Clinical trial NCT01951599: To Determine the Relative Bioavailability of Different Formulations of AZD9291 and the Effect of Food.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Phase I, healthy, bioavailability, pharmacokinetics, safety, tolerability.
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2013-09-26
Enrollment: 35
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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

Eligibility 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.

Primary outcomes:
measure: Pharmacokinetics of AZD9291 and its metabolites, by assessment of maximum plasma concentration (Cmax)
timeFrame: 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 outcomes:
measure: Pharmacokinetics of AZD9291 and its metabolites by assessment of the area under the plasma concentration-time curve from zero to infinity (AUC)
timeFrame: 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
measure: Pharmacokinetics of AZD9291 and its metabolites, by assessment of time to Cmax (tmax)
timeFrame: 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
measure: Pharmacokinetics of AZD9291 and its metabolites, by assessment of Terminal rate constant (λz)
timeFrame: 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
measure: Pharmacokinetics of AZD9291 and its metabolites, by assessment of Terminal half life (t1/2,λz)
timeFrame: 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
measure: Pharmacokinetics of AZD9291 and its metabolites, by assessment of lag time before observation of quantifiable analyte concentrations in plasma (tlag)
timeFrame: 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
measure: 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)]
timeFrame: 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
measure: Pharmacokinetics of AZD9291 and its metabolites, by assessment of area under the plasma concentration-time curve from zero to 72 hours [AUC(0-72)]
timeFrame: 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
measure: Pharmacokinetics of AZD9291 only, by assessment of apparent plasma clearance (CL/F).
timeFrame: 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
measure: Pharmacokinetics of AZD9291 only, apparent volume of distribution (Vz/F)
timeFrame: 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
measure: Pharmacokinetics of AZD9291 parent to metabolite ratio (calculated for both Cmax and AUC).
timeFrame: 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 outcomes:
measure: Safety variables (adverse events, physical exam, vital signs, ECG's, clinical laboratory safety tests, opthalmological examination)
timeFrame: Baseline (Day-1) to Day 28
Locations:
city: Overland Park
country: United States
facility: Research Site
state: Kansas
Study officials:
affiliation: Quintiles 6700 W 115th Street, Kansas, US
name: Phil Leese, MD
role: PRINCIPAL_INVESTIGATOR
References: