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NCT02093728 Clinical Trial

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

Solid Tumours Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data
NCT number NCT02093728
Other study ID # D1532C00083
Secondary ID
Status Completed
Phase Phase 1
First received March 20, 2014
Last updated June 29, 2015
Start date April 2014
Est. completion date June 2014

Study information
Verified date June 2015
Source AstraZeneca
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

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

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 information / eligibility
Status Completed
Enrollment 26
Est. completion date June 2014
Est. primary completion date June 2014
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Both
Age group 18 Years to 45 Years
Eligibility 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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

Intervention

Drug:
• selumetinib
Volunteers will recieve single oral dose of 25mg selumetinib in sequence 1, treatment A
• itraconazole
Volunteers will receive oral doses of itraconazole 200 mg twice daily on Day 1 to Day 7 in sequence 1 treatment B:
• itraconazole
Volunteers will recieve a single morning dose of 200mg itraconazole on Day 8 and twice daily doses of 200mg itraconazole on Day 8 to Day 11; sequence 1 treatment C.
• selumetinib
Volunteers willl recieve a single oral dose of 25 mg selumetinib (4 hours fasted state) on Day 8; sequence 1 treatment C.
• selumetinib
Volunteers will recieve single oral dose of 25mg selumetinib in sequence 2, treatment A.
• fluconazole
Volunteers will recieve a single dose of 400 mg fluconazole on Day 1 and daily doses of 200 mg fluconazole on Day 2 to Day 7; sequence 2 treatment D.
• fluconazole
Volunteers will receive a morning dose of 200mg fluconazole on Day 8 and daily doses of 200mg fluconazole on Day 8 to Day 11; sequence 2 treatment E
• selumetinib
Volunteers will receive a single dose of 25mg selumetinib (4 hours fasted state) on Day 8; sequence 2 treatment E

Locations
Country Name City State
United States Research Site Overland Park Kansas

Sponsors (1)
Lead Sponsor Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome
Type Measure Description Time frame Safety issue
Other Safety variables (adverse events, physical examinations, opthalmologic assessements, vital signs, clinical laboratory assessments and 12 lead electrocardiograms) Assessments performed during each of the 6 treatments Baseline (Day-1) up to Day 24 Yes
Primary Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assessment of area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC) Samples taken during each of the 6 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, 48, 72 and 96 hours post dose No
Secondary 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) Samples taken during each of the 6 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, 48, 72 and 96 hours post dose No
Secondary 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) Samples taken during each of the 6 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, 48, 72 and 96 hours post dose No
Secondary Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of maximum plasma concentration (Cmax) Samples taken during each of the 6 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, 48, 72 and 96 hours post dose No
Secondary Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of time to Cmax (tmax) Samples taken during each of the 6 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, 48, 72 and 96 hours post dose No
Secondary Pharmacokinetics of selumetinib by assesement of apparent oral plasma clearance (CL/F) Samples taken during each of the 6 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, 48, 72 and 96 hours post dose No
Secondary Pharmacokinetics of selumetinib by assesement of apparent volume at distribution steady state, (MRT)*CL/F (Vss/F) Samples taken during each of the 6 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, 48, 72 and 96 hours post dose No
Secondary Pharmacokinetics of selumetinib by assesement of apparent volume at distribution (Vz/F) Samples taken during each of the 6 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, 48, 72 and 96 hours post dose No
Secondary Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of terminal half-life (t1/2) Samples taken during each of the 6 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, 48, 72 and 96 hours post dose No
Secondary Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of terminal rate constant (?z) Samples taken during each of the 6 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, 48, 72 and 96 hours post dose No
Secondary Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of AUC metabolite to parent ratio (MRAUC) Samples taken during each of the 6 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, 48, 72 and 96 hours post dose No
Secondary Pharmacokinetics of selumetinib and N-desmethyl selumetinib by assesement of Cmax metabolite to parent ratio (MRCmax) Samples taken during each of the 6 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, 48, 72 and 96 hours post dose No
Secondary Pharmacokinetics of selumetinib by assesement of mean residence time (MRT) Samples taken during each of the 6 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, 48, 72 and 96 hours post dose No
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