To Assess the Effect of Food on the Pharmacokinetics of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Healthy Male Volunteers

Study Overview
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Brief Summary
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Study to assess the effect of food on the Pharmacokinetics of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Healthy Male Volunteers

Detailed Description
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A randomized, Open-label, Single-center, Crossover Study to Assess the Effect of Food on the Pharmacokinetics of a 75 mg Single Oral Dose of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Healthy Volunteers.

Official Title
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A Phase I, Randomized, Open-label, Single-center, Crossover Study to Assess the Effect of Food on the Pharmacokinetics of a 75 mg Single Oral Dose of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Healthy Male Volunteers Aged 18 to 45 Years

Conditions
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Solid Tumours

Intervention / Treatment
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* Drug: selumetinib (oral)


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 (inclusive) and weigh at least 50 kg and no more than 100 kg (inclusive). 2. Must not have smoked or used nicotine products within the previous 3 months. 3. Have a calculated creatinine clearance (CrCL) greater than 50 mL/min using the Cockcroft-Gault formula. Exclusion Criteria: 1. Current or past history of central serous retinopathy or retinal vein thrombosis, intra-ocular pressure greater than 21 mmHg or uncontrolled glaucoma. 2. Any clinically relevant abnormal findings in physical examination, hematology, clinical chemistry, urinalysis, vital signs, or ECG at baseline in the opinion of the investigator. 3. History or presence of any clinically significant disease or disorder in the opinion of the investigator. 4. Subjects of Japanese or non-Japanese Asian ethnicity. 5. 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.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: selumetinib 75mg (oral capsule fasted)<br>Volunteers will recieve selumetinib 75mg administered by mouth, as a capsule, in a fasted state. | Drug: selumetinib (oral)<br>* Volunteers will receive: 75 mg selumetinib oral dose in a fasted state (Treatment A) followed by a second 75 mg selumetinib oral dose in the fed state (Treatment B) with a washout period of at least 7 days between doses, or: 75 mg selumetinib oral dose in the fed state (Treatment B) followed by a second 75 mg selumetinib oral dose in the fasted state (Treatment A) with a washout period of at least 7 days between doses.<br>* Other names: AZD6244;|
| Experimental: selumetinib 75mg (oral capusle fed)<br>Volunteers will receive selumetinib 75mg administered by mouth, as a capsule, in a fed state. | Drug: selumetinib (oral)<br>* Volunteers will receive: 75 mg selumetinib oral dose in a fasted state (Treatment A) followed by a second 75 mg selumetinib oral dose in the fed state (Treatment B) with a washout period of at least 7 days between doses, or: 75 mg selumetinib oral dose in the fed state (Treatment B) followed by a second 75 mg selumetinib oral dose in the fasted state (Treatment A) with a washout period of at least 7 days between doses.<br>* Other names: AZD6244;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of selumetinib and N desmethyl selumetinib, by assessment of maximum plasma concentration (Cmax) | Curve taken during each of the 2 treatments | Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, and 48 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of selumetinib and N desmethyl selumetinib, by assessment of the area under the plasma concentration-time curve from time zero to infinity (AUC) | Curve taken during each of the 2 treatments | Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, and 48 hours postdose | 
| Pharmacokinetics of selumetinib and N desmethyl selumetinib, by assessment of the area under the plasma concentration-time curve from time zero to the time of the last measurable concentration AUC(0-t) | Curve taken during each of the 2 treatments | Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, and 48 hours postdose | 
| Pharmacokinetics of selumetinib and N desmethyl selumetinib, by assessment of area under the plasma concentration-time curve from time zero to 12 hours postdose AUC (0-12) | Curve taken during each of the 2 treatments | Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, and 48 hours postdose | 
| Pharmacokinetics of selumetinib and N desmethyl selumetinib, by assessment of time to Cmax (tmax) | Curve taken during each of the 2 treatments | Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, and 48 hours postdose | 
| Pharmacokinetics of selumetinib by assessment of apparent systemic plasma clearance (CL/F) | Curve taken during each of the 2 treatments | Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, and 48 hours postdose | 
| Pharmacokinetics of selumetinib by assessment of apparent volume at distribution equilibrium, mean residence time (MRT)*CL/F (Vss/F) | Curve taken during each of the 2 treatments | Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, and 48 hours postdose | 
| Pharmacokinetics of selumetinib by assessment of apparent volume at distribution (Vz/F) | Curve taken during each of the 2 treatments | Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, and 48 hours postdose | 
| Pharmacokinetics of selumetinib and N desmethyl selumetinib by assessment of terminal half-life (t½) | Curve taken during each of the 2 treatments | Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, and 48 hours postdose | 
| Pharmacokinetics of selumetinib and N desmethyl selumetinib by assessment of terminal rate constant (λz) | Curve taken during each of the 2 treatments | Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, and 48 hours postdose | 
| Pharmacokinetics of selumetinib and N desmethyl selumetinib by assessment of (MRT) | Curve taken during each of the 2 treatments | Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, and 48 hours postdose | 
| Pharmacokinetics of selumetinib and N desmethyl selumetinib by assessment of AUC metabolite to parent ratio, N-desmethyl selumetinib AUC/selumetinib (AUC MRAUC) | Curve taken during each of the 2 treatments | Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, and 48 hours postdose | 
| Pharmacokinetics of selumetinib and N desmethyl selumetinib by assessment of Cmax metabolite to parent ratio, N-desmethyl selumetinib Cmax/selumetinib Cmax (MRCmax) | Curve taken during each of the 2 treatments | Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, and 48 hours postdose | 

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