AZD3293 Thorough QT Study in Healthy Male Volunteers

Study Overview
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Brief Summary
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A thorough QT study of AZD3293

Detailed Description
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A Single-Center, Randomized, Double-Blinded, Placebo-Controlled, 4-way Cross-over Study to Assess the Effect of a Single Oral Dose of AZD3293 Administration on QTc Interval Compared to Placebo, Using Open-Label AVELOX (moxifloxacin) as a Positive Control, in Healthy Male Subjects

Official Title
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A Single-Center, Randomized, Double-Blinded, Placebo-Controlled, 4-way Cross-over Study to Assess the Effect of a Single Oral Dose of AZD3293 Administration on QTc Interval Compared to Placebo, Using Open-Label AVELOX (Moxifloxacin) as a Positive Control, in Healthy Male Subjects

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: AZD3293
* Drug: AZD3293
* Drug: Placebo
* Drug: Moxifloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed, written and dated informed consent prior to any study-specific procedures Healthy male subjects must be able to understand and be willing to comply with study procedures, restrictions and requirements Healthy male subjects aged 18 to 55 years Body weight ≥ 50 to ≤ 100 kg and body mass index (BMI) ≥19 to ≤30 Clinically normal findings on physical examination in relation to age, as judged by the investigator. Exclusion Criteria: History of any clinically significant disease or disorder which may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs History of previous or ongoing psychiatric disease/condition including psychosis, affective disorder, anxiety disorder, borderline state and personality disorder History of neurologic disease, including seizures (with the exception of febrile infantile seizures), recent memory impairment or clinically significant head injury History of psychotic disorder among first degree relatives

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD3293 dose A<br>AZD3293 therapeutic dose oral solution (low dose) | Drug: AZD3293<br>* AZD3293 oral solution - one single dose (low dose).<br>* Other names: beta secretase inhibitor;|
| Experimental: AZD3293 dose B<br>AZD3293 supratherapeutic dose oral solution (high dose) | Drug: AZD3293<br>* AZD3293 oral solution - one single dose (high dose).<br>|
| Placebo Comparator: Placebo<br>Placebo oral solution | Drug: Placebo<br>* Placebo oral solution - one single dose<br>|
| Active Comparator: Moxifloxacin<br>Moxifloxacin tablet | Drug: Moxifloxacin<br>* Moxifloxacin tablet - one single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of a single dose of AZD3293 low dose and high dose on the change in time-matched QTcF intervals compared with placebo. | The heart rate corrected QT (QTcF) will be calculated using Fridericia's formula | Up to 69 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of a single oral dose of moxifloxacin on the changes in time-matched QTcF intervals compared with placebo. | The heart rate corrected QT (QTcF) will be calculated using Fridericia's formula. | Up to 69 days | 
| The safety and tolerability of AZD3293 in healthy male subjects by assessing a panel of adverse events measures | Physical examination, electrocardiogram, pulse and blood pressure, weight and laboratory variables | Up to 69 days | 
| Plasma concentrations, AUC, Cmax and tmax of single dose AZD3293 and moxifloxacin in healthy male subjects | AUC(0-t): Area under the concentration versus time curve from time 0 to the time of the last quantifiable concentration to be calculated by a combination of linear and logarithmic trapezoidal methods (linear up-log down) Cmax: Maximum observed plasma concentration obtained directly from the concentration vs. time data tmax: Time to reach Cmax following dose, obtained directly from the concentration vs. time data | Up to 69 days | 
| The effect of AZD3293 on additional electrocardiogram (ECG) variables (heart rate, RR, PR, QRS, QT and QTcB) | RR: The time between corresponding points on 2 consecutive R waves on ECG. PR: ECG interval measured from the onset of the P wave to the onset of the QRS complex. QRS: ECG interval measured from the onset of the QRS complex to the J point. QT: ECG interval measured from the onset of the QRS complex to the offset of the T wave. QTcB: The heart rate corrected QT calculated using Bazett's formula. | Up to 69 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thorough QT study