, AZD8154 Placebo Monodose DPI presented in capsules
- Keywords
- Phase 1, Phosphoinositide 3-kinase inhibitor, open-label crossover study
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD8154 nebuliserDrug
Nebuliser suspension
AZD8154 Monodose DPI presented in capsulesDrug
AZD8154 Monodose DPI formulation delivered dose
AZD8154 Placebo Monodose DPI presented in capsulesDrug
The dose correspond to AZD8154 Monodose DPI formulation
| Study group | Role | What they receive |
|---|---|---|
| AZD8154 nebuliser suspension | Experimental | The study subjects will receive 1 mg delivered dose of AZD8154 nebuliser suspension Receives: Drug: AZD8154 nebuliser |
| AZD8154 Monodose | Experimental | The study subjects will receive 1 mg capsule delivered dose of AZD8154 Monodose DPI formulation Receives: 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 Receives: Drug: AZD8154 Placebo Monodose DPI presented in capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
To evaluate further PK parameters of AZD8154 following inhaled single dose administration of a Monodose DPI formulation and an inhaled single dose administration of a nebuliser suspension.
Measured: 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)
To evaluate further PK parameters of AZD8154 following inhaled single dose administration of a Monodose DPI formulation and an inhaled single dose administration of a nebuliser suspension.
Measured: 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)
To evaluate further PK parameters of AZD8154 following inhaled single dose administration of a Monodose DPI formulation and an inhaled single dose administration of a nebuliser suspension.
Measured: 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)
To evaluate further PK parameters of AZD8154 following inhaled single dose administration of a Monodose DPI formulation and an inhaled single dose administration of a nebuliser suspension.
Measured: 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)
To evaluate further PK parameters of AZD8154 following inhaled single dose administration of a Monodose DPI formulation and an inhaled single dose administration of a nebuliser suspension.
Measured: 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)
Volume of distribution following extravascular administration (based on terminal phase) (Vz/F)
To evaluate further PK parameters of AZD8154 following inhaled single dose administration of a Monodose DPI formulation and an inhaled single dose administration of a nebuliser suspension.
Measured: 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)
Number of subjects with adverse events
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: Day-1, 1 to 4 (Spontaneous plus pre dose, 3, 12, 24, 48 and 72 hrs post dose)
Number of subjects with abnormal blood pressure
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 (Predose and 72hrs post dose)
Number of subjects with abnormal pulse rate
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 (Predose and 72hrs post dose)
Number of subjects with abnormal tympanic temperature
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day 1 to 4 (Predose, 24, 48, and 72 hrs post dose)
Number of subjects with abnormal respiratory rate
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 (Predose and 72hrs post dose)
Number of subjects with abnormal ECG
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day 1 to 4 (Predose and 72 hrs post dose)
Number of subjects with abnormal physical examination
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit
Number of subjects with abnormal spirometry
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening(Day-28 to-2), Day-1, Day1 to 4 (Predose and 30min, 90min, 3hrs, 12hrs and 24hrs postdose)
Number of subjects with abnormal White blood cell (WBC) count
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Red blood cell (RBC) count
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Haemoglobin (Hb)
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Haematocrit (HCT)
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Mean corpuscular volume (MCV)
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Mean corpuscular haemoglobin (MCH)
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Mean corpuscular haemoglobin concentration (MCHC)
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Neutrophils absolute count
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Lymphocytes absolute count
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Monocytes absolute count
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Eosinophils absolute count
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Basophils absolute count
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Platelets
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Reticulocytes absolute count
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Sodium
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Potassium
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Urea
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Creatinine
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Albumin
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Calcium
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Phosphate
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Glucose(fasting)
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal C-reactive protein (CRP)
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Alkaline phosphatase (ALP)
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Alanine aminotransferase (ALT)
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Aspartate aminotransferase (AST)
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Gamma glutamyl transpeptidase (GGT)
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Total Bilirubin (TBL)
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Unconjugated bilirubin
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Urinalysis
To assess the safety of single doses of AZD8154 (Monodose DPI formulation and nebuliser suspension) or placebo (Monodose DPI formulation) in healthy subjects.
The parameters to be assessed are glucose, protein and blood in urine
Measured: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2020
- Study start17 Jul 2020
- Primary completion2 Sep 2020
- Study completion2 Sep 2020
Why it stopped: Need for evaluation of emerging pre-clinical toxicology findings
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04480879
- Sponsor's protocol ID
- D8900C00005
- Status last verified
- Aug 2021
- First submitted
- 17 Jul 2020
- Last updated
- 24 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, 3 Period, Single Dose, Open-label Crossover Study to Evaluate the Systemic Exposure of AZD8154 While Administered Via Inhalation Using a Nebuliser Formulation and a Monodose Dry Powder Inhaler (DPI) Formulation in Healthy Subjects
- ClinicalTrials.gov ID
- NCT04480879
- Acronym / sponsor ID
- D8900C00005
- Conditions
- Asthma
- Keywords
- Phase 1, Phosphoinositide 3-kinase inhibitor, open-label crossover study
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Need for evaluation of emerging pre-clinical toxicology findings
- Enrolment
- 10 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 17 Jul 2020 (actual)
- Primary completion
- 2 Sep 2020 (actual)
- Study completion
- 2 Sep 2020 (actual)
- First posted
- 21 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study will be a randomised, open-label, 3-period, single-dose, single-centre, crossover study in healthy males and healthy females of non-childbearing potential.
The study will comprise:
- A Screening Period of maximum 28 days;
- Three treatment periods during which subjects will be resident at the Clinical Unit from the morning of the day before dosing with AZD8154 or placebo (Day 1) until 72 hours following dosing for collection of PK samples; discharged on the morning of Day 4 of each treatment period;
- A Follow up Visit within 6 ± 1 days after last dose administration of investigational medicinal products (IMPs) (i.e., AZD8154 or placebo).
A total of 15 healthy subjects will be randomised in this study to ensure that at least 12 subjects are evaluable.
Each subject will be involved in the study for approximately 9 weeks.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| AZD8154 nebuliser suspension | Experimental | Drug: AZD8154 nebuliserThe study subjects will receive 1 mg delivered dose of AZD8154 nebuliser suspension |
| AZD8154 Monodose | Experimental | Drug: AZD8154 Monodose DPI presented in capsulesThe study subjects will receive 1 mg capsule delivered dose of AZD8154 Monodose DPI formulation |
| AZD8154 Placebo Monodose DPI | Placebo comparator | Drug: AZD8154 Placebo Monodose DPI presented in capsulesThe study subjects will receive AZD8154 placebo Monodose DPI formulation dosed to correspond to 1 mg delivered dose AZD8154 Monodose DPI formulation |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
- 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.
Key exclusion criteria (39 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD8154 nebuliserNebuliser suspension | Drug | AZD8154 nebuliser suspension |
| AZD8154 Monodose DPI presented in capsulesAZD8154 Monodose DPI formulation delivered dose | Drug | AZD8154 Monodose |
| AZD8154 Placebo Monodose DPI presented in capsulesThe dose correspond to AZD8154 Monodose DPI formulation | Drug | AZD8154 Placebo Monodose DPI |
Primary outcome
Area under the plasma concentration time curve from zero to infinity (AUCinf)
Time frame: 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)
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.
Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast)
Time frame: 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)
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.
Maximum observed plasma (peak) drug concentration (Cmax)
Time frame: 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)
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.
Dose normalised AUCinf
Time frame: 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)
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.
Dose normalised AUClast
Time frame: 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)
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.
Dose normalised Cmax
Time frame: 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)
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.
44 secondary outcomes
Time to reach peak or maximum observed concentration or response following drug administration (tmax)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Volume of distribution following extravascular administration (based on terminal phase) (Vz/F)
Time frame: 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)
Number of subjects with adverse events
Time frame: Day-1, 1 to 4 (Spontaneous plus pre dose, 3, 12, 24, 48 and 72 hrs post dose)
Number of subjects with abnormal blood pressure
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 (Predose and 72hrs post dose)
Number of subjects with abnormal pulse rate
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 (Predose and 72hrs post dose)
Number of subjects with abnormal tympanic temperature
Time frame: At screening (Day-28 to-2), Day-1, Day 1 to 4 (Predose, 24, 48, and 72 hrs post dose)
Number of subjects with abnormal respiratory rate
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 (Predose and 72hrs post dose)
Number of subjects with abnormal ECG
Time frame: At screening (Day-28 to-2), Day-1, Day 1 to 4 (Predose and 72 hrs post dose)
Number of subjects with abnormal physical examination
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit
Number of subjects with abnormal spirometry
Time frame: At screening(Day-28 to-2), Day-1, Day1 to 4 (Predose and 30min, 90min, 3hrs, 12hrs and 24hrs postdose)
Number of subjects with abnormal White blood cell (WBC) count
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Red blood cell (RBC) count
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Haemoglobin (Hb)
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Haematocrit (HCT)
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Mean corpuscular volume (MCV)
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Mean corpuscular haemoglobin (MCH)
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Mean corpuscular haemoglobin concentration (MCHC)
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Neutrophils absolute count
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Lymphocytes absolute count
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Monocytes absolute count
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Eosinophils absolute count
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Basophils absolute count
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Platelets
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Reticulocytes absolute count
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Sodium
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Potassium
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Urea
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Creatinine
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Albumin
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Calcium
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Phosphate
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Glucose(fasting)
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal C-reactive protein (CRP)
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Alkaline phosphatase (ALP)
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Alanine aminotransferase (ALT)
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Number of subjects with abnormal Aspartate aminotransferase (AST)
Time frame: At screening (Day-28 to-2), Day-1, Day1 to 4 and follow-up visit (6± 1 days post last dose)
Results and safety
The study was stopped early (reason given: Need for evaluation of emerging pre-clinical toxicology findings). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2021.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD8154 nebuliser and AZD8154 Monodose DPI presented in capsules in people with Asthma, run by AstraZeneca at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Need for evaluation of emerging pre-clinical toxicology findings). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the plasma concentration time curve from zero to infinity (AUCinf) (time frame: 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)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2021.