To Assess the Effect of Itraconazole and Fluconazole on the Pharmacokinetics of Selumetinib in Healthy Male Volunteers

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Solid Tumours

Treatments: Drug: fluconazole; Drug: itraconazole; Drug: selumetinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02093728

D1532C00083

Details and patient eligibility

About

Study to assess the effect of Itraconazole and Fluconazole on the pharmacokinetics of Selumetinib (AZD6244; ARRY-142866) ( Hyd-Sulfate) in Healthy Male Volunteers

Full description

A Open-label, Single-center Study to Assess the Effect of the CYP3A4 Inhibitor Itraconazole and the CYP2C19 Inhibitor Fluconazole on the Pharmacokinetics of a 25 mg Single Oral Dose of Selumetinib (AZD6244; ARRY-142866) ( Hyd-Sulfate) in Healthy Volunteers

Enrollment: 26 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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. 2. Female subjects of non-childbearing potential. 3. Have a calculated creatinine clearance (CrCL) >50 mL/min using the Cockcroft-Gault formula.

Exclusion Criteria: 1. Subjects of Japanese or non-Japanese Asian ethnicity. 2. Any one parent or grandparent (maternal or paternal) is Japanese or non-Japanese. Asian (ie, China, Taiwan, Korea, Philippines, Thailand, Vietnam and Malaysia). Asian Indians are acceptable. 3. Current or past history of central serous retinopathy or retinal vein thrombosis,intra-ocular pressure >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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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26 participants in 2 patient groups

selumetinib; itraconazole; selumetinib + itraconazole

Experimental group

Description:

Volunteers will receive selumetinib 25mg alone; itraconazole 200mg pre-dosing; selumetinib 25mg and itraconazole 200mg; all adminstered by mouth as a capsule

Treatment:

Drug: selumetinib

Drug: selumetinib

Drug: selumetinib

Drug: itraconazole

Drug: selumetinib

Drug: itraconazole

selumetinib; fluconazole; selumetinib + fluconazole

Experimental group

Description:

Volunteers will receive selumetinib 25mg alone administered by mouth as a capsule; fluconazole 400mg and fluconazole 200mg pre-dosing, administered by mouth as a tablet; selumetinib 25mg and fluconazole 200mg.

Treatment:

Drug: fluconazole

Drug: selumetinib

Drug: fluconazole

Drug: selumetinib

Drug: selumetinib

Drug: selumetinib