Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses of AZD8871 in Healthy Subjects

• Status: Completed
• Trial end date: 2016-11-28
• Target enrollment: 0
• Participant gender: Male

Summary

AZD8871 is a new chemical entity possessing long-acting effect in a single molecule which presents a novel treatment approach to chronic obstructive pulmonary disease [COPD] and potentially also asthma (in combination with an inhaled corticosteroid [ICS]). The therapeutic goal for AZD8871 is a treatment with greater efficacy than single mechanism bronchodilators, with an equivalent or superior safety and tolerability profile. The primary purpose of this study is to check the safety and tolerability of AZD8871 at steady state. A multiple ascending dose (MAD) design has been selected for this study following the first time in man (FTIM), single ascending dose (SAD) study. Three dose levels will be tested in an ascending manner. The first dose to be administered will be 300 μg and the 2 subsequent doses will be decided based on safety, tolerability and pharmacokinetic (PK) data generated in the previous dose. The aim of this study is to also enable further investigations in healthy subjects to evaluate and develop AZD8871 as a dual action bronchodilator with an acceptable side-effect profile compared to other inhaled bronchodilators on the market as a treatment for COPD and asthma.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: AstraZeneca
• Collaborator: Parexel

Criteria

Inclusion Criteria:

1. Provision of written informed consent prior to conducting any study-related procedures, including withdrawal of medications.

2. Male subjects aged 18 to 55 years, inclusive at Screening.

3. Body mass index (BMI) calculated as weight in kg/height in m2 from ≥18 to ≤30 kg/m2 and weight ≥50 kg at Screening.

4. Healthy, free from any clinically significant disease/ conditions (including all cardiovascular conditions), as determined by medical history, physical examination, clinical laboratory testing, 12-lead ECG findings at Screening and admission to the unit.

5. Spirometry readings (FEV1 and Forced Vital Capacity [FVC]) to be ≥80% of predicted value calculated using Quanjer 2012 reference equations (Quanjer et al 2012) at Screening.

6. Normal blood pressure (BP) (defined as systolic BP [SBP] ≥90 and ≤140 mmHg, and diastolic BP [DBP] ≥50 and ≤90 mmHg) at Screening and admission to the unit, measured after resting in supine position for at least 10 minutes.

7. Normal heart rate (HR) (defined as HR ≥45 and ≤90) measured after resting in supine position for at least 10 minutes at Screening and admission to the unit.

8. 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.

9. Negative for drugs of abuse and alcohol tests at Screening and admission to the unit.

10. Normal serum potassium at Screening and at admission to the unit.

11. Willing and able to comply with study specific procedures and restrictions

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. Surgical history clinically relevant for the purpose of the study or any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of Screening.

3. 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.

4. Current smokers, or a smoking history during the last 6 months or total smoking history of more than 10 pack-years. Use of electronic cigarettes or other forms of nicotine, current use or use within the last 6 months.

5. Prolonged QTcF interval, >450 ms at Screening, or family history of long QT syndrome.

6. Any clinically significant arrhythmia noted on telemetry recording, prior to randomisation.

7. History of excessive use or abuse of alcohol within the past 2 years.

8. History of drug abuse within the past 2 years.

9. Donation or loss >400 ml of blood and plasma within the previous 3 months prior to Visit 1, Screening.

10. History of presence of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity to any drug, as judged by the Investigator or history of hypersensitivity to drugs pharmacologically related to study drug.

11. PR (PQ) interval shortening <120 ms (PR >110 ms but <120 ms is acceptable if there is no evidence of ventricular pre-excitation) at Screening.

12. PR (PQ) interval prolongation (> 240 ms), intermittent second (Wenckebach block while asleep is not exclusive), or third degree atrioventricular block, or atrioventricular dissociation at Screening.

13. Persistent or intermittent complete bundle branch block (BBB), incomplete bundle branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS >110 ms.

14. Subject who does not agree to follow instructions to avoid partner pregnancy.

15. Subject who is not able to adhere to the restrictions on prior and concomitant medications.

16. Used any investigational drug within 3 months prior to Screening or within the equivalent time of 5 half-lives of receiving the last administration, whichever is longer, or on an extended follow-up after receiving an IMP.

17. Subjects unable to communicate reliably with the Investigator.

18. Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.