Chronic Obstructive Pulmonary Disease - COPDPhase 1NCT03159442
Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses of AZD8871 in Healthy Male Japanese Subjects
A Phase 1 study testing AZD8871 in people with Chronic Obstructive Pulmonary Disease - COPD, run by AstraZeneca at 1 site in United Kingdom.
Trial summary
AZD8871 is a new chemical entity possessing long-acting dual-pharmacology (muscarinic receptor antagonist and β2 adrenoceptor agonist [MABA]) in a single molecule. This type of agent presents a novel approach to the treatment of chronic obstructive pulmonary disease (COPD) and potentially asthma (in combination with… Read more about this study
- Who is it for?
- Ages 20 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease - COPD
- What is being tested?
- AZD8871
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 19 Jun 2017to 13 Oct 2017
- 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 20 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Provision of written informed consent prior to any study related procedures, including withdrawal of medications.
- Male Japanese subjects aged 20 to 55 years, inclusive at Screening.
- Body mass index (BMI) calculated as weight in kg/height in m2 from >= 18 to <= 30 kg/m2 and weight >= 50 kg at Screening.
- Healthy, free from any clinically significant disease/conditions (including all cardiovascular conditions), as determined by medical history, physical examination, clinical laboratory testing, 12-lead ECG findings at Screening and admission to the unit.
- Spirometry readings (Forced Expiratory Volume in 1 second and Forced Vital Capacity) to be >= 80% of predicted value calculated using equations at Screening (Quanjer et. al. 2012).
- Normal blood pressure (BP) (defined as systolic BP >= 90 and <= 140 mmHg and diastolic BP >= 50 and <= 90 mmHg) at Screening and admission to the unit, measured after resting in supine position for at least 10 minutes.
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- Normal heart rate (HR) (defined as HR >= 45 and <= 90) measured after resting in supine position for at least 10 minutes at Screening and admission to the unit.
- Negative hepatitis B surface antigen (HBsAg), hepatitis B core (HBc) antibody (IgM), hepatitis C antibody and human immunodeficiency virus (HIV) I and II antibodies at Screening.
- Negative drugs of abuse and alcohol tests at Screening and at admission to the unit.
- Willing and able to comply with study specific procedures and restrictions.
Who cannot join
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Surgical history clinically relevant for the purpose of the study or any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of Screening.
- History of malignancy of any organ system, treated or untreated within the past 5 years, with the exception of localised basal cell carcinoma of the skin.
- Current smokers, or a smoking history during the last 6 months or total smoking history of more than 10 pack years. Use of electronic cigarettes or other forms of nicotine, current use or use within the last 6 months.
- Note: Pack years are calculated by dividing the number of cigarettes smoked per day by 20 (the number of cigarettes per pack) and multiplying tis figure by the number of years a person has been smoking. For example, a person who smoked 40 cigarettes a day and has been smoking for 10 years would have a 20 pack-year smoking history (40 cigarettes per day at 20 cigarettes per pack =2; 2 x 10 years of smoking =20 pack-year history).
- Prolonged QTcF corrected using Fredericia's formulae) interval, > 450 ms at Screening, or family history of long QT syndrome.
Show all 26Show fewer
- Any clinically significant abnormalities in rhythm, conduction or morphology noted on physical examination, ECG or telemetry recording, prior to randomisation.
- History of excessive use or abuse of alcohol within the past 2 years, defined as: subjects consuming more than 21 (male subjects) units of alcohol a week (1 unit = 1 glass of wine (125 mL) = 1 measure of spirits = half pint of beer).
- History of drug abuse within the past 2 years prior to Screening.
- Donation or loss of > 400 ml blood and plasma within the previous 3 months prior to Screening.
- History or presence of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity to any drug, as judged by the Investigator or history of hypersensitivity to drugs pharmacologically related to study drug.
- PR (PQ) interval shortening < 120 ms (PR > 110 ms but < 120 ms is acceptable if there is no evidence of ventricular pre-excitation) at Screening.
- PR (PQ) interval prolongation (> 240 ms), intermittent second (Wenckebach block while asleep is not exclusive), or third degree AV block, or AV dissociation at Screening.
- Persistent or intermittent complete bundle branch block, incomplete bundle branch block.
- Intraventricular conduction delay with QRS (onset of ventricular depolarization) > 110 ms at Screening.
- Note: Subjects with QRS > 110 ms but < 115 ms are acceptable if there is no evidence of ventricular hypertrophy or pre-excitation.
- Subject who does not agree to follow instructions to avoid partner pregnancy.
- Subject who is not able to adhere to the restrictions on prior and concomitant medications.
- Administered any investigational drug within 3 months prior to first dosing in this study or within the equivalent time of 5 half lives of receiving the last IMP administration, whichever is longer, or on an extended Follow up after receiving an IMP.
- Subjects unable to communicate reliably with the Investigator, even with the help of an interpreter.
- Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
- Subjects who failed any Screening procedures will not be included in the study.
- Subjects with psychiatric disease with limitations to follow instructions in regards of study procedures.
- Subjects with serum potassium values < 3.5 mmol/L at Screening and on repeat testing.
- Note: Potassium replacement and repeat testing is allowed if serum potassium concentration was < 3.5 mmol/L at Screening.
- Any laboratory abnormality or suspicion of any clinically relevant disease or disorder (on history or examination), including uncontrolled diabetes, which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study, or any other safety concern in the opinion of the Investigator.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Single Centre, Randomised, Single Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses of Inhaled AZD8871 in Healthy Male Japanese Subjects.
AZD8871 is a new chemical entity possessing long-acting dual-pharmacology (muscarinic receptor antagonist and β2 adrenoceptor agonist [MABA]) in a single molecule. This type of agent presents a novel approach to the treatment of chronic obstructive pulmonary disease (COPD) and potentially asthma (in combination with an inhaled corticosteroid). AZD8871 is being developed for inhalation, formulated with alpha lactose monohydrate and delivered by dry powder inhaler (DPI) that allows delivery of a single dose of the study drug.
The primary objective is to investigate the safety and tolerability of AZD8871 at steady state in healthy male Japanese subjects.
Read the detailed description
This is a Phase I, single centre, randomised, single blind, placebo-controlled study to investigate the safety, tolerability and pharmacokinetics (PK) of single and multiple ascending doses of inhaled AZD8871 in healthy male Japanese subjects.
All subjects will sign an Informed Consent Form before starting any study-related procedures.
Twenty-four healthy subjects, aged 20 to 55 years, will participate in 3 cohorts. All subjects will be admitted to the unit the day preceding the 1st dose and will be housed in the unit until 96 hours (4 days) post last dose of investigational medicinal product (IMP) (Day 20).
Eight subjects will participate in each cohort and will receive either AZD8871 or placebo, randomised 3:1 (6 subjects to receive AZD8871:2 subjects to receive placebo). Each subject will only be dosed in 1 cohort. The study design allows a gradual escalation of dose (Cohorts 2 and 3) with intensive safety monitoring to ensure the safety of the subjects.
In Cohort 1, subjects will receive only a single dose of AZD8871 300 µg or placebo on Day 1, followed by once daily dosing on Days 5 to 16. The dosing schedule of all cohorts will be single dose of IMP (active or placebo) on Day 1, followed by once daily dosing on Days 5 to 16. Within 5 to 7 days of discharge from the unit, there will be two follow-up visits.
Following each cohort, a maximum dose of 2 times the dose administered in the previous cohort will be considered for the subsequent cohort. However, the planned dose for Cohort 2 is 600 µg and for Cohort 3 is 900 µg. Dosing of Cohorts 2 and 3 will be preceded by a SRC meeting, which will confirm the adequacy of the planned doses. A minimum of 5 subjects on active treatment need to complete dosing per cohort in order to proceed to the next dose level.
The total duration of the study for each subject will be approximately 58 days (from Screening [up to -28 days before randomization] to Final Follow up visit [Day 30]).
- Being tested
- AZD8871, Placebo
- Keywords
- Chronic obstructive pulmonary disease (COPD), Asthma, AZD8871, muscarinic receptor antagonist and β2 adrenoceptor agonist (MABA), Phase I, Safety, Tolerability, Pharmacokinetics, long-acting muscarinic antagonist (LAMA), long-acting β2-agonist (LABA), Japanese
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD8871Drug
Powder for inhalation administered via single dose DPI 300 and 600 µg/inhalation.
PlaceboDrug
Powder for inhalation administered via single dose DPI
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Multiple inhaled doses of AZD8871 will be administered via single dose DPI. Each subject will receive 300 μg AZD8871 or placebo. This dose will be given as 1 inhalation from the 300 μg AZD8871 or placebo inhaler.
Single inhaled dose of AZD8871 or placebo will be administered on Day 1 and then single once daily inhalations of AZD8871 or placebo will be administered for 12 days from Day 5 until Day 16. Receives: Drug: AZD8871; Drug: Placebo |
| Cohort 2 | Experimental | Multiple inhaled doses of AZD8871 will be administered via single dose DPI. Each subject will receive 600 μg AZD8871 as 1 inhalation from the 600 μg AZD8871 or placebo inhaler.
Single inhaled dose of AZD8871 or placebo will be administered on Day 1 and then single once daily inhalations of AZD8871 or placebo will be administered for 12 days from Day 5 until Day 16.
Dose escalation to 600 μg dose will be done only after the SRC has determined the adequacy of the dose to be given. Receives: Drug: AZD8871; Drug: Placebo |
| Cohort 3 | Experimental | Multiple inhaled doses of AZD8871 will be administered via single dose DPI. Each subject will receive 900 μg AZD8871 as 1 inhalation from the 300 μg AZD8871 inhaler and 1 inhalation from the 600 μg AZD8871 inhaler, or placebo as 2 inhalations from 2 different placebo inhalers.
Single inhaled dose of AZD8871 or placebo on Day 1 and then single once daily inhalations of AZD8871 or placebo will be administered for 12 days from Day 5 until Day 16.
Dose escalation to the 900 μg dose will be done only after the SRC has determined the adequacy of the dose to be given. Receives: Drug: AZD8871; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events.
Recording adverse events. An AE is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition can be symptoms (e.g., nausea, chest pain), signs (e.g., tachycardia, enlarged liver) or the abnormal results of an investigation (e.g., laboratory findings, ECG). In clinical studies, an AE can include an undesirable medical condition occurring at any time, including run-in or washout periods, even if no study treatment has been administered.
Measured: From time of ICF to Day 30 (end of follow-up period)
Concomitant medication.
Recording concomitant medications. Any concomitant medication or therapy given to the subject during the study conduct will be recorded.
Measured: Change from screening up to follow-up period (Day 30 +/- 1)
Physical examination.
A full physical examination will include the examination of the following: general appearance, eyes, ears, nose, throat, chest/respiratory, heart/cardiovascular, gastrointestinal/liver, musculoskeletal/extremities, dermatological/skin, thyroid/neck, lymph nodes, neurological/psychiatric.
A brief physical examination will include assessment of the following: skin, lungs, cardiovascular system and abdomen (liver and spleen).
A complete physical examination will be performed at the Screening and Follow-up visit.
Only relevant findings detected will be recorded in the physical examination findings.
Measured: Change from screening up to follow-up period (Day 30 +/- 1)
Vital signs.
Recording vital signs. Systolic and diastolic blood pressure (in mmHg) will be measured after at least 10 minutes (can be reduced to 5 minutes at collection time points within the 1st hour after dosing) resting, and also, before taking any blood sample and conducting any spirometry. Measurements will be carried out with subject in the supine position and preferably always on the same arm.
Subject's oral body temperature will be measured at each vital signs collection.
Measured: Change from screening up to follow-up period (Day 30 +/- 1)
Number of clinically relevant new findings or worsening of a pre-existing findings as assessed by Hematology.
Haematocrit, hemoglobin, erythrocytes (red blood cells), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), leucocytes (white blood cells), differential blood count (neutrophils, lymphocytes, monocytes, eosinophils and basophils) and thrombocytes (platelets)
Measured: Change from screening up to follow-up period (Day 30 +/- 1)
Number of clinically relevant new findings or worsening of a pre-existing findings as assessed by Clinical chemistry.
Electrolytes: sodium, potassium, calcium, chloride and inorganic phosphorus. Enzymes: AST, ALT, ALP, GGT, LDH, creatine kinase. Substrates: glucose (fasting), total cholesterol, triglycerides, creatinine, TBL, total protein, albumin, uric acid, urea and BUN.
Endocrinology: T4, TSH. Viral serology: HIV I and II antibodies, hepatitis C antibodies, HBsAg, HBc. Coagulation: INR, PT, aPTT.
Measured: Change from screening up to follow-up period (Day 30 +/- 1)
ECG.
A 12-lead ECG will be obtained after the subject rested in the supine position for at least 10 minutes (can be reduced to 5 minutes at collection time points within the first hour after dosing; using the sites own ECG machines when not performing dECGs and using the same machine as the dECGs when time points coincide).
Measured: Change from screening up to follow-up period (Day 30 +/- 1)
2-lead real-time telemetry ECG.
Recording telemetry findings. A 2-lead real-time telemetry ECG will be performed for at least 4 hours on Day 1 and then on Days 1, 10 and 16 from 30 minutes predose until 24 hours postdose.
Measured: Change from screening up to follow-up period (Day 30 +/- 1)
Number of clinically relevant new findings or worsening of a pre-existing findings as assessed by urinalysis report.
pH, blood, leucocytes, protein, glucose, bilirubin, urine bilirubin, ketones and nitrites.
If clinically relevant abnormalities are detected (positive result in dipstick), microscopy (RBC, WBC and cast [hyaline, granular and cellular]).
Measured: Change from screening up to follow-up period (Day 30 +/- 1)
Secondary outcomes (9)
Observed maximum concentration, taken directly from the individual concentration-time curve (Cmax) of AZD8871 and its metabolites.
Observed maximum concentration.
Measured: Day 1 and Day 16
Time to reach maximum concentration, taken directly from the individual concentration-time curve (tmax) of AZD8871 and its metabolites.
Time to reach maximum concentration.
Measured: Day 1 and Day 16
Terminal half-life (t½λz) of AZD8871 and its metabolites.
Terminal half-life, estimated as (ln2)/λz.
Measured: Day 1 and Day 16
Area under the plasma concentration-curve from time zero to 24 hours post-dose (AUCτ) of AZD8871 and its metabolites.
Area under the plasma concentration-curve from time zero to 24 hours post-dose
Measured: Day 1 and Day 16
Area under the concentration-time curve from time zero extrapolated to infinity (AUC) of AZD8871 and its metabolites.
Area under the concentration-time curve from time zero extrapolated to infinity. AUC is estimated by AUC0-last + C-last/λz where C-last is the last observed quantifiable concentration.
Measured: Day 1
Apparent clearance for parent drug (CL/F) estimated as dose divided by AUC of AZD8871 and its metabolites.
Apparent clearance for parent drug estimated as dose divided by AUC.
Measured: Day 1 and Day 16
Apparent volume of distribution for parent drug at terminal phase (Vz/F) of AZD8871 and its metabolites.
Apparent volume of distribution for parent drug at terminal phase (extravascular administration), estimated by dividing the apparent clearance (CL/F) by λz.
Measured: Day 1
Accumulation ratio for Cmax (Rac (Cmax)) of AZD8871 and metabolites after repeated administration.
Accumulation ratio for Cmax estimated as Cmax on Day 16/Cmax on Day 1.
Measured: Day 16
Accumulation ratio for AUCτ (RacAUCτ) of AZD8871 and metabolites after repeated administration.
Accumulation ratio for AUCτ estimated as AUCτ on Day 16/AUCτ on Day 1.
Measured: Day 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2017
- Study start19 Jun 2017
- Primary completion13 Oct 2017
- Study completion13 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary Disease - COPDStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single center, randomized, single blind, placebo-controlled study.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel, Industrias Farmacéuticas Almirall S.A., The Doctors Laboratory Ltd, Covance
- Responsible party
- Sponsor
- Investigators
- Muna Albayaty, MBChB, MSc, MFPM, Study chair, Parexel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03159442
- Sponsor's protocol ID
- D6640C00005
- Other IDs
- 2017-000890-35, 2017
- Status last verified
- Oct 2017
- First submitted
- 17 May 2017
- Last updated
- 25 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Balaguer V, Albayaty M, Jimenez E, Wahlby-Hamren U, Astbury C, Seoane B, Malice MP, Lei A, Aggarwal A, Psallidas I. Navafenterol (AZD8871) in healthy volunteers: safety, tolerability and pharmacokinetics of multiple ascending doses of this novel inhaled, long-acting, dual-pharmacology bronchodilator, in two phase I, randomised, single-blind, placebo-controlled studies. Respir Res. 2020 Sep 9;21(Suppl 1):212. doi: 10.1186/s12931-020-01474-1.
PubMed 32907575
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Single Centre, Randomised, Single Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses of Inhaled AZD8871 in Healthy Male Japanese Subjects.
- ClinicalTrials.gov ID
- NCT03159442
- Acronym / sponsor ID
- D6640C00005
- Keywords
- Chronic obstructive pulmonary disease (COPD), Asthma, AZD8871, muscarinic receptor antagonist and β2 adrenoceptor agonist (MABA), Phase I, Safety, Tolerability, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel, Industrias Farmacéuticas Almirall S.A., The Doctors Laboratory Ltd, Covance
- Study start
- 19 Jun 2017 (actual)
- Primary completion
- 13 Oct 2017 (actual)
- Study completion
- 13 Oct 2017 (actual)
- First posted
- 18 May 2017 (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.
AZD8871 is a new chemical entity possessing long-acting dual-pharmacology (muscarinic receptor antagonist and β2 adrenoceptor agonist [MABA]) in a single molecule. This type of agent presents a novel approach to the treatment of chronic obstructive pulmonary disease (COPD) and potentially asthma (in combination with an inhaled corticosteroid). AZD8871 is being developed for inhalation, formulated with alpha lactose monohydrate and delivered by dry powder inhaler (DPI) that allows delivery of a single dose of the study drug.
The primary objective is to investigate the safety and tolerability of AZD8871 at steady state in healthy male Japanese subjects.
Detailed description
This is a Phase I, single centre, randomised, single blind, placebo-controlled study to investigate the safety, tolerability and pharmacokinetics (PK) of single and multiple ascending doses of inhaled AZD8871 in healthy male Japanese subjects.
All subjects will sign an Informed Consent Form before starting any study-related procedures.
Twenty-four healthy subjects, aged 20 to 55 years, will participate in 3 cohorts. All subjects will be admitted to the unit the day preceding the 1st dose and will be housed in the unit until 96 hours (4 days) post last dose of investigational medicinal product (IMP) (Day 20).
Eight subjects will participate in each cohort and will receive either AZD8871 or placebo, randomised 3:1 (6 subjects to receive AZD8871:2 subjects to receive placebo). Each subject will only be dosed in 1 cohort. The study design allows a gradual escalation of dose (Cohorts 2 and 3) with intensive safety monitoring to ensure the safety of the subjects.
In Cohort 1, subjects will receive only a single dose of AZD8871 300 µg or placebo on Day 1, followed by once daily dosing on Days 5 to 16. The dosing schedule of all cohorts will be single dose of IMP (active or placebo) on Day 1, followed by once daily dosing on Days 5 to 16. Within 5 to 7 days of discharge from the unit, there will be two follow-up visits.
Following each cohort, a maximum dose of 2 times the dose administered in the previous cohort will be considered for the subsequent cohort. However, the planned dose for Cohort 2 is 600 µg and for Cohort 3 is 900 µg. Dosing of Cohorts 2 and 3 will be preceded by a SRC meeting, which will confirm the adequacy of the planned doses. A minimum of 5 subjects on active treatment need to complete dosing per cohort in order to proceed to the next dose level.
The total duration of the study for each subject will be approximately 58 days (from Screening [up to -28 days before randomization] to Final Follow up visit [Day 30]).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
- Model description
- Single center, randomized, single blind, placebo-controlled study.
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: AZD8871, Drug: PlaceboMultiple inhaled doses of AZD8871 will be administered via single dose DPI. Each subject will receive 300 μg AZD8871 or placebo. This dose will be given as 1 inhalation from the 300 μg AZD8871 or placebo inhaler. Single inhaled dose of AZD8871 or placebo will be administered on Day 1 and then single once daily inhalations of AZD8871 or placebo will be administered for 12 days from Day 5 until Day 16. |
| Cohort 2 | Experimental | Drug: AZD8871, Drug: PlaceboMultiple inhaled doses of AZD8871 will be administered via single dose DPI. Each subject will receive 600 μg AZD8871 as 1 inhalation from the 600 μg AZD8871 or placebo inhaler. Single inhaled dose of AZD8871 or placebo will be administered on Day 1 and then single once daily inhalations of AZD8871 or placebo will be administered for 12 days from Day 5 until Day 16. Dose escalation to 600 μg dose will be done only after the SRC has determined the adequacy of the dose to be given. |
| Cohort 3 | Experimental | Drug: AZD8871, Drug: PlaceboMultiple inhaled doses of AZD8871 will be administered via single dose DPI. Each subject will receive 900 μg AZD8871 as 1 inhalation from the 300 μg AZD8871 inhaler and 1 inhalation from the 600 μg AZD8871 inhaler, or placebo as 2 inhalations from 2 different placebo inhalers. Single inhaled dose of AZD8871 or placebo on Day 1 and then single once daily inhalations of AZD8871 or placebo will be administered for 12 days from Day 5 until Day 16. Dose escalation to the 900 μg dose will be done only after the SRC has determined the adequacy of the dose to be given. |
Who may qualify
- Ages
- 20 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Provision of written informed consent prior to any study related procedures, including withdrawal of medications.
- Male Japanese subjects aged 20 to 55 years, inclusive at Screening.
- Body mass index (BMI) calculated as weight in kg/height in m2 from >= 18 to <= 30 kg/m2 and weight >= 50 kg at Screening.
- Healthy, free from any clinically significant disease/conditions (including all cardiovascular conditions), as determined by medical history, physical examination, clinical laboratory testing, 12-lead ECG findings at Screening and admission to the unit.
- Spirometry readings (Forced Expiratory Volume in 1 second and Forced Vital Capacity) to be >= 80% of predicted value calculated using equations at Screening (Quanjer et. al. 2012).
Key exclusion criteria (26 listed)
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Surgical history clinically relevant for the purpose of the study or any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of Screening.
- History of malignancy of any organ system, treated or untreated within the past 5 years, with the exception of localised basal cell carcinoma of the skin.
- Current smokers, or a smoking history during the last 6 months or total smoking history of more than 10 pack years. Use of electronic cigarettes or other forms of nicotine, current use or use within the last 6 months.
- Note: Pack years are calculated by dividing the number of cigarettes smoked per day by 20 (the number of cigarettes per pack) and multiplying tis figure by the number of years a person has been smoking. For example, a person who smoked 40 cigarettes a day and has been smoking for 10 years would have a 20 pack-year smoking history (40 cigarettes per day at 20 cigarettes per pack =2; 2 x 10 years of smoking =20 pack-year history).
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 |
|---|---|---|
| AZD8871Powder for inhalation administered via single dose DPI 300 and 600 µg/inhalation. | Drug | Cohort 1, Cohort 2, Cohort 3 |
| PlaceboPowder for inhalation administered via single dose DPI | Drug | Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
Adverse events.
Time frame: From time of ICF to Day 30 (end of follow-up period)
Recording adverse events. An AE is the development of an undesirable medical condition or the deterioration of a preexisting medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. An undesirable medical condition can be symptoms (e.g., nausea, chest pain), signs (e.g., tachycardia, enlarged liver) or the abnormal results of an investigation (e.g., laboratory findings, ECG). In clinical studies, an AE can include an undesirable medical condition occurring at any time, including run-in or washout periods, even if no study treatment has been administered.
Concomitant medication.
Time frame: Change from screening up to follow-up period (Day 30 +/- 1)
Recording concomitant medications. Any concomitant medication or therapy given to the subject during the study conduct will be recorded.
Physical examination.
Time frame: Change from screening up to follow-up period (Day 30 +/- 1)
A full physical examination will include the examination of the following: general appearance, eyes, ears, nose, throat, chest/respiratory, heart/cardiovascular, gastrointestinal/liver, musculoskeletal/extremities, dermatological/skin, thyroid/neck, lymph nodes, neurological/psychiatric. A brief physical examination will include assessment of the following: skin, lungs, cardiovascular system and abdomen (liver and spleen). A complete physical examination will be performed at the Screening and Follow-up visit. Only relevant findings detected will be recorded in the physical examination findings.
Vital signs.
Time frame: Change from screening up to follow-up period (Day 30 +/- 1)
Recording vital signs. Systolic and diastolic blood pressure (in mmHg) will be measured after at least 10 minutes (can be reduced to 5 minutes at collection time points within the 1st hour after dosing) resting, and also, before taking any blood sample and conducting any spirometry. Measurements will be carried out with subject in the supine position and preferably always on the same arm. Subject's oral body temperature will be measured at each vital signs collection.
Number of clinically relevant new findings or worsening of a pre-existing findings as assessed by Hematology.
Time frame: Change from screening up to follow-up period (Day 30 +/- 1)
Haematocrit, hemoglobin, erythrocytes (red blood cells), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), leucocytes (white blood cells), differential blood count (neutrophils, lymphocytes, monocytes, eosinophils and basophils) and thrombocytes (platelets)
Number of clinically relevant new findings or worsening of a pre-existing findings as assessed by Clinical chemistry.
Time frame: Change from screening up to follow-up period (Day 30 +/- 1)
Electrolytes: sodium, potassium, calcium, chloride and inorganic phosphorus. Enzymes: AST, ALT, ALP, GGT, LDH, creatine kinase. Substrates: glucose (fasting), total cholesterol, triglycerides, creatinine, TBL, total protein, albumin, uric acid, urea and BUN. Endocrinology: T4, TSH. Viral serology: HIV I and II antibodies, hepatitis C antibodies, HBsAg, HBc. Coagulation: INR, PT, aPTT.
ECG.
Time frame: Change from screening up to follow-up period (Day 30 +/- 1)
A 12-lead ECG will be obtained after the subject rested in the supine position for at least 10 minutes (can be reduced to 5 minutes at collection time points within the first hour after dosing; using the sites own ECG machines when not performing dECGs and using the same machine as the dECGs when time points coincide).
2-lead real-time telemetry ECG.
Time frame: Change from screening up to follow-up period (Day 30 +/- 1)
Recording telemetry findings. A 2-lead real-time telemetry ECG will be performed for at least 4 hours on Day 1 and then on Days 1, 10 and 16 from 30 minutes predose until 24 hours postdose.
Number of clinically relevant new findings or worsening of a pre-existing findings as assessed by urinalysis report.
Time frame: Change from screening up to follow-up period (Day 30 +/- 1)
pH, blood, leucocytes, protein, glucose, bilirubin, urine bilirubin, ketones and nitrites. If clinically relevant abnormalities are detected (positive result in dipstick), microscopy (RBC, WBC and cast [hyaline, granular and cellular]).
9 secondary outcomes
Observed maximum concentration, taken directly from the individual concentration-time curve (Cmax) of AZD8871 and its metabolites.
Time frame: Day 1 and Day 16
Time to reach maximum concentration, taken directly from the individual concentration-time curve (tmax) of AZD8871 and its metabolites.
Time frame: Day 1 and Day 16
Terminal half-life (t½λz) of AZD8871 and its metabolites.
Time frame: Day 1 and Day 16
Area under the plasma concentration-curve from time zero to 24 hours post-dose (AUCτ) of AZD8871 and its metabolites.
Time frame: Day 1 and Day 16
Area under the concentration-time curve from time zero extrapolated to infinity (AUC) of AZD8871 and its metabolites.
Time frame: Day 1
Apparent clearance for parent drug (CL/F) estimated as dose divided by AUC of AZD8871 and its metabolites.
Time frame: Day 1 and Day 16
Apparent volume of distribution for parent drug at terminal phase (Vz/F) of AZD8871 and its metabolites.
Time frame: Day 1
Accumulation ratio for Cmax (Rac (Cmax)) of AZD8871 and metabolites after repeated administration.
Time frame: Day 16
Accumulation ratio for AUCτ (RacAUCτ) of AZD8871 and metabolites after repeated administration.
Time frame: Day 16
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2017.
- Derived from this study: PubMed 32907575Balaguer V, Albayaty M, Jimenez E, Wahlby-Hamren U, Astbury C, Seoane B, Malice MP, Lei A, Aggarwal A, Psallidas I. Navafenterol (AZD8871) in healthy volunteers: safety, tolerability and pharmacokinetics of multiple ascending doses of this novel inhaled, long-acting, dual-pharmacology bronchodilator, in two phase I, randomised, single-blind, placebo-controlled studies. Respir Res. 2020 Sep 9;21(Suppl 1):212. doi: 10.1186/s12931-020-01474-1.
- Individual participant dataSharing planned: Undecided
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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.
Muna Albayaty, MBChB, MSc, MFPM study chair
Parexel
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 AZD8871 in people with Chronic Obstructive Pulmonary Disease - COPD, run by AstraZeneca at 1 site in United Kingdom.
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 10 inclusion and 26 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: finished, as of the sponsor's last update on 25 Oct 2017. 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 United Kingdom. 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. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Adverse events. (time frame: From time of ICF to Day 30 (end of follow-up period)). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03159442, which also lists 1 linked publication.
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 25 Oct 2017.