AZD8683 Multiple Dose Study in Healthy Volunteers and Chronic Obstructive Pulmonary Disease (COPD) Patients

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01584739
First received: April 2, 2012
Last updated: November 30, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
COPD
Drug: AZD8683
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

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 [ Time Frame: Up to 13 days post dose. ] [ Designated as safety issue: Yes ]
    No formal statistical tests will be performed


Secondary Outcome Measures:
  • AZD8683 single dose pharmacokinetics from blood and urine in healthy volunteers. [ 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. ] [ Designated as safety issue: No ]
    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. [ 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. ] [ Designated as safety issue: No ]
    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. [ Time Frame: Predose, 5mins, 30mins, 1hr, 2hrs, and 4hrs on days 1 and 15. ] [ Designated as safety issue: No ]
    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. [ Time Frame: Predose, 5mins, 30mins, 1hr, 2hrs and 4hrs on days 1 and 12. ] [ Designated as safety issue: No ]
    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. [ Time Frame: Pre-dose, 30mins, 60mins, 90 mins, 2hrs and 4hrs, on days 1 and 15. ] [ Designated as safety issue: No ]
    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. [ Time Frame: Pre-dose, 30mins, 60mins, 90 mins, 2hrs and 4hrs on days 1 and 12. ] [ Designated as safety issue: No ]
    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. [ 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. ] [ Designated as safety issue: No ]
    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. [ 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. ] [ Designated as safety issue: No ]
    Average effect over the first 4 hrs (Eav, AUEC(0-4)/4 hours).Peak effect during the first 4 hrs (Emax).


Enrollment: 30
Study Start Date: June 2012
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AZD8683 Drug: AZD8683
Multiple dose, oral inhalation (Healthy volunteers) Multiple dose, oral inhalation (COPD patients)
Placebo Comparator: Placebo to AZD8683 Drug: Placebo
Multiple dose, oral inhalation (Healthy volunteers) Multiple dose, oral inhalation (COPD patients

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01584739

Locations
United Kingdom
London, United Kingdom
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Carin Jorup AstraZeneca Research and Development SE-431 83 Molndal Sweden
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01584739     History of Changes
Other Study ID Numbers: D1883C00002, Eudract 2011-005588-25
Study First Received: April 2, 2012
Last Updated: November 30, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:
Safety
tolerability
healthy
COPD (chronic obstructive pulmonary disease)
pharmacokinetic
pharmacodynamic
inhaled

Additional relevant MeSH terms:
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on April 14, 2014