A Study to Assess the Relative Bioavailability of Process Variants of Selumetinib in Healthy Male Volunteers
Condition: Healthy Volunteers Bioequivalence or Bioavailability Study
Intervention: selumetinib 75mg single dose; selumetinib 75mg single dose; selumetinib 75mg single dose
Intervention description: 3 blue capsules of 25 mg given as a single dose; 3 capsules of 25 mg given as a single dose; 3 capsules of 25 mg given as a single dose
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: Male
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: bioequivalence; bioavailability; pharmacokinetics; Phase I; AZD6244; cancer

Summary:

      A Study to assess, against a reference selumetinib capsule, if the drug levels of a variant
      of selumetinib capsule are comparable, and to assess how drug levels differed in another
      variant of Selumetinib in Healthy Male Volunteers.
    

Eligibility criteria:

        Inclusion Criteria:1.Provision of written informed consent 2.Healthy male volunteers aged
        18 to 45 years 3.Calculated creatinine clearance (CrCL) >50 mL/minute using the
        Cockcroft-Gault formula 4.Healthy volunteers with sexual partners who could become pregnant
        should agree to use 2 highly effective methods of contraception. Healthy volunteers with
        sexual partners who are pregnant should agree to use an effective method of contraception
        (barrier method) from the first administration until 12 weeks after the last administration
        of the investigational product. Healthy volunteers should avoid sperm donation during the
        study and for 12 weeks after the last administration of the investigational product 5.Use
        no nicotine containing products for at least 3 months prior to screening 6.For inclusion in
        the genetic component of the study, healthy volunteers provide written informed consent for
        genetic research.

        Exclusion Criteria:

        1.Healthy male volunteers of Japanese or non Japanese Asian, or Indian ethnicity 2.Any one
        parent or grandparent (maternal or paternal) is Japanese or non-Japanese Asian or Indian
        3.Involvement in the planning and/or conduct of the study. 4.Previous randomisation to
        treatment in the present study 5.Participation in another clinical study within 3 month
        before Visit 1, or participation in a method development study 1 month before Visit 1.
        6.Current or past history of central serous retinopathy or retinal vein thrombosis,
        intraocular pressure greater than 21 mmHg or uncontrolled glaucoma 7.Any clinically
        significant disease or disorder that may put the healthy volunteer at risk because of
        participation in the study, influence the result of the study or influence the healthy
        volunteer's ability to participate in the study 8.Any clinically relevant abnormal findings
        in physical examination, haematology, clinical chemistry, urinalysis, vital signs or
        12-lead ECG at Visit 1, which may put the healthy volunteer at risk because of his
        participation in the study. 9.Use of prescribed medications and over-the-counter drugs
        (including herbal remedies) known to have moderate or strong cytochrome P450 (CYP) 3A4 or
        CYP2C19 inducer or inhibitory effects from 30 days prior to the first administration of
        investigational product until the follow up visit 10.Use of any other prescribed
        medications and over-the-counter drugs (including herbal remedies, vitamins and minerals)
        within 2 weeks or 5 times the half life, whichever is longer, of the respective drug prior
        to Visit 2, with the exception of occasional use of acetaminophen (paracetamol or TYLENOL®)
        and over-the-counter adrenergic nasal spray for relief of nasal congestion. No medications
        known to prolong the QT/corrected QT interval (QTc) interval are allowed 11.Excessive
        intake of caffeine containing drinks or food. 12.Any intake of grapefruit and Seville
        oranges or other products containing grapefruit or Seville oranges within 7 days of the
        first admission 13.A definite or suspected personal history of intolerance or
        hypersensitivity to drugs and/or their excipients 14.Plasma donation or any blood
        donation/blood loss greater than 500 mL during the 3 months prior to screening 15.History
        of, or current alcohol or drug abuse. 16.A suspected/manifested infection according to the
        International Air Transport Association (IATA) Categories A and B infectious substances
        17.Healthy male volunteers who do not agree to use at least 2 effective methods of
        contraception 18.Positive results at screening for human immunodeficiency virus (HIV)
        and/or hepatitis B and/or hepatitis C 19.Planned inpatient surgery, dental procedure or
        hospitalisation during the study 20.Healthy male volunteers who, in the opinion of the
        Principal Investigator, should not participate in the study 21.Healthy male volunteers with
        a LVEF <55% 22.Previous bone marrow transplant 23.Whole blood transfusion within 120 days
        of the genetic sample collection