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To Determine the Relative Bioavailability of Different Formulations of AZD9291 and the Effect of Food.

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ClinicalTrials.gov Identifier: NCT01951599
Recruitment Status : Completed
First Posted : September 26, 2013
Last Update Posted : March 31, 2017
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
To determine the relative bioavailability of different oral formulations of AZD9291 and the effect of food in healthy volunteers.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: AZD9291 Phase 1

Detailed Description:
A Phase I, Open-label, Single-center, Sequential Design Study in Healthy Volunteers to Determine the Relative Bioavailability of Different Oral Formulations of AZD9291 and the Effect of Food

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Phase I, Open-label, Single-center, Sequential Design Study in Healthy Volunteers to Determine the Relative Bioavailability of Different Oral Formulations of AZD9291 and the Effect of Food
Actual Study Start Date : October 9, 2013
Actual Primary Completion Date : June 4, 2014
Actual Study Completion Date : June 4, 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Osimertinib

Arm Intervention/treatment
Experimental: AZD9291 20mg (oral capsule fasted)
Volunteers will receive AZD9291 20mg administered by mouth, as a capsule, in the fasted state.
Drug: AZD9291
Volunteers will receive a single 20-mg dose of AZD9291 as a capsule on day 1, in Part A, Period 1, in the fasted state. (Treatment A).

Experimental: AZD9291 20mg (oral solution fasted)
Volunteers will receive AZD9291 20mg administered by mouth, as a solution, in the fasted state.
Drug: AZD9291
Volunteers will receive a single 20-mg dose of AZD9291 as a solution on day 1, in Part A, Period 2, in the fasted state. (Treatment B).

Experimental: AZD9291 20mg (oral tablet fasted)
Volunteers will receive AZD9291 20mg administered by mouth, as a tablet, in the fasted state.
Drug: AZD9291
Volunteers will receive a single 20-mg dose of AZD9291 as a tablet on day 1, in Part A, Period 3, in the fasted state. (Treatment C).

Experimental: AZD9291 20mg (oral fasted)
Volunteers will receive AZD9291 20mg administered by mouth, as a capsule or tablet in the fasted state.
Drug: AZD9291
Volunteers will receive a single 20-mg dose of AZD9291 as a capsule or tablet on day 1, in Part B, Period 1, in the fasted state.

Experimental: AZD9291 20mg (oral fed)
Volunteers will receive AZD9291 20mg administered by mouth, as a capsule or tablet in the fed state.
Drug: AZD9291
Volunteers will receive a single 20-mg dose of AZD9291 as a capsule or tablet on day 1, in Part B, Period 2, in the fed state.




Primary Outcome Measures :
  1. Pharmacokinetics of AZD9291 and its metabolites, by assessment of maximum plasma concentration (Cmax) [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose ]
    Curve taken during each of the 5 treatments


Secondary Outcome Measures :
  1. Pharmacokinetics of AZD9291 and its metabolites by assessment of the area under the plasma concentration-time curve from zero to infinity (AUC) [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose ]
    Curve taken during each of the 5 treatments

  2. Pharmacokinetics of AZD9291 and its metabolites, by assessment of time to Cmax (tmax) [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose ]
    Curve taken during each of the 5 treatments

  3. Pharmacokinetics of AZD9291 and its metabolites, by assessment of Terminal rate constant (λz) [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose ]
    Curve taken during each of the 5 treatments

  4. Pharmacokinetics of AZD9291 and its metabolites, by assessment of Terminal half life (t1/2,λz) [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose ]
    Curve taken during each of the 5 treatments

  5. Pharmacokinetics of AZD9291 and its metabolites, by assessment of lag time before observation of quantifiable analyte concentrations in plasma (tlag) [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose ]
    Curve taken during each of the 5 treatments

  6. Pharmacokinetics of AZD9291 and its metabolites, by assessment of area under the plasma concentration-time curve from zero to time of last measurable concentration [AUC(0-t)] [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose ]
    Curve taken during each of the 5 treatments

  7. Pharmacokinetics of AZD9291 and its metabolites, by assessment of area under the plasma concentration-time curve from zero to 72 hours [AUC(0-72)] [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose ]
    Curve taken during each of the 5 treatments

  8. Pharmacokinetics of AZD9291 only, by assessment of apparent plasma clearance (CL/F). [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose ]
    Curve taken during each of the 5 treatments

  9. Pharmacokinetics of AZD9291 only, apparent volume of distribution (Vz/F) [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose ]
    Curve taken during each of the 5 treatments

  10. Pharmacokinetics of AZD9291 parent to metabolite ratio (calculated for both Cmax and AUC). [ Time Frame: Blood samples are collected pre dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, 216, 336, 504 hours post dose ]
    Curve taken during each of the 5 treatments


Other Outcome Measures:
  1. Safety variables (adverse events, physical exam, vital signs, ECG's, clinical laboratory safety tests, opthalmological examination) [ Time Frame: Baseline (Day-1) to Day 28 ]
    Assessments performed during each of the 5 treatments.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

1, Body mass index between 19 and 30 kg/m2 and weight at least 50 kg and no more than 100 kg. 2, Volunteers must be willing to use a condom, unless their partners are postmenopausal, surgically sterile, or using an effective hormonal method of contraception or intrauterine coil. 3. In addition, volunteers must agree to continue to take similar contraceptive precautions until 4 months after the last dose of AZD9291.

Exclusion Criteria:

  1. Any clinically relevant abnormalities in physical examination, vital signs, hematology, clinical chemistry, urinalysis or ECG at baseline in the opinion of the Investigator.
  2. Volunteers who have received live or live-attenuated vaccine in the 2 weeks prior to dosing.
  3. History of severe allergy/hypersensitivity or or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to AZD9291, its excipients, or drugs with a similar chemical structure or class.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01951599


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

Additional Information:
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01951599    
Other Study ID Numbers: D5160C00005
First Posted: September 26, 2013    Key Record Dates
Last Update Posted: March 31, 2017
Last Verified: March 2017
Keywords provided by AstraZeneca:
Phase I, healthy, bioavailability, pharmacokinetics, safety, tolerability.
Additional relevant MeSH terms:
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Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action