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

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

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.

Study Overview

• Status: Terminated
• Conditions: COPD
• Intervention / Treatment: Drug: AZD8683; Drug: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to 13 days post dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.
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.	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.
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.	Predose, 5mins, 30mins, 1hr, 2hrs, and 4hrs on days 1 and 15.
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.	Predose, 5mins, 30mins, 1hr, 2hrs and 4hrs on days 1 and 12.
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.	Pre-dose, 30mins, 60mins, 90 mins, 2hrs and 4hrs, on days 1 and 15.
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.	Pre-dose, 30mins, 60mins, 90 mins, 2hrs and 4hrs on days 1 and 12.
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).	30mins pre-dose and 25 mins, 5mins, 1hr 25 mins, 1hr 55 mins and 3 hr 55 mins, on days 1 and 15.
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).	30mins pre-dose and 25 mins, 5mins, 1hr 25 mins, 1hr 55 mins and 3 hr 55 mins on days 1 and 12.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Carin Jorup, AstraZeneca Research and Development SE-431 83 Molndal Sweden

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: April 2, 2012
• First Submitted That Met QC Criteria: April 24, 2012
• First Posted (Estimate): April 25, 2012

Study Record Updates

• Last Update Posted (Estimate): December 3, 2012
• Last Update Submitted That Met QC Criteria: November 30, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Safety; tolerability; pharmacokinetic; healthy; COPD (chronic obstructive pulmonary disease); pharmacodynamic; inhaled
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: D1883C00002; Eudract 2011-005588-25

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No