Back to resultsAZD8683 Multiple Dose Study in Healthy Volunteers and Chronic Obstructive Pulmonary Disease (COPD) Patients
Primary Purpose
COPD
Status
Terminated
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
AZD8683
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for COPD focused on measuring Safety, tolerability, healthy, COPD (chronic obstructive pulmonary disease), pharmacokinetic, pharmacodynamic, inhaled
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AZD8683
Placebo to AZD8683
Arm Description
Outcomes
Primary Outcome Measures
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
No formal statistical tests will be performed
Secondary Outcome Measures
AZD8683 single dose pharmacokinetics from blood and urine in healthy volunteers.
PK parameters:Cmax; tmax -Time to max plasma concentration; t½ λz,AUC-Area under the plasma concentration time curve from zero to infinity;AUC(0-t)-Area under plasma concentration time curve from zero to time of the last measurable concentration; AUC(0-24);AUC(0-72)-Area under the plasma concentration-time curve from zero to 72 hours; CL/F; Vz/F-Apparent volume of distribution during terminal phase; MRT-Mean residence time; Ae; Ae(0-t)-Cumulative amount of AZD8683 excreted unchanged in urine from zero (predose) to time t; fe-Fraction of dose excreted unchanged in urine; CLR-Renal clearance.
AZD8683 multiple dose pharmacokinetics from blood and urine in healthy volunteers.
PK paramaters:Cmax and Cmin (max and min plasma concentration);tmax;t½ λz-Terminal half-life; AUC(0-τ)-Area under the plasma concentration-time curve during the dosing interval; Cav-Average plasma concentration;CL/F-Apparent plasma clearance; Rac AUC(0-τ)-Accumulation ratio of AUC(0-τ)compared to AUC(0-24)Day1;Rac Cmax-Accumulation ratio of Cmax compared to Cmax Day 1;Ae(t1-t2), Ae(0-τ)-Amount of drug excreted unchanged in urine in a collection interval; and to the end of the dosing interval respectively;fe(0-τ)-fraction of drug excreted unchanged in urine during a dosing interva;CLR.
Description of the pharmacodynamic (PD) effects of AZD8683 in healthy volunteers in terms of : FEV1 and FVC.
Average effect over the first 4 hrs (Eav, AUEC(0-4)/4 hours).Peak effect during the first 4 hrs (Emax).FEV = Forced Expiratory Volume in 1 second. FVC = Forced Vital Capacity.
Description of the pharmacodynamic (PD) effects of AZD8683 in COPD patients in terms of : FEV1 and FVC.
Average effect over the first 4 hrs (Eav, AUEC(0-4)/4 hours).Peak effect during the first 4 hrs (Emax).FEV = Forced Expiratory Volume in 1 second. FVC = Forced Vital Capacity.
Description of the pharmacodynamic (PD) effects of AZD8683 in healthy volunteers in terms of : supine blood pressures and pulse rate.
Average effect over the first 4 hrs (Eav, AUEC(0-4)/4 hours).Peak effect during the first 4 hrs (Emax). For diastolic blood pressure the minimum value(Emin), will be used.
Description of the pharmacodynamic (PD) effects of AZD8683 in COPD patients in terms of : supine blood pressures and pulse rate.
Average effect over the first 4 hrs (Eav, AUEC(0-4)/4 hours).Peak effect during the first 4 hrs (Emax). For diastolic blood pressure the minimum value(Emin), will be used.
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.
Average effect over the first 4 hrs (Eav, AUEC(0-4)/4 hours).Peak effect during the first 4 hrs (Emax).
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.
Average effect over the first 4 hrs (Eav, AUEC(0-4)/4 hours).Peak effect during the first 4 hrs (Emax).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01584739
Brief Title
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
2. Study Status
Record Verification Date
November 2012
Overall Recruitment Status
Terminated
Study Start Date
June 2012 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
November 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COPD
Keywords
Safety, tolerability, healthy, COPD (chronic obstructive pulmonary disease), pharmacokinetic, pharmacodynamic, inhaled
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AZD8683
Arm Type
Experimental
Arm Title
Placebo to AZD8683
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
AZD8683
Intervention Description
Multiple dose, oral inhalation (Healthy volunteers) Multiple dose, oral inhalation (COPD patients)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Multiple dose, oral inhalation (Healthy volunteers) Multiple dose, oral inhalation (COPD patients
Primary Outcome Measure Information:
Title
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
Description
No formal statistical tests will be performed
Time Frame
Up to 13 days post dose.
Secondary Outcome Measure Information:
Title
AZD8683 single dose pharmacokinetics from blood and urine in healthy volunteers.
Description
PK parameters:Cmax; tmax -Time to max plasma concentration; t½ λz,AUC-Area under the plasma concentration time curve from zero to infinity;AUC(0-t)-Area under plasma concentration time curve from zero to time of the last measurable concentration; AUC(0-24);AUC(0-72)-Area under the plasma concentration-time curve from zero to 72 hours; CL/F; Vz/F-Apparent volume of distribution during terminal phase; MRT-Mean residence time; Ae; Ae(0-t)-Cumulative amount of AZD8683 excreted unchanged in urine from zero (predose) to time t; fe-Fraction of dose excreted unchanged in urine; CLR-Renal clearance.
Time Frame
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.
Title
AZD8683 multiple dose pharmacokinetics from blood and urine in healthy volunteers.
Description
PK paramaters:Cmax and Cmin (max and min plasma concentration);tmax;t½ λz-Terminal half-life; AUC(0-τ)-Area under the plasma concentration-time curve during the dosing interval; Cav-Average plasma concentration;CL/F-Apparent plasma clearance; Rac AUC(0-τ)-Accumulation ratio of AUC(0-τ)compared to AUC(0-24)Day1;Rac Cmax-Accumulation ratio of Cmax compared to Cmax Day 1;Ae(t1-t2), Ae(0-τ)-Amount of drug excreted unchanged in urine in a collection interval; and to the end of the dosing interval respectively;fe(0-τ)-fraction of drug excreted unchanged in urine during a dosing interva;CLR.
Time Frame
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.
Title
Description of the pharmacodynamic (PD) effects of AZD8683 in healthy volunteers in terms of : FEV1 and FVC.
Description
Average effect over the first 4 hrs (Eav, AUEC(0-4)/4 hours).Peak effect during the first 4 hrs (Emax).FEV = Forced Expiratory Volume in 1 second. FVC = Forced Vital Capacity.
Time Frame
Predose, 5mins, 30mins, 1hr, 2hrs, and 4hrs on days 1 and 15.
Title
Description of the pharmacodynamic (PD) effects of AZD8683 in COPD patients in terms of : FEV1 and FVC.
Description
Average effect over the first 4 hrs (Eav, AUEC(0-4)/4 hours).Peak effect during the first 4 hrs (Emax).FEV = Forced Expiratory Volume in 1 second. FVC = Forced Vital Capacity.
Time Frame
Predose, 5mins, 30mins, 1hr, 2hrs and 4hrs on days 1 and 12.
Title
Description of the pharmacodynamic (PD) effects of AZD8683 in healthy volunteers in terms of : supine blood pressures and pulse rate.
Description
Average effect over the first 4 hrs (Eav, AUEC(0-4)/4 hours).Peak effect during the first 4 hrs (Emax). For diastolic blood pressure the minimum value(Emin), will be used.
Time Frame
Pre-dose, 30mins, 60mins, 90 mins, 2hrs and 4hrs, on days 1 and 15.
Title
Description of the pharmacodynamic (PD) effects of AZD8683 in COPD patients in terms of : supine blood pressures and pulse rate.
Description
Average effect over the first 4 hrs (Eav, AUEC(0-4)/4 hours).Peak effect during the first 4 hrs (Emax). For diastolic blood pressure the minimum value(Emin), will be used.
Time Frame
Pre-dose, 30mins, 60mins, 90 mins, 2hrs and 4hrs on days 1 and 12.
Title
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.
Description
Average effect over the first 4 hrs (Eav, AUEC(0-4)/4 hours).Peak effect during the first 4 hrs (Emax).
Time Frame
30mins pre-dose and 25 mins, 5mins, 1hr 25 mins, 1hr 55 mins and 3 hr 55 mins, on days 1 and 15.
Title
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.
Description
Average effect over the first 4 hrs (Eav, AUEC(0-4)/4 hours).Peak effect during the first 4 hrs (Emax).
Time Frame
30mins pre-dose and 25 mins, 5mins, 1hr 25 mins, 1hr 55 mins and 3 hr 55 mins on days 1 and 12.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carin Jorup
Organizational Affiliation
AstraZeneca Research and Development SE-431 83 Molndal Sweden
Official's Role
Study Director
Facility Information:
City
London
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
AZD8683 Multiple Dose Study in Healthy Volunteers and Chronic Obstructive Pulmonary Disease (COPD) Patients
We'll reach out to this number within 24 hrs