Clinical trial NCT01584739: AZD8683 Multiple Dose Study in Healthy Volunteers and Chronic Obstructive Pulmonary Disease (COPD) Patients
Official title: A Phase I, Single Centre, Double-Blind, Randomised, Placebo- Controlled, Parallel-group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Inhaled Doses of AZD8683 in Healthy Volunteers and COPD Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: COPD
Keywords: Safety
tolerability
healthy
COPD (chronic obstructive pulmonary disease)
pharmacokinetic
pharmacodynamic
inhaled
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2012-04-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This study will investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending inhaled doses of AZD8683 in Healthy volunteers and repeated inhalation of one dose level of AZD8683 in patients with chronic obstructive pulmonary disease given once daily.

Detailed description: A Phase I, Single Centre, Double-Blind, Randomised, Placebo- controlled, Parallel-group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Inhaled Doses of AZD8683 in Healthy Volunteers and COPD patients

Eligibility criteria: Inclusion Criteria:

* Healthy male volunteers and healthy female volunteers of non-child bearing potential, aged 18 to 45 years inclusive with suitable veins for cannulation or repeated venepuncture - Healthy volunteers
* Have a body mass index (BMI) between 19 and 30 kg/m2 and weigh at least 50 kg and no more than 100 kg inclusive - Healthy volunteers and COPD patients
* Be able to inhale from the Turbuhaler® inhaler according to given instructions as well as be able to perform spirometry -Healthy volunteers and COPD patients.
* Male COPD patients or female COPD patients of non-childbearing potential (post menopausal or surgically sterilised) aged ≥40 years at Visit 1 - COPD patients
* Female healthy volunteers and female patients ≤60 years must have a negative pregnancy test at screening and on admission to the unit - Healthy volunteers and COPD patients

Exclusion Criteria:

* Prolonged QTcF \>450 ms or shortened QTcF \<340 ms or family history of long QT syndrome - Healthy volunteers and COPD patients
* History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD8683 or excipients:Healthy volunteers and COPD patients
* History or presence of gastrointestinal, pulmonary, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs - Healthy volunteers and COPD patients
* Any clinically significant illness (other than COPD), medical/surgical procedure or trauma within 4 weeks of the first administration of investigational product - COPD patients
* Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of investigational product - Healthy volunteers

Primary outcomes:
measure: Safety profile in terms of: adverse events, Supine vital signs (blood pressure and pulse rate), body temperature, ECG, Physical examinations, Laboratory variables (clinical chemistry, haematology and urinalysis), Spirometry
timeFrame: Up to 13 days post dose.
Secondary outcomes:
measure: AZD8683 single dose pharmacokinetics from blood and urine in healthy volunteers.
timeFrame: Blood: From days 1 and 15 - Pre-dose, 5, 15 and 30mons, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48, 72 hrs (also 96 and 120hrs and follow-up). Urine: From days 1 and 15: pre-dose and 6, 12, 24, 48 and 72hrs.
measure: AZD8683 multiple dose pharmacokinetics from blood and urine in healthy volunteers.
timeFrame: Blood: From days 1 and 15 - Pre-dose, 5, 15 and 30mins, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48, 72 hrs (also 96 and 120hrs and follow-up). Urine: From days 1 and 15: pre-dose and 6, 12, 24, 48 and 72hrs.
measure: Description of the pharmacodynamic (PD) effects of AZD8683 in healthy volunteers in terms of : FEV1 and FVC.
timeFrame: Predose, 5mins, 30mins, 1hr, 2hrs, and 4hrs on days 1 and 15.
measure: Description of the pharmacodynamic (PD) effects of AZD8683 in COPD patients in terms of : FEV1 and FVC.
timeFrame: Predose, 5mins, 30mins, 1hr, 2hrs and 4hrs on days 1 and 12.
measure: Description of the pharmacodynamic (PD) effects of AZD8683 in healthy volunteers in terms of : supine blood pressures and pulse rate.
timeFrame: Pre-dose, 30mins, 60mins, 90 mins, 2hrs and 4hrs, on days 1 and 15.
measure: Description of the pharmacodynamic (PD) effects of AZD8683 in COPD patients in terms of : supine blood pressures and pulse rate.
timeFrame: Pre-dose, 30mins, 60mins, 90 mins, 2hrs and 4hrs on days 1 and 12.
measure: Description of the pharmacodynamic (PD) effects of AZD8683 in healthy volunteers in terms of : QT interval corrected for heart rate using Fridericia's formula and heart rate.
timeFrame: 30mins pre-dose and 25 mins, 5mins, 1hr 25 mins, 1hr 55 mins and 3 hr 55 mins, on days 1 and 15.
measure: Description of the pharmacodynamic (PD) effects of AZD8683 in COPD patients in terms of : QT interval corrected for heart rate using Fridericia's formula and heart rate.
timeFrame: 30mins pre-dose and 25 mins, 5mins, 1hr 25 mins, 1hr 55 mins and 3 hr 55 mins on days 1 and 12.
Other outcomes:
Locations:
city: London
country: United Kingdom
Study officials:
affiliation: AstraZeneca Research and Development SE-431 83 Molndal Sweden
name: Carin Jorup
role: STUDY_DIRECTOR
References: