Two-part Safety, Tolerability, Pharmacodynamic and -Kinetic Study of Inhaled AZD8871 in Asthmatic and COPD Subjects

NCT ID: NCT02573155

Last Updated: 2018-11-08

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

134 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-31

Study Completion Date

2016-08-31

Brief Summary

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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

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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.

Conditions

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Asthma (Part 1) COPD (Part 2)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Sequence 1, Part 1

Period 1: Dose 1 Period 2: Dose 3 Period 3: Dose 5

Group Type EXPERIMENTAL

Dose 1, AZD8871 50 μg (Part 1)

Intervention Type DRUG

50 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Dose 3, AZD8871 300 μg (Part 1)

Intervention Type DRUG

300 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Dose 5, AZD8871 1200 µg (Part 1)

Intervention Type DRUG

1200 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Sequence 2, Part 1

Period 1: Placebo Period 2: Dose 3 Period 3: Dose 5

Group Type EXPERIMENTAL

Dose 3, AZD8871 300 μg (Part 1)

Intervention Type DRUG

300 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Dose 5, AZD8871 1200 µg (Part 1)

Intervention Type DRUG

1200 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Placebo, AZD8871 placebo (Part 1)

Intervention Type DRUG

AZD8871 placebo on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Sequence 3, Part 1

Period 1: Dose 1 Period 2: Placebo Period 3: Dose 5

Group Type EXPERIMENTAL

Dose 1, AZD8871 50 μg (Part 1)

Intervention Type DRUG

50 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Dose 5, AZD8871 1200 µg (Part 1)

Intervention Type DRUG

1200 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Placebo, AZD8871 placebo (Part 1)

Intervention Type DRUG

AZD8871 placebo on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Sequence 4, Part 1

Period 1: Dose 1 Period 2: Dose 3 Period 3: Placebo

Group Type EXPERIMENTAL

Dose 1, AZD8871 50 μg (Part 1)

Intervention Type DRUG

50 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Dose 3, AZD8871 300 μg (Part 1)

Intervention Type DRUG

300 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Placebo, AZD8871 placebo (Part 1)

Intervention Type DRUG

AZD8871 placebo on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Sequence 5, Part 1

Period 1: Dose 2 Period 2: Dose 4 Period 3: Dose 6

Group Type EXPERIMENTAL

Dose 2, AZD8871 100 μg (Part 1)

Intervention Type DRUG

100 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Dose 4, AZD8871 600 µg (Part 1)

Intervention Type DRUG

600 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Dose 6, AZD8871 1800 μg (Part 1)

Intervention Type DRUG

1800 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Sequence 6, Part 1

Period 1: Placebo Period 2: Dose 4 Period 3: Dose 6

Group Type EXPERIMENTAL

Dose 4, AZD8871 600 µg (Part 1)

Intervention Type DRUG

600 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Dose 6, AZD8871 1800 μg (Part 1)

Intervention Type DRUG

1800 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Placebo, AZD8871 placebo (Part 1)

Intervention Type DRUG

AZD8871 placebo on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Sequence 7, Part 1

Period 1: Dose 2 Period 2: Placebo Period 3: Dose 6

Group Type EXPERIMENTAL

Dose 2, AZD8871 100 μg (Part 1)

Intervention Type DRUG

100 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Dose 6, AZD8871 1800 μg (Part 1)

Intervention Type DRUG

1800 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Placebo, AZD8871 placebo (Part 1)

Intervention Type DRUG

AZD8871 placebo on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Sequence 8, Part 1

Period 1: Dose 2 Period 2: Dose 4 Period 3: Placebo

Group Type EXPERIMENTAL

Dose 2, AZD8871 100 μg (Part 1)

Intervention Type DRUG

100 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Dose 4, AZD8871 600 µg (Part 1)

Intervention Type DRUG

600 µg of AZD8871 on Day 1; each dose of AZD8871 inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Placebo, AZD8871 placebo (Part 1)

Intervention Type DRUG

AZD8871 placebo on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Sequence 1, Part 2

Period 1: Treatment A Period 2: Treatment B Period 3: Treatment E Period 4: Treatment C Period 5: Treatment D

Group Type EXPERIMENTAL

Treatment A, AZD8871 dose A (Part 2)

Intervention Type DRUG

AZD8871 dose A once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Treatment B, AZD8871 dose B (Part 2)

Intervention Type DRUG

AZD8871 dose B once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler(Genuair®)

Treatment C, Indacaterol 150 μg (Part 2)

Intervention Type DRUG

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

Treatment D, Tiotropium 18 μg (Part 2)

Intervention Type DRUG

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

Sequence 2, Part 2

Period 1: Treatment B Period 2: Treatment C Period 3: Treatment A Period 4: Treatment D Period 5: Treatment E

Group Type EXPERIMENTAL

Treatment A, AZD8871 dose A (Part 2)

Intervention Type DRUG

AZD8871 dose A once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Treatment B, AZD8871 dose B (Part 2)

Intervention Type DRUG

AZD8871 dose B once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler(Genuair®)

Treatment C, Indacaterol 150 μg (Part 2)

Intervention Type DRUG

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

Treatment D, Tiotropium 18 μg (Part 2)

Intervention Type DRUG

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

Sequence 3, Part 2

Period 1: Treatment C Period 2: Treatment D Period 3: Treatment B Period 4: Treatment E Period 5: Treatment A

Group Type EXPERIMENTAL

Treatment A, AZD8871 dose A (Part 2)

Intervention Type DRUG

AZD8871 dose A once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Treatment B, AZD8871 dose B (Part 2)

Intervention Type DRUG

AZD8871 dose B once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler(Genuair®)

Treatment C, Indacaterol 150 μg (Part 2)

Intervention Type DRUG

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

Treatment D, Tiotropium 18 μg (Part 2)

Intervention Type DRUG

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

Sequence 4, Part 2

Period 1: Treatment D Period 2: Treatment E Period 3: Treatment C Period 4: Treatment A Period 5: Treatment B

Group Type EXPERIMENTAL

Treatment A, AZD8871 dose A (Part 2)

Intervention Type DRUG

AZD8871 dose A once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Treatment B, AZD8871 dose B (Part 2)

Intervention Type DRUG

AZD8871 dose B once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler(Genuair®)

Treatment C, Indacaterol 150 μg (Part 2)

Intervention Type DRUG

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

Treatment D, Tiotropium 18 μg (Part 2)

Intervention Type DRUG

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

Sequence 5, Part 2

Period 1: Treatment E Period 2: Treatment A Period 3: Treatment D Period 4: Treatment B Period 5: Treatment C

Group Type EXPERIMENTAL

Treatment A, AZD8871 dose A (Part 2)

Intervention Type DRUG

AZD8871 dose A once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Treatment B, AZD8871 dose B (Part 2)

Intervention Type DRUG

AZD8871 dose B once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler(Genuair®)

Treatment C, Indacaterol 150 μg (Part 2)

Intervention Type DRUG

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

Treatment D, Tiotropium 18 μg (Part 2)

Intervention Type DRUG

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

Sequence 6, Part 2

Period 1: Treatment D Period 2: Treatment C Period 3: Treatment E Period 4: Treatment B Period 5: Treatment A

Group Type EXPERIMENTAL

Treatment A, AZD8871 dose A (Part 2)

Intervention Type DRUG

AZD8871 dose A once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Treatment B, AZD8871 dose B (Part 2)

Intervention Type DRUG

AZD8871 dose B once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler(Genuair®)

Treatment C, Indacaterol 150 μg (Part 2)

Intervention Type DRUG

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

Treatment D, Tiotropium 18 μg (Part 2)

Intervention Type DRUG

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

Sequence 7, Part 2

Period 1: Treatment E Period 2: Treatment D Period 3: Treatment A Period 4: Treatment C Period 5: Treatment B

Group Type EXPERIMENTAL

Treatment A, AZD8871 dose A (Part 2)

Intervention Type DRUG

AZD8871 dose A once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Treatment B, AZD8871 dose B (Part 2)

Intervention Type DRUG

AZD8871 dose B once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler(Genuair®)

Treatment C, Indacaterol 150 μg (Part 2)

Intervention Type DRUG

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

Treatment D, Tiotropium 18 μg (Part 2)

Intervention Type DRUG

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

Sequence 8, Part 2

Period 1: Treatment A Period 2: Treatment E Period 3: Treatment B Period 4: Treatment D Period 5: Treatment C

Group Type EXPERIMENTAL

Treatment A, AZD8871 dose A (Part 2)

Intervention Type DRUG

AZD8871 dose A once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Treatment B, AZD8871 dose B (Part 2)

Intervention Type DRUG

AZD8871 dose B once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler(Genuair®)

Treatment C, Indacaterol 150 μg (Part 2)

Intervention Type DRUG

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

Treatment D, Tiotropium 18 μg (Part 2)

Intervention Type DRUG

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

Sequence 9, Part 2

Period 1: Treatment B Period 2: Treatment A Period 3: Treatment C Period 4: Treatment E Period 5: Treatment D

Group Type EXPERIMENTAL

Treatment A, AZD8871 dose A (Part 2)

Intervention Type DRUG

AZD8871 dose A once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Treatment B, AZD8871 dose B (Part 2)

Intervention Type DRUG

AZD8871 dose B once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler(Genuair®)

Treatment C, Indacaterol 150 μg (Part 2)

Intervention Type DRUG

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

Treatment D, Tiotropium 18 μg (Part 2)

Intervention Type DRUG

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

Sequence 10, Part 2

Period 1: Treatment C Period 2: Treatment B Period 3: Treatment D Period 4: Treatment A Period 5: Treatment E

Group Type EXPERIMENTAL

Treatment A, AZD8871 dose A (Part 2)

Intervention Type DRUG

AZD8871 dose A once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler (Genuair®)

Treatment B, AZD8871 dose B (Part 2)

Intervention Type DRUG

AZD8871 dose B once on Day 1; each dose of AZD8871 placebo inhalation powder will be administered via single-dose dry powder inhaler(Genuair®)

Treatment C, Indacaterol 150 μg (Part 2)

Intervention Type DRUG

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

Treatment D, Tiotropium 18 μg (Part 2)

Intervention Type DRUG

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

Interventions

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Dose 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®)

Intervention Type DRUG

Dose 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®)

Intervention Type DRUG

Dose 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®)

Intervention Type DRUG

Dose 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®)

Intervention Type DRUG

Dose 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®)

Intervention Type DRUG

Dose 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®)

Intervention Type DRUG

Placebo, 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®)

Intervention Type DRUG

Treatment 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®)

Intervention Type DRUG

Treatment 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®)

Intervention Type DRUG

Treatment 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

Intervention Type DRUG

Treatment 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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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


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

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Muna Albayaty, MBChB, MSc,MFPM

Role: PRINCIPAL_INVESTIGATOR

PAREXEL Early Phase Clinical Unit, London, United Kingdom

Dave Singh, Prof.

Role: PRINCIPAL_INVESTIGATOR

The Medicines Evaluation Unit (MEU), Manchester, United Kingdom

Locations

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Research Site

Harrow, , United Kingdom

Site Status

Research Site

Manchester, , United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type DERIVED
PMID: 32907576 (View on PubMed)

Singh D, Balaguer V, Astbury C, Wahlby-Hamren U, Jimenez E, Seoane B, Villarroel C, Lei A, Aggarwal A, Psallidas I. Navafenterol (AZD8871) in patients with COPD: a randomized, double-blind, phase I study evaluating safety and pharmacodynamics of single doses of this novel, inhaled, long-acting, dual-pharmacology bronchodilator. Respir Res. 2020 Sep 9;21(Suppl 1):102. doi: 10.1186/s12931-020-01347-7.

Reference Type DERIVED
PMID: 32907566 (View on PubMed)

Other Identifiers

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2015-002906-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D6640C00001

Identifier Type: -

Identifier Source: org_study_id

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