AZD2115 Single Ascending Dose Study

Study Overview
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Brief Summary
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AZD2115 Single Ascending Dose Study

Official Title
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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

Conditions
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Chronic Obstructive Pulmonary Disease, Lung Disease Causing Persistent Narrowing of the Airways

Intervention / Treatment
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* Drug: AZD2115
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>AZD2115 | Drug: AZD2115<br>* Single dose, oral inhalation (nebuliser solution)<br>|
| Placebo Comparator: 2<br>Placebo to AZD2115 | Drug: Placebo<br>* Single dose, oral inhalation (nebuliser solution)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, tolerability, healthy, inhaled, respiratory disease