AZD2115 Single Ascending Dose Study

A Phase I, Single Centre, Double-blind, Randomised, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Inhaled AZD2115 After Single Ascending Doses in Healthy Male Subjects

AZD2115 Single Ascending Dose Study

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease; Lung Disease Causing Persistent Narrowing of the Airways
• Intervention / Treatment: Drug: AZD2115; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • UK
    • London, UK, United Kingdom
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male subjects aged 18 to 45 years with suitable veins for cannulation or repeated venepuncture
• Male subjects should be willing to use barrier contraception ie, condoms with spermicide, from the day of dosing until 3 months after dosing with the investigational product.
• Have a body mass index (BMI) between 18 and 30 kg/m2 and weigh at least 50 kg and no more than 100 kg
• Be able to inhale from a Spira nebuliser according to given instructions

Exclusion Criteria:

• Prolonged QTcF >450 ms or shortened QTcF <340 ms or family history of long QT syndrome

• Any clinically important abnormalities in heart rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes. This includes subjects with any of the following:

  • PR (PQ) interval prolongation >200 ms (first degree AV block)
  • Intermittent second or third degree AV block (based on screening or pre-dose ECG)
  • Incomplete, full or intermittent bundle branch block (QRS <110 ms with normal QRS and T wave morphology is acceptable if there is no evidence of left ventricular hypertrophy)
  • Abnormal T wave morphology, particularly in the protocol defined primary lead
  • Dropped beats
• 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 AZD2115 and/or excipients
• History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
• Serum potassium concentration of <3.80 mmol/L on admission (Day -1)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; AZD2115	Drug: AZD2115; Single dose, oral inhalation (nebuliser solution)
Placebo Comparator: 2; Placebo to AZD2115	Drug: Placebo; Single dose, oral inhalation (nebuliser solution)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the frequency of adverse events of inhaled single doses of AZD2115	Measurements will be taken at screening
To evaluate the laboratory safety assessments of inhaled single doses of AZD2115	Measurements will be taken at screening
To evaluate the vital signs of inhaled single doses of AZD2115	Measurements will be taken at screening
To evaluate the physical examination of inhaled single doses of AZD2115	Measurements will be taken at screening
To evaluate the ECG of inhaled single doses of AZD2115	Measurements will be taken at screening
To evaluate the frequency of adverse events of inhaled single doses of AZD2115	Measurements will be taken pre-dose
To evaluate the frequency of adverse events of inhaled single doses of AZD2115	Measurements will be taken at multiple timelpoints during dosing day through to 48 hours post-dose
To evaluate the frequency of adverse events of inhaled single doses of AZD2115	Measurements will be taken at follow up 7-13 days post dose.
To evaluate the laboratory safety assessments of inhaled single doses of AZD2115	Measurements will be taken at pre-dose
To evaluate the laboratory safety assessments of inhaled single doses of AZD2115	Measurements will be taken at multiple timelpoints during dosing day through to 48 hours post-dose
To evaluate the laboratory safety assessments of inhaled single doses of AZD2115	Measurements will be taken at follow up 7-13 days post dose.
To evaluate the vital signs of inhaled single doses of AZD2115	Measurements will be taken at pre-dose
To evaluate the vital signs of inhaled single doses of AZD2115	Measurements will be taken at multiple timelpoints during dosing day through to 48 hours post-dose
To evaluate the vital signs of inhaled single doses of AZD2115	Measurements will be taken at follow up 7-13 days post dose.
To evaluate the physical examination of inhaled single doses of AZD2115	Measurements will be taken at pre-dose
To evaluate the physical examination of inhaled single doses of AZD2115	Measurements will be taken at multiple timelpoints during dosing day through to 48 hours post-dose
To evaluate the physical examination of inhaled single doses of AZD2115	Measurements will be taken at follow up 7-13 days post dose.
To evaluate the ECG of inhaled single doses of AZD2115	Measurements will be taken at pre-dose
To evaluate the ECG of inhaled single doses of AZD2115	Measurements will be taken at multiple timelpoints during dosing day through to 48 hours post-dose
To evaluate the ECG of inhaled single doses of AZD2115	Measurements will be taken at follow up 7-13 days post dose.

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the pharmacokinetics of a single dose of AZD2115 by assessment of area under the curve over the time (AUC) and maximum concentration (Cmax).	Frequent sampling occasions during study days, before and up to 48 h after dosing
To investigate the pharmacodynamic effects of inhaled single ascending doses of AZD2115 - FEV1	Measurements will be taken at screening, pre-dose and at multiple timelpoints during dosing day through to 48 hours post-dose and then again at follow up 7-13 days post dose.
To investigate the pharmacodynamic effects of inhaled single ascending doses of AZD2115 - potassium	Measurements will be taken at screening, pre-dose and at multiple timelpoints during dosing day through to 48 hours post-dose and then again at follow up 7-13 days post dose.
To investigate the pharmacodynamic effects of inhaled single ascending doses of AZD2115 - glucose	Measurements will be taken at screening, pre-dose and at multiple timelpoints during dosing day through to 48 hours post-dose and then again at follow up 7-13 days post dose.
To investigate the pharmacodynamic effects of inhaled single ascending doses of AZD2115 - systolic and diastolic blood pressure	Measurements will be taken at screening, pre-dose and at multiple timelpoints during dosing day through to 48 hours post-dose and then again at follow up 7-13 days post dose.
To investigate the pharmacodynamic effects of inhaled single ascending doses of AZD2115 - pulse, heart rate	Measurements will be taken at screening, pre-dose and at multiple timelpoints during dosing day through to 48 hours post-dose and then again at follow up 7-13 days post dose.
To investigate the pharmacodynamic effects of inhaled single ascending doses of AZD2115 - QTcF	Measurements will be taken at screening, pre-dose and at multiple timelpoints during dosing day through to 48 hours post-dose and then again at follow up 7-13 days post dose.

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: January 5, 2011
• First Submitted That Met QC Criteria: January 25, 2011
• First Posted (Estimate): January 26, 2011

Study Record Updates

• Last Update Posted (Estimate): August 18, 2011
• Last Update Submitted That Met QC Criteria: August 17, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: Safety; tolerability; healthy; respiratory disease; inhaled
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: D3060C00001