To Determine the Relative Bioavailability of Different Formulations of AZD9291 and the Effect of Food.
- Registration Number
- NCT01951599
- Lead Sponsor
- AstraZeneca
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 35
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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description AZD9291 20mg (oral capsule fasted) AZD9291 Volunteers will receive AZD9291 20mg administered by mouth, as a capsule, in the fasted state. AZD9291 20mg (oral solution fasted) AZD9291 Volunteers will receive AZD9291 20mg administered by mouth, as a solution, in the fasted state. AZD9291 20mg (oral tablet fasted) AZD9291 Volunteers will receive AZD9291 20mg administered by mouth, as a tablet, in the fasted state. AZD9291 20mg (oral fasted) AZD9291 Volunteers will receive AZD9291 20mg administered by mouth, as a capsule or tablet in the fasted state. AZD9291 20mg (oral fed) AZD9291 Volunteers will receive AZD9291 20mg administered by mouth, as a capsule or tablet in the fed state.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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 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 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 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
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
Trial Locations
- Locations (1)
Research Site
🇺🇸Overland Park, Kansas, United States