Four-period Crossover Study to Assess the Effects of Single Oral Doses of ZD4054 (Zibotentan) (10mg and 30mg) on QTc Interval

Study Overview
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Brief Summary
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This Study compares two ZD4054 (Zibotentan) doses (10mg and 30mg) with a placebo and a positive control to look at ZD4054 (Zibotentan)'s effect on the ECG of Healthy Volunteer

Official Title
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A Phase I, Double-blind, Double-dummy, Placebo-controlled, Randomised, Four-period Crossover Study to Assess the Effects of Single Oral Doses of ZD4054 (Zibotentan) (10mg and 30mg) on QTc Interval Compared to Placebo, Using AVELOX (Moxifloxacin) as a Positive Control, in Healthy Volunteers Aged 18 to 45 Years.

Conditions
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Healthy

Intervention / Treatment
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* Drug: ZD4054
* Drug: Moxifloxacin
* Drug: ZD4054 Placebo
* Drug: Moxifloxacin placebo
* Drug: ZD4054 Placebo
* Drug: ZD4054
* Drug: ZD4054


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non Smoker Normal resting 12-lead ECG with normal QTc interval (<450 msec) Negative screens for serum hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency Virus (HIV) at screening Exclusion Criteria: Receipt of another new chemical entity in the 4 months before dosing in this study; participation in another study and participation in a non-invasive methodology study in which no drugs were given within 30 days before dosing in this study Risk (in the investigator's opinion) of transmitting, through blood or other body fluids, the agents responsible for acquired immune deficiency syndrome (AIDS), hepatitis B or hepatitis C Judgement by the investigator, that the healthy volunteer should not participate in the study

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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>ZD4054 + Moxifloxacin placebo | Drug: ZD4054<br>* ZD4054 10mg Tablet<br>* Other names: Zibotentan;Drug: Moxifloxacin placebo<br>* 1 capsule<br>Drug: ZD4054<br>* 30mg tablet<br>|
| Active Comparator: 2<br>ZD4054 placebo + Moxifloxacin | Drug: ZD4054<br>* ZD4054 10mg Tablet<br>* Other names: Zibotentan;Drug: Moxifloxacin<br>* 400 mg capsule<br>* Other names: AVELOX;Drug: ZD4054 Placebo<br>* 3 tablets<br>|
| Experimental: 3<br>ZD4054 + ZD4054 placebo + Moxifloxacin placebo | Drug: ZD4054<br>* ZD4054 10mg Tablet<br>* Other names: Zibotentan;Drug: Moxifloxacin placebo<br>* 1 capsule<br>Drug: ZD4054 Placebo<br>* 2 tablets<br>Drug: ZD4054<br>* 10mg tablet<br>|
| Placebo Comparator: 4<br>ZD4054 Placebo + Moxifloxacin placebo | Drug: ZD4054<br>* ZD4054 10mg Tablet<br>* Other names: Zibotentan;Drug: ZD4054 Placebo<br>* 3 tablets<br>Drug: Moxifloxacin placebo<br>* 1 capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to assess the maximum of the mean changes in time-matched QTcX (study specific correction) intervals after ZD4054 (Zibotentan) administration (10mg and 30mg) compared to placebo |  | Pre-dose, 0.5hr, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| assess the maximum of the mean changes in time-matched QT, QTcB (Bazett's correction), QTcF (Fridericia's correction) and QTcI (subject specific correction) intervals after ZD4054 (Zibotentan) administration (10mg and 30mg) compared to placebo |  | Pre-dose, 0.5hr, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h | 
| assess the maximum of mean changes in time-matched QTcX, QT, QTcB, QTcF and QTcI intervals after moxifloxacin administration compared to placebo. |  | Pre-dose, 0.5hr, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h | 
| further assess the safety and tolerability of ZD4054 (Zibotentan) by assessment of adverse events (AEs), laboratory variables and vital signs. |  | From time of Consent to Last Follow-up Visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ZD4054, Healthy Volunteers, QT interval