Two-part Safety, Tolerability, Pharmacodynamic and -Kinet... | NCT02573155

NCT02573155

ID	Type	Description	Link
2015-002906-36	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Sequence 1, Part 1	Experimental	Period 1: Dose 1 Period 2: Dose 3 Period 3: Dose 5	Drug: Dose 1, AZD8871 50 μg (Part 1) Drug: Dose 3, AZD8871 300 μg (Part 1) Drug: Dose 5, AZD8871 1200 µg (Part 1)
Sequence 2, Part 1	Experimental	Period 1: Placebo Period 2: Dose 3 Period 3: Dose 5	Drug: Dose 3, AZD8871 300 μg (Part 1) Drug: Dose 5, AZD8871 1200 µg (Part 1) Drug: Placebo, AZD8871 placebo (Part 1)
Sequence 3, Part 1	Experimental	Period 1: Dose 1 Period 2: Placebo Period 3: Dose 5	Drug: Dose 1, AZD8871 50 μg (Part 1) Drug: Dose 5, AZD8871 1200 µg (Part 1) Drug: Placebo, AZD8871 placebo (Part 1)
Sequence 4, Part 1	Experimental	Period 1: Dose 1 Period 2: Dose 3 Period 3: Placebo	Drug: Dose 1, AZD8871 50 μg (Part 1) Drug: Dose 3, AZD8871 300 μg (Part 1) Drug: Placebo, AZD8871 placebo (Part 1)
Sequence 5, Part 1	Experimental	Period 1: Dose 2 Period 2: Dose 4 Period 3: Dose 6

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Dose 1, AZD8871 50 μg (Part 1)	Drug	50 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)	Sequence 1, Part 1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	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.
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.	From the time of informed consent up to 36 hours after last dose of IP.
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.

Secondary Outcomes

Measure	Description	Time Frame
Cmax of AZD8871 in Parts 1 and 2	Cmax (maximum observed plasma drug concentrations) of AZD8871 on Day 1 of each treatment period.	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 of AZD8871 in Parts 1 and 2

Other Outcomes

Measure	Description	Time Frame
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	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 of AZD8871 in Parts 1 and 2

Eligibility Module

Eligibility Criteria

Inclusion Criteria:Part 1

Subjects who are able and willing to provide written informed consent prior to conducting any study-related procedures, including withdrawal of medications
Adult male subjects aged 18 to 70 years (both inclusive)
Body mass index (BMI) from 18 to 32 kg/m2 at screening
Clinical diagnosis of asthma (according to the Global Initiative for Asthma [GINA] guidelines) for at least 6 months prior to screening
Ability to change current asthma therapy, to discontinue previous prescribed medications after signature of informed consent as per required washout periods
Screening FEV1 value of ≥70% of the predicted normal value
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
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
Predose FEV1 value of first treatment period within the range of ± 20% of the FEV1 measured at screening prior to salbutamol inhalation
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
No other relevant pulmonary disease or history of thoracic surgery
Subjects who are otherwise healthy as determined by medical history, physical examination, 12-lead ECG findings
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
Subjects whose clinical laboratory test results are not clinically relevant and are acceptable to the Investigator.
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
Subjects who are negative for drugs of abuse and alcohol tests at screening and admission
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

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
Females must be of non-childbearing potential, confirmed at screening by fulfilling study predefined criteria
Post-salbutamol FEV1 <80% and ≥30% of the predicted normal value and post-salbutamol FEV1 / forced vital capacity (FVC) <70%
BMI < 40 kg/m2 at screening
Ability to change current COPD therapy, to discontinue previous prescribed medications after signature of informed consent as per required washout periods
Current or ex-smokers with a smoking history of ≥10 pack years
No evidence of clinically significant respiratory and / or cardiovascular conditions (e.g. uncontrolled hypertension) or laboratory abnormalities
No other relevant pulmonary disease or history of thoracic surgery
Subjects who are negative for HBsAg, HBc IgM, hepatitis C antibody and HIV I and II antibodies at screening
Subjects who are able and willing to provide written informed consent prior to conducting any study-related procedures, including withdrawal of medications
Medical history must be verified by either a personal physician or medical practitioner as appropriate
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):

Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
Previous enrolment or randomisation of treatment in the present study
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
Subjects with a surgical history clinically relevant for the purpose of the study
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
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)
Current diagnosis of COPD (for Part 1 only) or history of / or current diagnosis for asthma (for Part 2 only)
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
Use of daily oxygen therapy >10 h per day (for Part 2 only)
Use of systemic steroids for respiratory reasons within 6 weeks prior to screening
Lower respiratory tract infection within 6 weeks prior to screening or prior to randomisation
Upper respiratory tract infection requiring antibiotics within 6 weeks prior to screening or prior to randomisation
Current history of tuberculosis, bronchiectasis or other non-specific pulmonary disease
Subject with significant cardiovascular disease that may be vulnerable to cardiovascular instability
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
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
Subjects with serum potassium concentration < 3.5mmol/l at screening
Subjects with a history of excessive use or abuse of alcohol within the past 2 years
Subjects with a history of drug abuse within the past 2 years
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
Donation or loss >400 ml of blood and plasma within the previous 3 months prior to screening
Subjects with a significant infection or known inflammatory process at screening or prior to randomisation
Subjects with acute gastrointestinal symptoms at the time of screening or prior to randomisation (eg, nausea, vomiting, diarrhoea, heartburn)
Subjects with an acute infection such as influenza at the time of screening or prior to randomisation
Male subjects who do not agree to follow instructions to avoid pregnancies
Subjects who are not able to adhere to the restrictions on prior and concomitant medications
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
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
Subjects who have received the last dose of investigational product more than 3 months ago but who are on an extended follow-up
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

Contacts/Locations Module

Overall Officials

Name	Affiliation	Role
Muna Albayaty, MBChB, MSc,MFPM	PAREXEL Early Phase Clinical Unit, London, United Kingdom	Principal Investigator
Dave Singh, Prof.	The Medicines Evaluation Unit (MEU), Manchester, United Kingdom	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Harrow			United Kingdom
Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
32907576	Derived	Jimenez E, Astbury C, Albayaty M, Wahlby-Hamren U, Seoane B, Villarroel C, Pujol H, Bermejo MJ, Aggarwal A, Psallidas I. Navafenterol (AZD8871) in patients with mild asthma: a randomised placebo-controlled phase I study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of this novel inhaled long-acting dual-pharmacology bronchodilator. Respir Res. 2020 Sep 9;21(Suppl 1):211. doi: 10.1186/s12931-020-01470-5.
32907566

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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).
FG001	Overall Population - Part 2

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Drug: Dose 2, AZD8871 100 μg (Part 1)
Drug: Dose 4, AZD8871 600 µg (Part 1)
Drug: Dose 6, AZD8871 1800 μg (Part 1)

All randomized subjects who received at least 1 dose of the investigational product in Parts 1 and 2, respectively.

Arm/Group Information

ID	Title	Description
BG000	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).
BG001	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.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	OG0005 OG0015 OG0023 OG003

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.

Safety population: all randomized subjects who received at least 1 dose of the investigational product

Posted

Count of Participants

Participants

From the time of informed consent up to 36 hours after last dose of IP.

ID	Title	Description
OG000	AZD8871 50 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG001	AZD8871 200 μg (Part 1)

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.

Safety population: all randomized subjects who received at least 1 dose of the investigational product

Posted

Count of Participants

Participants

From the time of informed consent up to 36 hours after last dose of IP.

ID	Title	Description
OG000	AZD8871 50 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG001	AZD8871 200 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)

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.

Safety population: all randomized subjects who received at least 1 dose of the investigational product

Posted

Count of Participants

Participants

From the time of informed consent up to 7 days after the last dose of IP.

ID	Title	Description
OG000	AZD8871 50 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG001	AZD8871 200 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG002	AZD8871 400 μg (Part 1)

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)

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

Posted

Mean

Standard Deviation

Liters

Baseline (Day 1) to 36 hours post-dose (Day 2)

ID	Title	Description
OG000	AZD8871 50 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG001	AZD8871 200 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG002	AZD8871 400 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG003	AZD8871 900 μg (Part 1)

Secondary

Cmax of AZD8871 in Parts 1 and 2

Cmax (maximum observed plasma drug concentrations) of AZD8871 on Day 1 of each treatment period.

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).

Posted

Geometric Mean

Geometric Coefficient of Variation

pg/mL

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

ID	Title	Description
OG000	AZD8871 50 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG001	AZD8871 200 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG002	AZD8871 400 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG003	AZD8871 900 μg (Part 1)

Secondary

Tmax of AZD8871 in Parts 1 and 2

tmax (time to reach maximum concentration) of AZD8871 on Day 1 of each treatment period.

Posted

Median

Full Range

Hours

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

ID	Title	Description
OG000	AZD8871 50 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG001	AZD8871 200 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG002	AZD8871 400 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG003	AZD8871 900 μg (Part 1)

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

pg*h/mL

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

ID	Title	Description
OG000	AZD8871 50 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG001	AZD8871 200 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG002	AZD8871 400 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG003

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

pg*h/mL

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

ID	Title	Description
OG000	AZD8871 50 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG001	AZD8871 200 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG002	AZD8871 400 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG003	AZD8871 900 μg (Part 1)

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

Posted

Geometric Mean

Geometric Coefficient of Variation

pg*h/mL

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

ID	Title	Description
OG000	AZD8871 50 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG001	AZD8871 200 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG002	AZD8871 400 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG003	AZD8871 900 μg (Part 1)

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

Posted

Mean

Standard Deviation

Hours

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

ID	Title	Description
OG000	AZD8871 50 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG001	AZD8871 200 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG002	AZD8871 400 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)
OG003	AZD8871 900 μg (Part 1)

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	AZD8871 50 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)	0	6	5	6
EG001	AZD8871 200 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)	0	6	5	6
EG002	AZD8871 400 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)	0	6	3	6
EG003	AZD8871 900 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)	0	6	3	6
EG004	AZD8871 1800 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)	0	6	3	6
EG005	AZD8871 2100 μg (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)	0	5	2	5
EG006	Placebo (Part 1)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)	0	12	12	12
EG007	AZD8871 400 μg (Part 2)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)	1	34	8	34
EG008	AZD8871 1800 μg (Part 2)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)	0	31	4	31
EG009	Indacaterol 150 μg (Part 2)	Single-dose, oral inhalation by Onbrez Breezhaler® single-dose dry powder inhaler (DPI)	0	32	6	32
EG010	Tiotropium 18 μg (Part 2)	Single-dose, oral inhalation by HandiHaler® single-dose dry powder inhaler (DPI)	1	30	8	30
EG011	Placebo (Part 2)	Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)	0	32	8	32

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Spinal fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG0030 events0 affected6 at risk EG004
Physical assault	Social circumstances	MedDRA 18.1	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected6 at risk EG0030 events0 affected6 at risk EG0040 events0 affected6 at risk EG0052 events2 affected5 at risk EG0061 events1 affected12 at risk EG0071 events1 affected34 at risk EG0081 events1 affected31 at risk EG0092 events2 affected32 at risk EG0101 events1 affected30 at risk EG0111 events1 affected32 at risk
Headache	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0006 events3 affected6 at risk EG0011 events1 affected6 at risk EG0022 events2 affected6 at risk EG003
Chronic obstructive pulmonary disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Feeling hot	General disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Catheter site pain	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Chest discomfort	General disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0014 events1 affected6 at risk EG0020 events0 affected6 at risk EG003
Chest pain	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected6 at risk EG003
Fatigue	General disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Abscess oral	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected6 at risk EG003
Oral herpes	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected6 at risk EG003
Bronchitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Bronchitis viral	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected6 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected6 at risk EG003
Dizziness	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected6 at risk EG003
Dizziness postural	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Presyncope	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0004 events1 affected6 at risk EG0012 events1 affected6 at risk EG0020 events0 affected6 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected6 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected6 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0022 events1 affected6 at risk EG003
Skin irritation	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0012 events1 affected6 at risk EG0020 events0 affected6 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected6 at risk EG003

ID	Term
D001249	Asthma
D029424	Pulmonary Disease, Chronic Obstructive

Ancestor Terms

ID	Term
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012130	Respiratory Hypersensitivity
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
C000656189	AZD-8871
C510790	indacaterol
D000069447	Tiotropium Bromide

Ancestor Terms

ID	Term
D012602	Scopolamine Derivatives
D014326	Tropanes
D053961	Azabicyclo Compounds
D001372	Aza Compounds
D009930	Organic Chemicals
D000470	Alkaloids
D006571	Heterocyclic Compounds
D019086	Bridged Bicyclo Compounds, Heterocyclic
D006572	Heterocyclic Compounds, Bridged-Ring

Single-dose, oral inhalation by Genuair® single-dose dry powder inhaler (DPI)

EG0050 events0 affected5 at risk

EG0060 events0 affected12 at risk

EG0070 events0 affected34 at risk

EG0080 events0 affected31 at risk

EG0090 events0 affected32 at risk

EG0101 events1 affected30 at risk

EG0110 events0 affected32 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected5 at risk

EG0060 events0 affected12 at risk

EG0071 events1 affected34 at risk

EG0080 events0 affected31 at risk

EG0090 events0 affected32 at risk

EG0100 events0 affected30 at risk

EG0110 events0 affected32 at risk

EG0041 events1 affected6 at risk

EG0050 events0 affected5 at risk

EG0063 events3 affected12 at risk

EG0075 events5 affected34 at risk

EG0084 events3 affected31 at risk

EG0094 events4 affected32 at risk

EG0107 events7 affected30 at risk

EG0117 events7 affected32 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected5 at risk

EG0060 events0 affected12 at risk

EG0072 events2 affected34 at risk

EG0081 events1 affected31 at risk

EG0091 events1 affected32 at risk

EG0100 events0 affected30 at risk

EG0110 events0 affected32 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected5 at risk

EG0060 events0 affected12 at risk

EG0070 events0 affected34 at risk

EG0080 events0 affected31 at risk

EG0090 events0 affected32 at risk

EG0100 events0 affected30 at risk

EG0110 events0 affected32 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected5 at risk

EG0061 events1 affected12 at risk

EG0070 events0 affected34 at risk

EG0080 events0 affected31 at risk

EG0090 events0 affected32 at risk

EG0100 events0 affected30 at risk

EG0110 events0 affected32 at risk

EG0041 events1 affected6 at risk

EG0050 events0 affected5 at risk

EG0060 events0 affected12 at risk

EG0070 events0 affected34 at risk

EG0080 events0 affected31 at risk

EG0090 events0 affected32 at risk

EG0100 events0 affected30 at risk

EG0110 events0 affected32 at risk

EG0040 events0 affected6 at risk

EG0051 events1 affected5 at risk

EG0061 events1 affected12 at risk

EG0070 events0 affected34 at risk

EG0080 events0 affected31 at risk

EG0090 events0 affected32 at risk

EG0100 events0 affected30 at risk

EG0110 events0 affected32 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected5 at risk

EG0061 events1 affected12 at risk

EG0070 events0 affected34 at risk

EG0080 events0 affected31 at risk

EG0090 events0 affected32 at risk

EG0100 events0 affected30 at risk

EG0110 events0 affected32 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected5 at risk

EG0061 events1 affected12 at risk

EG0070 events0 affected34 at risk

EG0080 events0 affected31 at risk

EG0090 events0 affected32 at risk

EG0100 events0 affected30 at risk

EG0110 events0 affected32 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected5 at risk

EG0060 events0 affected12 at risk

EG0070 events0 affected34 at risk

EG0080 events0 affected31 at risk

EG0090 events0 affected32 at risk

EG0100 events0 affected30 at risk

EG0110 events0 affected32 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected5 at risk

EG0061 events1 affected12 at risk

EG0070 events0 affected34 at risk

EG0080 events0 affected31 at risk

EG0090 events0 affected32 at risk

EG0100 events0 affected30 at risk

EG0110 events0 affected32 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected5 at risk

EG0061 events1 affected12 at risk

EG0070 events0 affected34 at risk

EG0080 events0 affected31 at risk

EG0090 events0 affected32 at risk

EG0100 events0 affected30 at risk

EG0110 events0 affected32 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected5 at risk

EG0060 events0 affected12 at risk

EG0070 events0 affected34 at risk

EG0080 events0 affected31 at risk

EG0090 events0 affected32 at risk

EG0100 events0 affected30 at risk

EG0110 events0 affected32 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected5 at risk

EG0060 events0 affected12 at risk

EG0070 events0 affected34 at risk

EG0080 events0 affected31 at risk

EG0090 events0 affected32 at risk

EG0100 events0 affected30 at risk

EG0110 events0 affected32 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected5 at risk

EG0060 events0 affected12 at risk

EG0070 events0 affected34 at risk

EG0080 events0 affected31 at risk

EG0090 events0 affected32 at risk

EG0100 events0 affected30 at risk

EG0110 events0 affected32 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected5 at risk

EG0060 events0 affected12 at risk

EG0070 events0 affected34 at risk

EG0080 events0 affected31 at risk

EG0090 events0 affected32 at risk

EG0100 events0 affected30 at risk

EG0110 events0 affected32 at risk

EG0040 events0 affected6 at risk

EG0051 events1 affected5 at risk

EG0060 events0 affected12 at risk

EG0070 events0 affected34 at risk

EG0080 events0 affected31 at risk

EG0090 events0 affected32 at risk

EG0100 events0 affected30 at risk

EG0110 events0 affected32 at risk

EG0040 events0 affected6 at risk

EG0050 events0 affected5 at risk

EG0060 events0 affected12 at risk