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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: AZD9291; Drug: AZD9291; Drug: AZD9291; Drug: AZD9291; Drug: AZD9291

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

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / 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).; 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).; 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).; 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.; 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.
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 capsule on day 1, in Part A, Period 1, in the fasted state. (Treatment A).; 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).; 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).; 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.; 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.
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 capsule on day 1, in Part A, Period 1, in the fasted state. (Treatment A).; 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).; 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).; 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.; 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.
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 on day 1, in Part A, Period 1, in the fasted state. (Treatment A).; 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).; 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).; 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.; 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.
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 on day 1, in Part A, Period 1, in the fasted state. (Treatment A).; 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).; 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).; 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.; 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.

What is the study measuring?

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

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Phil Leese, MD, Quintiles 6700 W 115th Street, Kansas, US

Publications and helpful links

Helpful Links

• D5160C00005revised_csp_2_signed_31March 16_REDACTED
• D5160C00005_CSR_Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2013
• Primary Completion (Actual): June 4, 2014
• Study Completion (Actual): June 4, 2014

Study Registration Dates

• First Submitted: September 24, 2013
• First Submitted That Met QC Criteria: September 24, 2013
• First Posted (Estimate): September 26, 2013

Study Record Updates

• Last Update Posted (Actual): March 31, 2017
• Last Update Submitted That Met QC Criteria: March 30, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Phase I, healthy, bioavailability, pharmacokinetics, safety, tolerability.
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Osimertinib
• Other Study ID Numbers: D5160C00005