AZD3293 Thorough QT Study in Healthy Male Volunteers (AZD3293TQT)

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

A thorough QT study of AZD3293

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: AZD3293; Drug: AZD3293; Drug: Placebo; Drug: Moxifloxacin

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Provision of signed, written and dated informed consent prior to any study-specific procedures
2. Healthy male subjects must be able to understand and be willing to comply with study procedures, restrictions and requirements
3. Healthy male subjects aged 18 to 55 years
4. Body weight ≥ 50 to ≤ 100 kg and body mass index (BMI) ≥19 to ≤30
5. Clinically normal findings on physical examination in relation to age, as judged by the investigator.

Exclusion Criteria:

1. 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
2. History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
3. History of previous or ongoing psychiatric disease/condition including psychosis, affective disorder, anxiety disorder, borderline state and personality disorder
4. History of neurologic disease, including seizures (with the exception of febrile infantile seizures), recent memory impairment or clinically significant head injury
5. History of psychotic disorder among first degree relatives

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The relationship between plasma concentrations of AZD3293 and changes in QTcF parameters	The heart rate corrected QT (QTcF) will be calculated using Fridericia's formula	Up to 69 days

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel
• Investigators: Principal Investigator: Ronald Goldwater, MD, Parexel ECPU Baltimore

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: January 17, 2014
• First Submitted That Met QC Criteria: January 17, 2014
• First Posted (Estimate): January 20, 2014

Study Record Updates

• Last Update Posted (Estimate): July 3, 2014
• Last Update Submitted That Met QC Criteria: July 2, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Thorough QT study
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: D5010C00008