Healthy Volunteers
Conditions
Keywords
Phase I, healthy, bioavailability, pharmacokinetics, safety, tolerability.
Brief summary
To determine the relative bioavailability of different oral formulations of AZD9291 and the effect of food in healthy volunteers.
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
Interventions
DRUGAZD9291
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).
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of AZD9291 and its metabolites, by assessment of maximum plasma concentration (Cmax) | 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
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of AZD9291 and its metabolites by assessment of the area under the plasma concentration-time curve from zero to infinity (AUC) | 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 |
| Pharmacokinetics of AZD9291 and its metabolites, by assessment of time to Cmax (tmax) | 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 |
| Pharmacokinetics of AZD9291 and its metabolites, by assessment of Terminal rate constant (λz) | 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 |
| Pharmacokinetics of AZD9291 and its metabolites, by assessment of Terminal half life (t1/2,λz) | 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 |
| Pharmacokinetics of AZD9291 and its metabolites, by assessment of lag time before observation of quantifiable analyte concentrations in plasma (tlag) | 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 |
| Pharmacokinetics of AZD9291 and its metabolites, by assessment of area under the plasma concentration-time curve from zero to 72 hours [AUC(0-72)] | 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 |
| Pharmacokinetics of AZD9291 only, by assessment of apparent plasma clearance (CL/F). | 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 |
| Pharmacokinetics of AZD9291 only, apparent volume of distribution (Vz/F) | 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 |
| Pharmacokinetics of AZD9291 parent to metabolite ratio (calculated for both Cmax and AUC). | 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 |
| 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)] | 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
| Measure | Time frame | Description |
|---|---|---|
| Safety variables (adverse events, physical exam, vital signs, ECG's, clinical laboratory safety tests, opthalmological examination) | Baseline (Day-1) to Day 28 | Assessments performed during each of the 5 treatments. |
Countries
United States
Outcome results
None listed