Asthma (Part 1), COPD (Part 2)
Conditions
Keywords
Pharmacokinetics, Pharmacodynamics, AZD8871, Safety, Tolerability, mild persistent asthma, moderate to severe COPD
Brief summary
This is a phase I, randomised, placebo-controlled 2-part study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD8871 delivered by inhalation, in asthmatic and chronic obstructive pulmonary disease (COPD) subjects.
Detailed description
This study is an integrated Phase I protocol divided into 2 parts. Part 1: single ascending dose study (6 AZD8871 dose levels) in 16 male subjects with mild asthma. AZD8871 will be administered (by the Genuair® inhaler) under supervision at the study centre, according to the randomisation scheme Part 2: a 5 treatment period single dose study (of AZD8871 \[two doses\], indacaterol, tiotropium and placebo) in 40 male and non-childbearing female subjects with moderate to severe COPD. Each treatment period will be separated by a washout period of at least 7 days. The primary comparison for bronchodilation will be between AZD8871 doses and placebo.
Interventions
DRUGDose 1, AZD8871 50 μg (Part 1)
50 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)
DRUGDose 2, AZD8871 100 μg (Part 1)
100 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)
DRUGDose 3, AZD8871 300 μg (Part 1)
300 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)
DRUGDose 4, AZD8871 600 µg (Part 1)
600 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)
DRUGDose 5, AZD8871 1200 µg (Part 1)
1200 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)
DRUGDose 6, AZD8871 1800 μg (Part 1)
1800 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)
DRUGPlacebo, AZD8871 placebo (Part 1)
AZD8871 placebo on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)
DRUGTreatment A, AZD8871 dose A (Part 2)
AZD8871 dose A once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)
DRUGTreatment B, AZD8871 dose B (Part 2)
AZD8871 dose B once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler(Genuair®)
DRUGTreatment C, Indacaterol 150 μg (Part 2)
150 μg of Indacaterol once on Day 1; each dose of Indacaterol dry inhalation powder will be administered via a dry powder inhaler (Onbrez Breezhaler®) as 1 hard capsule
DRUGTreatment D, Tiotropium 18 μg (Part 2)
18 μg of Tiotropium once on Day 1; each dose of Indacaterol dry inhalation powder will be administered via a dry powder inhaler (HandiHaler®) as 1 hard capsule
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
Part 1 1. Subjects who are able and willing to provide written informed consent prior to conducting any study-related procedures, including withdrawal of medications 2. Adult male subjects aged 18 to 70 years (both inclusive) 3. Body mass index (BMI) from 18 to 32 kg/m2 at screening 4. Clinical diagnosis of asthma (according to the Global Initiative for Asthma \[GINA\] guidelines) for at least 6 months prior to screening 5. Ability to change current asthma therapy, to discontinue previous prescribed medications after signature of informed consent as per required washout periods 6. Screening FEV1 value of ≥70% of the predicted normal value 7. FEV1 reversibility of ≥12% and an absolute increase of at least 200 mL over the baseline value within 30 min after inhalation of 400 µg (4 puffs) of salbutamol via a metered dose inhaler, with spacer device 8. Subjects using intermittent salbutamol and / or subjects on a stable dose of low dose Inhaled corticosteroid (as defined by the GINA guidelines) at least 4 weeks prior to screening 9. Predose FEV1 value of first treatment period within the range of ± 20% of the FEV1 measured at screening prior to salbutamol inhalation 10. No current smokers, no subjects with a smoking history during the last 12 months and no subjects with a total smoking history of more than 10 pack-years 11. No other relevant pulmonary disease or history of thoracic surgery 12. Subjects who are otherwise healthy as determined by medical history, physical examination, 12-lead ECG findings 13. Normal blood pressure (defined as Systolic blood pressure \[SBP\] between 100 and 140 mmHg for subjects ≤59 years of age and between 100 and 150 mmHg for subjects ≥60 years of age, and Diastolic blood pressure \[DBP\] between 40 and 90 mmHg) at screening 14. Subjects whose clinical laboratory test results are not clinically relevant and are acceptable to the Investigator. 15. Subjects who are negative for 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 16. Subjects who are negative for drugs of abuse and alcohol tests at screening and admission 17. Subjects able to perform repeatable pulmonary function testing for FEV1 according to the American Thoracic Society (ATS) / European Respiratory Society (ERS) 2005(9) criteria at screening Inclusion Criteria: Part 2 1. Adult male and non-childbearing female subjects aged ≥40 years with a clinical diagnosis of stable moderate to severe COPD according to GOLD guidelines at screening 2. Females must be of non-childbearing potential, confirmed at screening by fulfilling study predefined criteria 3. Post-salbutamol FEV1 \<80% and ≥30% of the predicted normal value and post-salbutamol FEV1 / forced vital capacity (FVC) \<70% 4. BMI \< 40 kg/m2 at screening 5. Ability to change current COPD therapy, to discontinue previous prescribed medications after signature of informed consent as per required washout periods 6. Current or ex-smokers with a smoking history of ≥10 pack years 7. No evidence of clinically significant respiratory and / or cardiovascular conditions (e.g. uncontrolled hypertension) or laboratory abnormalities 8. No other relevant pulmonary disease or history of thoracic surgery 9. Subjects who are negative for HBsAg, HBc IgM, hepatitis C antibody and HIV I and II antibodies at screening 10. Subjects who are able and willing to provide written informed consent prior to conducting any study-related procedures, including withdrawal of medications 11. Medical history must be verified by either a personal physician or medical practitioner as appropriate 12. Subjects able to perform repeatable pulmonary function testing for FEV1 according to the ATS / ERS 2005(9) criteria at screening
Exclusion criteria
(Part 1 & 2): 1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) 2. Previous enrolment or randomisation of treatment in the present study 3. Current evidence or recent history of any clinically significant and unstable disease (other than asthma/COPD) or abnormality that could put the subject at risk or could confound the results of the study 4. Subjects with a surgical history clinically relevant for the purpose of the study 5. 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 6. Subjects with serious adverse reaction or serious hypersensitivity to Tiotropium (for Part 2 only), Indacaterol (for Part 2 only), or the formulation excipients (eg, lactose) or other drugs in the same pharmacologic class (for Part 1 and Part 2) 7. Current diagnosis of COPD (for Part 1 only) or history of / or current diagnosis for asthma (for Part 2 only) 8. Recent history of asthma / COPD exacerbation requiring hospitalisation or need for increased maintenance treatments for asthma / COPD within 6 weeks prior to screening or prior to randomisation 9. Use of daily oxygen therapy \>10 h per day (for Part 2 only) 10. Use of systemic steroids for respiratory reasons within 6 weeks prior to screening 11. Lower respiratory tract infection within 6 weeks prior to screening or prior to randomisation 12. Upper respiratory tract infection requiring antibiotics within 6 weeks prior to screening or prior to randomisation 13. Current history of tuberculosis, bronchiectasis or other non-specific pulmonary disease 14. Subject with significant cardiovascular disease that may be vulnerable to cardiovascular instability 15. QTcF (QT interval corrected, Fridericia formula QT\[msec\]/RR\[s\]) interval, \>450 ms for males and \>470 ms for females at screening or prior to randomisation, or history of long QT syndrome 16. PR (duration in milliseconds from the beginning of wave P to onset of ventricular depolarisation \[Q or R\]) interval \>200 ms at screening or prior to randomisation (for Part 1 only) Note: 4- 6 hours of ECG rhythm monitoring with telemetry will be performed on Day-1 to identify patients that may have any clinical significant abnormality prior to randomisation. If this occurs, patients should not participate in the study 17. Subjects with serum potassium concentration \< 3.5mmol/l at screening 18. Subjects with a history of excessive use or abuse of alcohol within the past 2 years 19. Subjects with a history of drug abuse within the past 2 years 20. Subjects who are positive for drugs of abuse and alcohol tests at screening and prior to randomisation. Subjects consuming more than 14 (female subjects) or 21 (male subjects) units of alcohol a week 21. Donation or loss \>400 ml of blood and plasma within the previous 3 months prior to screening 22. Subjects with a significant infection or known inflammatory process at screening or prior to randomisation 23. Subjects with acute gastrointestinal symptoms at the time of screening or prior to randomisation (eg, nausea, vomiting, diarrhoea, heartburn) 24. Subjects with an acute infection such as influenza at the time of screening or prior to randomisation 25. Male subjects who do not agree to follow instructions to avoid pregnancies 26. Subjects who are not able to adhere to the restrictions on prior and concomitant medications 27. Subjects who intend to use any concomitant medication not permitted by this protocol or who have not undergone the required washout period for a particular prohibited medication 28. Subjects who have used any investigational drug within 3 months prior to screening or within the equivalent time of 6 half-lives of receiving the last administration, whichever is longer 29. Subjects who have received the last dose of investigational product more than 3 months ago but who are on an extended follow-up 30. Subjects who are unlikely to co-operate with the requirements of the study, or the study center or the subjects who are unwilling or unable to follow the instructions of the principal investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Relevant Abnormalities in Clinical Biochemistry, Hematology and Urinalysis | From the time of informed consent up to 7 days after the last dose of IP. | A composite of clinically relevant abnormalities in clinical biochemistry, hematology and urinalysis laboratory evaluations. Laboratory tests (haematology, blood chemistry, and urinalysis) were performed at screening, at Day -1 (Part 1 only), at 24 hours (Day 2) and at follow-up (7 \[±2\] days) after IP administration. Coagulation was only performed at screening; TSH, T4 only at screening, at Day-1 and at follow-up. Abnormal findings were flagged to the principal investigator who assessed clinical relevance based on medical criteria at individual subject level. Clinically relevant findings were assessed until the abnormality was considered non-clinically relevant. |
| The Number of Participants With Mild Persistent Asthma (Part 1) and COPD (Part 2) With at Least 1 Treatment-emergent Adverse Event | From the time of informed consent up to 14 (±2) days after the last dose of investigational product. Unresolved AEs were followed up by the investigator for as long as medically indicated. | An adverse event is the development of an undesirable medical condition, or the deterioration of a pre-existing 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, signs, or the abnormal results of laboratory parameters (haematology, blood chemistry, urinalysis, physical examination, 12-lead ECGs and telemetry, and vital signs). AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) version 18.1. |
| Number of Participants With Clinically Relevant Abnormalities in Blood Pressure | From the time of informed consent up to 36 hours after last dose of IP. | Blood pressure (BP) measurements (diastolic \[DBP\] and systolic BP \[SBP\]) taken after \ 5 minutes rest in supine position, at screening, baseline (≤1 hour before IP administration), 10 and 30 minutes, 1, 2, 3, 4, 8, 12 hours (Day 1) and 24 and 36 hours (Day 2) after IP administration. Normal BP at screening: SBP 100-140 mmHg (subjects aged ≤59 years) and 100-150 mmHg (subjects aged ≥60 years), and DBP 40-90 mmHg. Criteria for notable changes in BP: High SBP: (≥180 and increase over baseline (predose) ≥20) or (≥200 and baseline \<200) Low SBP: (≤ 90 and decrease over baseline ≥20) or (≤75 and baseline \>75) High DBP: (≥105 and increase over baseline ≥15) or (≥115 and baseline \<115) Low DBP: (≤50 and decrease over baseline ≥15) or (≤40 and baseline \>40) All out of range values were flagged to the principal investigator who assessed clinical relevance based on medical criteria at individual subject level. Clinically relevant findings were assessed until considered non-clinically relevant. |
| Number of Participants With Clinically Relevant Abnormalities in Electrocardiograms (HR, QTcF and Other ECG Parameters). | From the time of informed consent up to 36 hours after last dose of IP. | HR, QTcF and other ECG abnormalities were assessed by local digital 12-lead ECG performed in triplicate at the time points indicated: ECG (Parts 1 and 2) was assessed at Screening, Day 1 baseline, 10 min, 30 min, 1 hour (h), 2 h, 3 h, 4 h, 8 h, 12 h, 24 h, 36 h after dosing. Telemetry (Part 1), assessed with at least 2 lead real time display, was recorded at Day -1 (4-6 hours continuous recording, at the time this was more convenient for the logistics of the unit) and on Day 1 from the time of the IP administration up to at least 24 hours, but if advised by the Investigator or designee, then up to 36 hours after IP administration. Abnormal findings were flagged to the principal investigator who assessed clinical relevance based on medical criteria at individual subject level. Clinically relevant findings were assessed until the abnormality was considered non-clinically relevant. |
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 2 | Baseline (Day 1) to 36 hours post-dose (Day 2) | Pharmacodynamics of AZD8871 before (-45 min and -15 min pre-dose) and after single dosing of AZD8871 Forced expiratory volume in 1 second (FEV1) on Day 2 (defined as the average of the values 23:00 and 24:00 hours after the morning dose of investigational product) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-24) of AZD8871 in Parts 1 and 2 | Pre-dose, and 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h (Day 1), 24 h, and 36 h (Day 2) post-dose | AUC(0-24) (area under the concentration-time curve from zero to 24h) of AZD8871 on Day 1 of each treatment period. |
| Cmax of AZD8871 in Parts 1 and 2 | Pre-dose, and 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h (Day 1), 24 h, and 36 h (Day 2) post-dose | Cmax (maximum observed plasma drug concentrations) of AZD8871 on Day 1 of each treatment period. |
| Tmax of AZD8871 in Parts 1 and 2 | Pre-dose, and 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h (Day 1), 24 h, and 36 h (Day 2) post-dose | tmax (time to reach maximum concentration) of AZD8871 on Day 1 of each treatment period. |
| AUC(0-t) of AZD8871 in Parts 1 and 2 | Pre-dose, and 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h (Day 1), 24 h, and 36 h (Day 2) post-dose | AUC(0-t) (area under the concentration-time curve from time zero to time of the last quantifiable measurable concentration) of AZD8871 on Day 1 of each treatment period. |
Other
| Measure | Time frame | Description |
|---|---|---|
| AUC of AZD8871 in Parts 1 and 2 | Predose, and 5 min, 15 min, 30 min, and 45 min, at 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h (Day 1), 24 h and 36 h (Day 2) post-dose | AUC (area under the concentration-time curve from time 0 to infinity) of AZD8871 on Day 1 of each treatment period |
| Elimination Half-life of AZD8871 in Parts 1 and 2 | Predose, and 5 min, 15 min, 30 min, and 45 min, at 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h (Day 1), 24 h and 36 h (Day 2) post-dose | Elimination half-life (t½λz) for AZD8871 on Day 1 of each treatment period. t½λz was generally calculated over a period of less than 3 times the resultant half-life |
Countries
United Kingdom
Participant flow
Recruitment details
This study was conducted at 2 centres in the UK (one for each part). In part 1 of the study, the first patient was screened in October 2015 and the last patient visit was in March 2016. In part 2 of the study, the first patient was screened in April 2016 and the last patient visit was in August 2016.
Pre-assignment details
2-part study: Part 1: single ascending doses of AZD8871 (planned 50, 100, 300, 600, 1200, 1800 μg; actual dose 50, 200, 400, 900, 1800, 2100 μg) or placebo over 3 treatment periods; 2 cohorts (male; mild persistent asthma). Part 2: 5-way complete cross-over, single-dose; M/F, moderate/severe COPD; 2 doses of AZD8871, placebo, or 2 active controls.
Participants by arm
| Arm | Count |
|---|---|
| Overall Population - Part 1 All individuals in Part 1 (patients who received single doses of AZD8871 \[50, 400, 1800 μg for Cohort 1; 200, 900, 2100 μg for Cohort 2\], or placebo, in 3 treatment periods separated by washout periods of 14 days). | 16 |
| Overall Population - Part 2 All individuals involved in Part 2 (patients who received single doses of AZD8871 \[400 and 1800 μg\], placebo, indacaterol 150 μg, or tiotropium 18 μg, in 5 treatment periods separated by washout periods of 7-21 days. | 38 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout Between Treatment Period 1 and 2 | Adverse Event | 0 | 3 |
| Washout Between Treatment Period 1 and 2 | Physician Decision | 0 | 1 |
| Washout Between Treatment Period 1 and 2 | Withdrawal by Subject | 0 | 1 |
| Washout Between Treatment Period 2 and 3 | Adverse Event | 0 | 2 |
| Washout Between Treatment Period 2 and 3 | Sponsor's decision | 1 | 0 |
| Washout Between Treatment Period 3 and 4 | Adverse Event | 0 | 1 |
| Washout Between Treatment Period 3 and 4 | Stability/variability criteria not met | 0 | 1 |
| Washout Between Treatment Period 4 and 5 | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Overall Population - Part 1 | Overall Population - Part 2 | Total |
|---|---|---|---|
| Age, Continuous | 39.0 Years STANDARD_DEVIATION 11.8 | 65.6 Years STANDARD_DEVIATION 6.4 | NA Years |
| Sex: Female, Male Female | 0 Participants | 16 Participants | 16 Participants |
| Sex: Female, Male Male | 16 Participants | 22 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 6 | 5 / 6 | 3 / 6 | 3 / 6 | 3 / 6 | 2 / 5 | 12 / 12 | 8 / 34 | 4 / 31 | 6 / 32 | 8 / 30 | 8 / 32 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 12 | 1 / 34 | 0 / 31 | 0 / 32 | 1 / 30 | 0 / 32 |
Outcome results
Primary
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 2
Pharmacodynamics of AZD8871 before (-45 min and -15 min pre-dose) and after single dosing of AZD8871 Forced expiratory volume in 1 second (FEV1) on Day 2 (defined as the average of the values 23:00 and 24:00 hours after the morning dose of investigational product)
Time frame: Baseline (Day 1) to 36 hours post-dose (Day 2)
Population: The PP population is defined as all randomised subjects who satisfied the main I/E criteria, received IP, completed at least 1 treatment period, and did not present major violations to the protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD8871 50 μg (Part 1) | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 2 | -0.0375 Liters | Standard Deviation 0.3449 |
| AZD8871 200 μg (Part 1) | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 2 | 0.2183 Liters | Standard Deviation 0.1631 |
| AZD8871 400 μg (Part 1) | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 2 | 0.2883 Liters | Standard Deviation 0.1418 |
| AZD8871 900 μg (Part 1) | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 2 | 0.1858 Liters | Standard Deviation 0.3528 |
| AZD8871 1800 μg (Part 1) | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 2 | 0.3275 Liters | Standard Deviation 0.0708 |
| AZD8871 2100 μg (Part 1) | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 2 | 0.4630 Liters | Standard Deviation 0.2065 |
| Placebo (Part 1) | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 2 | -0.0600 Liters | Standard Deviation 0.3099 |
| AZD8871 400 μg (Part 2) | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 2 | 0.0738 Liters | Standard Deviation 0.1212 |
| AZD8871 1800 μg (Part 2) | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 2 | 0.1731 Liters | Standard Deviation 0.1761 |
| Indacaterol 150 μg (Part 2) | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 2 | 0.1036 Liters | Standard Deviation 0.1286 |
| Tiotropium 18 μg (Part 2) | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 2 | 0.1055 Liters | Standard Deviation 0.1922 |
| Placebo (Part 2) | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 2 | -0.0294 Liters | Standard Deviation 0.0768 |
p-value: <0.000195% CI: [0.0585, 0.163]ANCOVA
p-value: <0.000195% CI: [0.156, 0.264]ANCOVA
Primary
Number of Participants With Clinically Relevant Abnormalities in Blood Pressure
Blood pressure (BP) measurements (diastolic \[DBP\] and systolic BP \[SBP\]) taken after \ 5 minutes rest in supine position, at screening, baseline (≤1 hour before IP administration), 10 and 30 minutes, 1, 2, 3, 4, 8, 12 hours (Day 1) and 24 and 36 hours (Day 2) after IP administration. Normal BP at screening: SBP 100-140 mmHg (subjects aged ≤59 years) and 100-150 mmHg (subjects aged ≥60 years), and DBP 40-90 mmHg. Criteria for notable changes in BP: High SBP: (≥180 and increase over baseline (predose) ≥20) or (≥200 and baseline \<200) Low SBP: (≤ 90 and decrease over baseline ≥20) or (≤75 and baseline \>75) High DBP: (≥105 and increase over baseline ≥15) or (≥115 and baseline \<115) Low DBP: (≤50 and decrease over baseline ≥15) or (≤40 and baseline \>40) All out of range values were flagged to the principal investigator who assessed clinical relevance based on medical criteria at individual subject level. Clinically relevant findings were assessed until considered non-clinically relevant.
Time frame: From the time of informed consent up to 36 hours after last dose of IP.
Population: Safety population: all randomized subjects who received at least 1 dose of the investigational product
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) | Dispersion |
|---|---|---|---|
| AZD8871 50 μg (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Blood Pressure | 0 Participants | 8.7 |
| AZD8871 200 μg (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Blood Pressure | 0 Participants | 2.1 |
| AZD8871 400 μg (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Blood Pressure | 0 Participants | 4.3 |
| AZD8871 900 μg (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Blood Pressure | 0 Participants | 7.2 |
| AZD8871 1800 μg (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Blood Pressure | 0 Participants | 3.4 |
| AZD8871 2100 μg (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Blood Pressure | 0 Participants | 11.7 |
| Placebo (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Blood Pressure | 0 Participants | 5.7 |
| AZD8871 400 μg (Part 2) | Number of Participants With Clinically Relevant Abnormalities in Blood Pressure | 0 Participants | 8.3 |
| AZD8871 1800 μg (Part 2) | Number of Participants With Clinically Relevant Abnormalities in Blood Pressure | 0 Participants | 4.5 |
| Indacaterol 150 μg (Part 2) | Number of Participants With Clinically Relevant Abnormalities in Blood Pressure | 0 Participants | 6.3 |
| Tiotropium 18 μg (Part 2) | Number of Participants With Clinically Relevant Abnormalities in Blood Pressure | 0 Participants | 6.8 |
| Placebo (Part 2) | Number of Participants With Clinically Relevant Abnormalities in Blood Pressure | 0 Participants | 9.6 |
Primary
Number of Participants With Clinically Relevant Abnormalities in Clinical Biochemistry, Hematology and Urinalysis
A composite of clinically relevant abnormalities in clinical biochemistry, hematology and urinalysis laboratory evaluations. Laboratory tests (haematology, blood chemistry, and urinalysis) were performed at screening, at Day -1 (Part 1 only), at 24 hours (Day 2) and at follow-up (7 \[±2\] days) after IP administration. Coagulation was only performed at screening; TSH, T4 only at screening, at Day-1 and at follow-up. Abnormal findings were flagged to the principal investigator who assessed clinical relevance based on medical criteria at individual subject level. Clinically relevant findings were assessed until the abnormality was considered non-clinically relevant.
Time frame: From the time of informed consent up to 7 days after the last dose of IP.
Population: Safety population: all randomized subjects who received at least 1 dose of the investigational product
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD8871 50 μg (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Clinical Biochemistry, Hematology and Urinalysis | 0 Participants |
| AZD8871 200 μg (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Clinical Biochemistry, Hematology and Urinalysis | 0 Participants |
| AZD8871 400 μg (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Clinical Biochemistry, Hematology and Urinalysis | 0 Participants |
| AZD8871 900 μg (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Clinical Biochemistry, Hematology and Urinalysis | 0 Participants |
| AZD8871 1800 μg (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Clinical Biochemistry, Hematology and Urinalysis | 0 Participants |
| AZD8871 2100 μg (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Clinical Biochemistry, Hematology and Urinalysis | 0 Participants |
| Placebo (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Clinical Biochemistry, Hematology and Urinalysis | 0 Participants |
| AZD8871 400 μg (Part 2) | Number of Participants With Clinically Relevant Abnormalities in Clinical Biochemistry, Hematology and Urinalysis | 0 Participants |
| AZD8871 1800 μg (Part 2) | Number of Participants With Clinically Relevant Abnormalities in Clinical Biochemistry, Hematology and Urinalysis | 0 Participants |
| Indacaterol 150 μg (Part 2) | Number of Participants With Clinically Relevant Abnormalities in Clinical Biochemistry, Hematology and Urinalysis | 0 Participants |
| Tiotropium 18 μg (Part 2) | Number of Participants With Clinically Relevant Abnormalities in Clinical Biochemistry, Hematology and Urinalysis | 0 Participants |
| Placebo (Part 2) | Number of Participants With Clinically Relevant Abnormalities in Clinical Biochemistry, Hematology and Urinalysis | 0 Participants |
Primary
Number of Participants With Clinically Relevant Abnormalities in Electrocardiograms (HR, QTcF and Other ECG Parameters).
HR, QTcF and other ECG abnormalities were assessed by local digital 12-lead ECG performed in triplicate at the time points indicated: ECG (Parts 1 and 2) was assessed at Screening, Day 1 baseline, 10 min, 30 min, 1 hour (h), 2 h, 3 h, 4 h, 8 h, 12 h, 24 h, 36 h after dosing. Telemetry (Part 1), assessed with at least 2 lead real time display, was recorded at Day -1 (4-6 hours continuous recording, at the time this was more convenient for the logistics of the unit) and on Day 1 from the time of the IP administration up to at least 24 hours, but if advised by the Investigator or designee, then up to 36 hours after IP administration. Abnormal findings were flagged to the principal investigator who assessed clinical relevance based on medical criteria at individual subject level. Clinically relevant findings were assessed until the abnormality was considered non-clinically relevant.
Time frame: From the time of informed consent up to 36 hours after last dose of IP.
Population: Safety population: all randomized subjects who received at least 1 dose of the investigational product
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) | Dispersion |
|---|---|---|---|
| AZD8871 50 μg (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Electrocardiograms (HR, QTcF and Other ECG Parameters). | 0 Participants | 4.5 |
| AZD8871 200 μg (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Electrocardiograms (HR, QTcF and Other ECG Parameters). | 0 Participants | 3.9 |
| AZD8871 400 μg (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Electrocardiograms (HR, QTcF and Other ECG Parameters). | 0 Participants | 3.7 |
| AZD8871 900 μg (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Electrocardiograms (HR, QTcF and Other ECG Parameters). | 0 Participants | 3.2 |
| AZD8871 1800 μg (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Electrocardiograms (HR, QTcF and Other ECG Parameters). | 0 Participants | 5.2 |
| AZD8871 2100 μg (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Electrocardiograms (HR, QTcF and Other ECG Parameters). | 0 Participants | 4.8 |
| Placebo (Part 1) | Number of Participants With Clinically Relevant Abnormalities in Electrocardiograms (HR, QTcF and Other ECG Parameters). | 0 Participants | 6.2 |
| AZD8871 400 μg (Part 2) | Number of Participants With Clinically Relevant Abnormalities in Electrocardiograms (HR, QTcF and Other ECG Parameters). | 0 Participants | 6.2 |
| AZD8871 1800 μg (Part 2) | Number of Participants With Clinically Relevant Abnormalities in Electrocardiograms (HR, QTcF and Other ECG Parameters). | 0 Participants | 7.7 |
| Indacaterol 150 μg (Part 2) | Number of Participants With Clinically Relevant Abnormalities in Electrocardiograms (HR, QTcF and Other ECG Parameters). | 0 Participants | 5.5 |
| Tiotropium 18 μg (Part 2) | Number of Participants With Clinically Relevant Abnormalities in Electrocardiograms (HR, QTcF and Other ECG Parameters). | 0 Participants | 4.7 |
| Placebo (Part 2) | Number of Participants With Clinically Relevant Abnormalities in Electrocardiograms (HR, QTcF and Other ECG Parameters). | 0 Participants | 6.1 |
Primary
The Number of Participants With Mild Persistent Asthma (Part 1) and COPD (Part 2) With at Least 1 Treatment-emergent Adverse Event
An adverse event is the development of an undesirable medical condition, or the deterioration of a pre-existing 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, signs, or the abnormal results of laboratory parameters (haematology, blood chemistry, urinalysis, physical examination, 12-lead ECGs and telemetry, and vital signs). AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) version 18.1.
Time frame: From the time of informed consent up to 14 (±2) days after the last dose of investigational product. Unresolved AEs were followed up by the investigator for as long as medically indicated.
Population: Safety population: all randomized subjects who received at least 1 dose of the investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD8871 50 μg (Part 1) | The Number of Participants With Mild Persistent Asthma (Part 1) and COPD (Part 2) With at Least 1 Treatment-emergent Adverse Event | 5 Participants |
| AZD8871 200 μg (Part 1) | The Number of Participants With Mild Persistent Asthma (Part 1) and COPD (Part 2) With at Least 1 Treatment-emergent Adverse Event | 5 Participants |
| AZD8871 400 μg (Part 1) | The Number of Participants With Mild Persistent Asthma (Part 1) and COPD (Part 2) With at Least 1 Treatment-emergent Adverse Event | 3 Participants |
| AZD8871 900 μg (Part 1) | The Number of Participants With Mild Persistent Asthma (Part 1) and COPD (Part 2) With at Least 1 Treatment-emergent Adverse Event | 3 Participants |
| AZD8871 1800 μg (Part 1) | The Number of Participants With Mild Persistent Asthma (Part 1) and COPD (Part 2) With at Least 1 Treatment-emergent Adverse Event | 3 Participants |
| AZD8871 2100 μg (Part 1) | The Number of Participants With Mild Persistent Asthma (Part 1) and COPD (Part 2) With at Least 1 Treatment-emergent Adverse Event | 2 Participants |
| Placebo (Part 1) | The Number of Participants With Mild Persistent Asthma (Part 1) and COPD (Part 2) With at Least 1 Treatment-emergent Adverse Event | 7 Participants |
| AZD8871 400 μg (Part 2) | The Number of Participants With Mild Persistent Asthma (Part 1) and COPD (Part 2) With at Least 1 Treatment-emergent Adverse Event | 18 Participants |
| AZD8871 1800 μg (Part 2) | The Number of Participants With Mild Persistent Asthma (Part 1) and COPD (Part 2) With at Least 1 Treatment-emergent Adverse Event | 7 Participants |
| Indacaterol 150 μg (Part 2) | The Number of Participants With Mild Persistent Asthma (Part 1) and COPD (Part 2) With at Least 1 Treatment-emergent Adverse Event | 12 Participants |
| Tiotropium 18 μg (Part 2) | The Number of Participants With Mild Persistent Asthma (Part 1) and COPD (Part 2) With at Least 1 Treatment-emergent Adverse Event | 11 Participants |
| Placebo (Part 2) | The Number of Participants With Mild Persistent Asthma (Part 1) and COPD (Part 2) With at Least 1 Treatment-emergent Adverse Event | 11 Participants |
Secondary
AUC(0-24) of AZD8871 in Parts 1 and 2
AUC(0-24) (area under the concentration-time curve from zero to 24h) of AZD8871 on Day 1 of each treatment period.
Time frame: Pre-dose, and 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h (Day 1), 24 h, and 36 h (Day 2) post-dose
Population: Pharmacokinetic population: defined as all randomised subjects who have received at least 1 dose of investigational product in at least 1 treatment period and have evaluable PK parameters. AZD8871 plasma PK assessed following dosing with AZD8871 only (not placebo, indacaterol, or tiotropium).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD8871 50 μg (Part 1) | AUC(0-24) of AZD8871 in Parts 1 and 2 | 118.9 pg*h/mL | Geometric Coefficient of Variation 60.19 |
| AZD8871 200 μg (Part 1) | AUC(0-24) of AZD8871 in Parts 1 and 2 | 567.9 pg*h/mL | Geometric Coefficient of Variation 29.74 |
| AZD8871 400 μg (Part 1) | AUC(0-24) of AZD8871 in Parts 1 and 2 | 1265 pg*h/mL | Geometric Coefficient of Variation 32.44 |
| AZD8871 900 μg (Part 1) | AUC(0-24) of AZD8871 in Parts 1 and 2 | 3020 pg*h/mL | Geometric Coefficient of Variation 25.71 |
| AZD8871 1800 μg (Part 1) | AUC(0-24) of AZD8871 in Parts 1 and 2 | 5587 pg*h/mL | Geometric Coefficient of Variation 25.4 |
| AZD8871 2100 μg (Part 1) | AUC(0-24) of AZD8871 in Parts 1 and 2 | 5922 pg*h/mL | Geometric Coefficient of Variation 34.32 |
| AZD8871 400 μg (Part 2) | AUC(0-24) of AZD8871 in Parts 1 and 2 | 1195 pg*h/mL | Geometric Coefficient of Variation 38.91 |
| AZD8871 1800 μg (Part 2) | AUC(0-24) of AZD8871 in Parts 1 and 2 | 5659 pg*h/mL | Geometric Coefficient of Variation 43.68 |
Secondary
AUC(0-t) of AZD8871 in Parts 1 and 2
AUC(0-t) (area under the concentration-time curve from time zero to time of the last quantifiable measurable concentration) of AZD8871 on Day 1 of each treatment period.
Time frame: Pre-dose, and 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h (Day 1), 24 h, and 36 h (Day 2) post-dose
Population: Pharmacokinetic population: defined as all randomised subjects who have received at least 1 dose of investigational product in at least 1 treatment period and have evaluable PK parameters. AZD8871 plasma PK assessed following dosing with AZD8871 only (not placebo, indacaterol, or tiotropium).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD8871 50 μg (Part 1) | AUC(0-t) of AZD8871 in Parts 1 and 2 | 110 pg*h/mL | Geometric Coefficient of Variation 69.17 |
| AZD8871 200 μg (Part 1) | AUC(0-t) of AZD8871 in Parts 1 and 2 | 631.3 pg*h/mL | Geometric Coefficient of Variation 30.4 |
| AZD8871 400 μg (Part 1) | AUC(0-t) of AZD8871 in Parts 1 and 2 | 1397 pg*h/mL | Geometric Coefficient of Variation 31.41 |
| AZD8871 900 μg (Part 1) | AUC(0-t) of AZD8871 in Parts 1 and 2 | 3299 pg*h/mL | Geometric Coefficient of Variation 27 |
| AZD8871 1800 μg (Part 1) | AUC(0-t) of AZD8871 in Parts 1 and 2 | 6055 pg*h/mL | Geometric Coefficient of Variation 24.98 |
| AZD8871 2100 μg (Part 1) | AUC(0-t) of AZD8871 in Parts 1 and 2 | 6418 pg*h/mL | Geometric Coefficient of Variation 35.13 |
| AZD8871 400 μg (Part 2) | AUC(0-t) of AZD8871 in Parts 1 and 2 | 1239 pg*h/mL | Geometric Coefficient of Variation 37.7 |
| AZD8871 1800 μg (Part 2) | AUC(0-t) of AZD8871 in Parts 1 and 2 | 6159 pg*h/mL | Geometric Coefficient of Variation 44.3 |
Secondary
Cmax of AZD8871 in Parts 1 and 2
Cmax (maximum observed plasma drug concentrations) of AZD8871 on Day 1 of each treatment period.
Time frame: Pre-dose, and 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h (Day 1), 24 h, and 36 h (Day 2) post-dose
Population: Pharmacokinetic population: defined as all randomised subjects who have received at least 1 dose of investigational product in at least 1 treatment period and have evaluable PK parameters. AZD8871 plasma PK assessed following dosing with AZD8871 only (not placebo, indacaterol, or tiotropium).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD8871 50 μg (Part 1) | Cmax of AZD8871 in Parts 1 and 2 | 34.77 pg/mL | Geometric Coefficient of Variation 60.77 |
| AZD8871 200 μg (Part 1) | Cmax of AZD8871 in Parts 1 and 2 | 174.1 pg/mL | Geometric Coefficient of Variation 43.74 |
| AZD8871 400 μg (Part 1) | Cmax of AZD8871 in Parts 1 and 2 | 313.4 pg/mL | Geometric Coefficient of Variation 46.56 |
| AZD8871 900 μg (Part 1) | Cmax of AZD8871 in Parts 1 and 2 | 797.3 pg/mL | Geometric Coefficient of Variation 20.99 |
| AZD8871 1800 μg (Part 1) | Cmax of AZD8871 in Parts 1 and 2 | 1351 pg/mL | Geometric Coefficient of Variation 20.32 |
| AZD8871 2100 μg (Part 1) | Cmax of AZD8871 in Parts 1 and 2 | 1243 pg/mL | Geometric Coefficient of Variation 24.33 |
| AZD8871 400 μg (Part 2) | Cmax of AZD8871 in Parts 1 and 2 | 199.3 pg/mL | Geometric Coefficient of Variation 37.4 |
| AZD8871 1800 μg (Part 2) | Cmax of AZD8871 in Parts 1 and 2 | 810.8 pg/mL | Geometric Coefficient of Variation 36.59 |
Secondary
Tmax of AZD8871 in Parts 1 and 2
tmax (time to reach maximum concentration) of AZD8871 on Day 1 of each treatment period.
Time frame: Pre-dose, and 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h (Day 1), 24 h, and 36 h (Day 2) post-dose
Population: Pharmacokinetic population: defined as all randomised subjects who have received at least 1 dose of investigational product in at least 1 treatment period and have evaluable PK parameters. AZD8871 plasma PK assessed following dosing with AZD8871 only (not placebo, indacaterol, or tiotropium).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD8871 50 μg (Part 1) | Tmax of AZD8871 in Parts 1 and 2 | 0.88 Hours |
| AZD8871 200 μg (Part 1) | Tmax of AZD8871 in Parts 1 and 2 | 0.86 Hours |
| AZD8871 400 μg (Part 1) | Tmax of AZD8871 in Parts 1 and 2 | 1.00 Hours |
| AZD8871 900 μg (Part 1) | Tmax of AZD8871 in Parts 1 and 2 | 1.00 Hours |
| AZD8871 1800 μg (Part 1) | Tmax of AZD8871 in Parts 1 and 2 | 1.49 Hours |
| AZD8871 2100 μg (Part 1) | Tmax of AZD8871 in Parts 1 and 2 | 1.02 Hours |
| AZD8871 400 μg (Part 2) | Tmax of AZD8871 in Parts 1 and 2 | 1.00 Hours |
| AZD8871 1800 μg (Part 2) | Tmax of AZD8871 in Parts 1 and 2 | 2.00 Hours |
Other Pre-specified
AUC of AZD8871 in Parts 1 and 2
AUC (area under the concentration-time curve from time 0 to infinity) of AZD8871 on Day 1 of each treatment period
Time frame: Predose, and 5 min, 15 min, 30 min, and 45 min, at 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h (Day 1), 24 h and 36 h (Day 2) post-dose
Population: Pharmacokinetic population: defined as all randomised subjects who have received at least 1 dose of investigational product in at least 1 treatment period and have evaluable PK parameters. AZD8871 plasma PK assessed following dosing with AZD8871 only (not placebo, indacaterol, or tiotropium).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD8871 50 μg (Part 1) | AUC of AZD8871 in Parts 1 and 2 | 123.1 pg*h/mL | Geometric Coefficient of Variation 75.48 |
| AZD8871 200 μg (Part 1) | AUC of AZD8871 in Parts 1 and 2 | 774.5 pg*h/mL | Geometric Coefficient of Variation 32.64 |
| AZD8871 400 μg (Part 1) | AUC of AZD8871 in Parts 1 and 2 | 1671 pg*h/mL | Geometric Coefficient of Variation 28.54 |
| AZD8871 900 μg (Part 1) | AUC of AZD8871 in Parts 1 and 2 | 3831 pg*h/mL | Geometric Coefficient of Variation 28.72 |
| AZD8871 1800 μg (Part 1) | AUC of AZD8871 in Parts 1 and 2 | 6941 pg*h/mL | Geometric Coefficient of Variation 22.23 |
| AZD8871 2100 μg (Part 1) | AUC of AZD8871 in Parts 1 and 2 | 7164 pg*h/mL | Geometric Coefficient of Variation 34.1 |
| AZD8871 400 μg (Part 2) | AUC of AZD8871 in Parts 1 and 2 | 1459 pg*h/mL | Geometric Coefficient of Variation 39.19 |
| AZD8871 1800 μg (Part 2) | AUC of AZD8871 in Parts 1 and 2 | 6769 pg*h/mL | Geometric Coefficient of Variation 44.65 |
Other Pre-specified
Elimination Half-life of AZD8871 in Parts 1 and 2
Elimination half-life (t½λz) for AZD8871 on Day 1 of each treatment period. t½λz was generally calculated over a period of less than 3 times the resultant half-life
Time frame: Predose, and 5 min, 15 min, 30 min, and 45 min, at 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h (Day 1), 24 h and 36 h (Day 2) post-dose
Population: Pharmacokinetic population: defined as all randomised subjects who have received at least 1 dose of investigational product in at least 1 treatment period and have evaluable PK parameters. AZD8871 plasma PK assessed following dosing with AZD8871 only (not placebo, indacaterol, or tiotropium).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD8871 50 μg (Part 1) | Elimination Half-life of AZD8871 in Parts 1 and 2 | 9.439 Hours | Standard Deviation 7.35 |
| AZD8871 200 μg (Part 1) | Elimination Half-life of AZD8871 in Parts 1 and 2 | 23.10 Hours | Standard Deviation 2.809 |
| AZD8871 400 μg (Part 1) | Elimination Half-life of AZD8871 in Parts 1 and 2 | 20.81 Hours | Standard Deviation 5.384 |
| AZD8871 900 μg (Part 1) | Elimination Half-life of AZD8871 in Parts 1 and 2 | 18.86 Hours | Standard Deviation 3.959 |
| AZD8871 1800 μg (Part 1) | Elimination Half-life of AZD8871 in Parts 1 and 2 | 19.29 Hours | Standard Deviation 5.468 |
| AZD8871 2100 μg (Part 1) | Elimination Half-life of AZD8871 in Parts 1 and 2 | 15.96 Hours | Standard Deviation 2.789 |
| AZD8871 400 μg (Part 2) | Elimination Half-life of AZD8871 in Parts 1 and 2 | 14.20 Hours | Standard Deviation 5.521 |
| AZD8871 1800 μg (Part 2) | Elimination Half-life of AZD8871 in Parts 1 and 2 | 12.89 Hours | Standard Deviation 2.268 |