Clinical trial NCT02093728: To Assess the Effect of Itraconazole and Fluconazole on the Pharmacokinetics of Selumetinib in Healthy Male Volunteers
Official title: A Phase I, 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 Aged 18 to 45 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumours
Keywords: Phase I, healthy, pharmacokinetics
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2014-03-21
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

Eligibility 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.

Primary outcomes:
measure: Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assessment of area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC)
timeFrame: 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
Secondary outcomes:
measure: 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)
timeFrame: 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
measure: 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)
timeFrame: 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
measure: Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of maximum plasma concentration (Cmax)
timeFrame: 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
measure: Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of time to Cmax (tmax)
timeFrame: 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
measure: Pharmacokinetics of selumetinib by assesement of apparent oral plasma clearance (CL/F)
timeFrame: 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
measure: Pharmacokinetics of selumetinib by assesement of apparent volume at distribution steady state, (MRT)*CL/F (Vss/F)
timeFrame: 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
measure: Pharmacokinetics of selumetinib by assesement of apparent volume at distribution (Vz/F)
timeFrame: 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
measure: Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of terminal half-life (t1/2)
timeFrame: 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
measure: Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of terminal rate constant (λz)
timeFrame: 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
measure: Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of AUC metabolite to parent ratio (MRAUC)
timeFrame: 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
measure: Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of Cmax metabolite to parent ratio (MRCmax)
timeFrame: 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
measure: Pharmacokinetics of selumetinib by assesement of mean residence time (MRT)
timeFrame: 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
Other outcomes:
measure: Safety variables (adverse events, physical examinations, opthalmologic assessements, vital signs, clinical laboratory assessments and 12 lead electrocardiograms)
timeFrame: Baseline (Day-1) up to Day 24
Locations:
city: Overland Park
country: United States
facility: Research Site
state: Kansas
Study officials:
affiliation: Quintiles 6700 W 115th Street, Kansas, US
name: David R Mathews, MD
role: PRINCIPAL_INVESTIGATOR
References: