To Assess the Effect of Itraconazole and Fluconazole on the Pharmacokinetics of Selumetinib in Healthy Male Volunteers
Phase 1
Completed
- Conditions
- Solid Tumours
- Interventions
- Registration Number
- NCT02093728
- Lead Sponsor
- AstraZeneca
- Brief Summary
Study to assess the effect of Itraconazole and Fluconazole on the pharmacokinetics of Selumetinib (AZD6244; ARRY-142866) ( Hyd-Sulfate) in Healthy Male Volunteers
- Detailed 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 26
Inclusion Criteria
- 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.
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Exclusion Criteria
- 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.
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description selumetinib; itraconazole; selumetinib + itraconazole itraconazole Volunteers will receive selumetinib 25mg alone; itraconazole 200mg pre-dosing; selumetinib 25mg and itraconazole 200mg; all adminstered by mouth as a capsule selumetinib; itraconazole; selumetinib + itraconazole selumetinib Volunteers will receive selumetinib 25mg alone; itraconazole 200mg pre-dosing; selumetinib 25mg and itraconazole 200mg; all adminstered by mouth as a capsule selumetinib; fluconazole; selumetinib + fluconazole selumetinib 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. selumetinib; fluconazole; selumetinib + fluconazole fluconazole 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.
- Primary Outcome Measures
Name Time Method Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assessment of area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC) Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose Samples taken during each of the 6 treatments
- Secondary Outcome Measures
Name Time Method Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of area under the plasma concentration-time from time zero to the time of the last quantifiable concentration (AUC(0-t) Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose Samples taken during each of the 6 treatments
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of area under the plasma concentration-time curve from time zero to 12 hours post-dose AUC(0-12) Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose Samples taken during each of the 6 treatments
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of maximum plasma concentration (Cmax) Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose Samples taken during each of the 6 treatments
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of time to Cmax (tmax) Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose Samples taken during each of the 6 treatments
Pharmacokinetics of selumetinib by assesement of apparent oral plasma clearance (CL/F) Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose Samples taken during each of the 6 treatments
Pharmacokinetics of selumetinib by assesement of apparent volume at distribution steady state, (MRT)*CL/F (Vss/F) Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose Samples taken during each of the 6 treatments
Pharmacokinetics of selumetinib by assesement of apparent volume at distribution (Vz/F) Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose Samples taken during each of the 6 treatments
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of terminal half-life (t1/2) Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose Samples taken during each of the 6 treatments
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of terminal rate constant (λz) Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose Samples taken during each of the 6 treatments
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of AUC metabolite to parent ratio (MRAUC) Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose Samples taken during each of the 6 treatments
Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of Cmax metabolite to parent ratio (MRCmax) Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose Samples taken during each of the 6 treatments
Pharmacokinetics of selumetinib by assesement of mean residence time (MRT) Blood samples are collected pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 hours post dose Samples taken during each of the 6 treatments
Trial Locations
- Locations (1)
Research Site
🇺🇸Overland Park, Kansas, United States