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

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ClinicalTrials.gov Identifier: NCT01974349
Recruitment Status : Completed
First Posted : November 1, 2013
Last Update Posted : August 13, 2014
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE October 28, 2013
First Posted Date  ICMJE November 1, 2013
Last Update Posted Date August 13, 2014
Study Start Date  ICMJE November 2013
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 31, 2013)
Pharmacokinetics of selumetinib and N desmethyl selumetinib, by assessment of maximum plasma concentration (Cmax) [ Time Frame: 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 ]
Curve taken during each of the 2 treatments
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2013)
  • Pharmacokinetics of selumetinib and N desmethyl selumetinib, by assessment of the area under the plasma concentration-time curve from time zero to infinity (AUC) [ Time Frame: 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 ]
    Curve taken during each of the 2 treatments
  • 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) [ Time Frame: 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 ]
    Curve taken during each of the 2 treatments
  • 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) [ Time Frame: 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 ]
    Curve taken during each of the 2 treatments
  • Pharmacokinetics of selumetinib and N desmethyl selumetinib, by assessment of time to Cmax (tmax) [ Time Frame: 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 ]
    Curve taken during each of the 2 treatments
  • Pharmacokinetics of selumetinib by assessment of apparent systemic plasma clearance (CL/F) [ Time Frame: 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 ]
    Curve taken during each of the 2 treatments
  • Pharmacokinetics of selumetinib by assessment of apparent volume at distribution equilibrium, mean residence time (MRT)*CL/F (Vss/F) [ Time Frame: 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 ]
    Curve taken during each of the 2 treatments
  • Pharmacokinetics of selumetinib by assessment of apparent volume at distribution (Vz/F) [ Time Frame: 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 ]
    Curve taken during each of the 2 treatments
  • Pharmacokinetics of selumetinib and N desmethyl selumetinib by assessment of terminal half-life (t½) [ Time Frame: 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 ]
    Curve taken during each of the 2 treatments
  • Pharmacokinetics of selumetinib and N desmethyl selumetinib by assessment of terminal rate constant (λz) [ Time Frame: 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 ]
    Curve taken during each of the 2 treatments
  • Pharmacokinetics of selumetinib and N desmethyl selumetinib by assessment of (MRT) [ Time Frame: 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 ]
    Curve taken during each of the 2 treatments
  • Pharmacokinetics of selumetinib and N desmethyl selumetinib by assessment of AUC metabolite to parent ratio, N-desmethyl selumetinib AUC/selumetinib (AUC MRAUC) [ Time Frame: 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 ]
    Curve taken during each of the 2 treatments
  • Pharmacokinetics of selumetinib and N desmethyl selumetinib by assessment of Cmax metabolite to parent ratio, N-desmethyl selumetinib Cmax/selumetinib Cmax (MRCmax) [ Time Frame: 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 ]
    Curve taken during each of the 2 treatments
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 31, 2013)
Safety variables (adverse events, physical examinations, ophthalmologic assessments, vital signs, clinical laboratory assessments, and 12 lead electrocardiograms) [ Time Frame: Baseline (Day-1) up to Day 24 ]
Assessments performed during each of the 2 treatments
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE To Assess the Effect of Food on the Pharmacokinetics of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Healthy Male Volunteers
Official Title  ICMJE 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
Brief Summary Study to assess the effect of food on the Pharmacokinetics of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Healthy Male Volunteers
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Solid Tumours
Intervention  ICMJE Drug: selumetinib (oral)
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.
Other Name: AZD6244
Study Arms  ICMJE
  • Experimental: selumetinib 75mg (oral capsule fasted)
    Volunteers will recieve selumetinib 75mg administered by mouth, as a capsule, in a fasted state.
    Intervention: Drug: selumetinib (oral)
  • Experimental: selumetinib 75mg (oral capusle fed)
    Volunteers will receive selumetinib 75mg administered by mouth, as a capsule, in a fed state.
    Intervention: Drug: selumetinib (oral)
Publications * Tomkinson H, McBride E, Martin P, Lisbon E, Dymond AW, Cantarini M, So K, Holt D. Comparison of the Pharmacokinetics of the Phase II and Phase III Capsule Formulations of Selumetinib and the Effects of Food on Exposure: Results From Two Randomized Crossover Trials in Healthy Male Subjects. Clin Ther. 2017 Nov;39(11):2260-2275.e1. doi: 10.1016/j.clinthera.2017.08.022. Epub 2017 Oct 4.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 12, 2014)
39
Original Estimated Enrollment  ICMJE
 (submitted: October 31, 2013)
34
Actual Study Completion Date  ICMJE February 2014
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01974349
Other Study ID Numbers  ICMJE D1532C00069
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Eleanor Lisbon, MD Quintiles 6700 W 115th Street, Kansas, US
PRS Account AstraZeneca
Verification Date August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP