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

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

Detailed Description
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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

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: AZD9291
* Drug: AZD9291
* Drug: AZD9291
* Drug: AZD9291
* Drug: AZD9291


Participation Criteria
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Eligibility Criteria
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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: Any clinically relevant abnormalities in physical examination, vital signs, hematology, clinical chemistry, urinalysis or ECG at baseline in the opinion of the Investigator. Volunteers who have received live or live-attenuated vaccine in the 2 weeks prior to dosing. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD9291 20mg (oral capsule fasted)<br>Volunteers will receive AZD9291 20mg administered by mouth, as a capsule, in the fasted state. | Drug: AZD9291<br>* 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).<br>|
| Experimental: AZD9291 20mg (oral solution fasted)<br>Volunteers will receive AZD9291 20mg administered by mouth, as a solution, in the fasted state. | Drug: AZD9291<br>* 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).<br>|
| Experimental: AZD9291 20mg (oral tablet fasted)<br>Volunteers will receive AZD9291 20mg administered by mouth, as a tablet, in the fasted state. | Drug: AZD9291<br>* 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).<br>|
| Experimental: AZD9291 20mg (oral fasted)<br>Volunteers will receive AZD9291 20mg administered by mouth, as a capsule or tablet in the fasted state. | Drug: AZD9291<br>* 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.<br>|
| Experimental: AZD9291 20mg (oral fed)<br>Volunteers will receive AZD9291 20mg administered by mouth, as a capsule or tablet in the fed state. | Drug: AZD9291<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of AZD9291 and its metabolites, by assessment of maximum plasma concentration (Cmax) | Curve taken during each of the 5 treatments | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of AZD9291 and its metabolites by assessment of the area under the plasma concentration-time curve from zero to infinity (AUC) | Curve taken during each of the 5 treatments | 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 | 
| Pharmacokinetics of AZD9291 and its metabolites, by assessment of time to Cmax (tmax) | Curve taken during each of the 5 treatments | 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 | 
| Pharmacokinetics of AZD9291 and its metabolites, by assessment of Terminal rate constant (λz) | Curve taken during each of the 5 treatments | 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 | 
| Pharmacokinetics of AZD9291 and its metabolites, by assessment of Terminal half life (t1/2,λz) | Curve taken during each of the 5 treatments | 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 | 
| Pharmacokinetics of AZD9291 and its metabolites, by assessment of lag time before observation of quantifiable analyte concentrations in plasma (tlag) | Curve taken during each of the 5 treatments | 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 | 
| 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)] | Curve taken during each of the 5 treatments | 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 | 
| Pharmacokinetics of AZD9291 and its metabolites, by assessment of area under the plasma concentration-time curve from zero to 72 hours [AUC(0-72)] | Curve taken during each of the 5 treatments | 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 | 
| Pharmacokinetics of AZD9291 only, by assessment of apparent plasma clearance (CL/F). | Curve taken during each of the 5 treatments | 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 | 
| Pharmacokinetics of AZD9291 only, apparent volume of distribution (Vz/F) | Curve taken during each of the 5 treatments | 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 | 
| Pharmacokinetics of AZD9291 parent to metabolite ratio (calculated for both Cmax and AUC). | Curve taken during each of the 5 treatments | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, healthy, bioavailability, pharmacokinetics, safety, tolerability.