A Multiple Ascending Dose Study With AZD9164 Given for 13 Days in Healthy Male and Female Subjects and in Patients With Chronic Obstructive Pulmonary Disease

A Phase I, Multi Centre, Double-blind, Randomised, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses of AZD9164 Given Once Daily as Inhaled Formulation Via Turbuhaler for 13 Days in Healthy Male and Female Subjects and in Patients With Chronic Obstructive Pulmonary Disease (COPD)

The purpose of this study is to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of inhaled AZD9164 following administration of multiple ascending doses in healthy male and female subjects and COPD patients.

Study Overview

• Status: Terminated
• Conditions: Healthy; COPD
• Intervention / Treatment: Drug: AZD9164 Turbuhaler®; Drug: Placebo Turbuhaler®

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Linkoping, Sweden
    • Research Site
  • Luleå, Sweden
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and female, age 18-45, COPD patients > 40 years
• Healthy subjects and COPD patients; Provision of signed and dated, written informed consent prior to any study specific procedures
• Healthy subjects; Females must have a negative pregnancy test, must not be lactating and must be of non-child-bearing potential, by the following criteria: - irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy
• COPD patients; Females must have a negative pregnancy test, must not be lactating and must be of non-child-bearing potential, by the following criteria: Post menopausal. Woman below 50 years old will be considered post menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments, and with LH and FSH levels in the post menopausal range. Women over 50 years of age will be considered post menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment. - irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy
• Healthy subjects; Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg
• COPD patients; Have a body mass index (BMI) between 18 and 32 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg

Exclusion Criteria:

• Healthy subjects; Any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results of the subject's ability to participate in the study
• COPD patients; Any clinically significant disease or disorder (other than COPD) which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results of the subject's ability to participate in the study
• Healthy subject and COPD patients; Any clinically significant abnormalities in clinical chemistry, haematology, urinalysis or physical examination results as judged by the investigator
• Healthy subject and COPD patients; Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: A; AZD9164	Drug: AZD9164 Turbuhaler®; Dry powder for inhalation via Turbuhaler, MAD. Starting dose in healthy volunteers is 400 µg with up to two dose escalations not exceeding AstraZeneca pre-defined exposure limits. The COPD patients will receive a dose of 1000 µg.
PLACEBO_COMPARATOR: B; Placebo	Drug: Placebo Turbuhaler®; Dry powder for inhalation via Turbuhaler, MAD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety measurements (ECG's, Telemetry, Pulse, Blood Pressure, Safety Laboratory and Adverse Events)	Safety will be monitored continously and safety assessments will be made on several occasions throughout the whole study

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics samples for AZD9164	PK sampling during the residential period and intense PK sampling day 1 and 15 in healthy and day 13 in COPD patients
Investigation of PD effects	Spirometry at screening and during the residential stay

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Carin Jorup, AstraZeneca R&D, Lund, Sweden

Publications and helpful links

General Publications

• Jorup C, Bengtsson T, Strandgarden K, Sjobring U. Transient paradoxical bronchospasm associated with inhalation of the LAMA AZD9164: analysis of two Phase I, randomised, double-blind, placebo-controlled studies. BMC Pulm Med. 2014 Mar 27;14:52. doi: 10.1186/1471-2466-14-52.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (ACTUAL): June 1, 2010
• Study Completion (ACTUAL): June 1, 2010

Study Registration Dates

• First Submitted: November 19, 2009
• First Submitted That Met QC Criteria: November 19, 2009
• First Posted (ESTIMATE): November 20, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): November 19, 2010
• Last Update Submitted That Met QC Criteria: November 18, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: Phase I; AZD9164; Safety study
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: D1882C00002; EudraCT number: 2009-015645-23