AZD2115 Multiple Ascending Dose Study

Study Overview
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Brief Summary
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This study will investigate the safety and tolerability of AZD2115 following administration of multiple ascending doses.

Detailed Description
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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 Multiple Ascending Inhaled Doses of AZD2115 in Healthy Male Subjects.

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 Multiple Ascending Inhaled Doses of AZD2115 in Healthy Male Subjects

Conditions
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Healthy

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 and spermicide, from the day of first administration of the AZD2115 until 3 months after administration and must not donate sperm for 3 months after follow-up Have a body mass index (BMI) between 18 and 30 kg/m2 and weigh at least 50 kg and no more than 100 kg Exclusion Criteria: Abnormal vital signs, after 10 minutes supine rest, defined as any of the following: Systolic BP >140 mmHg Diastolic BP >90 mmHg Heart rate <40 or >85 bpm Prolonged QTcF >450 ms or shortened QTcF <340 ms or family history of long QT syndrome Serum potassium concentration of < 3.80 mmol/L on admission (Day -1) History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with the same class to AZD2115 or to excipients 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

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: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of the safety profile in terms of adverse events, blood pressure, pulse, temperature, ECG (Electrocardiogram), lung function (Spirometry), physical examination, safety labs | No formal statistical tests will be performed. Abnormalities will be listed without statistical analysis | baseline, up to 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of the pharmacokinetics (PK) of AZD2115 in terms of area under the curve over the time (AUC) and maximum concentration (Cmax) and terminal half-life | PK samples collected post-dose at 5mins, 20mins, 40mins, 1hr, 1.5hrs, 2 hrs, 4hrs, 6hrs, 8hrs, 12hrs, 24hrs 36 hrs, 48hrs | day 1 | 
| Description of pharmacokinetics (PK) of AZD2115 in terms of Cmax, area under the plasma concentration-time curve from zero to the end of the dosing interval (AUC(0-τ)) | PK samples collected post-dose at 5mins, 20mins, 40mins, 1hr, 1.5hrs, 2 hrs, 4hrs, 6hrs, 8hrs, 12hrs, 24hrs 36 hrs, 48hrs 72hrs, 96hrs, 120hrs and 168hrs. | day 17 | 
| Description of achievement of plasma drug concentration steady state | An exploratory analysis of achievement of steady state will be evaluated graphically. | PK samples collected pre-dose on day 1, day 4, day 6, day 10, day 14, day 17 | 
| Description of pharmacodynamics of AZD2115 in terms of FEV1 (forced expiratory volume in the first second), FVC (forced vital capacity), potassium, glucose, systolic and diastolic blood pressure, pulse rate, heart rate, QTcF | QTcF defined as QT interval corrected for heart rate using Fridericia's formula | day 1, day 17 | 

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