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Trial record 8 of 91 for:    MEK Inhibitor AZD-6244

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01974349
First received: October 28, 2013
Last updated: August 12, 2014
Last verified: August 2014
  Purpose
Study to assess the effect of food on the Pharmacokinetics of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Healthy Male Volunteers

Condition Intervention Phase
Solid Tumours
Drug: selumetinib (oral)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: 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

Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Curve taken during each of the 2 treatments


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Curve taken during each of the 2 treatments


Other Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    Assessments performed during each of the 2 treatments


Enrollment: 39
Study Start Date: November 2013
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: selumetinib 75mg (oral capsule fasted)
Volunteers will recieve selumetinib 75mg administered by mouth, as a capsule, in a fasted state.
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
Experimental: selumetinib 75mg (oral capusle fed)
Volunteers will receive selumetinib 75mg administered by mouth, as a capsule, in a fed state.
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

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.
  Eligibility

Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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 (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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01974349

Locations
United States, Kansas
Research Site
Overland Park, Kansas, United States
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Eleanor Lisbon, MD Quintiles 6700 W 115th Street, Kansas, US
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01974349     History of Changes
Other Study ID Numbers: D1532C00069 
Study First Received: October 28, 2013
Last Updated: August 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Phase I, healthy, pharmacokinetics, food effect.

ClinicalTrials.gov processed this record on December 02, 2016