A Single-Centre, Double-blind, Double-dummy, Randomised, Placebo Controlled, Four Period Crossover Study to Assess the Effect of Single Oral Doses of AZD5672 (600mg and 150mg) on QT/QTc Interval, Compared to Placebo, using Moxifloxacin (Avelox®) as a Positive Control, in Healthy Male Volunteers
- Conditions
- rheumatoid arthritisMedDRA version: 9.1Level: HLTClassification code 10039075Term: Rheumatoid arthritis and associated conditions
- Registration Number
- EUCTR2009-011044-20-GB
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 64
1.Provision of informed consent prior to any study specific procedures.
2.Male aged between 18 and 45 years (inclusive).
3.Body Mass Index (BMI) of between 18 and 30 kg/m2. Minimum weight 50 kg.
4.Non-smoker.
For inclusion in the genetic component of the study, subjects must fulfil the following additional criterion:
1.Provision of signed, written and dated informed consent for genetic research. If a subject declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject.
The subject will not be excluded from other aspects of the study described in this Clinical Study Protocol, so long as they consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
2.Previous randomisation to treatment in the present study.
3.Participation in a clinical study involving an investigational product within 5 half-lives of active moieties of the last dose of investigational product or 3 months prior to dosing (whichever is longer). Healthy volunteers involved in non-drug methodology studies (either invasive or non-invasive) may be included without
delay, at the discretion of the investigator. Consideration should be given to a longer washout for biological agents
4.History of additional risk factors for Torsade de Pointes (e.g. heart failure, hypokalemia, personal or family history of arrhythmia or long QT syndrome).
5.Marked QTc prolongation at baseline e.g. repeated demonstration of QTc interval >450 ms or marked shortening of QTcF <350 ms.
6.Use of concomitant medications that prolong QT/QTc interval.
7.Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of the QTc interval changes. This includes volunteers with any of the following:
-Clinically significant PR (PQ) interval prolongation
-Intermittent second or third degree AV block
-Incomplete, full or intermittent bundle branch block (QRS <110ms with normal QRS and T wave morphology is acceptable if there is no evidence of ventricular hypertrophy)
-Abnormal T wave morphology, particularly in the protocol defined primary lead V2
8.Allergy or hypersensitivity to agents of the same or similar mechanism to AZD5672; allergy or hypersensitivity to Moxifloxacin or other quinolones, or any condition which could modify the absorption of Moxifloxacin as judged by the Investigator.
9.Suspected or known risk of the healthy volunteer transmitting HIV, Hepatitis B or C via infected blood. Volunteers must have negative serology for HIV, Hepatitis B and C viruses.
10.Clinically significant abnormalities in clinical chemistry, haematology or urinalysis results at any pre-dose assessment.
11.History or presence of gastrointestinal (GI), hepatic or renal disease or other condition known to interfere with the absorption, distribution, metabolism and excretion of drugs.
12.History of malignancy or neoplastic disease, except successfully treated basal or squamous cell carcinoma of the skin occurring >5 years ago.
13.Known or suspected drug abuse or positive drugs of abuse test.
14.History of excessive alcohol consumption. Excessive intake of alcohol is defined as a regular maximum weekly intake of greater than 28 units for men and 21 units for women (where 1 unit equals a half pint (285 mL) of beer or a glass of wine (125 mL) or a single measure of spirits (25 mL)).
15.If participation in the study would result in the subject donating more than 1350 mL of blood in the 12 months or 500 mL of blood in the 3 months before the end of the study.
16.Whole blood transfusion within 120 days of the date of genetic sample collection.
17.Use of prescribed medication (including IV and oral antibiotics (prescribed or over-the-counter), live/live-attenuated vaccines or St John’s Wort) in the 4 weeks prior to dosing or use of over-the-counter drugs (including herbals, vitamins and minerals) 1 week prior to dosing (excluding occasional paracetamol use).
18.Acute illness or surgical procedure within the 2 weeks prior to dosing in the opinion of the investigator or his/her dele
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the change in time-matched QTcF intervals of single dose AZD5672 600mg compared to placebo. ;Primary end point(s): To evaluate the change in time-matched QTcF intervals of single dose AZD5672 600 mg compared to placebo. ;Secondary Objective: 1.To evaluate the change in time-matched QT intervals of single dose AZD5672 150mg compared to placebo.<br>2.To evaluate the change in time matched ECG parameters (QTcB, QTcX, RR, PR and QRS) of single dose AZD5672 600mg and 150mg compared to placebo.<br>3.To assess the pharmacokinetics of single dose AZD5672 600mg and 150mg in healthy volunteers.<br>4.To evaluate the safety and tolerability of single dose AZD5672 600mg and 150mg<br>
- Secondary Outcome Measures
Name Time Method