To Assess the Effects of Single Oral Dose of Selumetinib [AZD6244; ARRY-142886] [Hyd-Sulfate]), on QTc Interval in Healthy Male Volunteers

Study Overview
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Brief Summary
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Study to assess the effect of Selumetinib [AZD6244; ARRY-142886] [Hyd-Sulfate]), on QTc interval in healthy male volunteers.

Detailed Description
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A double-blind (Selumetinib [AZD6244; ARRY-142886] [Hyd-Sulfate]), Placebo-controlled, Open-Label (Moxifloxacin) Positive-controlled, Randomized, Three-period Crossover Study to Assess the Effects of Single Oral Dose of Selumetinib (75 mg) on QTc Interval Compared to Placebo, using AVELOX (Moxifloxacin) as a Positive Control, in Healthy Male Volunteers

Official Title
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A Phase I, Double-blind (Selumetinib [AZD6244; ARRY-142886] [Hyd-Sulfate]), Placebo-controlled, Open-Label (Moxifloxacin) Positive-controlled, Randomized, Three-period Crossover Study to Assess the Effects of Single Oral Dose of Selumetinib (75 mg) on QTc Interval Compared to Placebo, Using AVELOX (Moxifloxacin) as a Positive Control, in Healthy Male Volunteers Aged 18 to 45 Years

Conditions
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Solid Tumours

Intervention / Treatment
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* Drug: Selumetinib
* Drug: Moxifloxacin
* Drug: selumetinib placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Have a body mass index (BMI) between 18 and 30 kg/m2 and weigh at least 50 kg and no more than 100 kg (inclusive). 2. Must have not smoked in the last 30 days prior to screening for this study. 3. Have a calculated creatinine clearance (CrCL) greater than 50 mL/min using the Cockcroft-Gault formula. Exclusion Criteria: 1. Subjects of Japanese or non-Japanese Asian ethnicity. 2. Subjects where any one parent or grandparent (maternal or paternal) is Japanese or non-Japanese Asian (e.g. China, Taiwan, Korea, Philippines, Thailand, Vietnam, and Malaysia). Asian Indians are acceptable. 3. Past history of central serous retinopathy or retinal vein thrombosis,intraocular pressure greater than 21 mmHg or uncontrolled glaucoma. 4. Any clinically relevant abnormal findings in physical examination, hematology, clinical chemistry, urinalysis, vital signs or ECG at baseline in the opinion of the investigator. 5. History or presence of any clinically significant disease or disorder in the opinion of the investigator.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selumetinib 75mg<br>Volunteers will receive selumetinib 75mg administered by mouth, as a capsule | Drug: Selumetinib<br>* Volunteers will receive 75 mg selumetinib oral dose (Treatment A)<br>* Other names: AZD6244;|
| Active Comparator: Moxifloxacin 400 mg<br>Volunteers will receive moxifloxacin 400mg administered by mouth, as a capsule | Drug: Moxifloxacin<br>* Volunteers will receive 400 mg Moxifloxacin oral dose (Treatment B)<br>* Other names: Avelox®;|
| Placebo Comparator: Selumetinib 75mg placebo<br>Volunteers will receive selumetinib 75mg placebo, administered by mouth, as a capsule. | Drug: selumetinib placebo<br>* Volunteers will receive selumetinib placebo oral dose (Treatment C)<br>* Other names: AZD6244 placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in QTcF | Change from baseline in QTcF at 30 minutes (msec) | 30 min | 
| Change From Baseline in QTcF | Change from baseline in QTcF at 1 hour (msec) | 1 hour | 
| Change From Baseline in QTcF | Change from baseline in QTcF at 1 hour 30 min (msec) | 1 hour 30 min | 
| Change From Baseline in QTcF | Change from baseline in QTcF at 2 hours (msec) | 2 hours | 
| Change From Baseline in QTcF | Change from baseline in QTcF at 3 hours (msec) | 3 hours | 
| Change From Baseline in QTcF | Change from baseline in QTcF at 4 hours (msec) | 4 hours | 
| Change From Baseline in QTcF | Change from baseline in QTcF at 6 hours (msec) | 6 hours | 
| Change From Baseline in QTcF | Change from baseline in QTcF at 8 hours (msec) | 8 hours | 
| Change From Baseline in QTcF | Change from baseline in QTcF at 12 hours (msec) | 12 hours | 
| Change From Baseline in QTcF | Change from baseline in QTcF at 24 hours (msec) | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, healthy, pharmacokinetics